DAILYBULLETIN

Denver, Colorado

Where today’s science meets tomorrow’s care™

Opening Ceremony Blends ATS Highlights and Humor

T he ATS 2015 International Confer-ence opened with a mix of highlights of the Society’s programs and standup

comedy Saturday evening as ATS leaders reviewed milestones and recognized a variety of accomplishments before The Daily Show Senior Correspondent Aasif Mandvi offered his punchy take on science, politics, and race.

ATS President Thomas Ferkol, MD, wel-comed attendees to Denver and noted the importance of Colorado in ATS history.

“As many, but perhaps not all, of you know, the Society began in 1905 as the American Sanatorium Society, which was established to promote the treatment and prevention of tuberculosis,” Dr. Ferkol said. “Around that time, thousands of people with tuberculosis were moving to Colorado, believing the clean air was an effective treat-ment strategy.”

As the ATS celebrates its 110th anniversary, the Society has become an international orga-nization focusing on patient care and research in adult and pediatric pulmonary, critical care, and sleep medicine, Dr. Ferkol said. This year’s conference reflects that growth with the introduction of the ATS Discoveries Series, a collection of lectures from leading scientists

and clinicians about scientific and clinical breakthroughs.

The work of several ATS members and groups was recognized during the session. Dr. Ferkol discussed the creation of the ATS Acad-emy to support early career professionals, as well as the first class of ATS Scholars and ATS Educators. He also praised the development of the ATS Section on Medical Education that supports the development of teaching skills to all members of the society. And he acknowl-edged the development of the ATS Fellow-

ship in Health Equality and this year’s Health Equality Award winners, Juan C. Celedón, MD, MPH, DrPH, and Alysa Ellis, MD.

Dr. Ferkol also praised the ATS Foundation, which has awarded $11 million in grants to 183 investigators in the 10 years since the launch of the Foundation Research Program.

“With the help of this seed money, these investigators have gone on to win a total of $143 million in major grants, and many have published original research in high-impact

ATS Discoveries Series Today: Lung Regeneration, TB

T oday’s Discoveries Series lectures will cover lung regen-

eration and tuberculosis. The lectures, which will chart seminal clinical and scientific breakthroughs, will be given concurrently from 8:30 to 9:15 a.m. The Discoveries Series is presented in celebra-tion of the American Thoracic Society’s 110th anniversary.

LUNG REGENERATION: AN ACHIEVABLE MISSIONFour Seasons Ballroom 1-2 (Lower Level), Colorado Convention Center

Darrell Kotton, MD, director of regenerative medicine at Boston Uni-versity, is optimistic about the prospect for lung re-generation with new tools and a better understand-ing of the lung and how it responds to injury.

“The great hope is that we can move beyond our current approach of minimiz-ing harm to actual reparative therapies, where we regenerate lungs and make people better,” Dr. Kotton says.

In a Pulmonary Perspective article published in the June 15, 2012, Ameri-can Journal of Respiratory and Critical

Care Medicine, titled “Next-Generation Regeneration: the Hope and Hype of Lung Stem Cell Research,” Dr. Kotton surveyed three broad areas scientists in the field are advancing:

• Understanding lung epithelial responses to injury;

• Developing tissue-specific candidate lung stem/progenitor cells with the capacity for broad differentiation;

• Exogenous derivation of lung epithe-lia from embryonic stem (ES) cells or induced pluripotent stem (iPS) cells.

Dr. Kotton’s research focuses on iPS cells, which sidestep the political and ethi-cal barriers to ES cell research. Induced

MONDAYMAY 18, 2015

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ATS President Thomas Ferkol discusses Society highlights during the Opening Ceremony Saturday.

What are you looking for in

the Exhibit Hall to help you

in your research or clinical

care?

“New technology ad-

vances that may help

in the development of

new drugs to help with

disease.”

Reinilde Heyrman, MD

Neshanic Station, NJ

“I’m a researcher, and

I’m very interested

in imaging devices,

including ultrasound

and CT scans.”

Yimu Yang, MD, PhD

Aurora, CO

“I’m a pulmonologist,

and I think the pleurx

catheter is efficacious.

Patients can be taught

how to unclamp and

drain them at home

when they start to get

short of breath or feel like fluid is building

up. It cuts down on costs because you

don’t have someone coming into the

clinic or hospital. It’s also more comfort-

able for patients and has less risk of

infection.”

Angel Brown, MD, BSN

Birmingham, AL

“Mostly for my clinical

practice, I’m looking

for information about

new medications and

devices.”

Mohamed Zeitouni, MD

Brooklyn, NY

“I’m a clinician, and

I’m looking for new

technology, such as

new noninvasive

monitoring.”

Dora Alvarez, MD

Passaic, NJ

Question of the Day

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 20152

Q: What have you found most gratifying during your term as president?

A: I take pride in what the American Tho-racic Society has accomplished this year. Our membership is diverse, which is the strength of our Society, and we expanded programs to encourage and promote our early career colleagues in their varied academic pursuits vital to our mission. The fruition of the ATS Academy has been particularly gratifying. We will name the first class of ATS Scholars and ATS Educators at the upcoming International Conference, recognizing our younger mem-bers who have either received awards or have been recognized by their own assemblies for their accomplishments in research or medical education. In addition, we invested even more funds into the ATS Foundation grants pro-gram to support young physician-scientists as they begin their careers.

I am pleased to see the culmination of our 110th anniversary in the Discoveries Series, which has given us the opportunity to do something truly different. The ATS journals and ATS 2015 International Conference have coordinated their efforts to highlight many

of the advances in patient care and research in adult and pediatric pulmonary, critical care, and sleep medicine. The ATS Discover-ies Series is a new collection of articles and talks that features major scientific and clinical breakthroughs, which have changed the lives of the patients we treat, as told by leading sci-entists and clinicians. The program allows us to highlight where we have been and what we have achieved, but more important where we are going, which will have the greatest value to the practice of medicine.

Finally, we’ve also made great strides in in-creasing our visibility, which we have accom-plished by coordinating our communications efforts, upgrading our website, increasing our social media activities, and producing an annual report. All of these initiatives tell our story much more efficiently and effectively than we have in the past.

Q: In your role as president, what have you witnessed as being a big challenge

to the fields of pulmonary, critical care, and sleep medicine?A: It must be the shrinking number of individuals who are interested in pursuing academic careers worldwide. Whether you are talking about individuals who are entering a career as physician-scientists or educators teaching tomorrow’s leaders, thus defining the course of the next generation of physicians and other health professionals, the numbers

are quite worrisome. With fewer entering pul-monary research, who will make the discover-ies that will lead to scientific breakthroughs and novel treatments for children and adults with lung diseases? Without teachers, who will train the next generation and allow them to understand the many opportunities that exist in research? Who will advocate for the patients we treat? It is a threat that we must address.

I hope that the ATS Academy and a new initiative, ATS Global Scholars, which was introduced by President-Elect Atul Malhotra, MD, during the Opening Ceremony, will be-gin a larger effort to draw the best and bright-est into our fields. These programs are early but necessary steps in the right direction.

Q: Can you speak to the value of collabo-ration between the ATS and its sister

societies throughout the world?A: Only after I began my tenure four years ago did I grasp how global the American Thoracic Society was. Historically, the Society has sup-ported the creation of respiratory societies, and we have maintained strong relationships with our partners around the world. Conse-quently, I have been on the road quite a bit this past year, visiting with our sister societies, including the Japanese Respiratory Society, British Thoracic Society, Canadian Thoracic Society, Chinese Association of Chest Physi-cians, Asian Pacific Society of Respirology,

Brazilian Thoracic Society, and Turkish Tho-racic Society, to name just a few. Our visits this past year have helped to further cement these friendships.

These experiences have only confirmed my belief that the voice of many is more power-ful than the voice of one, as evidenced by the Forum of International Respiratory Societ-ies (FIRS), of which the American Thoracic Society is a founding member. The Forum is comprised of the leading international respi-ratory societies and together enhances our efforts to improve global lung health. This col-laboration led to our invitation to the United Nations High-Level Review on the Prevention and Control of Non-communicable Diseases in July 2014, and we continue our work with the Forum and the Non-communicable Dis-ease (NCD) Alliance to reduce the burden of pulmonary diseases worldwide.

Q: What do you hope to accomplish in your upcoming role as immediate past

president?A: As the immediate past president, my responsibility will be to ensure continuity and provide “institutional memory” for the Execu-tive Committee and the Board of Directors. Atul and I have spoken nearly every week this year, so the transition will be smooth. Indeed, many of his plans and goals for this year build on our recent efforts. I think they are all really quite laudable.

ATS President Thomas Ferkol, MDQ&A:An interview with

Thomas Ferkol, MD, ATS President

Former Surgeon General Speaks

Diversity Forum attendees chat with guest speaker Richard H. Carmona (right), MD, MPH, FACS,

17th Surgeon General of the United States; vice chairman, Canyon Ranch; president, Canyon

Ranch Institute; and Distinguished Professor, University of Arizona, Tucson. During the Sunday

forum, 20 talented individuals also received Minority Trainee Diversity Scholarships.

An attendee poses a question during

the New England Journal of Medicine

and the Journal of the American Medical

Association “Discussion on the Edge”

session. Eight papers about pulmonary

and critical care research published by

the New England Journal of Medicine

and the Journal of the American Medical

Association were discussed in separate

sessions Sunday. In the Pulmonary

Research session, Jeffrey M. Drazen,

MD, NEJM editor-in-chief, and George T.

O’Connor, MD, MS, JAMA associate edi-

tor, discussed four papers and answered

questions from the audience. In the

Critical Care Research session, Derek C.

Angus, MD, MPH, JAMA associate edi-

tor, and Dr. Drazen reviewed four more

papers.

JAMA, NEJM Editors Discuss Research Papers

Question of the Day

“I’m interested in new mo-

dalities to deliver treatment

options as well as variable

forms of inhaler therapy,

new broncoscopic treat-

ment options, and things

like that for my clinical

practice.”

Sheri Tran, MD

San Diego

What are you looking for in the Exhibit Hall to help you in your

research or clinical care?I’m a clinician-researcher,

and we’re looking for more

efficient ways of making a

diagnosis, so I’m looking

for any new diagnostic

therapeutic products and

medications that can help

our patients.”

Rahul Argula, MBBS, MPH

Charleston, SC

to expanding healthcare

options for individuals living with

cardiovascular and respiratory diseases

through innovative research, access,

and education programs.

Gilead is committed

© 2013 Gilead Sciences, Inc. All rights reserved. UNBP0196 August 2013Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc.

ATS President Thomas Ferkol, MD

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 20154

Read the ATS journals today at atsjournals.org

Want comprehensive coverage of the latest advances in adult and pediatric pulmonary, critical care, and sleep medicine beyond the ATS 2015 International Conference? Look no further than the journals of the American Thoracic Society, published all year long and constantly improving:

ATS Journals Cover the Entire Spectrum All Year Long

American Journal of Respiratory and Critical Care Medicine • New Fast-Tracked Clinical Trial

Protocol Review• New Early Career Group• New State-of-the-Art Articles• New Update Series Articles

• Podcasts, Videos, and More High-Quality Graphics and Charts

• New Discoveries Series Celebrating the ATS 110th Anniversary

• Blue Editor on Twitter: @ATSBlueEditor

American Journal of Respiratory Cell and Molecular Biology• First Decision in 18 Days• Junior Investigator Award to Highlight

Best Paper• New Research and Correspondence

Letters

• More High Quality Graphics and Charts

• New Discoveries Series Celebrating the ATS 110th Anniversary

Annals of the American Thoracic Society• New ATS Core Curriculum Series

(CME, ABIM, and ABP MOC Opportunities)

• New ATS Clinical Practice Guideline: Summary Series (CME, MOC Opportunities)

• Podcasts, Videos, and More High-Quality Graphics and Charts

• New Discoveries Series Celebrating the ATS 110th Anniversary

• AnnalsATS Editor on Twitter: @AnnalsATSEditor

ATS Journals App for ANDROID Now Available!

A TS 2015 attendees gathered for a special evening reception Saturday when the ATS Foundation kicked

off its Seventh Annual ATS Foundation Research Program Benefit.

The gala, featuring music, dancing, and food stations, celebrated the Foundation’s 10th anniversary and the launch of count-less highly successful research careers. In addition, the Research Program Benefit has raised a record-breaking $500,000 for the Foundation.

More than 600 attendees gathered at the Hyatt Regency Denver to socialize with friends; honor grant awardees; recognize Marvin Schwarz, MD, the recipient of the 2015 Breathing for Life Award; and celebrate the ATS Foundation’s Research Program successes of the past 10 years.

Since 2004, the ATS Foundation has pro-vided $11 million in grants to more than 183 junior investigators, launching the careers of a new generation of researchers.

“Our investigators have attracted more than $143 million in subsequent grant fund-ing, published hundreds of articles relevant to their ATS Foundation awards and have, in turn, become mentors,” says James F. Donohue, MD, chair of the ATS Foundation Board of Trustees.

In 2015, the ATS Foundation will fund more than 20 awards, including unrestricted research awards in pulmonary, critical care,

and sleep medicine; research partner awards; and awards for outstanding alumni from the Methods in Epidemiologic, Clinical and Operations Research Program. Applications for the 2015 Research Program are being accepted now, with letters of intent due by June 5, 2015.

“Through the funds raised yesterday, we hope to continue to help protect struggling young investigators who represent the future of our profession,” Dr. Donohue says.

“In its second decade, the ATS Founda-tion would like to build on the successes of the Research Program,” Dr. Donohue adds. “Through the 10th Anniversary Campaign, we propose to raise $3 million over the next three years, launching the careers of early-stage investigators dedicated to scientific discovery and better patient care.”

Dr. Schwarz was presented with the 2015 Breathing for Life Award, the highest honor given by the ATS Foundation for philanthro-py and mentoring of young investigators.

Dr. Schwarz is a legend in pulmonary medicine, particularly in the field of pulmo-nary fibrosis. His level of expertise has led many fellows and seasoned clinicians to try (usually unsuccessfully) to “Stump Marvin Schwarz” with a difficult case at the ATS Fel-lows Case Conference.

Grateful for the dedicated mentorship he received under Morton Ziskind, MD, at Tulane University, Dr. Schwarz has paid it

forward by mentoring more than 150 physi-cians and scientists, including Talmadge King Jr., MD, the 2012 Breathing for Life awardee.

“Marvin’s commitment to better un-derstanding of the causes and treatment of interstitial lung disease has been with-

out peer,” says Dr. King. “In addition, he spawned a generation of others’ interests in the disease.”

Dr. Schwarz oversaw the Fellowship Pro-gram of the Pulmonary Sciences and Critical Care Medicine Division at the University of

WHAT TO EAT & DRINK AT ATS 2015

BISTRO ATS

A well-balanced buffet lunch including beverages and dessert located in the Exhibit Hall. Tickets available at ATS registration and at the Bistro ATS.

BREATHE EASY BAR

Unwind after a full day at this Happy Hour hot spot in Lobby B. Help benefit the ATS Foundation with the purchase of the Marvin Schwarz signature drink. Open from 3:00 p.m. to 6:00 p.m. on Sunday, Monday, and Tuesday. Sponsored by MEDA Pharmaceuticals.

The Hydration Stations

Fill up your ATS water bottle fromone of 15 water coolers or 22 water fountains located around the Colorado Convention Center. Supported by Gilead Sciences, Inc.

Donors Dance and Dine in Support of Respiratory Research

James F. Donohue (left), the ATS Foundation Board of Trustees chair, presents the 2015 Breathing for Life Award to

Marvin Schwarz.

see FOUNDATION page 8

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 2015 5

ATS MEMBER

Not an ATS member? You could be!Join at the ATS Center here in Denver. Not only will you save on your International Conference registration* but you will also benefit from:• Subscriptions to three cutting-edge medical journals**,• Membership in up to three ATS Assemblies – choose from 14 assembly “interest groups” in your

area of practice that help set standards for medical care, • Professional development – at member rates – at the International Conference,• Additional learning opportunities and networking at chapter meetings,• Local and global advocacy efforts that benefit you and your patients,• Career development programs and services.Members save more than $1,000 on ATS products and services.

The American Thoracic Society:• Advances respiratory science• Fosters scientific exchange & dialogue• Disseminates knowledge• Provides guidance on clinical care• Supports young professionals

• Enhances public health• Promotes global health• Advances patient care• Nurtures local collaboration through its chapters

It pays to be an

* You must join ATS before registering for the conference to receive the discounted registration rate.** Some journals are delivered electronically only.

If you have an ATS question while you are in Denver, visit the ATS Center or send a text message to 929-224-4411 and staff will reply to you promptly.

ATS 2015

BONUS:1. Fellows/trainees receive their first year of

membership for FREE, and international members pay reduced member rates.

2. Join or renew your membership at the ATS Center and receive a FREE conference T-shirt.

Visit the ATS Center in the Exhibit Hall, booth #725 or in the F Atrium (Street Level)of the Colorado Convention Center.

ATS Develops Decision Aid for Lung Cancer Screening with CT

I n February, the Centers for Medicare & Medicaid Services issued its final coverage policy for CT lung cancer screening under

Medicare, allowing coverage of annual low-dose CT lung cancer scans for beneficiaries who meet specific criteria.

“This is the first time that Medicare has required a decision aid and the use of shared decision-making for reimbursement of a

screening test,” says Renda Wiener, MD, MPH, who as a member of the ATS Thoracic Oncology Assembly developed and reviewed the Decision Aid with Christopher Slatore, MD, MS, chair; Doug Arenberg, MD; and Marianna Sockrider, MD, DrPh, ATS medical editor for patient education.

Dr. Wiener attributes the impetus for the CMS policy requiring use of a decision aid to evidence about the benefits and harms of screening. The National Lung Screening Trial showed a 20 percent reduction in lung cancer mortality with annual CT screening, but the trial also showed a high false-positive rate—pulmonary nodules requiring further evaluation were detected in about 40 percent of patients.

Physicians can use this tool, which is avail-able at thoracic.org and will be on hand at the Assembly of Thoracic Oncology meeting from 5 to 7 p.m. tonight at the Hyatt Regency Den-ver, to help patients systematically go through the pros and cons of lung cancer screening.

“We designed the Decision Aid with lan-guage and visuals that are easy for patients to understand. It’s a useful tool to help guide the discussion about the tradeoffs of lung cancer screening and to achieve the shared decision-making that is necessary for Medicare reim-bursement,” says Dr. Wiener, assistant profes-sor of medicine at Boston University and an investigator at Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA.

The Decision Aid describes all of the considerations for lung cancer screening, including the resources for smoking cessa-tion, benefits of screening, symptoms of lung cancer, risk factors for lung cancer, research

about the benefits of screen-ing, harms of screening, physician interventions to prevent screen harms, and screening process.

“Although 95 percent of nodules detected through screening turn out to be false-positive results, the evaluation process can

expose patients to harm,” Dr. Wiener says. “That includes anxiety and distress about undergoing radiographic surveillance and not knowing whether they have cancer, physical complications for those needing a biopsy, and, in the worst-case scenario, the possibility of unnecessary surgery to remove a nodule that is thought to be malignant and turns out to be benign. Surgery, of course, has the potential for complications, including death.”

The high false-positive rate could be attrib-uted to variability in CT scan readings.

“There is a large effort to standardize the way that CT scans are read using a structured reporting system, such as Lung-RADS that has been proposed by the American College of Radiology,” Dr. Wiener says.

Renda Wiener

CRITERIA FOR MEDICARE REIMBURSEMENT

M edicare will cover lung cancer

screening with low-dose CT

once per year for Medicare

beneficiaries who meet all of the following

criteria:

• They are age 55–77, and are either current

smokers or have quit smoking within the

last 15 years;

• They have a tobacco smoking history of at

least 30 “pack years” (an average of one

pack a day for 30 years); and

• They receive a written order from a physi-

cian or qualified non-physician practitioner

that meets certain requirements.

Medicare coverage includes a visit for

counseling and shared decision-making

on the benefits and risks of lung cancer

screening. The National Coverage Deter-

mination also includes required data col-

lection and specific coverage eligibility cri-

teria for radiologists and radiology imaging

centers, consistent with the National Lung

Screening Trial protocol, U.S. Preventive

Services Task Force recommendations,

and multisociety, multidisciplinary stake-

holder evidence-based guidelines.

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 20156

David White

P resenters of a Monday afternoon scientific symposium will discuss the state of the art of personalized

medicine for obstructive sleep apnea (OSA). “Currently, the vast majority of patients

with OSA are treated with nasal continu-ous positive airway pressure (CPAP), which, although effective, is poorly tolerated by most patients and is unacceptable to many,” says David White, MD, a professor of sleep medicine at Harvard Medical School and a senior physician in the Division of Sleep Medicine at Brigham and Women’s Hospi-tal, Boston.

“Although there are other potential thera-pies, most only work in a sub-segment of OSA patients with no real way, other than

trial and error, to determine in whom these therapies might be effective. Thus many patients remain untreated,” Dr. White adds.

Dr. White and Allan Richard Schwartz, MD, professor of medicine at Johns Hop-kins University, Baltimore, are co-chairs of “Personalized Medicine for Sleep Apnea: State of the Art” from 2:15 to 4:15 p.m. in Mile High Ballroom 2B/3B (Lower Level) Colorado Convention Center.

Speakers will discuss novel ways to de-termine why a given patient has OSA, with four traits dictating those with and without OSA:

• Pharyngeal anatomy and site of collapse• Upper airway muscle control asleep• Respiratory arousal threshold

• Loop gain (ventilator control instability)“With this knowledge, therapies can be

targeted at the individual pathology with reasonable expectations for success,” says Dr. White, adding that such therapies can in-clude devices, surgery, and drugs, which can be used alone or in combination to achieve optimal results.

Symposium speakers will address sophis-ticated pharmaceutical approaches to OSA therapy, as well as more standard ones, such as surgery and oral appliances.

“This is a fundamental change in the ap-proach to OSA therapy, which to date has been

‘one size fits all,’ plus ‘trial and error.’ It also will allow the introduction of new therapies, which previously would not have been considered reasonable options,” Dr. White says.

For additional programming concen-trating on sleep-disordered breathing in personalized medicine, plan to attend today’s abstract-based mini symposium “Picking Winners. Predicting Response to Treatment of Sleep-Disordered Breath-ing in an Era of Personalized Medicine” and Wednesday’s symposium “Impact of Sleep-Disordered Breathing on Maternal and Fetal Outcomes of Pregnancy.” Both will be from 9:30 to 11:30 a.m. in Mile High Ballroom 2B/3B (Lower Level) Colorado Convention Center.

Sleep Apnea Session Delves into New Approaches for Patient Selection

Try New Apps and Grab Print Journals

B rowse the latest iPad apps from leading publishers and pick up free copies of medical journals

and news magazines at the ATS 2015 Journal & Magazine Annex in Lobby A (Street Level) in the Colorado Convention Center.

EACH IPAD KIOSK FEATURES FULL ACCESS TO:

• ATS Journals • ERS Publications• JAMA Network Reader• Journal of Hospital Medicine• Journal of Thoracic and

Cardiovascular Surgery• NEJM iPad Edition• Sleep Medicine Journals

FREE IN THE ANNEX:• American Journal of Respiratory and

Critical Care Medicine• American Journal of Respiratory Cell

and Molecular Biology• Annals of the American Thoracic

Society• Annals of Internal Medicine• Clinical Respiratory Journal• European Respiratory Journal• European Respiratory Reviews• Journal of Applied Physiology• Journal of Cystic Fibrosis• Journal of Hospital Medicine• Journal of Pediatrics• Journal of the American Medical

Association• Journal of Thoracic and

Cardiovascular Surgery• The Lancet• The Lancet Respiratory Medicine• Lung Cancer • New England Journal of Medicine• Paediatric Respiratory Reviews• Pediatric Pulmonology• Respiration• Respiratory Medicine• Sleep Medicine • Sleep Medicine Reviews • Thorax

You are cordially invited to attend an evening symposium

Nick Kim, MD, Program ChairUniversity of California, San DiegoLa Jolla, California

Tuesday, May 19, 20156:30 PM–7:00 PM Registration and Dinner7:00 PM–8:30 PM Symposium

W. Colfax Ave.

Broadway

Lincoln St

Sherman St

Grant St

W. 14th Ave

16th St

15th St

14th St

13th St

E. 17th St

Court Pl

Tremont P

lGlanarm

PlWelton Pl

E

Civic Center Park

Colorado State Capitol

ColoradoConvention Center

Sheraton Denver DowntownPlaza Ballroom DEF, Concourse Level,

Plaza Building1550 Court PlaceDenver, Colorado

Sheraton DenverDowntown

Register on-site or online at: www.PAHsymposium.com

EXPERT PERSPECTIVES: A HANDS-ONLOOK AT A CHANGING PAH LANDSCAPE

Welcome, Introductions, and PAH OverviewNick Kim, MD, Program ChairUniversity of California, San DiegoLa Jolla, California

PAH: Clinical Practice vs. Clinical TrialsNick Kim, MD

Disease Progression in PAH:Key Learnings from Recent Analyses Sean Gaine, MD, PhDMater Misericordiae University HospitalUniversity College DublinDublin, Ireland

Ronald Oudiz, MDLos Angeles Biomedical ResearchInstitute at Harbor-UCLA Medical CenterTorrance, California

Panel DiscussionAll Faculty

Concluding RemarksNick Kim, MD, Program Chair

Dinner will not be provided to physicians and other healthcare professionalslicensed in Vermont or other states where gifts and meals are prohibited. Dinnerprovided to physicians will be subject to reporting under Federal law. We regretthat spouses and other guests may not be accommodated.

An Industry-Organized Symposium at the ATS 2015 International Conference. Anon-CME educational program sponsored by Actelion Pharmaceuticals US, Inc.Open to all ATS 2015 International Conference attendees.

©2015 Actelion Pharmaceuticals US, Inc.All rights reserved. ACT-00802 0415

ATS_2015 Daily Bulletin Ad:ATS 5/1/15 11:08 AM Page 1

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 20158

ATS PAR Forum Connects Patients, Experts

S aturday’s ATS Public Advisory Roundtable (ATS PAR) gave patients and family members the opportunity

to spend a half-day meeting with experts in pulmonary, critical care, and sleep medicine, and the popularity of the forum is catching on. Attendance increased to 248 this year from 190 at ATS 2014.

The Meet-the-Experts forum featured insight-ful talks on “Lungs and Environmental Health” during the morning. Participants then met with disease experts in breakout sessions focusing on pulmonary hypertension, lipoarabinoman-nan/tuberous sclerosis, sarcoidois, scleroderma, pulmonary fibrosis, rare lung diseases, children’s interstitial lung disease, and Alpha-1.

The program resonated with Marj Korn, of Arvado, CO, who was diagnosed with idio-pathic pulmonary fibrosis in 2011. She says she appreciated the awareness she gained about her disease, current research, and how better to live her life.

“Many other people really care and want to find solutions to diseases that affect the lives of others. I thought it was fabulous,” she says.

Now in their 30s, twins Candice and Crystal Sipe were diagnosed with Hermansky-Pudlak Sydrome when they were 13. Because they live in Arizona where air quality is poor, Candice says she was fascinated by the air quality pre-sentations. Crystal says she appreciated the tips to help her overcome her irregular sleep pat-terns. Both have attended the last four forums and plan to attend ATS 2016 in San Francisco.

Meet-the-Expert Moderator Teresa Barnes has lost five family members to pulmonary fibrosis. Beyond giving patients the power to improve their lives, the ATS PAR event gives family members and caregivers a renewed

understanding of what their family members go through, says Ms. Barnes, past chair of ATS PAR and vice president of the Coalition for Pulmonary Fibrosis.

“A lot of times, there is a disconnect between a patient and family member or a caregiver. They understand the person has a disease, see them day to day and know the realities of the disease, but sometimes they don’t understand why mom is always tired, why she sleeps more than most people, why she sometimes is ir-ritable, or why she gets anxious and pulls back from the family,” Ms. Barnes says. “For them to talk to experts and understand the reasons people feel the way they do, I think they have a renewed understanding of what their family member is going through and a better relation-ship as a result.”

An Industry-Organized Symposium at the ATS 2015 International Conference

Sponsored by

TARGET AUDIENCE: A non-CmE educationalprogram sponsored by The France Foundation opento all ATS 2015 International Conference attendees.

STATEMENT OF NEED: Care of patients with IpF hasbeen transformed since the 2014 FDA approval ofpirfenidone and nintedanib for the treatment ofpatients with IpF. Furthermore, clinical results fromthe ASCEND, INpULSIS, and pANTHER trials haveraised many questions in the treatment of thesepatients. providers considering these drugs for theirpatients face decisions of which drug is best for anindividual patient, when to start, switch or combinetreatments, and how to manage side effects anddosing. This case based symposium will explorereal-world issues of treating patients with IpF.

EDUCATIONAL ACTIVITY LEARNING OBJECTIVESUpon completion of this course, the participantsshould be able to:• Describe the evidence using triple therapy or NAC to treat IpF• Discuss the efficacy, safety, and clinical application of new treatment options for patients with IpF

COMMERCIAL SUPPORT ACKNOWLEDGMENTThis activity is supported by an educational grantfrom Boehringer Ingelheim.

The France Foundation fully complies with thelegal requirements of the Americans with

Disabilities Act and the rules and regulations thereof.

There is no fee for this educational activity. Seating will be provided on a first-come, first-served basis.

TUESDAY, MAY 19, 2015 • 6:30–9:30 PMSilverton Ballroom • Embassy Suites Denver–Downtown/Convention Center

TRANSLATING IPF CLINICAL TRIALS TO

REAL LIFE PATIENTS

AGENDA & FACULTY6:30 pm Gather and Dinner

6:45 pm Welcome and Introductions LUCA RICHELDI, MD, PhD (Chair)

University of Southampton

7:00 pm Newly Available Therapies: Discussing the Difficult Questions LUCA RICHELDI, MD, PhD

7:30 pm Selecting the Right Treatment: Which Patients and When to Start Treatment? HAROLD R. COLLARD, MD University of California, San Francisco

8:00 pm Switching Drugs: When, and is There a Time for Change in Therapy? KEVIN K. BROWN, MD National Jewish Health

8:30 pm Managing Side Effects and Dosing: Need for Individualized Strategies? MARILYN K. GLASSBERG, MD University of miami miller School of medicine

9:00 pm Question & Answer

Register at: francefoundation.com/denver

A CA S E - B A S E D S Y M P O S I U M

02.ATS PILOT daily ad.qxp_Layout 1 4/28/15 3:29 PM Page 1

Controversies in Lung Cancer Screenings Put to Pro/Con Debate

T he National Lung Screening Trial (NLST) demonstrated a 20 percent relative reduction in lung cancer spe-

cific mortality with the use of annual low-dose CT scans. Current guidelines from the ATS and other organizations recommend that screening should be offered to those at high risk of developing lung cancer. The Centers for Medicare and Medicaid Services and other insurance providers now cover lung cancer screening. However, given the high false-positive rate, significant concerns remain about the harms of screening and whether the results of the NLST will trans-late to improvements in mortality among patients in routine clinical care. Most health systems are at various stages of developing screening programs.

The session “Controversies in Lung Cancer Screening: Pro/Con Debate” from 9:30 to 11:30 a.m. today in Room 605/607 (Street Level) Colorado Convention Center will explore the tradeoffs benefits and harms of screening.

“Lung cancer screening can provide ben-efit, but it can also cause harm. More people are harmed by screening than are helped, and one of the primary goals is to reduce the frequency and severity of that harm.

Implementation decisions are very impor-tant for determining that balance of benefit and harm,” says Christopher Slatore, MD, co-leader for the Lung Cancer Screening Clinical Demonstration Project at the Veter-ans Affairs Portland Health Care System and assistant professor of medicine at Oregon Health & Science University.

Dr. Slatore is co-chair of the debate with Anil Vachani, MD, MS, assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine, Philadelphia, and Nichole Tanner, MD, MSCR, assistant professor of pulmonary, critical care, allergy, and sleep medicine at the Medical University of South Carolina, Charleston.

The speakers will discuss aspects of screening where the balance of benefit and harm may be altered, depending on how it is implemented.

“The pro/con format is designed to high-light different balances of risk and harm, but not provide simplistic answers for the right or wrong ways to implement screening,” Dr. Slatore says.

Presenters will provide pro and con perspectives for whether or not lung cancer screening should adhere to U.S. Preven-tive Services Task Force criteria, whether

screening should be available at all centers, if biomarkers are ready for clinical use, and if overdiagnosis is a real problem.

“The topics are designed to provide a framework for how to weigh the benefits and risks about lung cancer screening implementation so that attendees can use them when designing their own programs,” Dr. Slatore says.

If this session interests you, don’t miss “Inflammatory Signaling Pathways Link-ing COPD and Lung Cancer: New Peaks on the Rocky Climb to a Cure” from 9:30 to 11:30 a.m. Wednesday in Room 605/607 (Street Level) Colorado Convention Center. Speakers will discuss novel insights into the biological links between COPD and lung cancer, the role of NF-kB pathway in carcinogen-induced lung cancer, the role of tumor-associated neutrophils in lung tumorigenesis, and cigarette smoke, COPD, and lung cancer.

“Controversies in Lung Cancer Screening: Pro/Con Debate” is supported by educational grants from AstraZeneca LP, Genentech, and Pfizer Inc.

Christopher Slatore

Colorado Medical Center and also served as head of the division. Although he stepped down as division director several years ago, he hasn’t hung up his lab coat. At age 75, he remains committed to his research.

Dr. Schwarz believes in the ATS Foun-dation’s mission of fostering the career development of young investigators.

“The Research Program is vitally im-portant, offering seed funding to junior investigators encouraging them to pursue careers in lung research,” says Dr. Schwarz. “Without a steady pipeline of investiga-tors leading the way, research will stall and patients will suffer.”

The ATS Foundation thanks the many individuals and 27 medical institutions that have stepped forward to support the Re-search Program during a difficult financial climate for research.

The ATS Foundation thanks Genentech for support at the Sapphire Level; Boeh-ringer Ingelheim Pharmaceuticals, Inc., and Genentech-Novartis at the Platinum Level; AstraZeneca LP and the University of Colo-rado Health at the Gold Level; Freeman, MEDA Pharmaceuticals, Inc., and Teva Respiratory at the Silver Level.

For the most up-to-date list of generous donations from individuals, medical institu-tions, and corporate supporters of the ATS Foundation, visit foundation.thoracic.org.

FOUNDATION Continued from page 4

see PAR page 27

Experts met with patients and family members during

Saturday’s ATS PAR Forum.

EXPERIENCEOUR EXPANDING PORTFOLIO

VISIT BOOTH #160

Please read Brief Summary of full Prescribing Information for SYMBICORT, including Boxed WARNING on adjacent pages. Please visit Booth 160 for full Prescribing Information.

SYMBICORT, PULMICORT FLEXHALER, and PRESSAIR are registered trademarks of the AstraZeneca group of companies. DALIRESP is a registered trademark of Takeda GmbH. TUDORZA is a registered trademark of ALMIRALL, S.A. ©2015 AstraZeneca. All rights reserved. 3117402 4/15

KJob Number: 21264Revision No: 0Date: 5/1/15

YMC083-42487 Page 1

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SYMBICORT® 80/4.5(budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol

SYMBICORT® 160/4.5(budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg)Inhalation Aerosol

For Oral Inhalation Only

Rx only

WARNING: ASTHMA RELATED DEATH

Long-acting beta2-adrenergic agonists (LABA), such as formoterol one of the active ingredients in SYMBICORT,increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safetyof another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed anincrease in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a classeffect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrentuse of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-relateddeath from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-relatedhospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, SYMBICORTshould only be used for patients not adequately controlled on a long-term asthma control medication, such as aninhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled cortico-steroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue SYMBICORT) if possible without loss of asthma control and maintain the patienton a long-term asthma control medication, such as an inhaled corticosteroid. Do not use SYMBICORT for patientswhose asthma is adequately controlled on low or medium dose inhaled corticosteroids [see WARNINGS ANDPRECAUTIONS].

BRIEF SUMMARYBefore prescribing, please see full Prescribing Information for SYMBICORT® (budesonide/formoterol fumarate dihydrate).

INDICATIONS AND USAGETreatment of AsthmaSYMBICORT is indicated for the treatment of asthma in patients 12 years of age and older.

Long-acting beta2-adrenergic agonists, such as formoterol one of the active ingredients in SYMBICORT, increase the risk ofasthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients [see WARNINGS AND PRECAUTIONS]. Therefore, when treating patientswith asthma, SYMBICORT should only be used for patients not adequately controlled on a long-term asthma-controlmedication such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both aninhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals andstep down therapy (e.g. discontinue SYMBICORT) if possible without loss of asthma control, and maintain the patient on along-term asthma control medication, such as inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma isadequately controlled on low or medium dose inhaled corticosteroids.

Important Limitations of Use:

• SYMBICORT is NOT indicated for the relief of acute bronchospasm.

Maintenance Treatment of Chronic Obstructive Pulmonary Disease (COPD)SYMBICORT 160/4.5 is indicated for the twice daily maintenance treatment of airflow obstruction in patients with chronicobstructive pulmonary disease (COPD) including chronic bronchitis and emphysema. SYMBICORT 160/4.5 is the onlyapproved dosage for the treatment of airflow obstruction in COPD.

Important Limitations of Use: SYMBICORT is not indicated for the relief of acute bronchospasm.

DOSAGE AND ADMINISTRATIONSYMBICORTshould be administered twice daily every day by the orally inhaled route only. After inhalation, the patient should rinsethe mouth with water without swallowing [see PATIENT COUNSELING INFORMATION in full Prescribing Information (17.4)].

Prime SYMBICORT before using for the first time by releasing two test sprays into the air away from the face, shaking well for5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped,prime the inhaler again by shaking well before each spray and releasing two test sprays into the air away from the face.

More frequent administration or a higher number of inhalations (more than 2 inhalations twice daily) of the prescribedstrength of SYMBICORT is not recommended as some patients are more likely to experience adverse effects with higherdoses of formoterol. Patients using SYMBICORT should not use additional long-acting beta2-agonists for any reason [seeWARNINGS AND PRECAUTIONS].

AsthmaIf asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief.

Adult and Adolescent Patients 12 Years of Age and Older: For patients 12 years of age and older, the dosage is 2 inhalationstwice daily (morning and evening, approximately 12 hours apart).

The recommended starting dosages for SYMBICORT for patients 12 years of age and older are based upon patients’ asthma severity.

The maximum recommended dosage is SYMBICORT 160/4.5 mcg twice daily.

Improvement in asthma control following inhaled administration of SYMBICORT can occur within 15 minutes of beginningtreatment, although maximum benefit may not be achieved for 2 weeks or longer after beginning treatment. Individual patientswill experience a variable time to onset and degree of symptom relief.

For patients who do not respond adequately to the starting dose after 1-2 weeks of therapy with SYMBICORT 80/4.5,replacement with SYMBICORT 160/4.5 may provide additional asthma control.

If a previously effective dosage regimen of SYMBICORT fails to provide adequate control of asthma, the therapeutic regimenshould be re-evaluated and additional therapeutic options, (e.g., replacing the lower strength of SYMBICORT with the higherstrength, adding additional inhaled corticosteroid, or initiating oral corticosteroids) should be considered.

Chronic Obstructive Pulmonary Disease (COPD)For patients with COPD the recommended dose is SYMBICORT 160/4.5, two inhalations twice daily.

If shortness of breath occurs in the period between doses, an inhaled, short-acting beta2-agonist should be taken forimmediate relief.

CONTRAINDICATIONSThe use of SYMBICORT is contraindicated in the following conditions:

• Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required.

• Hypersensitivity to any of the ingredients in SYMBICORT.

WARNINGS AND PRECAUTIONSAsthma-Related DeathLong-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in SYMBICORT, increase the risk ofasthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroidsor other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data fromcontrolled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescentpatients. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequatelycontrolled on a long-term asthma-control medication, such as an inhaled corticosteroid or whose disease severity clearlywarrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved andmaintained, assess the patient at regular intervals and step down therapy (e.g. discontinue SYMBICORT) if possible withoutloss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

A 28-week, placebo controlled US study comparing the safety of salmeterol with placebo, each added to usual asthmatherapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated withsalmeterol vs 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). This finding with salmeterol isconsidered a class effect of the LABA, including formoterol, one of the active ingredients in SYMBICORT. No study adequateto determine whether the rate of asthma-related death is increased with SYMBICORT has been conducted.

Clinical studies with formoterol suggested a higher incidence of serious asthma exacerbations in patients who receivedformoterol than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups.

Deterioration of Disease and Acute Episodes SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthmaor COPD. SYMBICORT has not been studied in patients with acutely deteriorating asthma or COPD. The initiation ofSYMBICORT in this setting is not appropriate.

Increasing use of inhaled, short-acting beta2-agonists is a marker of deteriorating asthma. In this situation, the patientrequires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possibleneed for replacing the current strength of SYMBICORT with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use more than 2 inhalations twice daily (morning and evening) of SYMBICORT.

SYMBICORT should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodesof bronchospasm. An inhaled, short-acting beta2-agonist, not SYMBICORT, should be used to relieve acute symptoms such as shortness of breath. When prescribing SYMBICORT, the physician must also provide the patient with an inhaled,short-acting beta2-agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning andevening) use of SYMBICORT.

When beginning treatment with SYMBICORT, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs.

Excessive Use of SYMBICORT and Use with Other Long-Acting Beta2-AgonistsAs with other inhaled drugs containing beta2-adrenergic agents, SYMBICORT should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing long-acting beta2-agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported inassociation with excessive use of inhaled sympathomimetic drugs. Patients using SYMBICORT should not use an additionallong-acting beta2-agonist (e.g., salmeterol, formoterol fumarate, arformoterol tartrate) for any reason, including preventionof exercise-induced bronchospasm (EIB) or the treatment of asthma or COPD.

Local EffectsIn clinical studies, the development of localized infections of the mouth and pharynx with Candida albicans has occurred inpatients treated with SYMBICORT. When such an infection develops, it should be treated with appropriate local or systemic(i.e., oral antifungal) therapy while treatment with SYMBICORT continues, but at times therapy with SYMBICORT may need tobe interrupted. Patients should rinse the mouth after inhalation of SYMBICORT.

Pneumonia and Other Lower Respiratory Tract Infections Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical featuresof pneumonia and exacerbations frequently overlap. Lower respiratory tract infections, including pneumonia, have beenreported following the inhaled administration of corticosteroids.

In a 6 month study of 1,704 patients with COPD, there was a higher incidence of lung infections other than pneumonia (e.g.,bronchitis, viral lower respiratory tract infections, etc.) in patients receiving SYMBICORT 160/4.5 (7.6%) than in thosereceiving SYMBICORT 80/4.5 (3.2%), formoterol 4.5 mcg (4.6%) or placebo (3.3%). Pneumonia did not occur with greaterincidence in the SYMBICORT 160/4.5 group (1.1 %) compared with placebo (1.3%). In a 12-month study of 1,964 patientswith COPD, there was also a higher incidence of lung infections other than pneumonia in patients receiving SYMBICORT160/4.5 (8.1%) than in those receiving SYMBICORT 80/4.5 (6.9%), formoterol 4.5 mcg (7.1%) or placebo (6.2%). Similar tothe 6 month study, pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group (4.0%) compared withplacebo (5.0%).

ImmunosuppressionPatients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals.Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults usingcorticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular careshould be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroidtreatment to the risk is also not known. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenousimmunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscularimmunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. The immune responsiveness to varicella vaccine was evaluated in pediatric patients with asthma ages 12 months to 8 years with budesonide inhalation suspension.

An open-label, nonrandomized clinical study examined the immune responsiveness to varicella vaccine in 243 asthmapatients 12 months to 8 years of age who were treated with budesonide inhalation suspension 0.25 mg to 1 mg daily (n=151)or noncorticosteroid asthma therapy (n=92) (i.e., beta2-agonists, leukotriene receptor antagonists, cromones). The percentage of patients developing a seroprotective antibody titer of ≥5.0 (gpELISA value) in response to the vaccinationwas similar in patients treated with budesonide inhalation suspension (85%), compared to patients treated with noncortico-steroid asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a resultof vaccination.

Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of therespiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Transferring Patients From Systemic Corticosteroid TherapyParticular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled cortico-steroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer fromsystemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic cortico-steroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be mostsusceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period ofHPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, orinfection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although SYMBICORT may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessaryfor coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids shouldbe instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for furtherinstruction. These patients should also be instructed to carry a warning card indicating that they may need supplementarysystemic corticosteroids during periods of stress or a severe asthma attack.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring toSYMBICORT. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basisduring therapy with SYMBICORT. Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peakexpiratory flow [PEF], beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oralcorticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptomsof adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

Transfer of patients from systemic corticosteroid therapy to inhaled corticosteroids or SYMBICORT may unmask conditionspreviously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilicconditions). Some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/ormuscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.

Hypercorticism and Adrenal SuppressionBudesonide, a component of SYMBICORT, will often help control asthma symptoms with less suppression of HPA functionthan therapeutically equivalent oral doses of prednisone. Since budesonide is absorbed into the circulation and can besystemically active at higher doses, the beneficial effects of SYMBICORT in minimizing HPA dysfunction may be expected onlywhen recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.

Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with SYMBICORT should be

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observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patientspostoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis)may appear in a small number of patients, particularly when budesonide is administered at higher than recommended dosesover prolonged periods of time. If such effects occur, the dosage of SYMBICORT should be reduced slowly, consistent withaccepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.

Drug Interactions With Strong Cytochrome P450 3A4 InhibitorsCaution should be exercised when considering the coadministration of SYMBICORT with ketoconazole, and other knownstrong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir,telithromycin) because adverse effects related to increased systemic exposure to budesonide may occur [see DRUGINTERACTIONS and CLINICAL PHARMACOLOGY in full Prescribing Information (12.3)].

Paradoxical Bronchospasm and Upper Airway SymptomsAs with other inhaled medications, SYMBICORT can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with SYMBICORT, it should be treated immediately with an inhaled,short-acting bronchodilator, SYMBICORT should be discontinued immediately, and alternative therapy should be instituted.

Immediate Hypersensitivity ReactionsImmediate hypersensitivity reactions may occur after administration of SYMBICORT, as demonstrated by cases of urticaria,angioedema, rash, and bronchospasm.

Cardiovascular and Central Nervous System EffectsExcessive beta-adrenergic stimulation has been associated with seizures, angina, hypertension or hypotension, tachycardiawith rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise,and insomnia [see OVERDOSAGE]. Therefore, SYMBICORT, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Formoterol, a component of SYMBICORT, can produce a clinically significant cardiovascular effect in some patients asmeasured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration offormoterol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have beenreported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segmentdepression. The clinical significance of these findings is unknown. Fatalities have been reported in association with excessiveuse of inhaled sympathomimetic drugs.

Reduction in Bone Mineral DensityDecreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaledcorticosteroids. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture isunknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, familyhistory of osteoporosis, post menopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that canreduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards ofcare. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended priorto initiating SYMBICORT and periodically thereafter. If significant reductions in BMD are seen and SYMBICORT is stillconsidered medically important for that patient’s COPD therapy, use of medication to treat or prevent osteoporosis should bestrongly considered.

Effects of treatment with SYMBICORT 160/4.5, SYMBICORT 80/4.5, formoterol 4.5, or placebo on BMD was evaluated in asubset of 326 patients (females and males 41 to 88 years of age) with COPD in the 12-month study. BMD evaluations of thehip and lumbar spine regions were conducted at baseline and 52 weeks using dual energy x-ray absorptiometry (DEXA)scans. Mean changes in BMD from baseline to end of treatment were small (mean changes ranged from -0.01 - 0.01 g/cm2).ANCOVA results for total spine and total hip BMD based on the end of treatment time point showed that all geometric LS Meanratios for the pairwise treatment group comparisons were close to 1, indicating that overall, bone mineral density for total hipand total spine regions for the 12 month time point were stable over the entire treatment period.

Effect on GrowthOrally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor thegrowth of pediatric patients receiving SYMBICORT routinely (e.g., via stadiometry). To minimize the systemic effects of orallyinhaled corticosteroids, including SYMBICORT, titrate each patient’s dose to the lowest dosage that effectively controls his/hersymptoms [see DOSAGE AND ADMINISTRATION and USE IN SPECIFIC POPULATIONS].

Glaucoma and CataractsGlaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma and COPD following the long-term administration of inhaled corticosteroids, including budesonide, a component of SYMBICORT. Therefore, close monitoring is warranted in patients with a change in vision or with history of increased intraocular pressure, glaucoma,and/or cataracts.

Effects of treatment with SYMBICORT 160/4.5, SYMBICORT 80/4.5, formoterol 4.5, or placebo on development of cataracts or glaucoma were evaluated in a subset of 461 patients with COPD in the 12-month study. Ophthalmic examinationswere conducted at baseline, 24 weeks, and 52 weeks. There were 26 subjects (6%) with an increase in posterior subcapsularscore from baseline to maximum value (>0.7) during the randomized treatment period. Changes in posterior subcapsularscores of >0.7 from baseline to treatment maximum occurred in 11 patients (9.0%) in the SYMBICORT 160/4.5 group, 4 patients (3.8%) in the SYMBICORT 80/4.5 group, 5 patients (4.2%) in the formoterol group, and 6 patients (5.2%) in theplacebo group.

Eosinophilic Conditions and Churg-Strauss SyndromeIn rare cases, patients on inhaled corticosteroids may present with systemic eosinophilic conditions. Some of these patientshave clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemiccorticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal oforal corticosteroid therapy following the introduction of inhaled corticosteroids. Physicians should be alert to eosinophilia,vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between budesonide and these underlying conditions has not been established.

Coexisting ConditionsSYMBICORT, like all medications containing sympathomimetic amines, should be used with caution in patients withconvulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of therelated beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexistingdiabetes mellitus and ketoacidosis.

Hypokalemia and HyperglycemiaBeta-adrenergic agonist medications may produce significant hypokalemia in some patients, possibly through intracellularshunting, which has the potential to produce adverse cardiovascular effects [see CLINICAL PHARMACOLOGY in fullPrescribing Information (12.2)]. The decrease in serum potassium is usually transient, not requiring supplementation.Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical studies withSYMBICORT at recommended doses.

ADVERSE REACTIONS Long-acting beta2-adrenergic agonists, such as formoterol one of the active ingredients in SYMBICORT, increase the riskof asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled cortico-steroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA.Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization inpediatric and adolescent patients. Data from a large placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-relateddeaths in patients receiving salmeterol [see WARNINGS AND PRECAUTIONS].

Systemic and inhaled corticosteroid use may result in the following:- Candida albicans infection [see WARNINGS AND PRECAUTIONS]- Pneumonia or lower respiratory tract infections in patients with COPD [see WARNINGS AND PRECAUTIONS] - Immunosuppression [see WARNINGS AND PRECAUTIONS]- Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]- Growth effects in pediatric patients [see WARNINGS AND PRECAUTIONS]- Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience in Asthma Patients 12 years and older

The overall safety data in adults and adolescents are based upon 10 active- and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated withSYMBICORT 80/4.5 or 160/4.5 mcg taken two inhalations once or twice daily for 12 to 52 weeks. In these trials, the patientson SYMBICORT had a mean age of 38 years and were predominantly Caucasian (82%).

The incidence of common adverse events in Table 1 below is based upon pooled data from three 12-week, double-blind,placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years andolder were treated with two inhalations of SYMBICORT 80/4.5 or SYMBICORT 160/4.5 twice daily. The SYMBICORT groupwas composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV1 atbaseline of 76 and 68 for the 80/4.5 mcg and 160/4.5 mcg treatment groups, respectively. Control arms for comparisonincluded two inhalations of budesonide HFA metered dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI)4.5 mcg, or placebo (MDI and DPI) twice daily. Table 1 includes all adverse events that occurred at an incidence of ≥3% inany one SYMBICORT group and more commonly than in the placebo group with twice-daily dosing. In considering these data,the increased average duration of patient exposure for SYMBICORT patients should be taken into account, as incidences arenot adjusted for an imbalance of treatment duration.

Table 1 Adverse reactions occurring at an incidence of ≥3% and more commonly than placebo in the SYMBICORTgroups: pooled data from three 12-week, double-blind, placebo-controlled clinical asthma trials in patients12 years and older

Treatment* SYMBICORT Budesonide Formoterol Placebo

Adverse Event 80/4.5 mcg 160/4.5 mcg 80 mcg 160 mcg 4.5 mcgN = 277 N =124 N =121 N = 109 N = 237 N = 400

% % % % % %

Nasopharyngitis 10.5 9.7 14.0 11.0 10.1 9.0

Headache 6.5 11.3 11.6 12.8 8.9 6.5

Upper respiratory tract infection 7.6 10.5 8.3 9.2 7.6 7.8

Pharyngolaryngeal pain 6.1 8.9 5.0 7.3 3.0 4.8

Sinusitis 5.8 4.8 5.8 2.8 6.3 4.8

Influenza 3.2 2.4 6.6 0.9 3.0 1.3

Back pain 3.2 1.6 2.5 5.5 2.1 0.8

Nasal congestion 2.5 3.2 2.5 3.7 1.3 1.0

Stomach discomfort 1.1 6.5 2.5 4.6 1.3 1.8

Vomiting 1.4 3.2 0.8 2.8 1.7 1.0

Oral Candidiasis 1.4 3.2 0 0 0 0.8

Average Duration of Exposure (days) 77.7 73.8 77.0 71.4 62.4 55.9

* All treatments were administered as two inhalations twice daily.

Long-term safety - asthma clinical trials in patients 12 years and olderLong-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year at doses up to1280/36 mcg/day (640/18 mcg twice daily), revealed neither clinically important changes in the incidence nor new types ofadverse events emerging after longer periods of treatment. Similarly, no significant or unexpected patterns of abnormalitieswere observed for up to 1 year in safety measures including chemistry, hematology, ECG, Holter monitor, and HPA-axisassessments.

Clinical Trials Experience in Chronic Obstructive Pulmonary DiseaseThe incidence of common adverse events in Table 2 below is based upon pooled data from two double-blind, placebo-controlled clinical studies (6 and 12 months in duration) in which 771 adult COPD patients (496 males and 275 females) 40 years of age and older were treated with SYMBICORT 160/4.5, two inhalations twice daily. Of these patients 651 weretreated for 6 months and 366 were treated for 12 months. The SYMBICORT group was composed of mostly Caucasian (93%)patients with a mean age of 63 years, and a mean percent predicted FEV1 at baseline of 33%. Control arms for comparisonincluded two inhalations of budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg or placebo (MDI and DPI) twice daily.Table 2 includes all adverse events that occurred at an incidence of ≥3% in the SYMBICORT group and more commonly thanin the placebo group. In considering these data, the increased average duration of patient exposure to SYMBICORT should betaken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 2 Adverse reactions occurring at an incidence of ≥3% and more commonly than placebo in the SYMBICORT group: pooled data from two double-blind, placebo-controlled clinical COPD trials

Treatment* SYMBICORT Budesonide Formoterol Placebo

160/4.5 mcg 160 mcg 4.5 mcgN = 771 N = 275 N = 779 N = 781

Adverse Event % % % %

Nasopharyngitis 7.3 3.3 5.8 4.9

Oral candidiasis 6.0 4.4 1.2 1.8

Bronchitis 5.4 4.7 4.5 3.5

Sinusitis 3.5 1.5 3.1 1.8

Upper respiratory tract infection viral 3.5 1.8 3.6 2.7

Average Duration of Exposure (days) 255.2 157.1 240.3 223.7

* All treatments were administered as two inhalations twice daily.

Lung infections other than pneumonia (mostly bronchitis) occurred in a greater percentage of subjects treated withSYMBICORT 160/4.5 compared with placebo (7.9% vs. 5.1%, respectively). There were no clinically important or unexpectedpatterns of abnormalities observed for up to 1 year in chemistry, haematology, ECG, ECG (Holter) monitoring, HPA-axis, bonemineral density and ophthalmology assessments.

Postmarketing ExperienceThe following adverse reactions have been reported during post-approval use of SYMBICORT. Because these reactions arereported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency orestablish a causal relationship to drug exposure. Some of these adverse reactions may also have been observed in clinicalstudies with SYMBICORT.

Cardiac disorders: angina pectoris, tachycardia, atrial and ventricular tachyarrhythmias, atrial fibrillation, extrasystoles, palpitations

Endocrine disorders: hypercorticism, growth velocity reduction in pediatric patients

Eye disorders: cataract, glaucoma, increased intraocular pressure

Gastrointestinal disorders: oropharyngeal candidiasis, nausea

Immune system disorders: immediate and delayed hypersensitivity reactions, such as anaphylactic reaction, angioedema,bronchospasm, urticaria, exanthema, dermatitis, pruritus

Metabolic and nutrition disorders: hyperglycemia, hypokalemia

Musculoskeletal, connective tissue, and bone disorders: muscle cramps

Nervous system disorders: tremor, dizziness

Psychiatric disorders: behavior disturbances, sleep disturbances, nervousness, agitation, depression, restlessness

Respiratory, thoracic, and mediastinal disorders: dysphonia, cough, throat irritation

Skin and subcutaneous tissue disorders: skin bruising

Vascular disorders: hypotension, hypertension

DRUG INTERACTIONSIn clinical studies, concurrent administration of SYMBICORT and other drugs, such as short-acting beta2-agonists, intranasalcorticosteroids, and antihistamines/decongestants has not resulted in an increased frequency of adverse reactions. No formaldrug interaction studies have been performed with SYMBICORT.

SYMBICORT® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol 2

Flat Size: 7.25 in (W) x 10.5 in (H) | Finished Size: 14.5 in (W) x 10.5 in (H) Flat Size: 7.25 in (W) x 10.5 in (H) | Finished Size: 14.5 in (W) x 10.5 in (H)

083-42487 Page 2 BWJob Number: 21264Revision No: 0Date: 5/1/15

Trim 7.875 x 10.5

SYMBICORT® 80/4.5(budesonide 80 mcg and formoterol fumarate dihydrate 4.5 mcg) Inhalation Aerosol

SYMBICORT® 160/4.5(budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg)Inhalation Aerosol

For Oral Inhalation Only

Rx only

WARNING: ASTHMA RELATED DEATH

Long-acting beta2-adrenergic agonists (LABA), such as formoterol one of the active ingredients in SYMBICORT,increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safetyof another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed anincrease in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a classeffect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrentuse of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-relateddeath from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-relatedhospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, SYMBICORTshould only be used for patients not adequately controlled on a long-term asthma control medication, such as aninhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled cortico-steroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue SYMBICORT) if possible without loss of asthma control and maintain the patienton a long-term asthma control medication, such as an inhaled corticosteroid. Do not use SYMBICORT for patientswhose asthma is adequately controlled on low or medium dose inhaled corticosteroids [see WARNINGS ANDPRECAUTIONS].

BRIEF SUMMARYBefore prescribing, please see full Prescribing Information for SYMBICORT® (budesonide/formoterol fumarate dihydrate).

INDICATIONS AND USAGETreatment of AsthmaSYMBICORT is indicated for the treatment of asthma in patients 12 years of age and older.

Long-acting beta2-adrenergic agonists, such as formoterol one of the active ingredients in SYMBICORT, increase the risk ofasthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients [see WARNINGS AND PRECAUTIONS]. Therefore, when treating patientswith asthma, SYMBICORT should only be used for patients not adequately controlled on a long-term asthma-controlmedication such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both aninhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals andstep down therapy (e.g. discontinue SYMBICORT) if possible without loss of asthma control, and maintain the patient on along-term asthma control medication, such as inhaled corticosteroid. Do not use SYMBICORT for patients whose asthma isadequately controlled on low or medium dose inhaled corticosteroids.

Important Limitations of Use:

• SYMBICORT is NOT indicated for the relief of acute bronchospasm.

Maintenance Treatment of Chronic Obstructive Pulmonary Disease (COPD)SYMBICORT 160/4.5 is indicated for the twice daily maintenance treatment of airflow obstruction in patients with chronicobstructive pulmonary disease (COPD) including chronic bronchitis and emphysema. SYMBICORT 160/4.5 is the onlyapproved dosage for the treatment of airflow obstruction in COPD.

Important Limitations of Use: SYMBICORT is not indicated for the relief of acute bronchospasm.

DOSAGE AND ADMINISTRATIONSYMBICORTshould be administered twice daily every day by the orally inhaled route only. After inhalation, the patient should rinsethe mouth with water without swallowing [see PATIENT COUNSELING INFORMATION in full Prescribing Information (17.4)].

Prime SYMBICORT before using for the first time by releasing two test sprays into the air away from the face, shaking well for5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped,prime the inhaler again by shaking well before each spray and releasing two test sprays into the air away from the face.

More frequent administration or a higher number of inhalations (more than 2 inhalations twice daily) of the prescribedstrength of SYMBICORT is not recommended as some patients are more likely to experience adverse effects with higherdoses of formoterol. Patients using SYMBICORT should not use additional long-acting beta2-agonists for any reason [seeWARNINGS AND PRECAUTIONS].

AsthmaIf asthma symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be taken for immediate relief.

Adult and Adolescent Patients 12 Years of Age and Older: For patients 12 years of age and older, the dosage is 2 inhalationstwice daily (morning and evening, approximately 12 hours apart).

The recommended starting dosages for SYMBICORT for patients 12 years of age and older are based upon patients’ asthma severity.

The maximum recommended dosage is SYMBICORT 160/4.5 mcg twice daily.

Improvement in asthma control following inhaled administration of SYMBICORT can occur within 15 minutes of beginningtreatment, although maximum benefit may not be achieved for 2 weeks or longer after beginning treatment. Individual patientswill experience a variable time to onset and degree of symptom relief.

For patients who do not respond adequately to the starting dose after 1-2 weeks of therapy with SYMBICORT 80/4.5,replacement with SYMBICORT 160/4.5 may provide additional asthma control.

If a previously effective dosage regimen of SYMBICORT fails to provide adequate control of asthma, the therapeutic regimenshould be re-evaluated and additional therapeutic options, (e.g., replacing the lower strength of SYMBICORT with the higherstrength, adding additional inhaled corticosteroid, or initiating oral corticosteroids) should be considered.

Chronic Obstructive Pulmonary Disease (COPD)For patients with COPD the recommended dose is SYMBICORT 160/4.5, two inhalations twice daily.

If shortness of breath occurs in the period between doses, an inhaled, short-acting beta2-agonist should be taken forimmediate relief.

CONTRAINDICATIONSThe use of SYMBICORT is contraindicated in the following conditions:

• Primary treatment of status asthmaticus or other acute episodes of asthma or COPD where intensive measures are required.

• Hypersensitivity to any of the ingredients in SYMBICORT.

WARNINGS AND PRECAUTIONSAsthma-Related DeathLong-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in SYMBICORT, increase the risk ofasthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroidsor other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data fromcontrolled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescentpatients. Therefore, when treating patients with asthma, SYMBICORT should only be used for patients not adequatelycontrolled on a long-term asthma-control medication, such as an inhaled corticosteroid or whose disease severity clearlywarrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved andmaintained, assess the patient at regular intervals and step down therapy (e.g. discontinue SYMBICORT) if possible withoutloss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid.Do not use SYMBICORT for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.

A 28-week, placebo controlled US study comparing the safety of salmeterol with placebo, each added to usual asthmatherapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated withsalmeterol vs 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). This finding with salmeterol isconsidered a class effect of the LABA, including formoterol, one of the active ingredients in SYMBICORT. No study adequateto determine whether the rate of asthma-related death is increased with SYMBICORT has been conducted.

Clinical studies with formoterol suggested a higher incidence of serious asthma exacerbations in patients who receivedformoterol than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups.

Deterioration of Disease and Acute Episodes SYMBICORT should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthmaor COPD. SYMBICORT has not been studied in patients with acutely deteriorating asthma or COPD. The initiation ofSYMBICORT in this setting is not appropriate.

Increasing use of inhaled, short-acting beta2-agonists is a marker of deteriorating asthma. In this situation, the patientrequires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possibleneed for replacing the current strength of SYMBICORT with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use more than 2 inhalations twice daily (morning and evening) of SYMBICORT.

SYMBICORT should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodesof bronchospasm. An inhaled, short-acting beta2-agonist, not SYMBICORT, should be used to relieve acute symptoms such as shortness of breath. When prescribing SYMBICORT, the physician must also provide the patient with an inhaled,short-acting beta2-agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily (morning andevening) use of SYMBICORT.

When beginning treatment with SYMBICORT, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs.

Excessive Use of SYMBICORT and Use with Other Long-Acting Beta2-AgonistsAs with other inhaled drugs containing beta2-adrenergic agents, SYMBICORT should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing long-acting beta2-agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported inassociation with excessive use of inhaled sympathomimetic drugs. Patients using SYMBICORT should not use an additionallong-acting beta2-agonist (e.g., salmeterol, formoterol fumarate, arformoterol tartrate) for any reason, including preventionof exercise-induced bronchospasm (EIB) or the treatment of asthma or COPD.

Local EffectsIn clinical studies, the development of localized infections of the mouth and pharynx with Candida albicans has occurred inpatients treated with SYMBICORT. When such an infection develops, it should be treated with appropriate local or systemic(i.e., oral antifungal) therapy while treatment with SYMBICORT continues, but at times therapy with SYMBICORT may need tobe interrupted. Patients should rinse the mouth after inhalation of SYMBICORT.

Pneumonia and Other Lower Respiratory Tract Infections Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical featuresof pneumonia and exacerbations frequently overlap. Lower respiratory tract infections, including pneumonia, have beenreported following the inhaled administration of corticosteroids.

In a 6 month study of 1,704 patients with COPD, there was a higher incidence of lung infections other than pneumonia (e.g.,bronchitis, viral lower respiratory tract infections, etc.) in patients receiving SYMBICORT 160/4.5 (7.6%) than in thosereceiving SYMBICORT 80/4.5 (3.2%), formoterol 4.5 mcg (4.6%) or placebo (3.3%). Pneumonia did not occur with greaterincidence in the SYMBICORT 160/4.5 group (1.1 %) compared with placebo (1.3%). In a 12-month study of 1,964 patientswith COPD, there was also a higher incidence of lung infections other than pneumonia in patients receiving SYMBICORT160/4.5 (8.1%) than in those receiving SYMBICORT 80/4.5 (6.9%), formoterol 4.5 mcg (7.1%) or placebo (6.2%). Similar tothe 6 month study, pneumonia did not occur with greater incidence in the SYMBICORT 160/4.5 group (4.0%) compared withplacebo (5.0%).

ImmunosuppressionPatients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals.Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible children or adults usingcorticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular careshould be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroidtreatment to the risk is also not known. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenousimmunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscularimmunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents may be considered. The immune responsiveness to varicella vaccine was evaluated in pediatric patients with asthma ages 12 months to 8 years with budesonide inhalation suspension.

An open-label, nonrandomized clinical study examined the immune responsiveness to varicella vaccine in 243 asthmapatients 12 months to 8 years of age who were treated with budesonide inhalation suspension 0.25 mg to 1 mg daily (n=151)or noncorticosteroid asthma therapy (n=92) (i.e., beta2-agonists, leukotriene receptor antagonists, cromones). The percentage of patients developing a seroprotective antibody titer of ≥5.0 (gpELISA value) in response to the vaccinationwas similar in patients treated with budesonide inhalation suspension (85%), compared to patients treated with noncortico-steroid asthma therapy (90%). No patient treated with budesonide inhalation suspension developed chicken pox as a resultof vaccination.

Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of therespiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Transferring Patients From Systemic Corticosteroid TherapyParticular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled cortico-steroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer fromsystemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic cortico-steroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be mostsusceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period ofHPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, orinfection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although SYMBICORT may provide control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessaryfor coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids shouldbe instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for furtherinstruction. These patients should also be instructed to carry a warning card indicating that they may need supplementarysystemic corticosteroids during periods of stress or a severe asthma attack.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring toSYMBICORT. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basisduring therapy with SYMBICORT. Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peakexpiratory flow [PEF], beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oralcorticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptomsof adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

Transfer of patients from systemic corticosteroid therapy to inhaled corticosteroids or SYMBICORT may unmask conditionspreviously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilicconditions). Some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/ormuscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.

Hypercorticism and Adrenal SuppressionBudesonide, a component of SYMBICORT, will often help control asthma symptoms with less suppression of HPA functionthan therapeutically equivalent oral doses of prednisone. Since budesonide is absorbed into the circulation and can besystemically active at higher doses, the beneficial effects of SYMBICORT in minimizing HPA dysfunction may be expected onlywhen recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.

Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with SYMBICORT should be

Trim 7.875 x 10.5

observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patientspostoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis)may appear in a small number of patients, particularly when budesonide is administered at higher than recommended dosesover prolonged periods of time. If such effects occur, the dosage of SYMBICORT should be reduced slowly, consistent withaccepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.

Drug Interactions With Strong Cytochrome P450 3A4 InhibitorsCaution should be exercised when considering the coadministration of SYMBICORT with ketoconazole, and other knownstrong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir,telithromycin) because adverse effects related to increased systemic exposure to budesonide may occur [see DRUGINTERACTIONS and CLINICAL PHARMACOLOGY in full Prescribing Information (12.3)].

Paradoxical Bronchospasm and Upper Airway SymptomsAs with other inhaled medications, SYMBICORT can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with SYMBICORT, it should be treated immediately with an inhaled,short-acting bronchodilator, SYMBICORT should be discontinued immediately, and alternative therapy should be instituted.

Immediate Hypersensitivity ReactionsImmediate hypersensitivity reactions may occur after administration of SYMBICORT, as demonstrated by cases of urticaria,angioedema, rash, and bronchospasm.

Cardiovascular and Central Nervous System EffectsExcessive beta-adrenergic stimulation has been associated with seizures, angina, hypertension or hypotension, tachycardiawith rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise,and insomnia [see OVERDOSAGE]. Therefore, SYMBICORT, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Formoterol, a component of SYMBICORT, can produce a clinically significant cardiovascular effect in some patients asmeasured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration offormoterol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have beenreported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segmentdepression. The clinical significance of these findings is unknown. Fatalities have been reported in association with excessiveuse of inhaled sympathomimetic drugs.

Reduction in Bone Mineral DensityDecreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaledcorticosteroids. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture isunknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, familyhistory of osteoporosis, post menopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that canreduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards ofcare. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended priorto initiating SYMBICORT and periodically thereafter. If significant reductions in BMD are seen and SYMBICORT is stillconsidered medically important for that patient’s COPD therapy, use of medication to treat or prevent osteoporosis should bestrongly considered.

Effects of treatment with SYMBICORT 160/4.5, SYMBICORT 80/4.5, formoterol 4.5, or placebo on BMD was evaluated in asubset of 326 patients (females and males 41 to 88 years of age) with COPD in the 12-month study. BMD evaluations of thehip and lumbar spine regions were conducted at baseline and 52 weeks using dual energy x-ray absorptiometry (DEXA)scans. Mean changes in BMD from baseline to end of treatment were small (mean changes ranged from -0.01 - 0.01 g/cm2).ANCOVA results for total spine and total hip BMD based on the end of treatment time point showed that all geometric LS Meanratios for the pairwise treatment group comparisons were close to 1, indicating that overall, bone mineral density for total hipand total spine regions for the 12 month time point were stable over the entire treatment period.

Effect on GrowthOrally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor thegrowth of pediatric patients receiving SYMBICORT routinely (e.g., via stadiometry). To minimize the systemic effects of orallyinhaled corticosteroids, including SYMBICORT, titrate each patient’s dose to the lowest dosage that effectively controls his/hersymptoms [see DOSAGE AND ADMINISTRATION and USE IN SPECIFIC POPULATIONS].

Glaucoma and CataractsGlaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma and COPD following the long-term administration of inhaled corticosteroids, including budesonide, a component of SYMBICORT. Therefore, close monitoring is warranted in patients with a change in vision or with history of increased intraocular pressure, glaucoma,and/or cataracts.

Effects of treatment with SYMBICORT 160/4.5, SYMBICORT 80/4.5, formoterol 4.5, or placebo on development of cataracts or glaucoma were evaluated in a subset of 461 patients with COPD in the 12-month study. Ophthalmic examinationswere conducted at baseline, 24 weeks, and 52 weeks. There were 26 subjects (6%) with an increase in posterior subcapsularscore from baseline to maximum value (>0.7) during the randomized treatment period. Changes in posterior subcapsularscores of >0.7 from baseline to treatment maximum occurred in 11 patients (9.0%) in the SYMBICORT 160/4.5 group, 4 patients (3.8%) in the SYMBICORT 80/4.5 group, 5 patients (4.2%) in the formoterol group, and 6 patients (5.2%) in theplacebo group.

Eosinophilic Conditions and Churg-Strauss SyndromeIn rare cases, patients on inhaled corticosteroids may present with systemic eosinophilic conditions. Some of these patientshave clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemiccorticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal oforal corticosteroid therapy following the introduction of inhaled corticosteroids. Physicians should be alert to eosinophilia,vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between budesonide and these underlying conditions has not been established.

Coexisting ConditionsSYMBICORT, like all medications containing sympathomimetic amines, should be used with caution in patients withconvulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of therelated beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexistingdiabetes mellitus and ketoacidosis.

Hypokalemia and HyperglycemiaBeta-adrenergic agonist medications may produce significant hypokalemia in some patients, possibly through intracellularshunting, which has the potential to produce adverse cardiovascular effects [see CLINICAL PHARMACOLOGY in fullPrescribing Information (12.2)]. The decrease in serum potassium is usually transient, not requiring supplementation.Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical studies withSYMBICORT at recommended doses.

ADVERSE REACTIONS Long-acting beta2-adrenergic agonists, such as formoterol one of the active ingredients in SYMBICORT, increase the riskof asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled cortico-steroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA.Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization inpediatric and adolescent patients. Data from a large placebo-controlled US study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-relateddeaths in patients receiving salmeterol [see WARNINGS AND PRECAUTIONS].

Systemic and inhaled corticosteroid use may result in the following:- Candida albicans infection [see WARNINGS AND PRECAUTIONS]- Pneumonia or lower respiratory tract infections in patients with COPD [see WARNINGS AND PRECAUTIONS] - Immunosuppression [see WARNINGS AND PRECAUTIONS]- Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]- Growth effects in pediatric patients [see WARNINGS AND PRECAUTIONS]- Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience in Asthma Patients 12 years and older

The overall safety data in adults and adolescents are based upon 10 active- and placebo-controlled clinical trials in which 3393 patients ages 12 years and older (2052 females and 1341 males) with asthma of varying severity were treated withSYMBICORT 80/4.5 or 160/4.5 mcg taken two inhalations once or twice daily for 12 to 52 weeks. In these trials, the patientson SYMBICORT had a mean age of 38 years and were predominantly Caucasian (82%).

The incidence of common adverse events in Table 1 below is based upon pooled data from three 12-week, double-blind,placebo-controlled clinical studies in which 401 adult and adolescent patients (148 males and 253 females) age 12 years andolder were treated with two inhalations of SYMBICORT 80/4.5 or SYMBICORT 160/4.5 twice daily. The SYMBICORT groupwas composed of mostly Caucasian (84%) patients with a mean age of 38 years, and a mean percent predicted FEV1 atbaseline of 76 and 68 for the 80/4.5 mcg and 160/4.5 mcg treatment groups, respectively. Control arms for comparisonincluded two inhalations of budesonide HFA metered dose inhaler (MDI) 80 or 160 mcg, formoterol dry powder inhaler (DPI)4.5 mcg, or placebo (MDI and DPI) twice daily. Table 1 includes all adverse events that occurred at an incidence of ≥3% inany one SYMBICORT group and more commonly than in the placebo group with twice-daily dosing. In considering these data,the increased average duration of patient exposure for SYMBICORT patients should be taken into account, as incidences arenot adjusted for an imbalance of treatment duration.

Table 1 Adverse reactions occurring at an incidence of ≥3% and more commonly than placebo in the SYMBICORTgroups: pooled data from three 12-week, double-blind, placebo-controlled clinical asthma trials in patients12 years and older

Treatment* SYMBICORT Budesonide Formoterol Placebo

Adverse Event 80/4.5 mcg 160/4.5 mcg 80 mcg 160 mcg 4.5 mcgN = 277 N =124 N =121 N = 109 N = 237 N = 400

% % % % % %

Nasopharyngitis 10.5 9.7 14.0 11.0 10.1 9.0

Headache 6.5 11.3 11.6 12.8 8.9 6.5

Upper respiratory tract infection 7.6 10.5 8.3 9.2 7.6 7.8

Pharyngolaryngeal pain 6.1 8.9 5.0 7.3 3.0 4.8

Sinusitis 5.8 4.8 5.8 2.8 6.3 4.8

Influenza 3.2 2.4 6.6 0.9 3.0 1.3

Back pain 3.2 1.6 2.5 5.5 2.1 0.8

Nasal congestion 2.5 3.2 2.5 3.7 1.3 1.0

Stomach discomfort 1.1 6.5 2.5 4.6 1.3 1.8

Vomiting 1.4 3.2 0.8 2.8 1.7 1.0

Oral Candidiasis 1.4 3.2 0 0 0 0.8

Average Duration of Exposure (days) 77.7 73.8 77.0 71.4 62.4 55.9

* All treatments were administered as two inhalations twice daily.

Long-term safety - asthma clinical trials in patients 12 years and olderLong-term safety studies in adolescent and adult patients 12 years of age and older, treated for up to 1 year at doses up to1280/36 mcg/day (640/18 mcg twice daily), revealed neither clinically important changes in the incidence nor new types ofadverse events emerging after longer periods of treatment. Similarly, no significant or unexpected patterns of abnormalitieswere observed for up to 1 year in safety measures including chemistry, hematology, ECG, Holter monitor, and HPA-axisassessments.

Clinical Trials Experience in Chronic Obstructive Pulmonary DiseaseThe incidence of common adverse events in Table 2 below is based upon pooled data from two double-blind, placebo-controlled clinical studies (6 and 12 months in duration) in which 771 adult COPD patients (496 males and 275 females) 40 years of age and older were treated with SYMBICORT 160/4.5, two inhalations twice daily. Of these patients 651 weretreated for 6 months and 366 were treated for 12 months. The SYMBICORT group was composed of mostly Caucasian (93%)patients with a mean age of 63 years, and a mean percent predicted FEV1 at baseline of 33%. Control arms for comparisonincluded two inhalations of budesonide HFA (MDI) 160 mcg, formoterol (DPI) 4.5 mcg or placebo (MDI and DPI) twice daily.Table 2 includes all adverse events that occurred at an incidence of ≥3% in the SYMBICORT group and more commonly thanin the placebo group. In considering these data, the increased average duration of patient exposure to SYMBICORT should betaken into account, as incidences are not adjusted for an imbalance of treatment duration.

Table 2 Adverse reactions occurring at an incidence of ≥3% and more commonly than placebo in the SYMBICORT group: pooled data from two double-blind, placebo-controlled clinical COPD trials

Treatment* SYMBICORT Budesonide Formoterol Placebo

160/4.5 mcg 160 mcg 4.5 mcgN = 771 N = 275 N = 779 N = 781

Adverse Event % % % %

Nasopharyngitis 7.3 3.3 5.8 4.9

Oral candidiasis 6.0 4.4 1.2 1.8

Bronchitis 5.4 4.7 4.5 3.5

Sinusitis 3.5 1.5 3.1 1.8

Upper respiratory tract infection viral 3.5 1.8 3.6 2.7

Average Duration of Exposure (days) 255.2 157.1 240.3 223.7

* All treatments were administered as two inhalations twice daily.

Lung infections other than pneumonia (mostly bronchitis) occurred in a greater percentage of subjects treated withSYMBICORT 160/4.5 compared with placebo (7.9% vs. 5.1%, respectively). There were no clinically important or unexpectedpatterns of abnormalities observed for up to 1 year in chemistry, haematology, ECG, ECG (Holter) monitoring, HPA-axis, bonemineral density and ophthalmology assessments.

Postmarketing ExperienceThe following adverse reactions have been reported during post-approval use of SYMBICORT. Because these reactions arereported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency orestablish a causal relationship to drug exposure. Some of these adverse reactions may also have been observed in clinicalstudies with SYMBICORT.

Cardiac disorders: angina pectoris, tachycardia, atrial and ventricular tachyarrhythmias, atrial fibrillation, extrasystoles, palpitations

Endocrine disorders: hypercorticism, growth velocity reduction in pediatric patients

Eye disorders: cataract, glaucoma, increased intraocular pressure

Gastrointestinal disorders: oropharyngeal candidiasis, nausea

Immune system disorders: immediate and delayed hypersensitivity reactions, such as anaphylactic reaction, angioedema,bronchospasm, urticaria, exanthema, dermatitis, pruritus

Metabolic and nutrition disorders: hyperglycemia, hypokalemia

Musculoskeletal, connective tissue, and bone disorders: muscle cramps

Nervous system disorders: tremor, dizziness

Psychiatric disorders: behavior disturbances, sleep disturbances, nervousness, agitation, depression, restlessness

Respiratory, thoracic, and mediastinal disorders: dysphonia, cough, throat irritation

Skin and subcutaneous tissue disorders: skin bruising

Vascular disorders: hypotension, hypertension

DRUG INTERACTIONSIn clinical studies, concurrent administration of SYMBICORT and other drugs, such as short-acting beta2-agonists, intranasalcorticosteroids, and antihistamines/decongestants has not resulted in an increased frequency of adverse reactions. No formaldrug interaction studies have been performed with SYMBICORT.

SYMBICORT® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol 2

Flat Size: 7.25 in (W) x 10.5 in (H) | Finished Size: 14.5 in (W) x 10.5 in (H) Flat Size: 7.25 in (W) x 10.5 in (H) | Finished Size: 14.5 in (W) x 10.5 in (H)

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Flat Size: 7.25 in (W) x 10.5 in (H) | Finished Size: 14.5 in (W) x 10.5 in (H)

Trim 7.875 x 10.5

Inhibitors of Cytochrome P450 3A4The main route of metabolism of corticosteroids, including budesonide, a component of SYMBICORT, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the meanplasma concentration of orally administered budesonide increased. Concomitant administration of CYP3A4 may inhibit the metabolism of, and increase the systemic exposure to, budesonide. Caution should be exercised when considering the coadministration of SYMBICORT with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see WARNINGS AND PRECAUTIONS].

Monoamine Oxidase Inhibitors and Tricyclic AntidepressantsSYMBICORT should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclicantidepressants, or within 2 weeks of discontinuation of such agents, because the action of formoterol, a component ofSYMBICORT, on the vascular system may be potentiated by these agents. In clinical trials with SYMBICORT, a limited numberof COPD and asthma patients received tricyclic antidepressants, and, therefore, no clinically meaningful conclusions onadverse events can be made.

Beta-Adrenergic Receptor Blocking AgentsBeta-blockers (including eye drops) may not only block the pulmonary effect of beta-agonists, such as formoterol, a component of SYMBICORT, but may produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be noacceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselectivebeta-blockers could be considered, although they should be administered with caution.

DiureticsThe ECG changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of SYMBICORT with non–potassium-sparing diuretics.

USE IN SPECIFIC POPULATIONSPregnancyTeratogenic Effects: Pregnancy Category C.There are no adequate and well-controlled studies of SYMBICORT in pregnant women. SYMBICORT was teratogenic andembryocidal in rats. Budesonide alone was teratogenic and embryocidal in rats and rabbits, but not in humans at therapeuticdoses. Formoterol fumarate alone was teratogenic in rats and rabbits. Formoterol fumarate was also embryocidal, increasedpup loss at birth and during lactation, and decreased pup weight in rats. SYMBICORT should be used during pregnancy onlyif the potential benefit justifies the potential risk to the fetus.

SYMBICORTIn a reproduction study in rats, budesonide combined with formoterol fumarate by the inhalation route at doses approximately1/7 and 1/3, respectively, the maximum recommended human daily inhalation dose on a mg/m2 basis produced umbilicalhernia. No teratogenic or embryocidal effects were detected with budesonide combined with formoterol fumarate by theinhalation route at doses approximately 1/32 and 1/16, respectively, the maximum recommended human daily inhalation doseon a mg/m2 basis.

BudesonideStudies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administeredduring pregnancy. The results from a large population-based prospective cohort epidemiological study reviewing data fromthree Swedish registries covering approximately 99% of the pregnancies from 1995-1997 (ie, Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology Registry) indicate no increased risk for congenitalmalformations from the use of inhaled budesonide during early pregnancy. Congenital malformations were studied in 2014 infants born to mothers reporting the use of inhaled budesonide for asthma in early pregnancy (usually 10-12 weeksafter the last menstrual period), the period when most major organ malformations occur. The rate of recorded congenitalmalformations was similar compared to the general population rate (3.8% vs 3.5%, respectively). In addition, after exposureto inhaled budesonide, the number of infants born with orofacial clefts was similar to the expected number in the normalpopulation (4 children vs 3.3, respectively).

These same data were utilized in a second study bringing the total to 2534 infants whose mothers were exposed to inhaledbudesonide. In this study, the rate of congenital malformations among infants whose mothers were exposed to inhaled budes-onide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%).

Budesonide produced fetal loss, decreased pup weight, and skeletal abnormalities at subcutaneous doses in rabbits less thanthe maximum recommended human daily inhalation dose on a mcg/m2 basis and in rats at doses approximately 6 times the maximum recommended human daily inhalation dose on a mcg/m2 basis. In another study in rats, no teratogenic orembryocidal effects were seen at inhalation doses up to 3 times the maximum recommended human daily inhalation dose ona mcg/m2 basis.

Experience with oral corticosteroids since their introduction in pharmacologic as opposed to physiologic doses suggests thatrodents are more prone to teratogenic effects from corticosteroids than humans.

FormoterolFormoterol fumarate has been shown to be teratogenic, embryocidal, to increase pup loss at birth and during lactation, andto decrease pup weights in rats when given at oral doses 1400 times and greater the maximum recommended human dailyinhalation dose on a mcg/m2 basis. Umbilical hernia was observed in rat fetuses at oral doses 1400 times and greater themaximum recommended human daily inhalation dose on a mcg/m2 basis. Brachygnathia was observed in rat fetuses at anoral dose 7000 times the maximum recommended human daily inhalation dose on a mcg/m2 basis. Pregnancy was prolongedat an oral dose 7000 times the maximum recommended human daily inhalation dose on a mcg/m2 basis. In another study inrats, no teratogenic effects were seen at inhalation doses up to 500 times the maximum recommended human daily inhalationdose on a mcg/m2 basis.

Subcapsular cysts on the liver were observed in rabbit fetuses at an oral dose 54,000 times the maximum recommendedhuman daily inhalation dose on a mcg/m2 basis. No teratogenic effects were observed at oral doses up to 3200 times themaximum recommended human daily inhalation dose on a mcg/m2 basis.

Nonteratogenic EffectsHypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should becarefully observed.

Labor and DeliveryThere are no well-controlled human studies that have investigated the effects of SYMBICORT on preterm labor or labor atterm. Because of the potential for beta-agonist interference with uterine contractility, use of SYMBICORT for management ofasthma during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

Nursing MothersSince there are no data from controlled trials on the use of SYMBICORT by nursing mothers, a decision should be made whetherto discontinue nursing or to discontinue SYMBICORT, taking into account the importance of SYMBICORT to the mother.

Budesonide, like other corticosteroids, is secreted in human milk. Data with budesonide delivered via dry powder inhalerindicates that the total daily oral dose of budesonide available in breast milk to the infant is approximately 0.3% to 1% of the dose inhaled by the mother [see CLINICAL PHARMACOLOGY, Pharmacokinetics in full Prescribing Information (12.3)].For SYMBICORT, the dose of budesonide available to the infant in breast milk, as a percentage of the maternal dose, would beexpected to be similar.

In reproductive studies in rats, formoterol was excreted in the milk. It is not known whether formoterol is excreted in human milk.

Pediatric UseSafety and effectiveness of SYMBICORT in asthma patients 12 years of age and older have been established in studies up to 12 months. In the two 12-week, double-blind, placebo-controlled US pivotal studies 25 patients 12 to 17 years of age weretreated with SYMBICORT twice daily [see CLINICAL STUDIES in full Prescribing Information (14.1)]. Efficacy results in thisage group were similar to those observed in patients 18 years and older. There were no obvious differences in the type or frequency of adverse events reported in this age group compared with patients 18 years of age and older.

The safety and effectiveness of SYMBICORT in asthma patients 6 to <12 years of age has not been established.

Overall 1447 asthma patients 6 to <12 years of age participated in placebo- and active-controlled SYMBICORT studies. Of these 1447 patients, 539 received SYMBICORT twice daily. The overall safety profile of these patients was similar to thatobserved in patients ≥12 years of age who also received SYMBICORT twice daily in studies of similar design.

Controlled clinical studies have shown that orally inhaled corticosteroids including budesonide, a component of SYMBICORT,may cause a reduction in growth velocity in pediatric patients. This effect has been observed in the absence of laboratoryevidence of HPA-axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroidexposure in pediatric patients than some commonly used tests of HPA-axis function. The long-term effect of this reduction ingrowth velocity associated with orally inhaled corticosteroids, including the impact on final height are unknown. The potentialfor “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequatelystudied.

In a study of asthmatic children 5-12 years of age, those treated with budesonide DPI 200 mcg twice daily (n=311) had a 1.1 centimeter reduction in growth compared with those receiving placebo (n=418) at the end of one year; the differencebetween these two treatment groups did not increase further over three years of additional treatment. By the end of 4 years,children treated with budesonide DPI and children treated with placebo had similar growth velocities. Conclusions drawn fromthis study may be confounded by the unequal use of corticosteroids in the treatment groups and inclusion of data frompatients attaining puberty during the course of the study.

The growth of pediatric patients receiving orally inhaled corticosteroids, including SYMBICORT, should be monitored. If achild or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularlysensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against theclinical benefits obtained. To minimize the systemic effects of orally inhaled corticosteroids, including SYMBICORT, each patientshould be titrated to the lowest strength that effectively controls his/her asthma [see DOSAGE AND ADMINISTRATION].

Geriatric UseOf the total number of patients in asthma clinical studies treated with SYMBICORT twice daily, 149 were 65 years of age or older, of whom 25 were 75 years of age or older.

In the COPD studies of 6 to 12 months duration, 349 patients treated with SYMBICORT 160/4.5 twice daily were 65 years oldand above and of those, 73 patients were 75 years of age and older. No overall differences in safety or effectiveness wereobserved between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

As with other products containing beta2-agonists, special caution should be observed when using SYMBICORT in geriatricpatients who have concomitant cardiovascular disease that could be adversely affected by beta2-agonists.

Based on available data for SYMBICORT or its active components, no adjustment of dosage of SYMBICORT in geriatricpatients is warranted.

Hepatic Impairment Formal pharmacokinetic studies using SYMBICORT have not been conducted in patients with hepatic impairment. However,since both budesonide and formoterol fumarate are predominantly cleared by hepatic metabolism, impairment of liverfunction may lead to accumulation of budesonide and formoterol fumarate in plasma. Therefore, patients with hepatic diseaseshould be closely monitored.

Renal Impairment Formal pharmacokinetic studies using SYMBICORT have not been conducted in patients with renal impairment.

OVERDOSAGESYMBICORTSYMBICORT contains both budesonide and formoterol; therefore, the risks associated with overdosage for the individualcomponents described below apply to SYMBICORT. In pharmacokinetic studies, single doses of 960/54 mcg (12 actuationsof SYMBICORT 80/4.5) and 1280/36 mcg (8 actuations of 160/4.5), were administered to patients with COPD. A total of1920/54 mcg (12 actuations of SYMBICORT 160/4.5) was administered as a single dose to both healthy subjects and patientswith asthma. In a long-term active-controlled safety study in asthma patients, SYMBICORT 160/4.5 was administered for upto 12 months at doses up to twice the highest recommended daily dose. There were no clinically significant adverse reactionsobserved in any of these studies.

Clinical signs in dogs that received a single inhalation dose of SYMBICORT (a combination of budesonide and formoterol) ina dry powder included tremor, mucosal redness, nasal catarrh, redness of intact skin, abdominal respiration, vomiting, andsalivation; in the rat, the only clinical sign observed was increased respiratory rate in the first hour after dosing. No deathsoccurred in rats given a combination of budesonide and formoterol at acute inhalation doses of 97 and 3 mg/kg, respectively(approximately 1200 and 1350 times the maximum recommended human daily inhalation dose on a mcg/m2 basis). No deaths occurred in dogs given a combination of budesonide and formoterol at the acute inhalation doses of 732 and 22 mcg/kg, respectively (approximately 30 times the maximum recommended human daily inhalation dose of budesonide andformoterol on a mcg/m2 basis).

BudesonideThe potential for acute toxic effects following overdose of budesonide is low. If used at excessive doses for prolonged periods,systemic corticosteroid effects such as hypercorticism may occur [see WARNINGS AND PRECAUTIONS]. Budesonide at fivetimes the highest recommended dose (3200 mcg daily) administered to humans for 6 weeks caused a significant reduction(27%) in the plasma cortisol response to a 6-hour infusion of ACTH compared with placebo (+1%). The corresponding effectof 10 mg prednisone daily was a 35% reduction in the plasma cortisol response to ACTH.

In mice, the minimal inhalation lethal dose was 100 mg/kg (approximately 600 times the maximum recommended humandaily inhalation dose on a mcg/m2 basis). In rats, there were no deaths following the administration of an inhalation dose of68 mg/kg (approximately 900 times the maximum recommended human daily inhalation dose on a mcg/m2 basis). Theminimal oral lethal dose in mice was 200 mg/kg (approximately 1300 times the maximum recommended human dailyinhalation dose on a mcg/m2 basis) and less than 100 mg/kg in rats (approximately 1300 times the maximum recommendedhuman daily inhalation dose on a mcg/m2 basis).

FormoterolAn overdose of formoterol would likely lead to an exaggeration of effects that are typical for beta2-agonists: seizures, angina, hypertension, hypotension, tachycardia, atrial and ventricular tachyarrhythmias, nervousness, headache, tremor,palpitations, muscle cramps, nausea, dizziness, sleep disturbances, metabolic acidosis, hyperglycemia, hypokalemia. As withall sympathomimetic medications, cardiac arrest and even death may be associated with abuse of formoterol. No clinicallysignificant adverse reactions were seen when formoterol was delivered to adult patients with acute bronchoconstriction at a dose of 90 mcg/day over 3 hours or to stable asthmatics 3 times a day at a total dose of 54 mcg/day for 3 days.

Treatment of formoterol overdosage consists of discontinuation of the medication together with institution of appropriatesymptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered,bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of formoterol. Cardiac monitoring is recommended in cases of overdosage.

No deaths were seen in mice given formoterol at an inhalation dose of 276 mg/kg (more than 62,200 times the maximumrecommended human daily inhalation dose on a mcg/m2 basis). In rats, the minimum lethal inhalation dose was 40 mg/kg(approximately 18,000 times the maximum recommended human daily inhalation dose on a mcg/m2 basis). No deaths were seen in mice that received an oral dose of 2000 mg/kg (more than 450,000 times the maximum recommended humandaily inhalation dose on a mcg/m2 basis). Maximum nonlethal oral doses were 252 mg/kg in young rats and 1500 mg/kg in adult rats (approximately 114,000 times and 675,000 times the maximum recommended human inhalation dose on a mcg/m2 basis).

SYMBICORT is a trademark of the AstraZeneca group of companies.© AstraZeneca 2008, 2009, 2010, 2012

Manufactured for: AstraZeneca LP, Wilmington, DE 19850By: AstraZeneca Dunkerque Production, Dunkerque, France

Product of France

Rev. 5/12 2839500 8/13

SYMBICORT® (budesonide/formoterol fumarate dihydrate) Inhalation Aerosol 3

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ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 2015 13

ATS Foundation Thanks 2014 Contributors for Their Support

T he ATS is pleased to recognize its generous donors who contributed to the Foundation’s Funds for the Future

Annual Campaign from Jan. 1, 2014, to Dec. 31, 2014.

RESEARCH PROGRAM PARTNERS*

$80,000 OR MORE• Pulmonary Hypertension Association

$60,000–$99,999• Scleroderma Foundation

$30,000–$59,999• Alpha-1 Foundation

• Breathe California of Los Angeles County

• chILD Foundation

• Coalition for Pulmonary Fibrosis

• Hermansky-Pudlak Syndrome Network

• Pulmonary Fibrosis Foundation

$10,000–$29,999• Alliance for Academic Internal Medicine/The

Association of Specialty Professions

• American Lung Association

* Dollars represent the total amount pledged for new and

ongoing 2014 awards

SIXTH ANNUAL RESEARCH PROGRAM BENEFIT CORPORATE SUPPORTERS

$60,000 PLATINUM SUPPORTER• Boehringer Ingelheim Pharmaceuticals, Inc.

$25,000 GOLD LEVEL SUPPORTERS• AstraZeneca LP

• Genentech/Novartis

• Sunovion Pharmaceuticals, Inc.

$10,000 SILVER LEVEL SUPPORTER• Forest Laboratories, Inc.

• Gilead Sciences, Inc.

• InterMune, Inc.

• Teva Respiratory

$5,000 BRONZE LEVEL SUPPORTERS• Bayer HealthCare

• MEDA Pharmaceuticals

THE EDWARD LIVINGSTON TRUDEAU SOCIETY**

• William C. Bailey, MD

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• James F. Donohue, MD

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• Jo Rae Wright, PhD†

INDIVIDUAL GIFTS VISIONARIES: $10,000 OR MORE• David W. Cugell, MD

• James F. Donohue, MD

• Francis Family Foundation

• Freeman Decorating Services, Inc.

• Susan Nestor

• University of Alabama at Birmingham, Division

of Pulmonary, Allergy, and Critical Care

Medicine—Victor J. Thannickal, MD, and

William C. Bailey, MD

INNOVATORS: $5,000–$9,999• Rebecca Bascom, MD, MPH

• Brigham and Women’s Hospital

• Sonia Buist, MD

• Peter Finn

• Philip C. Hopewell, MD

• Ohio State University Medical Center

• Dean E. Schraufnagel, MD

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• University of California-San Diego, Division

of Pulmonary, Critical Care, and Sleep

Medicine—Atul Malhotra, MD

• University of Chicago, Division of Pulmonary

and Critical Care Medicine—Jesse B. Hall,

MD

• University of Pittsburgh, Division of

Pulmonary, Allergy, and Critical Care

Medicine—Mark T. Gladwin, MD

• University of Wisconsin-Madison, Division

of Allergy, Pulmonary, and Critical Care

Medicine—Nizar N. Jarjour, MD

FOUNDERS: $2,500–$4,999• Boston University School of Medicine—David

Center, MD

• William W. Busse, MD

• Cedars-Sinai Medical Center

• Cleveland Clinic Respiratory Institute—Serpil

C. Erzurum, MD, and Herbert P. Wiedemann,

MD

• Michelle M. Cloutier, MD

• Stephen C. Crane, PhD, MPH

• Division of Pulmonary and Critical Care

Medicine, Washington University School of

Medicine—Michael J. Holtzman, MD

• Jeffrey L. Glassroth, MD

• Alan H. Jobe, MD, PhD

• Talmadge E. King Jr., MD

• Jerry A. Krishnan, MD, PhD

• William E. Lawson, MD and Laura L. Lawson,

MD

• Loma Linda University—Takkin Lo, MD

• Massachusetts General Hospital—Benjamin

Medoff, MD, and Andrew W. Tager, MD

• Richard A. Matthay, MD

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• Perry G. Nystrom, MD

• Y. S. Prakash, MD, PhD

• Sharon I. S. Rounds, MD

• Sheldon L. Spector, MD

• Temple Lung Center/Temple Health—Gerard

J. Criner, MD

• University of California Los Angeles, Division

of Pulmonary and Critical Care Medicine—

Steven Dubinett, MD

• University of California San Diego, Rady

Children’s Hospital of San Diego, Division

of Pediatric Respiratory Medicine—James

Hagood, MD

• University of Colorado Denver—Mark W.

Geraci, MD

• University of Illinois at Chicago—Patricia W.

Finn, MD

• University of Southern California—Zea Borok,

MD, and Edward Crandall, MD

• Washington University in St. Louis, School

of Medicine, Departments of Pediatrics and

Medicine—Thomas W. Ferkol, MD

• Carolyn H. Welsh, MD

• Yale University—Naftali Kaminski, MD

DISCOVERERS: $1,000–$2,499• Micheala Aldred, PhD

• Donna J. Appell, RN

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• David H. Au, MD, MS

• Teresa Richardson Barnes

• Thomas P. Bleck, MD

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B. Panitch, MD, and Julian Allen, MD

• John W. Christman, MD

• Vanessa J. Craig, MD

• Myrna Crain

• James D. Crapo, MD

• J. Randall Curtis, MD, MPH

• Jeffrey L. Curtis, MD

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• Bethany B. Moore, PhD

• Alan H. Morris, MD

• Marc Moss, MD

• Alfred Munzer, MD

• Richard K. Murray, MD

• Jay A. Nadel, MD

• Samya Z. Nasr, MD

• National Board for Respiratory Care

• Lydia Neumann

• Mary A. Nevin, MD

• Linda Nici, MD

• Heber C. Nielsen, MD

• Mitchell A. Olman, MA, MD

• Amit D. Parulekar, MD

• Susheel P. Patil, MD, PhD

• Penn Respiration Group—John H. Hansen-

Flaschen, MD

• Marc Peters-Golden, MD

• Charles A. Powell, MD

• J. Usha Raj, MD

• David M. Rapoport, MD

• Lee B. Reichman, MD, MPH

• Theodore F. Reiss, MD, MBE

• Stephen I. Rennard, MD

• David Riccio

• Karen M. Ridge, PhD

• William N. Rom, MD, MPH

• Bernard J. Roth, MD

• Jonathan M. Samet, MD

• David A. Schwartz, MD

• Steven Shak, MD

• John W. Shigeoka, MD

• Ryan Snyder

• Brian Derris Southern, MD

• Roger G. Spragg, MD

• Kent Steele

• Charlie B. Strange III, MD

• Robert M. Strieter, MD

• Kingman P. Strohl, MD

• Albert S. Sun, MD

• Elizabeth K. Tam, MD

• Gregory N. Thompson, MD

• Bruce C. Trapnell, MD

• Michelle Turenne

• Vanderbilt University, Division of Allergy,

Pulmonary, and Critical Care Medicine

• Shekhar T. Venkataraman, MD

• William M. Vollmer, PhD

• Jeffrey S. Wagener, MD

• David Warburton, MD

• Lorraine B. Ware, MD

• Debra E. Weese-Mayer, MD

• Gail G. Weinmann, MD

• Sally E. Wenzel-Morganroth, MD

• Mark D. Wewers, MD

• Mary Ellen Wewers, PhD

• Eric S. White, MD

• Ok Hi Yoo, MD

PIONEERS: $500–$999• Jerrold L. Abraham, MD

• Andrea J. Apter, MA, MD, MSc

• Charles W. Atwood Jr., MD

• M. Safwan Badr, MD

• Raquel R. Bartz, MD, MMCi

• James M. Beck, MD

• Timothy D. Bigby, MD

• Peter B. Bitterman, MD

• Zea Borok, MD

• Jane Elizabeth Bourke, BS(Hons), PhD

• V. Courtney Broaddus, MD

• Steven L. Brody, MD

• Derek E. Byers, MD, PhD

• Christy Cappelletti, BPharm, PharmD

• Brent Carter, MD

• Antonino Catanzaro, MD

• Brian W. Christman, MD

• Convention Data Services

• Ernest K. Cotton, MD

• Courtney Crim Sr., MD

• David E. Dines, MD

• Anne E. Dixon, MD

• Gregory P. Downey, MD

• Drexel Medicine—Edward S. Schulman, MD

• Anthony D. D’Urzo, MD

• Element Designs

• David J. Erle, MD

• Karen A. Fagan, MD

• Daniel C. Files, MD

• Christine S. Fukui, MD

• Michelle A. Gill

• David Gozal, MD

• Michael B. Green, MBA, MD

• John E. Heffner, MD

• Mary Elizabeth C. Hernandez, MD

• Leslie A. Hoffman, PhD

• Fernando Holguin, MD, MPH

• Douglas B. Hornick, MD

• David L. Hotchkin, MSc, MD

• Terri Lee Hough, MD, MSc

see DONORS page 14

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 201514

• Rolf D. Hubmayr, MD

• Omar Hussain, DO

• Robert E. Hyatt, MD

• David H. Ingbar, MD

• Kazuo Isono, MD

• Shannon Jamieson

• Seong-Joo Jeong, MD

• Naftali Kaminski, MD

• David W. Kamp, MD

• Gwendolyn Kerby, MD

• Gurjit Khurana Hershey, MD, PhD

• Dong Soon Kim, MD, PhD

• John Kimball

• Robert A. Klocke, MD

• Jane Q. Koenig, PhD

• Geoffrey Kurland, MD

• Janet L. Larson, PhD, RN

• Robert F. Lemanske Jr., MD

• Shu S. Lin, MD, PhD

• James E. Loyd, MD

• David M. Mannino III, MD

• Clay B. Marsh, MD

• Andrew A. Martin, MD

• William J. Martin II, MD

• Gustavo Matute-Bello, MD

• Janet R. Maurer, MD

• Frank J. Mayo, MD

• Stephen A. McCurdy, MD, MPH

• Tom McKarns

• Atul C. Mehta, MBBS

• Peter E. Morris, MD

• Andrew M. Namen, MD

• Edward T. Naureckas, MD

• Harold S. Nelson, MD

• Lawrence M. Nogee, MD

• Angela Panoskaltsis-Mortari, PhD

• Ohio State University College of Nursing

• Sam B. Patel, RPh, MBA

• James R. Patterson, MD

• Alan L. Plummer, MD

• Vsevolod Y. Polotsky, MD, PhD

• Mark A. Powers, MD

• Ravindra C. Rajmane, MD

• S. Bhimsen S. Rao, MD

• Carrie A. Redlich, MD, MPH

• Susan S. Redline, MD

• Jeremy B. Richards, MD, MA

• Andrew L. Ries, MD, MPH

• Richard A. Robbins, MD

• John D. Roehrs, MD

• Jesse Roman Rodriguez, MD

• Cecile S. Rose, MD, MPH

• Margaret Rosenfeld, MD

• David P.L. Sachs, MD

• Lynn M. Schnapp, MD

• Richard M. Schwartzstein, MD

• Robert M. Senior, MD

• Sanjay Sethi, MD

• Alessandro Sette

• Gulshan Sharma, MD, MPH

• Chang S. Shim, MD

• Thomas M. Siler, MD

• Lewis J. Smith, MD

• Howard Sohn

• Christine A. Sorkness, PharmD

• Ronald L. Sorkness, PhD

• Peter H. S. Sporn, MD

• Michael L. Stanchina, MD

• John E. Stevenson, MD

• Thomas B. Stibolt Jr., MD

• Paul C. Stillwell, MD

• Stuart W. Stoloff, MD

• Taylor Thompson, MD

• J. Daryl Thornton, MD, MPH

• Louis P. Voigt, MD

• Judith A. Voynow, MD

• Jeanne M. Wallace, MD

• Angela C. Wang, MD

• Adam Wanner, MD

• Robert A. Wise, MD

• David A. Wyszomierski, MD

• Lisa R. Young, MD

• Pamela L. Zeitlin, MD, PhD

• Richard L. Zuwallack, MD

INVESTIGATORS: $250–$499• Yossef Aelony, MD

• Mohinder P. Ahluwalia, MD

• Reshma Amin, MD

• Douglas A. Arenberg, MD

• Kewal Asosingh, PhD

• Kamran Atabai, MD

• Patrice T. Attal, MD

• Christine Marie Aubry, MD

• David B. Badesch, MD

• John R. Balmes, MD

• John Bernardo, MD

• Jonathan A. Bernstein, MD

• Jahar Bhattacharya, MD

• Gordon R. Bloomberg, MD

• Jeffrey B. Bloomer, MD

• Catherine M. Bonuccelli, MD

• Homer A. Boushey Jr., MD

• Eoin Brodie

• Irwin A. Buchwald, MD

• G. Scott Budinger, MD

• Esteban Gonzalez Burchard, MD, MPH

• Jacqueline E. Carsanaro, MBA

• E. Jane Carter, MD

• Thomas B. Casale, MD

• Juan C. Celedon, DrPH, MD

• Peter Chen, MD

• Shan C. Chu, MD

• Joan G. Clark, MD

• Charlotte W. Collins, JD

• Michael P. Coppola, MD

• Danielle Anna Corrigan, MD

• Kristina A. Crothers, MD

• Bruce H. Culver, MD

• Sonye K. Danoff, MD, PhD

• Jeanine M. D’Armiento, MD, PhD

• Stephanie D. Davis, MD

• Larry Di Fabrizio, MD

• Edward J. Diamond, MD

• Claire M. Doerschuk, MD

• Dennis E. Doherty, MD

• DorAnne M. Donesky, PhD, ANP-BC

• Alexander G. Duarte, MD

• Edward Eden, MD

• Marie E. Egan, MD

• Alison C. P. Elder, PhD

• Marlowe W. Eldridge, MD

• Darlene J. Elias, MD

• Charles W. Emala Sr., MD

• Joshua Englert

• Barry L. Fanburg, MD

• Humam Farah, MD, and The Farah Family

Trust

• Joshua Patrick Fessel, MD, PhD

• Henry E. Fessler, MD

• Andrew P. Fontenot, MD

• Janet Fox, MD

• Regina Frants, MD

• Carolyn M. Fruci, MD, PhD

• Etsuo Fujita, MD

• Peter Gehr, PhD

• James E. Gern, MD

• Ronaldo C. Go, MD

• John J. Godleski, MD

• Philip M. Gold, MD

• Christopher H. Goss, MD, MSc

• John I. Gotchall, MD

• Michael K. Gould, MD, MS

• Yvette M. Gozzo, MD

• David M. Guidot, MD

• Susan H. Guttentag, MD

• James S. Hagood, MD

• Teal S. Hallstrand, MD, MPH

• Jack R. Harkema, DVM, PhD

• Michelle S. Harkins, MD

• Tina V. Hartert, MD, MPH

• Paul K. Henneberger, ScD

• Robert Duncan Hite, MD

• Joseph H. Hoffman, MD

• Anne E. Holland, PhD

• Laurence Huang, MD

• Yuh-Chin T. Huang, MHS, MD

• Robert C. Hyzy, MD

• Jonathan S. Ilowite, MD

• Yoshikazu Inoue

• Elliot Israel, MD

• Myron H. Jacobs, MD

• Jeffrey R. Jacobson, MD

• Christine R. Jenkins, MD, MBBS

• Martin F. Joyce-Brady, MD

• Robert J. Kaner, MD

• John Karafilidis

• Joel D. Kaufman, MD, MPH

• Steven M. Kawut, MD, MS

• Raouf A. Kayaleh, MD

• Homayoun Kazemi, MD

• H. William Kelly, PharmD

• Jack Kelly, Lymphangiomatosis and

Gorham’s Disease Alliance

• Anthony P. Khalifah, MD

• Leila Kheirandish-Gozal, MSc, MD

• R. John Kimoff, MD

• Howard M. Kipen, MD, MPH

• Steven Howard Kirtland, MD

• Lawrence E. Kline, DO

• Kirsten Marie Kloepfer, MD

• Lester Kobzik, MD

• Phillip E. Korenblat, MD

• Stella Kourembanas, MD

• Melissa Ann Kovach, MD

• Anna Lam, MD

• Lourdes R. Laraya-Cuasay, MD

• Angeline A. Lazarus, MD

• Stephen C. Lazarus, MD

• Albin B. Leong, MD

• Andrew H. Liu, MD

• Neil R. MacIntyre, MD

• Yolanda N. Mageto, MD, MPH

• Jess Mandel, MD

• Anthony M. Marinelli, MD

• Guy B. Marks, MBBS, PhD

• John G. Mastronarde, MD

• Sadis Matalon, PhD

• Praveen N. Mathur, MBBS

• Francis X. McCormack, Jr., MD

• Ivan F. McMurtry, PhD

• Don L. McNeil, MD

• Michelle Deanna Miller, MD

• Evelyn Montalvo Stanton, MD

• Luis M. Moreta-Sainz, MD

• Wayne J. Morgan, MD

• Alison M. Morris, MD, MS

• Leonard C. Moses, MD

• John F. Murray, MD

• Haydee Muse, MD, FCCP, MBA

• Gokhan M. Mutlu, MD

• Genevieve Mylott

• Naomi K. Nakagawa

• Shigenori Nakajima, MD, PhD

• Michael S. Niederman, MD

• Theodore Oslick, MD

• Robert Paine III, MD

• Ulo Palm, MD

• Priyada Suresh Pandya, MD

• David R. Park, MD

• Gibbe H. Parsons, MD

• Sanjay R. Patel, MD

• William Peppo, DO

• Stephen P. Peters, MD, PhD

• Irina Petrache, MD

• Barbara A. Phillips, MD, MPH

• Wanda Phipatanakul, MD

• Kent E. Pinkerton, PhD

• Michael I. Plotnick, MD

• David J. Prezant, MD

• Paul M. Quinton, PhD

• Jonathan M. Raskin, MD

• Lynn F. Reinke, PhD, APRN, BC

• Clement L. Ren, MD

• Herbert Y. Reynolds, MD

• Linda Rogers, MD

• James A. Rowley, MD

• David Bernard Rubin, MD

• Abdulghani Sankari, PhD, MD

• Catherine S. Sassoon, MD

• Edwin N. Schachter, MD

• Michael Schatz, MD

• Neil W. Schluger, MD

• Scott A. Schroeder, MD

• Paul T. Schumacker, PhD

• Richard J. Schwab, MD

• Jay Schwartz, MBA, RPh

• Anthony S. Shen, MD

• Rebecca A. Shilling, MD

• Deborah Shure, MD

• Jonathan M. Siner, MD

• Benjamin David Singer, MD

• Jonathan P. Singer, MS, MD

• Cecilia M. Smith, DO

• Angela R. Snydsman

• Guy W. Soo Hoo, MD, MPH

• Katharine Squires

• Theodore J. Standiford, MD

• Renee D. Stapleton, PhD, MD

• Jeffrey R. Starke, MD

• John L. Stauffer, MD

• David A. Stempel, MD

• Arvey M. Stone, MD

• Eileen Storey, MD, MPH

• Eugene J. Sullivan, MD

• Stanley J. Szefler, MD

• Donald P. Tashkin, MD

• Markus K. Tauscher, MD

• Peter B. Terry, MD

• Krishna Thavarajah, MD

• Alvin V. Thomas Jr., MD

• Carey C. Thomson, MPH, MD

• Jonathon D. Truwit, MBA, MD

• Homer L. Twigg III, MD

• Dona J. Upson, MA, MD

• Steve Varon, MD

• Diana E. Weaver, MD

• Jadwiga A. Wedzicha, MD, PhD

• Paul B. Weinberg, MD

• Christine H. Wendt, MD

• Sandra R. Wilson, PhD

• Richard G. Wunderink, MD

• Syed A. Zaidi, MD

• Edward M. Zoratti, MD

STAFF CAMPAIGN• Julia Acevedo

• Meleta Adams

• Muricia N. Alexander

• Stephen Altobelli

• Nicole Anthony

• Marc Bendian

• Nicola Black

• May Ling Brantman

• D’Ann Brown

• Emily Catanzaro, CMP

• Alyssa Z. Chase, MPH

• Soledad Chauca

• Kevin Chiu

• Aashna Choudhary, PHR

DONORS Continued from page 13

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 2015 15

• Eric Chu

• Michael Clayton

• Francine Comi

• Judy Corn

• Stephen C. Crane, PhD, MPH

• Fran Du Melle

• Nathaniel Dunford

• Lara Endreszl

• Gary Ewart

• Daniel J. Fallon

• Stephanie Fulgione

• Dorcas Gelabert

• Diane Gern

• Nancy Guerrero

• Eric Gumpert

• Elizabeth Kay Guzman

• Rhina Guzman, PHR

• John Harmon

• Syed O. Hassan

• Barbara Horner

• Laura Houston

• Christopher L. Hughes

• Jennifer A. Ian MBA, CAE

• Vlada Kaganovskaya

• Brian Kell

• Neil Kerley

• Duncan Krassikoff

• Eileen Larsson

• Kimberly Lawrence

• Maribel Lim

• Andre Lindsay

• Fay Ling

• Lauren G. Lynch

• Shane McDermott

• Stacy McManus, CEM

• Mary Mobley

• Katharine T. Moore

• Nuala Moore

• Erin Marie Nebel, MA

• Lydia Neumann

• Kyle O’Donnell

• Catherine O’Hare

• Shannon L. Payne

• Dioliver Perez

• Matthew Reid

• Jessica Lynn Rivera, MBA

• Miriam Rodriguez

• Liliana Rozon

• Aprille Russell

• Jennifer Siegel-Gasiewski

• Sean Slifer

• Michelle Turenne

• Sherryl-Anne F. Vega

• Courtney White

• Rory Williams

• Kevin C. Wilson, MD

IN MEMORY OF• In Memory of Juan Acevedo

Julia Acevedo

• In Memory of Sanford Adler

Robert H. Brown, MD

• In Memory of Diane Argiros

Christopher L. Hughes

• In Memory of Mary Lynn Badr

M. Safwan Badr, MD

• In Memory of David V. Bates, MD

George D. Thurston, DSc

• In Memory of Betty June Behney

Alice M. Boylan, MD

• In Memory of Therese Blackshaw

Stacy McManus, CEM

• In Memory of Jeannie Carlson

Vince McGee

Rose Marie McSwiggin

• In Memory of Dwayne Chapman

Elizabeth Kay Guzman

• In Memory of Young Soo Choi, MD

Joshua Englert

• In Memory of Willa Mae Clark

Mary Mobley

• In Memory of Rose Comi

Francine Comi

• In Memory of Leo Cosgrove

Gregory P. Cosgrove, MD

• In Memory of Marjo Dorine Crain

Myrna Crain

• In Memory of Benjamin Boyce Davis, PhD,

MS

George Cardinet Anna Karnopp

• In Memory of Gabriel Elias, MD

Erica Herzog, MD, PhD

• In Memory of Carl Fifield

David W. Kamp, MD

• In Memory of Julian Guidot, MD

David M. Guidot, MD

• In Memory of Burt Gusky

Jeffrey A. Gold, MD

• In Memory of Fatima Tammy Hernandez

Mary Elizabeth C. Hernandez, MD

• In Memory of Stuart J. Hirst, PhD

Jane Elizabeth Bourke, BS(Hons), PhD

• In Memory of Roland H. Ingram, MD

Stephen H. Loring, MD

• In Memory of Joe Kirby

Gary Ewart

• In Memory of Mary Lou Leeds

C. Sheri and Ken Leeds Sr.

• In Memory of Averill Liebow, MD

Jerrold L. Abraham, MD

• In Memory of Barbara and Patrick McDermott

Shane McDermott

• In Memory of Robert Mellins, MD

Beverley J. Sheares, MD, MS

Jeffrey S. Wagener, MD

• In Memory of Pauline Mendelowitz

Carrie and Carl Helmsmeier

• In Memory of Frances Mularski

Richard A. Mularski, MD

• In Memory of Raymond C. Myers

United States Bankruptcy Court—

Northern District of Ohio

• In Memory of Julio Naranjo

Nancy Guerrero

• In Memory of Frederick Owen

Caroline A. Owen, MD, PhD

• In Memory of Glenn Eugene Parris

Michelle and Lars Bader

Kevin Creedon

Bob Dwyer

Patti Gowan

Beata Klecha

Ashlyn Kress

Kamal Maragh

Scott Mitchell

David Musselman

Mike Pierce

Matthew Price

Sarah Stevens

Rick Van Vleet

• In Memory of Dulce Perez

Dioliver Perez

see DONORS page 18

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ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 201518

• In Memory of Rosa M. Reed

Jessica Lynn Rivera, MBA

• In Memory of Wayne Reilly

Robert H. Brown, MD

• In Memory of Cecilia Rodriguez

Kristen Pomponio

• In Memory of Earl Rose, MD

Cecile S. Rose, MD, MPH

• In Memory of Bill Simonds

Katharine Squires

• In Memory of Gordon Snider, MD

Mark L. Brantly, MD

• In Memory of Bill Wells

James C. Lavelle IV, MD

• In Memory of Mary Ellen and Martin Wohl

Dennis C. Stokes, MD, MPH

• In Memory of Jo Rae Wright, PhD

Eileen Larsson

Susanna A. McColley, MD

IN HONOR OF• In Honor of Dr. Margot Becklake as a pioneer

in capacity building for pulmonary research in

Africa

Rebecca Bascom, MD, MPH

• In Honor of Carl Booberg

Brian Kell

• In Honor of A. Sonia Buist, MD

Jerrold L. Abraham, MD

Songul Buyukkale, MD

Alfred Munzer, MD

Yelda Varol, MD

• In Honor of William W. Busse, MD

Gordon R. Bloomberg, MD

Rebecca S. Gruchalla, MD, PhD

Gurjit Khurana Hershey, MD, PhD

Nizar N. Jarjour, MD

David M. Lang, MD

Marc Rothenberg, MD

Lawrence Schwartz, MD

• In Honor of Reuben M. Cherniack, MD

Talmadge E. King Jr., MD

• In Honor of James F. Donohue, MD

M. Patricia Rivera, MD

• In Honor of Patricia Finn, MD

Peter Finn

• In Honor of Richard Hyde, MD

John W. Shigeoka, MD

• In Honor of Monica Kraft, MD

Jennifer L. Ingram, PhD

• In Honor of Steve McCurdy, MD

Thomas Newman

• In Honor of Marilyn Morris

Alan H. Morris, MD

• In Honor of Karen Patterson, MD

Anne I. Sperling, PhD

• In Honor of Lynn F. Reinke, PhD, APRN, BC

DorAnne M. Donesky, PhD, ANP-BC

• In Honor of Marvin I. Schwarz, MD

David A. Schwartz, MD

• In Honor of Clare Sime

Patricia J. Sime, MD

• In Honor of B.K. Singaraju, MD

Raj Singaraju

• In Honor of Pamela Chauca and Jonathan

Marin

Soledad Chauca

IN HONOR OF MY MENTOR• In Honor of My Mentor Edward Block, MD

C. Michael Hart, MD

• In Honor of My Mentor Homer Boushey, MD

Steven Shak, MD

• In Honor of My Mentor John Butler, MD

Bruce H. Culver, MD

• In Honor of My Mentor Henry Chrystyn, MD

Wesam Ghazi Ammari, PhD

• In Honor of My Mentor W. Hal Cragun, MD

Bernard J. Roth, MD

• In Honor of My Mentor Nickolai Dulin, MD

Nathan K. Sandbo, MD

• In Honor of My Mentor Jack Elias, MD

Erica Herzog, MD, PhD

• In Honor of My Mentor James C. Hogg, MD

Claire M. Doerschuk, MD

• In Honor of My Mentor Steven Kawut, MD

Corey E. Ventetuolo, MD

• In Honor of My Mentor Richard A. Matthay, MD

Gulshan Sharma, MD, MPH

• In Honor of My Mentor Jay Nadel, MD

Arthur F. Gelb, MD

• In Honor of My Mentor David Orenstein, MD

Blakeslee E. Noyes, MD

• In Honor of My Mentor Polly Parsons, MD

Renee D. Stapleton, PhD, MD

• In Honor of My Mentor Thomas L. Petty, MD

Richard A. Matthay, MD

• In Honor of My Mentor Carrie Redlich, MD

Mridu Gulati, MD

• In Honor of My Mentor Steven Sahn, MD

John E. Heffner, MD

• In Honor of My Mentor Henry Williams, MD

Ok Hi Yoo, MD

•

**These individuals have included the

ATS Foundation in their estate plans.

† Deceased

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How Do You Treat PE?See us at Booth #321

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An Industry Theater Presentation at the ATS 2015 International Conference. This presentation is sponsored by United Therapeutics. Due to regulatory restrictions, this presentation is only available to attendees from the United States.

LEARN ABOUT TYVASO, AN INHALED PROSTACYCLIN, AT INDUSTRY THEATER #2 ON MONDAY, MAY 18 AT 11:45 am

IMPORTANT SAFETY INFORMATION FOR TYVASO• Tyvaso is intended for oral inhalation only. Tyvaso is approved

for use only with the Tyvaso Inhalation System• The safety and e� cacy of Tyvaso have not been established

in patients with signi  cant underlying lung disease (such as asthma or chronic obstructive pulmonary disease) and in patients under 18 years of age. Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug e� ect

• Tyvaso may increase the risk of bleeding, particularly in patients receiving anticoagulants

• In patients with low systemic arterial pressure, Tyvaso may cause symptomatic hypotension. The concomitant use of Tyvaso with diuretics, antihypertensives, or other vasodilators may increase the risk of symptomatic hypotension

• Hepatic or renal insu� ciency may increase exposure to Tyvaso and decrease tolerability. Tyvaso dosage adjustments may be necessary if inhibitors of CYP2C8, such as gem  brozil, or inducers of CYP2C8, such as rifampin, are added or withdrawn

• There are no adequate and well-controlled studies with Tyvaso in pregnant women. It is not known whether treprostinil is excreted in human milk

• The most common adverse events seen with Tyvaso in ≥4% of PAH patients and more than 3% greater than placebo in the placebo-controlled clinical study were cough (54% vs 29%), headache (41% vs 23%), throat irritation/pharyngolaryngeal pain (25% vs 14%), nausea (19% vs 11%), � ushing (15% vs <1%), and syncope (6% vs <1%)

Please see brief summary of Full Prescribing Information on following page. For more information, please see Full Prescribing Information, Patient Package Insert, and the Tyvaso Inhalation System Instructions for Use manual. These items are available at www.tyvaso.com.

For additional information about Tyvaso, visit www.tyvaso.com or call 1-877-UNITHER (1-877-864-8437).

INDICATIONTyvaso is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing e� ectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).The e� ects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildena  l (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.

Tyvaso is a registered trademark of United Therapeutics Corporation.© 2015 United Therapeutics Corporation. All rights reserved. US/TYV/FEB15/313(1)

Request a visit from a Tyvaso sales representative by visiting www.tyvaso.com.

TO YOUR PAH TREATMENT STRATEGY

VISIT BOOTH 1157

US_TYV_FEB15_313_10314160_ATS_Program_Ad_FR4.indd 1 5/4/15 6:02 PM

BRIEF SUMMARY

The following is a brief summary of the full prescribing information for TYVASO® (treprostinil) Inhalation Solution. Please review the full prescribing information prior to prescribing TYVASO.

INDICATIONS AND USAGE

TYVASO is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%). The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities. While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

Patients with Pulmonary Disease or Pulmonary Infections–The safety and efficacy of TYVASO have not been established in patients with significant underlying lung disease (e.g., asthma or chronic obstructive pulmonary disease). Patients with acute pulmonary infections should be carefully monitored to detect any worsening of lung disease and loss of drug effect.

Risk of Symptomatic Hypotension– Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with TYVASO may produce symptomatic hypotension. Patients with Hepatic or Renal Insufficiency–Titrate slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function. Risk of Bleeding–Since TYVASO inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulant therapy. Effect of Other Drugs on Treprostinil–Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness.

ADVERSE REACTIONS

The following potential adverse reactions are described in Warnings and Precautions:

• Decrease in systemic blood pressure • Bleeding

Adverse Reactions Identified in Clinical Trials–Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a 12-week placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions to TYVASO included: cough and throat irritation; headache, gastrointestinal effects, muscle, jaw or bone pain, flushing and syncope. Table 1 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with TYVASO than with placebo.

The safety of TYVASO was also studied in a long-term, open-label extension study in which 206 patients were dosed for a mean duration of 2.3 years with a maximum exposure of 5.4 years. Eighty-nine (89%) percent of patients achieved the target dose of nine breaths, four times daily. Forty-two (42%) percent achieved a dose of 12 breaths four times daily. The adverse events during this chronic dosing study were qualitatively similar to those observed in the 12-week placebo controlled trial. Adverse Events Associated with Route of Administration–Adverse events in the treated group during the double-blind and open-label phase reflecting irritation to the respiratory tract included: cough, throat irritation, pharyngeal pain, epistaxis, hemoptysis and wheezing. Serious adverse events during the open-label portion of the study included pneumonia in 15 subjects. There were three serious episodes of hemoptysis (one fatal) noted during the open-label experience. Adverse Reactions Identified in Post-Marketing Experience–The following adverse reaction has been identified during the postapproval use of Tyvaso. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure: Angioedema

DRUG INTERACTIONS

Pharmacokinetic/pharmacodynamic interaction studies have not been conducted with inhaled treprostinil (TYVASO); however, some of such studies have been conducted with orally (treprostinil diolamine) and subcutaneously administered treprostinil (Remodulin®).Pharmacodynamics–Antihypertensive Agents or Other Vasodilators– Concomitant administration of TYVASO with diuretics, antihypertensive agents or other vasodilators may increase the risk of symptomatic hypotension. Anticoagulants–Since treprostinil inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants. Pharmacokinetics–Bosentan– In a human pharmacokinetic study conducted with bosentan (250 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and bosentan were observed. Sildenafil– In a human pharmacokinetic study conducted with sildenafil (60 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and sildenafil were observed. Effect of Cytochrome P450 Inhibitors and Inducers– In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A. Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8. Effect of Other Drugs on Treprostinil–Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil.

Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S-warfarin and the INR in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

USE IN SPECIFIC POPULATIONS

Pregnancy—Pregnancy Category B–There are no adequate and well controlled studies with TYVASO in pregnant women. Animal reproduction studies have not been conducted with treprostinil administered by the inhalation route. However, studies in pregnant rabbits using continuous subcutaneous (sc) infusions of treprostinil sodium at infusion rates higher than the recommended human sc infusion rate resulted in an increased incidence of fetal skeletal variations associated with maternal toxicity. Animal reproduction studies are not always predictive of human response.Labor and Delivery–No treprostinil treatment-related effects on labor and delivery were seen in animal studies. The effect of treprostinil on labor and delivery in humans is unknown. Nursing Mothers–It is not known whether treprostinil is excreted in human milk. Pediatric Use–Safety and effectiveness in pediatric patients have not been established. Clinical studies of TYVASO did not include patients younger than 18 years to determine whether they respond differently from older patients. Geriatric Use–Clinical studies of TYVASO did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy. Patients with Hepatic Insufficiency–Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency. Patients with Renal Insufficiency–No studies have been performed in patients with renal insufficiency. Since treprostinil and its metabolites are excreted mainly through the urinary route, patients with renal insufficiency may have decreased clearance of the drug and its metabolites and consequently, dose-related adverse outcomes may be more frequent.

OVERDOSAGE

In general, symptoms of overdose with TYVASO include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

Tyvaso manufactured for: United Therapeutics Corporation Research Triangle Park, NC 27709

Rx only February 2015

www.tyvaso.com

Table 1: Adverse Events in ≥4% of PAH Patients Receiving TYVASO and More Frequent* than Placebo

Adverse Event Treatment n (%)

TYVASO n = 115

Placebo n = 120

Cough 62 (54) 35 (29)

Headache 47 (41) 27 (23)

Throat Irritation/ Pharyngolaryngeal Pain 29 (25) 17 (14)

Nausea 22 (19) 13 (11)

Flushing 17 (15) 1 (<1)

Syncope 7 (6) 1 (<1)

*More than 3% greater than placebo

S:10.25”

S:14”

US_TYV_FEB15_313_10314160_ATS_Program_Ad_BS_FR3.indd 1 4/2/15 5:40 PM

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 2015 21

Symposium Examines Global Threat of Air Pollution

A ir pollution inflicts a huge burden of illness—from respiratory problems caused by asthma, COPD, and lung

cancer to non-respiratory issues brought on by coronary artery disease, hypertension, and cancer. Air pollution stunts lung growth and increases susceptibility to respiratory infec-tions in infants and children. Additionally, it predisposes adults to respiratory diseases, including asthma, bronchiolitis, COPD, and lung cancer.

“Air Pollution: A Major Global Threat to Lung Health” from 9:30 to 11:30 a.m. today in Centennial Ballroom D (Third Floor) Hyatt Regency Denver at the Colorado Conven-tion Center, will bring together experts from around the world to discuss the impact of outdoor and indoor air pollution on lung disease, consider ways of reducing the burden

of air pollution, and discuss mechanisms of lung injury.

“Indoor air pollution contributes to 75 percent of COPD in developing nations, affecting young mothers and children who are most heavily exposed to smoke from fires and

cooking instruments indoors,” says Gregory P. Downey, MD, executive vice president of academic affairs at National Jewish Health and professor of medicine at the University of Colorado School of Medicine, Denver. “Under-standing how air pollution contributes to lung disease is critical in preventing and mitigating the effects of air pollution.”

Dr. Downey is chair of the scientific sympo-sium with three other experts: Peter J. Barnes, DSc, MD, Margaret Turner-Warwick Chair at the Imperial College of London; Sundeep Salvi, MD, PhD, director of the Chest Research

Foundation, Pune, India; and Ross Vlahos, PhD, associate professor of clinical sciences at the Royal Melbourne Institute of Technology.

Attendees will learn about the enormous impact of air pollution on global lung health, gain an understanding of the components of indoor and outdoor air pollution that dam-age lung health, and learn about public health measures needed to reduce air pollution and lung disease.

Those interested in this session are also en-couraged to attend “‘OMICS’ of Environmen-tally-Induced Lung Diseases” from 2:15 to 4:15 p.m. today. This mini symposium will be held in the same location—Centennial Ball-room E (Third Floor) Hyatt Regency Denver at the Colorado Convention Center.

Gregory P. Downey

Air Pollution: A Major Global Threat to Lung Health9:30 to 11:30 a.m. todayCentennial Ballroom D (Third Floor) Hyatt Regency Denver at the Colorado Convention Center

C elebrate the achievements of four expert researchers during the Rec-ognition Awards for Scientific Ac-

complishments from 2:15 to 4:15 p.m. today in Room 107/109/111/113 (Street Level) in the Colorado Convention Center.

These awards are given to individuals for outstanding scientific contributions in basic or clinical research to the understanding, prevention, and treatment of lung disease.

J.W. Christman, MD, Columbus, OH, and P.W. Finn, MD, Chicago, IL, are chairs of the session. Awardees will make 25-minute presentations about their research.

• 2:15: Reynold A. Panettieri Jr., MD,

the University of Pennsylvania, Philadelphia, presents “Airway Smooth Muscle: A Novel Therapeutic Target in Severe Asthma.”

• 2:45: Annie Pardo, PhD, Universidad Nacional Autonoma de Mexico, Mexico City, presents “Untan-gling the Knot in IPF: Developing Irre-versible Scars Despite Increased MMPs.”

• 3:15: William C. Parks, PhD, Cedars–Sinai Medical Center, Los Angeles,

presents “MMPs in Lung Repair and Fibrosis.”

• 3:45: Lorraine B. Ware, MD, Vanderbilt University, Nashville, presents “Seeing Red: Free Hemoglobin and the Pathogen-esis of Sepsis and ARDS.”

Four to Receive Awards for Scientific Accomplishments

William C. ParksAnnie PardoReynold A. Panettieri Jr.

Lorraine B. Ware

SECONDARY ENDPOINT: SERIAL FEV1 (0-25 HOURS)1,2

References: 1. Boscia JA, Pudi KK, Zvarich MT, Sanford L, Siederer SK, Crim C. Effect of once-daily fl uticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study. Clin Ther. 2012;34(8):1655-1666. 2. Data on fi le, GSK. 3. Kerwin EM, Scott-Wilson C, Sanford L, et al. A randomised trial of fl uticasone furoate/vilanterol (50/25 μg; 100/25 μg) on lung function in COPD. Respir Med. 2013;107(4):560-569.

Please see Brief Summary of Prescribing Information, including Boxed Warning, for BREO ELLIPTA on the following pages.

BREO ELLIPTA was developed in collaboration with

www.breoinfo.com

Important Safety Information (cont’d)WARNINGS AND PRECAUTIONS (cont’d)• Glaucoma, increased intraocular pressure, and cataracts have been

reported in patients with COPD following the long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

• Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS• The most common adverse reactions (≥3% and more common than

placebo) reported in two 6-month clinical trials with BREO ELLIPTA (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).

• In addition to the events reported in the 6-month studies, adverse reactions occurring in ≥3% of the subjects treated with BREO ELLIPTA in two 1-year studies included COPD, back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, infl uenza, pharyngitis, diarrhea, peripheral edema, and pyrexia.

DRUG INTERACTIONS• Caution should be exercised when considering the coadministration of

BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfi navir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.

• BREO ELLIPTA should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists, such as vilanterol, on the cardiovascular system may be potentiated by these agents.

• Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with reversible obstructive airways disease.

• Use with caution in patients taking non–potassium-sparing diuretics, as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

USE IN SPECIFIC POPULATIONS• Use BREO ELLIPTA with caution in patients with moderate or severe

hepatic impairment. Fluticasone furoate exposure may increase in these patients. Monitor for systemic corticosteroid effects.

Important Safety Information

WARNING: ASTHMA-RELATED DEATH • Long-acting beta2-adrenergic agonists (LABAs), such as

vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths in subjects receiving salmeterol. This fi nding with salmeterol is considered a class effect of all LABAs, including vilanterol.

• The safety and effi cacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.

CONTRAINDICATIONS• BREO ELLIPTA is contraindicated in patients with severe hypersensitivity

to milk proteins or who have demonstrated hypersensitivity to either fl uticasone furoate, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS• BREO ELLIPTA should not be initiated in patients during rapidly

deteriorating or potentially life-threatening episodes of COPD.• BREO ELLIPTA should not be used for the relief of acute symptoms,

i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.

• BREO ELLIPTA should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result. Clinically signifi cant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BREO ELLIPTA should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

• Oropharyngeal candidiasis has occurred in patients treated with BREO ELLIPTA. Advise patients to rinse the mouth without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.

• An increase in the incidence of pneumonia has been observed in subjects with COPD receiving BREO ELLIPTA. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal.— In replicate 12-month studies of 3255 subjects with COPD who

had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving BREO ELLIPTA 100/25 mcg (6% [51 of 806 subjects]), fl uticasone furoate (FF)/vilanterol (VI) 50/25 mcg (6% [48 of 820 subjects]), and FF/VI 200/25 mcg (7% [55 of 811 subjects]) than in

subjects receiving VI 25 mcg (3% [27 of 818 subjects]). There was no fatal pneumonia in subjects receiving VI or FF/VI 50/25 mcg. There was fatal pneumonia in 1 subject receiving BREO ELLIPTA at the approved strength (100/25 mcg) and in 7 subjects receiving FF/VI 200/25 mcg (<1% for each treatment group).

• Physicians should remain vigilant for the possible development of pneumonia in patients with COPD, as the clinical features of such infections overlap with the symptoms of COPD exacerbations.

• Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections.

• Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insuffi ciency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to BREO ELLIPTA.

• Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals. If such changes occur, discontinue BREO ELLIPTA slowly.

• Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfi navir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.

• If paradoxical bronchospasm occurs, discontinue BREO ELLIPTA and institute alternative therapy.

• Vilanterol can produce clinically signifi cant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO ELLIPTA may need to be discontinued. BREO ELLIPTA should be used with caution in patients with cardiovascular disorders, especially coronary insuffi ciency, cardiac arrhythmias, and hypertension.

• Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating BREO ELLIPTA and periodically thereafter.

The fi rst and only once-daily ICS/LABA for the maintenance treatment of COPD

Improves patients’ lung function for a full 24 hours with one inhalation, once daily1*

Also approved to reduce COPD exacerbations in patients with a history of exacerbations

HOUR24

‡At screening, patients had a mean postbronchodilator % predicted FEV1 of 49.8%, a mean postbronchodilator FEV1/FVC ratio of 52.9%, and a mean % reversibility of 8.8%. FEV1=forced expiratory volume in 1 second; FVC=forced vital capacity.

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FEV

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HOURS POSTDOSE

300

200

100

0

–100

–200128 20 24226420† 16

†Zero=dose administration time (between 6 AM and 10 AM).

Lung function assessed over 1 full day at Days 28 and 29

PLACEBO (n=51)Hour 25=18 mL

BREO (n=33)Hour 25=166 mL

* A multicenter, randomized, double-blind, placebo-controlled, crossover study evaluated the effect of 28 days of treatment with BREO ELLIPTA on lung function over 24 hours in 54 patients (mean age: 57.9 years) with COPD.‡ The primary endpoint was weighted mean FEV1 (0-24 hours) at the end of the 28-day treatment period (period Days 28 and 29). This was calculated from predose FEV1 (mean of –30- and –5-minute measurements) and postdose FEV1 after 5, 15, 30, and 60 minutes and 2, 4, 6, 8, 12, 16, 20, 22, 23, and 24 hours. The secondary endpoint was serial FEV1 (0-25 hours) at period Days 28 and 29.

Once-daily BREO ELLIPTA provided sustained improvement in lung function for a full 24 hours

PRIMARY ENDPOINT: BREO ELLIPTA provided a 220 mL improvement in weighted mean FEV1 (0-24 hours) from period baseline compared with placebo (P<0.001) at end of the 28-day treatment period.1

In a separate 6-month lung-function study: a multicenter, randomized, double-blind, parallel-group study compared the effect of BREO vs fl uticasone furoate (FF) 100 mcg and vs placebo (each administered once daily by the ELLIPTA inhaler) on lung function in 1030 patients (mean age: 62.7 years) with COPD.§ For the co-primary endpoints, BREO signifi cantly improved weighted mean FEV1 (0-4 hours) postdose on Day 168 by 120 mL vs FFll and 173 mL vs placebo (P<0.001 for both); and BREO demonstrated a greater difference in LS mean change from baseline in trough FEV1 at Day 169 of 115 mL vs placebo (95% CI: 60, 169; P<0.001); the 48 mL difference vs vilanterol 25 mcg¶ did not achieve statistical signifi cance (95% CI: –6, 102; P=0.082).2,3

§ At screening, patients had a mean postbronchodilator % predicted FEV1 of 48.3%, a mean postbronchodilator FEV1/FVC ratio of 47.6%, and a mean % reversibility of 15.9%.ll The weighted mean comparison of BREO with FF, the ICS component, was assessed to evaluate the contribution of vilanterol to BREO. ICSs are not approved as monotherapy for COPD. ¶The trough FEV1 comparison of BREO with vilanterol, the LABA component, was assessed to evaluate the contribution of FF to BREO. Vilanterol is not approved as monotherapy.

Indications• BREO ELLIPTA is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) indicated for the long-term, once-daily, maintenance

treatment of airfl ow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. • BREO ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.• BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma.

HOUR242424

©2015 GSK group of companies. All rights reserved. Printed in USA. 320114R0 March 2015

S:9.5” S:9.5”

S:12”

T:21”

T:13”

B:21.25”

B:13.25”

SECONDARY ENDPOINT: SERIAL FEV1 (0-25 HOURS)1,2

References: 1. Boscia JA, Pudi KK, Zvarich MT, Sanford L, Siederer SK, Crim C. Effect of once-daily fl uticasone furoate/vilanterol on 24-hour pulmonary function in patients with chronic obstructive pulmonary disease: a randomized, three-way, incomplete block, crossover study. Clin Ther. 2012;34(8):1655-1666. 2. Data on fi le, GSK. 3. Kerwin EM, Scott-Wilson C, Sanford L, et al. A randomised trial of fl uticasone furoate/vilanterol (50/25 μg; 100/25 μg) on lung function in COPD. Respir Med. 2013;107(4):560-569.

Please see Brief Summary of Prescribing Information, including Boxed Warning, for BREO ELLIPTA on the following pages.

BREO ELLIPTA was developed in collaboration with

www.breoinfo.com

Important Safety Information (cont’d)WARNINGS AND PRECAUTIONS (cont’d)• Glaucoma, increased intraocular pressure, and cataracts have been

reported in patients with COPD following the long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.

• Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

• Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS• The most common adverse reactions (≥3% and more common than

placebo) reported in two 6-month clinical trials with BREO ELLIPTA (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).

• In addition to the events reported in the 6-month studies, adverse reactions occurring in ≥3% of the subjects treated with BREO ELLIPTA in two 1-year studies included COPD, back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, infl uenza, pharyngitis, diarrhea, peripheral edema, and pyrexia.

DRUG INTERACTIONS• Caution should be exercised when considering the coadministration of

BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfi navir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.

• BREO ELLIPTA should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists, such as vilanterol, on the cardiovascular system may be potentiated by these agents.

• Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with reversible obstructive airways disease.

• Use with caution in patients taking non–potassium-sparing diuretics, as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

USE IN SPECIFIC POPULATIONS• Use BREO ELLIPTA with caution in patients with moderate or severe

hepatic impairment. Fluticasone furoate exposure may increase in these patients. Monitor for systemic corticosteroid effects.

Important Safety Information

WARNING: ASTHMA-RELATED DEATH • Long-acting beta2-adrenergic agonists (LABAs), such as

vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths in subjects receiving salmeterol. This fi nding with salmeterol is considered a class effect of all LABAs, including vilanterol.

• The safety and effi cacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.

CONTRAINDICATIONS• BREO ELLIPTA is contraindicated in patients with severe hypersensitivity

to milk proteins or who have demonstrated hypersensitivity to either fl uticasone furoate, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS• BREO ELLIPTA should not be initiated in patients during rapidly

deteriorating or potentially life-threatening episodes of COPD.• BREO ELLIPTA should not be used for the relief of acute symptoms,

i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.

• BREO ELLIPTA should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result. Clinically signifi cant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BREO ELLIPTA should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

• Oropharyngeal candidiasis has occurred in patients treated with BREO ELLIPTA. Advise patients to rinse the mouth without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.

• An increase in the incidence of pneumonia has been observed in subjects with COPD receiving BREO ELLIPTA. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal.— In replicate 12-month studies of 3255 subjects with COPD who

had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving BREO ELLIPTA 100/25 mcg (6% [51 of 806 subjects]), fl uticasone furoate (FF)/vilanterol (VI) 50/25 mcg (6% [48 of 820 subjects]), and FF/VI 200/25 mcg (7% [55 of 811 subjects]) than in

subjects receiving VI 25 mcg (3% [27 of 818 subjects]). There was no fatal pneumonia in subjects receiving VI or FF/VI 50/25 mcg. There was fatal pneumonia in 1 subject receiving BREO ELLIPTA at the approved strength (100/25 mcg) and in 7 subjects receiving FF/VI 200/25 mcg (<1% for each treatment group).

• Physicians should remain vigilant for the possible development of pneumonia in patients with COPD, as the clinical features of such infections overlap with the symptoms of COPD exacerbations.

• Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections.

• Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insuffi ciency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to BREO ELLIPTA.

• Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals. If such changes occur, discontinue BREO ELLIPTA slowly.

• Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfi navir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and cardiovascular adverse effects may occur.

• If paradoxical bronchospasm occurs, discontinue BREO ELLIPTA and institute alternative therapy.

• Vilanterol can produce clinically signifi cant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO ELLIPTA may need to be discontinued. BREO ELLIPTA should be used with caution in patients with cardiovascular disorders, especially coronary insuffi ciency, cardiac arrhythmias, and hypertension.

• Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating BREO ELLIPTA and periodically thereafter.

The fi rst and only once-daily ICS/LABA for the maintenance treatment of COPD

Improves patients’ lung function for a full 24 hours with one inhalation, once daily1*

Also approved to reduce COPD exacerbations in patients with a history of exacerbations

HOUR24

‡At screening, patients had a mean postbronchodilator % predicted FEV1 of 49.8%, a mean postbronchodilator FEV1/FVC ratio of 52.9%, and a mean % reversibility of 8.8%. FEV1=forced expiratory volume in 1 second; FVC=forced vital capacity.

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†Zero=dose administration time (between 6 AM and 10 AM).

Lung function assessed over 1 full day at Days 28 and 29

PLACEBO (n=51)Hour 25=18 mL

BREO (n=33)Hour 25=166 mL

* A multicenter, randomized, double-blind, placebo-controlled, crossover study evaluated the effect of 28 days of treatment with BREO ELLIPTA on lung function over 24 hours in 54 patients (mean age: 57.9 years) with COPD.‡ The primary endpoint was weighted mean FEV1 (0-24 hours) at the end of the 28-day treatment period (period Days 28 and 29). This was calculated from predose FEV1 (mean of –30- and –5-minute measurements) and postdose FEV1 after 5, 15, 30, and 60 minutes and 2, 4, 6, 8, 12, 16, 20, 22, 23, and 24 hours. The secondary endpoint was serial FEV1 (0-25 hours) at period Days 28 and 29.

Once-daily BREO ELLIPTA provided sustained improvement in lung function for a full 24 hours

PRIMARY ENDPOINT: BREO ELLIPTA provided a 220 mL improvement in weighted mean FEV1 (0-24 hours) from period baseline compared with placebo (P<0.001) at end of the 28-day treatment period.1

In a separate 6-month lung-function study: a multicenter, randomized, double-blind, parallel-group study compared the effect of BREO vs fl uticasone furoate (FF) 100 mcg and vs placebo (each administered once daily by the ELLIPTA inhaler) on lung function in 1030 patients (mean age: 62.7 years) with COPD.§ For the co-primary endpoints, BREO signifi cantly improved weighted mean FEV1 (0-4 hours) postdose on Day 168 by 120 mL vs FFll and 173 mL vs placebo (P<0.001 for both); and BREO demonstrated a greater difference in LS mean change from baseline in trough FEV1 at Day 169 of 115 mL vs placebo (95% CI: 60, 169; P<0.001); the 48 mL difference vs vilanterol 25 mcg¶ did not achieve statistical signifi cance (95% CI: –6, 102; P=0.082).2,3

§ At screening, patients had a mean postbronchodilator % predicted FEV1 of 48.3%, a mean postbronchodilator FEV1/FVC ratio of 47.6%, and a mean % reversibility of 15.9%.ll The weighted mean comparison of BREO with FF, the ICS component, was assessed to evaluate the contribution of vilanterol to BREO. ICSs are not approved as monotherapy for COPD. ¶The trough FEV1 comparison of BREO with vilanterol, the LABA component, was assessed to evaluate the contribution of FF to BREO. Vilanterol is not approved as monotherapy.

Indications• BREO ELLIPTA is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) indicated for the long-term, once-daily, maintenance

treatment of airfl ow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. • BREO ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.• BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma.

HOUR242424

©2015 GSK group of companies. All rights reserved. Printed in USA. 320114R0 March 2015

S:9.5” S:9.5”

S:12”

T:21”

T:13”

B:21.25”

B:13.25”

BREO ELLIPTA BRIEF SUMMARY(fluticasone furoate and vilanterol inhalation powder)FOR ORAL INHALATION USE The following is a brief summary only; see full prescribing information for complete product information.

WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of another LABA (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including vilanterol, an active ingredient in BREO® ELLIPTA® [see Warnings and Precautions (5.1)]. The safety and efficacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.

1 INDICATIONS AND USAGEBREO ELLIPTA is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. BREO ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.Important Limitations of Use: BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma.

4 CONTRAINDICATIONSThe use of BREO ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients [see Warnings and Precautions (5.11), Description (11) of full prescribing information].

5 WARNINGS AND PRECAUTIONS5.1 Asthma-Related Death Data from a large placebo-controlled trial in subjects with asthma showed that LABA may increase the risk of asthma-related death. Data are not available to determine whether the rate of death in patients with COPD is increased by LABA. A 28-week, placebo-controlled, US trial comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol vs 3/13,179 in subjects treated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]). The increased risk of asthma-related death is considered a class effect of LABA, including vilanterol, one of the active ingredients in BREO ELLIPTA. No study adequate to determine whether the rate of asthma-related death is increased in subjects treated with BREO ELLIPTA has been conducted. The safety and efficacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.5.2 Deterioration of Disease and Acute Episodes BREO ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. BREO ELLIPTA has not been studied in patients with acutely deteriorating COPD. The initiation of BREO ELLIPTA in this setting is not appropriate. BREO ELLIPTA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. BREO ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist. When beginning treatment with BREO ELLIPTA, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs and to use them only for symptomatic relief of acute respiratory symptoms. When prescribing BREO ELLIPTA, the healthcare provider should also prescribe an inhaled, short-acting beta2-agonist and instruct the patient on how it should be used. Increasing inhaled, short-acting beta2-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If BREO ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting, beta2-agonist becomes less effective; or the patient needs more short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of BREO ELLIPTA beyond the recommended dose is not appropriate in this situation.5.3 Excessive Use of BREO ELLIPTA and Use With Other Long-Acting Beta2-Agonists BREO ELLIPTA should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BREO ELLIPTA should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.5.4 Local Effects of Inhaled Corticosteroids In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with BREO ELLIPTA. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with BREO ELLIPTA continues, but at times therapy with BREO ELLIPTA may need to be interrupted. Advise the patient to rinse his/her mouth without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.5.5 Pneumonia An increase in the incidence of pneumonia has been observed in subjects with COPD receiving the fluticasone furoate/vilanterol combination, including BREO ELLIPTA 100 mcg/25 mcg, in clinical trials. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. In replicate 12-month trials in 3,255 subjects with COPD who had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: 6% [48 of 820 subjects]; 100 mcg/25 mcg: 6% [51 of 806 subjects]; or 200 mcg/25 mcg: 7% [55 of 811 subjects]) than in subjects receiving vilanterol 25 mcg (3% [27 of 818 subjects]). There was no fatal pneumonia in subjects receiving vilanterol or fluticasone furoate/vilanterol 50 mcg/25 mcg. There was fatal pneumonia in 1 subject receiving fluticasone furoate/vilanterol 100 mcg/25 mcg and in 7 subjects receiving fluticasone furoate/vilanterol 200 mcg/25 mcg (less than 1% for each treatment group).5.6 Immunosuppression Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.5.7 Transferring Patients From Systemic Corticosteroid Therapy Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although BREO ELLIPTA may control COPD symptoms during these episodes, in recommended doses it supplies less than normal physiological amount of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe COPD exacerbation, patients who have been withdrawn

from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe COPD exacerbation. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to BREO ELLIPTA. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with BREO ELLIPTA. Lung function (mean forced expiratory volume in 1 second [FEV1]), beta-agonist use, and COPD symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to BREO ELLIPTA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.5.8 Hypercorticism and Adrenal Suppression Inhaled fluticasone furoate is absorbed into the circulation and can be systemically active. Effects of fluticasone furoate on the HPA axis are not observed with the therapeutic dose of BREO ELLIPTA. However, exceeding the recommended dosage or coadministration with a strong cytochrome P450 3A4 (CYP3A4) inhibitor may result in HPA dysfunction [see Warnings and Precautions (5.9), Drug Interactions (7.1)]. Because of the possibility of significant systemic absorption of inhaled corticosteroids in sensitive patients, patients treated with BREO ELLIPTA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, BREO ELLIPTA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of COPD symptoms should be considered.5.9 Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and increased cardiovascular adverse effects may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3) of full prescribing information].5.10 Paradoxical Bronchospasm As with other inhaled medicines, BREO ELLIPTA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with BREO ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; BREO ELLIPTA should be discontinued immediately; and alternative therapy should be instituted.5.11 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of BREO ELLIPTA. Discontinue BREO ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use BREO ELLIPTA [see Contraindications (4)].5.12 Cardiovascular Effects Vilanterol, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO ELLIPTA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, although the clinical significance of these findings is unknown. In healthy subjects, large doses of inhaled fluticasone furoate/vilanterol (4 times the recommended dose of vilanterol, representing a 12-fold higher systemic exposure than seen in patients with COPD) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias. Therefore, BREO ELLIPTA, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.13 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating BREO ELLIPTA and periodically thereafter. If significant reductions in BMD are seen and BREO ELLIPTA is still considered medically important for that patient’s COPD therapy, use of medicine to treat or prevent osteoporosis should be strongly considered. In replicate 12-month trials in 3,255 subjects with COPD, bone fractures were reported by 2% of subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: 2% [14 of 820 subjects]; 100 mcg/25 mcg: 2% [19 of 806 subjects]; or 200 mcg/25 mcg: 2% [14 of 811 subjects]) than in subjects receiving vilanterol 25 mcg alone (less than 1% [8 of 818 subjects]).5.14 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with COPD following the long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. In replicate 12-month trials in 3,255 subjects with COPD, similar incidences of ocular effects (including glaucoma and cataracts) were reported in subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: less than 1% [7 of 820 subjects]; 100 mcg/25 mcg: 1% [12 of 806 subjects]; 200 mcg/25 mcg: less than 1% [7 of 811 subjects]) as those receiving vilanterol 25 mcg alone (1% [9 of 818 subjects]).5.15 Coexisting Conditions BREO ELLIPTA, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of the related beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.5.16 Hypokalemia and Hyperglycemia Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. Beta-agonist medications may produce transient hyperglycemia in some patients. In 4 clinical trials of 6- and 12-month duration evaluating BREO ELLIPTA in subjects with COPD, there was no evidence of a treatment effect on serum glucose or potassium.

6 ADVERSE REACTIONSLABA, such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. BREO ELLIPTA is not indicated for the treatment of asthma. [See Boxed Warnings and Warnings and Precautions (5.1).] Systemic and local corticosteroid use may result in the following: Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5)]; Increased risk for decrease in bone mineral density [see Warnings and Precautions (5.13)].6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical program for BREO ELLIPTA included 7,700 subjects with COPD in two 6-month lung function trials, two 12-month exacerbation trials, and 6 other trials of shorter duration. A total of 2,034 subjects have received at least 1 dose of BREO ELLIPTA 100 mcg/25 mcg, and 1,087 subjects have received higher doses of fluticasone furoate/vilanterol. The safety data described below are based on the confirmatory 6-month and 12-month trials. Adverse reactions observed in the other trials were similar to those observed in the confirmatory trials.6-Month Trials: The incidence of adverse reactions associated with BREO ELLIPTA in Table 1 is based on 2 placebo-controlled, 6-month clinical trials (Trials 1 and 2; n = 1,224 and n = 1,030, respectively). Of the 2,254 subjects, 70% were male and 84% were Caucasian. They had a mean age of 62 years and an average smoking history of 44 pack years, with 54% identified as current smokers. At screening, the mean postbronchodilator percent predicted FEV1 was 48% (range: 14% to 87%), the mean postbronchodilator FEV1/forced vital capacity (FVC) ratio was 47% (range: 17% to 88%), and the mean percent reversibility was 14% (range: -41% to 152%). Subjects received 1 inhalation once daily of the following: BREO ELLIPTA 100 mcg/25 mcg, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate/vilanterol 200 mcg/25 mcg, fluticasone furoate 100 mcg, fluticasone furoate 200 mcg, vilanterol 25 mcg, or placebo.

Table 1. Adverse Reactions With ≥3% Incidence and More Common Than Placebo With BREO ELLIPTA in Subjects With Chronic Obstructive Pulmonary Disease

Adverse Event

BREO ELLIPTA 100 mcg/25 mcg

(n = 410)%

Vilanterol 25 mcg

(n = 408)%

Fluticasone Furoate100 mcg(n = 410)

%

Placebo(n = 412)

%

Infections and infestations

Nasopharyngitis 9 10 8 8

Upper respiratory tract infection

7 5 4 3

Oropharyngeal candidiasisa 5 2 3 2

Nervous system disordersHeadache 7 9 7 5

a Includes terms oral candidiasis, oropharyngeal candidiasis, candidiasis, and oropharyngitis fungal.

12-Month Trials: Long-term safety data is based on two 12-month trials (Trials 3 and 4; n = 1,633 and n = 1,622, respectively). Trials 3 and 4 included 3,255 subjects, of which 57% were male and 85% were Caucasian. They had a mean age of 64 years and an average smoking history of 46 pack years, with 44% identified as current smokers. At screening, the mean postbronchodilator percent predicted FEV1 was 45% (range: 12% to 91%), and the mean postbronchodilator FEV1/FVC ratio was 46% (range: 17% to 81%), indicating that the subject population had moderate to very severely impaired airflow obstruction. Subjects received 1 inhalation once daily of the following: BREO ELLIPTA 100 mcg/25 mcg, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate/vilanterol 200 mcg/25 mcg, or vilanterol 25 mcg. In addition to the events shown in Table 1, adverse reactions occurring in greater than or equal to 3% of the subjects treated with BREO ELLIPTA (N = 806) for 12 months included COPD, back pain, pneumonia [see Warnings and Precautions (5.5)], bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, influenza, pharyngitis, diarrhea, peripheral edema, and pyrexia.6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of BREO ELLIPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to BREO ELLIPTA or a combination of these factors. Immune System Disorders: Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria.

7 DRUG INTERACTIONS7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone furoate and vilanterol, the individual components of BREO ELLIPTA, are both substrates of CYP3A4. Concomitant administration of the potent CYP3A4 inhibitor ketoconazole increases the systemic exposure to fluticasone furoate and vilanterol. Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.3) of full prescribing information].7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Vilanterol, like other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias.7.3 Beta-Adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as vilanterol, a component of BREO ELLIPTA, but may produce severe bronchospasm in patients with reversible obstructive airways disease. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.7.4 Non–Potassium-Sparing Diuretics The electrocardiographic changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with non–potassium-sparing diuretics.

8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy Teratogenic Effects: Pregnancy Category C. There are no adequate and well-controlled trials with BREO ELLIPTA in pregnant women. Corticosteroids and beta2-agonists have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal studies are not always predictive of human response, BREO ELLIPTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking BREO ELLIPTA. Fluticasone Furoate and Vilanterol: There was no evidence of teratogenic interactions between fluticasone furoate and vilanterol in rats at approximately 9 and 40 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mcg/m2 basis at maternal inhaled doses of fluticasone furoate and vilanterol, alone or in combination, up to approximately 95 mcg/kg/day). Fluticasone Furoate: There were no teratogenic effects in rats and rabbits at approximately 9 and 2 times, respectively, the MRHDID in adults (on a mcg/m2 basis at maternal inhaled doses up to 91 and 8 mcg/kg/day in rats and rabbits, respectively). There were no effects on perinatal and postnatal development in rats at approximately 3 times the MRHDID in adults (on a mcg/m2 basis at maternal doses up to 27 mcg/kg/day). Vilanterol: There were no teratogenic effects in rats and rabbits at approximately 13,000 and 160 times, respectively, the MRHDID in adults (on a mcg/m2 basis at maternal inhaled doses up to 33,700 mcg/kg/day in rats and on an AUC basis at maternal inhaled doses up to 591 mcg/kg/day in rabbits). However, fetal skeletal variations were observed in rabbits at approximately 1,000 times the MRHDID in adults (on an AUC basis at maternal inhaled or subcutaneous doses of 5,740 or 300 mcg/kg/day, respectively). The skeletal variations included decreased or absent ossification in cervical vertebral centrum and metacarpals. There were no effects on perinatal and postnatal development in rats at approximately 3,900 times the MRHDID in adults (on a mcg/m2 basis at maternal oral doses up to 10,000 mcg/kg/day).Nonteratogenic Effects: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.8.2 Labor and Delivery There are no adequate and well-controlled human trials that have investigated the effects of BREO ELLIPTA during labor and delivery. Because beta-agonists may potentially interfere with uterine contractility, BREO ELLIPTA should be used during labor only if the potential benefit justifies the potential risk.8.3 Nursing Mothers It is not known whether fluticasone furoate or vilanterol are excreted in human breast milk. However, other corticosteroids and beta2-agonists have been detected in human milk. Since there are no data from controlled trials on the use of BREO ELLIPTA by nursing mothers, caution should be exercised when it is administered to a nursing woman.8.5 Geriatric Use Based on available data, no adjustment of the dosage of BREO ELLIPTA in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. Clinical trials of BREO ELLIPTA for COPD included 2,508 subjects aged 65 and older and 564 subjects aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects.8.6 Hepatic Impairment Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. Hepatic impairment had no effect on vilanterol systemic exposure. Use BREO ELLIPTA with caution in patients with moderate or severe hepatic impairment. Monitor patients for corticosteroid-related side effects [see Clinical Pharmacology (12.3) of full prescribing information].8.7 Renal Impairment There were no significant increases in either fluticasone furoate or vilanterol exposure in subjects with severe renal impairment (CrCl<30 mL/min) compared with healthy subjects. No dosage adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3) of full prescribing information].

10 OVERDOSAGENo human overdosage data has been reported for BREO ELLIPTA. BREO ELLIPTA contains both fluticasone furoate and vilanterol; therefore, the risks associated with overdosage for the individual components described below apply to BREO ELLIPTA.10.1 Fluticasone Furoate Because of low systemic bioavailability (15.2%) and an absence of acute drug-related systemic findings in clinical trials, overdosage of fluticasone furoate is unlikely to require any treatment other than observation. If used at excessive doses for prolonged periods, systemic effects such as hypercorticism may occur [see Warnings and Precautions (5.8)]. Single- and repeat-dose trials of fluticasone furoate at doses of 50 to 4,000 mcg have been studied in human subjects. Decreases in mean serum cortisol were observed at dosages of 500 mcg or higher given once daily for 14 days.10.2 Vilanterol The expected signs and symptoms with overdosage of vilanterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of vilanterol. Treatment of overdosage consists of discontinuation of BREO ELLIPTA together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medicine can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage.

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityBREO ELLIPTA: No studies of carcinogenicity, mutagenicity, or impairment of fertility were conducted with BREO ELLIPTA; however, studies are available for the individual components, fluticasone furoate and vilanterol, as described below.Fluticasone Furoate: Fluticasone furoate produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 9 and 19 mcg/kg/day, respectively (approximately equal to the MRHDID in adults on a mcg/m2 basis). Fluticasone furoate did not induce gene mutation in bacteria or chromosomal damage in a mammalian cell mutation test in mouse lymphoma L5178Y cells in vitro. There was also no evidence of genotoxicity in the in vivo micronucleus test in rats. No evidence of impairment of fertility was observed in male and female rats at inhaled fluticasone furoate doses up to 29 and 91 mcg/kg/day, respectively (approximately 3 and 9 times, respectively, the MRHDID in adults on a mcg/m2 basis).Vilanterol: In a 2-year carcinogenicity study in mice, vilanterol caused a statistically significant increase in ovarian tubulostromal adenomas in females at an inhalation dose of 29,500 mcg/kg/day (approximately 8,750 times the MRHDID in adults on an AUC basis). No increase in tumors was seen at an inhalation dose of 615 mcg/kg/day (approximately 530 times the MRHDID in adults on an AUC basis). In a 2-year carcinogenicity study in rats, vilanterol caused statistically significant increases in mesovarian leiomyomas in females and shortening of the latency of pituitary tumors at inhalation doses greater than or equal to 84.4 mcg/kg/day (greater than or equal to approximately 45 times the MRHDID in adults on an AUC basis). No tumors were seen at an inhalation dose of 10.5 mcg/kg/day (approximately 2 times the MRHDID in adults on an AUC basis). These tumor findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Vilanterol tested negative in the following genotoxicity assays: the in vitro Ames assay, in vivo rat bone marrow micronucleus assay, in vivo rat unscheduled DNA synthesis (UDS) assay, and in vitro Syrian hamster embryo (SHE) cell assay. Vilanterol tested equivocal in the in vitro mouse lymphoma assay. No evidence of impairment of fertility was observed in reproductive studies conducted in male and female rats at inhaled vilanterol doses up to 31,500 and 37,100 mcg/kg/day, respectively (approximately 12,000 and 14,000 times, respectively, the MRHDID in adults on a mcg/m2 basis).

17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).17.1 Asthma-Related Death Patients should be informed that LABA, such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. BREO ELLIPTA is not indicated for the treatment of asthma.17.2 Not for Acute Symptoms BREO ELLIPTA is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose. Acute symptoms should be treated with a rescue inhaler such as albuterol. The physician should provide the patient with such medicine and instruct the patient in how it should be used. Patients should be instructed to notify their physicians immediately if they experience any of the following: Symptoms get worse; Need for more inhalations than usual of their rescue inhaler; Significant decrease in lung function as outlined by the physician. Patients should not stop therapy with BREO ELLIPTA without physician/provider guidance since symptoms may recur after discontinuation.17.3 Do Not Use Additional Long-Acting Beta2-Agonists When patients are prescribed BREO ELLIPTA, other medicines containing a LABA should not be used.17.4 Risks Associated With Corticosteroid TherapyLocal Effects: Patients should be advised that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with BREO ELLIPTA, but at times therapy with BREO ELLIPTA may need to be temporarily interrupted under close medical supervision. Rinsing the mouth without swallowing after inhalation is advised to help reduce the risk of thrush.Pneumonia: Patients with COPD who have received BREO ELLIPTA have a higher risk of pneumonia and should be instructed to contact their healthcare providers if they develop symptoms of pneumonia (e.g., fever, chills, change in sputum color, increase in breathing problems).Immunosuppression: Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.Hypercorticism and Adrenal Suppression: Patients should be advised that BREO ELLIPTA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, patients should be instructed that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids.Reduction in Bone Mineral Density: Patients who are at an increased risk for decreased BMD should be advised that the use of corticosteroids may pose an additional risk.Ocular Effects: Long-term use of inhaled corticosteroids may increase the risk of some eye problems (cataracts or glaucoma); regular eye examinations should be considered.17.5 Risks Associated With Beta-Agonist Therapy Patients should be informed of adverse effects associated with beta2-agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.17.6 Hypersensitivity Reactions, Including Anaphylaxis Advise patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash, urticaria) may occur after administration of BREO ELLIPTA. Instruct patients to discontinue BREO ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use BREO ELLIPTA.

BREO and ELLIPTA are registered trademarks of the GSK group of companies.

BREO ELLIPTA was developed in collaboration with .

GlaxoSmithKline Research Triangle Park, NC 27709

©2014, the GSK group of companies. All rights reserved.Revised 09/2014 BRE:3BRS

©2015 GSK group of companies. All rights reserved. Printed in USA. 320114R0 March 2015

S:9.5” S:9.5”

S:12”

T:21”

T:13”

B:21.25”

B:13.25”

BREO ELLIPTA BRIEF SUMMARY(fluticasone furoate and vilanterol inhalation powder)FOR ORAL INHALATION USE The following is a brief summary only; see full prescribing information for complete product information.

WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABA) increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of another LABA (salmeterol) with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of LABA, including vilanterol, an active ingredient in BREO® ELLIPTA® [see Warnings and Precautions (5.1)]. The safety and efficacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.

1 INDICATIONS AND USAGEBREO ELLIPTA is a combination inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA) indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. BREO ELLIPTA is also indicated to reduce exacerbations of COPD in patients with a history of exacerbations.Important Limitations of Use: BREO ELLIPTA is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma.

4 CONTRAINDICATIONSThe use of BREO ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients [see Warnings and Precautions (5.11), Description (11) of full prescribing information].

5 WARNINGS AND PRECAUTIONS5.1 Asthma-Related Death Data from a large placebo-controlled trial in subjects with asthma showed that LABA may increase the risk of asthma-related death. Data are not available to determine whether the rate of death in patients with COPD is increased by LABA. A 28-week, placebo-controlled, US trial comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol vs 3/13,179 in subjects treated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]). The increased risk of asthma-related death is considered a class effect of LABA, including vilanterol, one of the active ingredients in BREO ELLIPTA. No study adequate to determine whether the rate of asthma-related death is increased in subjects treated with BREO ELLIPTA has been conducted. The safety and efficacy of BREO ELLIPTA in patients with asthma have not been established. BREO ELLIPTA is not indicated for the treatment of asthma.5.2 Deterioration of Disease and Acute Episodes BREO ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD. BREO ELLIPTA has not been studied in patients with acutely deteriorating COPD. The initiation of BREO ELLIPTA in this setting is not appropriate. BREO ELLIPTA should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. BREO ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist. When beginning treatment with BREO ELLIPTA, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs and to use them only for symptomatic relief of acute respiratory symptoms. When prescribing BREO ELLIPTA, the healthcare provider should also prescribe an inhaled, short-acting beta2-agonist and instruct the patient on how it should be used. Increasing inhaled, short-acting beta2-agonist use is a signal of deteriorating disease for which prompt medical attention is indicated. COPD may deteriorate acutely over a period of hours or chronically over several days or longer. If BREO ELLIPTA no longer controls symptoms of bronchoconstriction; the patient’s inhaled, short-acting, beta2-agonist becomes less effective; or the patient needs more short-acting beta2-agonist than usual, these may be markers of deterioration of disease. In this setting a re-evaluation of the patient and the COPD treatment regimen should be undertaken at once. Increasing the daily dose of BREO ELLIPTA beyond the recommended dose is not appropriate in this situation.5.3 Excessive Use of BREO ELLIPTA and Use With Other Long-Acting Beta2-Agonists BREO ELLIPTA should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using BREO ELLIPTA should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.5.4 Local Effects of Inhaled Corticosteroids In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with BREO ELLIPTA. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with BREO ELLIPTA continues, but at times therapy with BREO ELLIPTA may need to be interrupted. Advise the patient to rinse his/her mouth without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.5.5 Pneumonia An increase in the incidence of pneumonia has been observed in subjects with COPD receiving the fluticasone furoate/vilanterol combination, including BREO ELLIPTA 100 mcg/25 mcg, in clinical trials. There was also an increased incidence of pneumonias resulting in hospitalization. In some incidences these pneumonia events were fatal. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. In replicate 12-month trials in 3,255 subjects with COPD who had experienced a COPD exacerbation in the previous year, there was a higher incidence of pneumonia reported in subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: 6% [48 of 820 subjects]; 100 mcg/25 mcg: 6% [51 of 806 subjects]; or 200 mcg/25 mcg: 7% [55 of 811 subjects]) than in subjects receiving vilanterol 25 mcg (3% [27 of 818 subjects]). There was no fatal pneumonia in subjects receiving vilanterol or fluticasone furoate/vilanterol 50 mcg/25 mcg. There was fatal pneumonia in 1 subject receiving fluticasone furoate/vilanterol 100 mcg/25 mcg and in 7 subjects receiving fluticasone furoate/vilanterol 200 mcg/25 mcg (less than 1% for each treatment group).5.6 Immunosuppression Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.5.7 Transferring Patients From Systemic Corticosteroid Therapy Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although BREO ELLIPTA may control COPD symptoms during these episodes, in recommended doses it supplies less than normal physiological amount of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or a severe COPD exacerbation, patients who have been withdrawn

from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe COPD exacerbation. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to BREO ELLIPTA. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with BREO ELLIPTA. Lung function (mean forced expiratory volume in 1 second [FEV1]), beta-agonist use, and COPD symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Transfer of patients from systemic corticosteroid therapy to BREO ELLIPTA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.5.8 Hypercorticism and Adrenal Suppression Inhaled fluticasone furoate is absorbed into the circulation and can be systemically active. Effects of fluticasone furoate on the HPA axis are not observed with the therapeutic dose of BREO ELLIPTA. However, exceeding the recommended dosage or coadministration with a strong cytochrome P450 3A4 (CYP3A4) inhibitor may result in HPA dysfunction [see Warnings and Precautions (5.9), Drug Interactions (7.1)]. Because of the possibility of significant systemic absorption of inhaled corticosteroids in sensitive patients, patients treated with BREO ELLIPTA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, BREO ELLIPTA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of COPD symptoms should be considered.5.9 Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid and increased cardiovascular adverse effects may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3) of full prescribing information].5.10 Paradoxical Bronchospasm As with other inhaled medicines, BREO ELLIPTA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with BREO ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; BREO ELLIPTA should be discontinued immediately; and alternative therapy should be instituted.5.11 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of BREO ELLIPTA. Discontinue BREO ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use BREO ELLIPTA [see Contraindications (4)].5.12 Cardiovascular Effects Vilanterol, like other beta2-agonists, can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, BREO ELLIPTA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression, although the clinical significance of these findings is unknown. In healthy subjects, large doses of inhaled fluticasone furoate/vilanterol (4 times the recommended dose of vilanterol, representing a 12-fold higher systemic exposure than seen in patients with COPD) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias. Therefore, BREO ELLIPTA, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. 5.13 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating BREO ELLIPTA and periodically thereafter. If significant reductions in BMD are seen and BREO ELLIPTA is still considered medically important for that patient’s COPD therapy, use of medicine to treat or prevent osteoporosis should be strongly considered. In replicate 12-month trials in 3,255 subjects with COPD, bone fractures were reported by 2% of subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: 2% [14 of 820 subjects]; 100 mcg/25 mcg: 2% [19 of 806 subjects]; or 200 mcg/25 mcg: 2% [14 of 811 subjects]) than in subjects receiving vilanterol 25 mcg alone (less than 1% [8 of 818 subjects]).5.14 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with COPD following the long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. In replicate 12-month trials in 3,255 subjects with COPD, similar incidences of ocular effects (including glaucoma and cataracts) were reported in subjects receiving the fluticasone furoate/vilanterol combination (50 mcg/25 mcg: less than 1% [7 of 820 subjects]; 100 mcg/25 mcg: 1% [12 of 806 subjects]; 200 mcg/25 mcg: less than 1% [7 of 811 subjects]) as those receiving vilanterol 25 mcg alone (1% [9 of 818 subjects]).5.15 Coexisting Conditions BREO ELLIPTA, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Doses of the related beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.5.16 Hypokalemia and Hyperglycemia Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. Beta-agonist medications may produce transient hyperglycemia in some patients. In 4 clinical trials of 6- and 12-month duration evaluating BREO ELLIPTA in subjects with COPD, there was no evidence of a treatment effect on serum glucose or potassium.

6 ADVERSE REACTIONSLABA, such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. BREO ELLIPTA is not indicated for the treatment of asthma. [See Boxed Warnings and Warnings and Precautions (5.1).] Systemic and local corticosteroid use may result in the following: Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5)]; Increased risk for decrease in bone mineral density [see Warnings and Precautions (5.13)].6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical program for BREO ELLIPTA included 7,700 subjects with COPD in two 6-month lung function trials, two 12-month exacerbation trials, and 6 other trials of shorter duration. A total of 2,034 subjects have received at least 1 dose of BREO ELLIPTA 100 mcg/25 mcg, and 1,087 subjects have received higher doses of fluticasone furoate/vilanterol. The safety data described below are based on the confirmatory 6-month and 12-month trials. Adverse reactions observed in the other trials were similar to those observed in the confirmatory trials.6-Month Trials: The incidence of adverse reactions associated with BREO ELLIPTA in Table 1 is based on 2 placebo-controlled, 6-month clinical trials (Trials 1 and 2; n = 1,224 and n = 1,030, respectively). Of the 2,254 subjects, 70% were male and 84% were Caucasian. They had a mean age of 62 years and an average smoking history of 44 pack years, with 54% identified as current smokers. At screening, the mean postbronchodilator percent predicted FEV1 was 48% (range: 14% to 87%), the mean postbronchodilator FEV1/forced vital capacity (FVC) ratio was 47% (range: 17% to 88%), and the mean percent reversibility was 14% (range: -41% to 152%). Subjects received 1 inhalation once daily of the following: BREO ELLIPTA 100 mcg/25 mcg, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate/vilanterol 200 mcg/25 mcg, fluticasone furoate 100 mcg, fluticasone furoate 200 mcg, vilanterol 25 mcg, or placebo.

Table 1. Adverse Reactions With ≥3% Incidence and More Common Than Placebo With BREO ELLIPTA in Subjects With Chronic Obstructive Pulmonary Disease

Adverse Event

BREO ELLIPTA 100 mcg/25 mcg

(n = 410)%

Vilanterol 25 mcg

(n = 408)%

Fluticasone Furoate100 mcg(n = 410)

%

Placebo(n = 412)

%

Infections and infestations

Nasopharyngitis 9 10 8 8

Upper respiratory tract infection

7 5 4 3

Oropharyngeal candidiasisa 5 2 3 2

Nervous system disordersHeadache 7 9 7 5

a Includes terms oral candidiasis, oropharyngeal candidiasis, candidiasis, and oropharyngitis fungal.

12-Month Trials: Long-term safety data is based on two 12-month trials (Trials 3 and 4; n = 1,633 and n = 1,622, respectively). Trials 3 and 4 included 3,255 subjects, of which 57% were male and 85% were Caucasian. They had a mean age of 64 years and an average smoking history of 46 pack years, with 44% identified as current smokers. At screening, the mean postbronchodilator percent predicted FEV1 was 45% (range: 12% to 91%), and the mean postbronchodilator FEV1/FVC ratio was 46% (range: 17% to 81%), indicating that the subject population had moderate to very severely impaired airflow obstruction. Subjects received 1 inhalation once daily of the following: BREO ELLIPTA 100 mcg/25 mcg, fluticasone furoate/vilanterol 50 mcg/25 mcg, fluticasone furoate/vilanterol 200 mcg/25 mcg, or vilanterol 25 mcg. In addition to the events shown in Table 1, adverse reactions occurring in greater than or equal to 3% of the subjects treated with BREO ELLIPTA (N = 806) for 12 months included COPD, back pain, pneumonia [see Warnings and Precautions (5.5)], bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, hypertension, influenza, pharyngitis, diarrhea, peripheral edema, and pyrexia.6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of BREO ELLIPTA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to BREO ELLIPTA or a combination of these factors. Immune System Disorders: Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria.

7 DRUG INTERACTIONS7.1 Inhibitors of Cytochrome P450 3A4 Fluticasone furoate and vilanterol, the individual components of BREO ELLIPTA, are both substrates of CYP3A4. Concomitant administration of the potent CYP3A4 inhibitor ketoconazole increases the systemic exposure to fluticasone furoate and vilanterol. Caution should be exercised when considering the coadministration of BREO ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.3) of full prescribing information].7.2 Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Vilanterol, like other beta2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias.7.3 Beta-Adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as vilanterol, a component of BREO ELLIPTA, but may produce severe bronchospasm in patients with reversible obstructive airways disease. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.7.4 Non–Potassium-Sparing Diuretics The electrocardiographic changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with non–potassium-sparing diuretics.

8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy Teratogenic Effects: Pregnancy Category C. There are no adequate and well-controlled trials with BREO ELLIPTA in pregnant women. Corticosteroids and beta2-agonists have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal studies are not always predictive of human response, BREO ELLIPTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking BREO ELLIPTA. Fluticasone Furoate and Vilanterol: There was no evidence of teratogenic interactions between fluticasone furoate and vilanterol in rats at approximately 9 and 40 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mcg/m2 basis at maternal inhaled doses of fluticasone furoate and vilanterol, alone or in combination, up to approximately 95 mcg/kg/day). Fluticasone Furoate: There were no teratogenic effects in rats and rabbits at approximately 9 and 2 times, respectively, the MRHDID in adults (on a mcg/m2 basis at maternal inhaled doses up to 91 and 8 mcg/kg/day in rats and rabbits, respectively). There were no effects on perinatal and postnatal development in rats at approximately 3 times the MRHDID in adults (on a mcg/m2 basis at maternal doses up to 27 mcg/kg/day). Vilanterol: There were no teratogenic effects in rats and rabbits at approximately 13,000 and 160 times, respectively, the MRHDID in adults (on a mcg/m2 basis at maternal inhaled doses up to 33,700 mcg/kg/day in rats and on an AUC basis at maternal inhaled doses up to 591 mcg/kg/day in rabbits). However, fetal skeletal variations were observed in rabbits at approximately 1,000 times the MRHDID in adults (on an AUC basis at maternal inhaled or subcutaneous doses of 5,740 or 300 mcg/kg/day, respectively). The skeletal variations included decreased or absent ossification in cervical vertebral centrum and metacarpals. There were no effects on perinatal and postnatal development in rats at approximately 3,900 times the MRHDID in adults (on a mcg/m2 basis at maternal oral doses up to 10,000 mcg/kg/day).Nonteratogenic Effects: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.8.2 Labor and Delivery There are no adequate and well-controlled human trials that have investigated the effects of BREO ELLIPTA during labor and delivery. Because beta-agonists may potentially interfere with uterine contractility, BREO ELLIPTA should be used during labor only if the potential benefit justifies the potential risk.8.3 Nursing Mothers It is not known whether fluticasone furoate or vilanterol are excreted in human breast milk. However, other corticosteroids and beta2-agonists have been detected in human milk. Since there are no data from controlled trials on the use of BREO ELLIPTA by nursing mothers, caution should be exercised when it is administered to a nursing woman.8.5 Geriatric Use Based on available data, no adjustment of the dosage of BREO ELLIPTA in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. Clinical trials of BREO ELLIPTA for COPD included 2,508 subjects aged 65 and older and 564 subjects aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects.8.6 Hepatic Impairment Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. Hepatic impairment had no effect on vilanterol systemic exposure. Use BREO ELLIPTA with caution in patients with moderate or severe hepatic impairment. Monitor patients for corticosteroid-related side effects [see Clinical Pharmacology (12.3) of full prescribing information].8.7 Renal Impairment There were no significant increases in either fluticasone furoate or vilanterol exposure in subjects with severe renal impairment (CrCl<30 mL/min) compared with healthy subjects. No dosage adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3) of full prescribing information].

10 OVERDOSAGENo human overdosage data has been reported for BREO ELLIPTA. BREO ELLIPTA contains both fluticasone furoate and vilanterol; therefore, the risks associated with overdosage for the individual components described below apply to BREO ELLIPTA.10.1 Fluticasone Furoate Because of low systemic bioavailability (15.2%) and an absence of acute drug-related systemic findings in clinical trials, overdosage of fluticasone furoate is unlikely to require any treatment other than observation. If used at excessive doses for prolonged periods, systemic effects such as hypercorticism may occur [see Warnings and Precautions (5.8)]. Single- and repeat-dose trials of fluticasone furoate at doses of 50 to 4,000 mcg have been studied in human subjects. Decreases in mean serum cortisol were observed at dosages of 500 mcg or higher given once daily for 14 days.10.2 Vilanterol The expected signs and symptoms with overdosage of vilanterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of vilanterol. Treatment of overdosage consists of discontinuation of BREO ELLIPTA together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medicine can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage.

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityBREO ELLIPTA: No studies of carcinogenicity, mutagenicity, or impairment of fertility were conducted with BREO ELLIPTA; however, studies are available for the individual components, fluticasone furoate and vilanterol, as described below.Fluticasone Furoate: Fluticasone furoate produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 9 and 19 mcg/kg/day, respectively (approximately equal to the MRHDID in adults on a mcg/m2 basis). Fluticasone furoate did not induce gene mutation in bacteria or chromosomal damage in a mammalian cell mutation test in mouse lymphoma L5178Y cells in vitro. There was also no evidence of genotoxicity in the in vivo micronucleus test in rats. No evidence of impairment of fertility was observed in male and female rats at inhaled fluticasone furoate doses up to 29 and 91 mcg/kg/day, respectively (approximately 3 and 9 times, respectively, the MRHDID in adults on a mcg/m2 basis).Vilanterol: In a 2-year carcinogenicity study in mice, vilanterol caused a statistically significant increase in ovarian tubulostromal adenomas in females at an inhalation dose of 29,500 mcg/kg/day (approximately 8,750 times the MRHDID in adults on an AUC basis). No increase in tumors was seen at an inhalation dose of 615 mcg/kg/day (approximately 530 times the MRHDID in adults on an AUC basis). In a 2-year carcinogenicity study in rats, vilanterol caused statistically significant increases in mesovarian leiomyomas in females and shortening of the latency of pituitary tumors at inhalation doses greater than or equal to 84.4 mcg/kg/day (greater than or equal to approximately 45 times the MRHDID in adults on an AUC basis). No tumors were seen at an inhalation dose of 10.5 mcg/kg/day (approximately 2 times the MRHDID in adults on an AUC basis). These tumor findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Vilanterol tested negative in the following genotoxicity assays: the in vitro Ames assay, in vivo rat bone marrow micronucleus assay, in vivo rat unscheduled DNA synthesis (UDS) assay, and in vitro Syrian hamster embryo (SHE) cell assay. Vilanterol tested equivocal in the in vitro mouse lymphoma assay. No evidence of impairment of fertility was observed in reproductive studies conducted in male and female rats at inhaled vilanterol doses up to 31,500 and 37,100 mcg/kg/day, respectively (approximately 12,000 and 14,000 times, respectively, the MRHDID in adults on a mcg/m2 basis).

17 PATIENT COUNSELING INFORMATIONAdvise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).17.1 Asthma-Related Death Patients should be informed that LABA, such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. BREO ELLIPTA is not indicated for the treatment of asthma.17.2 Not for Acute Symptoms BREO ELLIPTA is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose. Acute symptoms should be treated with a rescue inhaler such as albuterol. The physician should provide the patient with such medicine and instruct the patient in how it should be used. Patients should be instructed to notify their physicians immediately if they experience any of the following: Symptoms get worse; Need for more inhalations than usual of their rescue inhaler; Significant decrease in lung function as outlined by the physician. Patients should not stop therapy with BREO ELLIPTA without physician/provider guidance since symptoms may recur after discontinuation.17.3 Do Not Use Additional Long-Acting Beta2-Agonists When patients are prescribed BREO ELLIPTA, other medicines containing a LABA should not be used.17.4 Risks Associated With Corticosteroid TherapyLocal Effects: Patients should be advised that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with BREO ELLIPTA, but at times therapy with BREO ELLIPTA may need to be temporarily interrupted under close medical supervision. Rinsing the mouth without swallowing after inhalation is advised to help reduce the risk of thrush.Pneumonia: Patients with COPD who have received BREO ELLIPTA have a higher risk of pneumonia and should be instructed to contact their healthcare providers if they develop symptoms of pneumonia (e.g., fever, chills, change in sputum color, increase in breathing problems).Immunosuppression: Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex.Hypercorticism and Adrenal Suppression: Patients should be advised that BREO ELLIPTA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, patients should be instructed that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids.Reduction in Bone Mineral Density: Patients who are at an increased risk for decreased BMD should be advised that the use of corticosteroids may pose an additional risk.Ocular Effects: Long-term use of inhaled corticosteroids may increase the risk of some eye problems (cataracts or glaucoma); regular eye examinations should be considered.17.5 Risks Associated With Beta-Agonist Therapy Patients should be informed of adverse effects associated with beta2-agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.17.6 Hypersensitivity Reactions, Including Anaphylaxis Advise patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, rash, urticaria) may occur after administration of BREO ELLIPTA. Instruct patients to discontinue BREO ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use BREO ELLIPTA.

BREO and ELLIPTA are registered trademarks of the GSK group of companies.

BREO ELLIPTA was developed in collaboration with .

GlaxoSmithKline Research Triangle Park, NC 27709

©2014, the GSK group of companies. All rights reserved.Revised 09/2014 BRE:3BRS

©2015 GSK group of companies. All rights reserved. Printed in USA. 320114R0 March 2015

S:9.5” S:9.5”

S:12”

T:21”

T:13”

B:21.25”

B:13.25”

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 201526

BECOME A CARE CENTER NETWORK SITE

PFF_ATS daily_1/2pg_F.indd 1 4/28/15 9:27 AM

TODAY6:45 to 7:45 a.m.Pediatric Clinical Core Curriculum: “Radiology for the Pediatric Pulmonologist”Room 205/207 (Street Level)Colorado Convention Center

6:45 to 8:15 a.m.Critical Care Clinical Core Curriculum IBellco Theatre Section 1 (Street Level)Colorado Convention Center

7 to 8 a.m.Center for Career Development opens with Meet and Greet with Fellows Track Symposium Faculty and light complimentary breakfastRoom 103/105 (Street Level) Colorado Convention Center

7 to 8 a.m.Science and Innovation Center opens with light complimentary breakfastE Concourse (Street Level) Colorado Convention Center

7:30 to 8 a.m.Clinicians Center opens with light complimen-tary breakfastE Concourse (Street Level) Colorado Convention Center

8:30 to 9:15 a.m.ATS Discoveries Series: “Two Billion and Counting: Reinvigorating the Battle Against Our Old Foe, TB”Bellco Theatre Section 2 (Street Level)Colorado Convention Center

“Lung Regeneration: An Achievable Mission”Four Seasons Ballroom 1-2 (Lower Level)Colorado Convention Center

9:30 to 11: 30 a.m.Basic Science Core: “How Pathogens Evade Immune Defenses and How We Can Fight Back”Mile High Ballroom 2A/3A (Lower Level)Colorado Convention Center

9:30 to 11:30 a.m.Clinical Year in Review 2Bellco Theatre Section 2 (Street Level)Colorado Convention Center

10:30 a.m. to 5 p.m.Exhibit Hall opens with complimentary coffeeHalls D–F (Upper Level) Colorado Convention Center

11 a.m. to 2:30 p.m.Bistro ATS Opens in the Exhibit HallHall F (Upper Level) Colorado Convention Center

11:45 a.m. to 1:15 p.m.Women’s Forum: Judith Albino, PhDCrystal Ballroom (3rd Floor) Embassy Suites Hotel

Noon to 1 p.m.Center for Career Development: Early Career Researchers Group with AJRCCM Editor Jad-wiga Wedzicha, MDRoom 103/105 (Street Level) Colorado Convention Center

1:15 to 2:15 p.m.Unopposed Exhibit Hall TimeHalls D–F (Upper Level) Colorado Convention Center

1:30 to 2:30 p.m.Science and Innovation Center: Scientific Abstract AwardsE Concourse (Street Level) Colorado Convention Center

2:15 to 4:15 p.m.Sleep Medicine Clinical Core Curriculum IIBellco Theatre Section 2 (Street Level)Colorado Convention Center

2:15 to 4: 15 p.m.Basic Science Core: “Us Versus Them: Mucins and Biofilms in the Battle for the Lungs”Mile High Ballroom 2A/3A (Lower Level)Colorado Convention Center

2:15 to 4:15 p.m.Pediatric Year in ReviewRoom 205/207 (Street Level)Colorado Convention Center

4 to 5 p.m.Clinicians Center: Outstanding Clinician Award PresentationE Concourse (Street Level) Colorado Convention Center

5 to 7 p.m.Assembly Membership MeetingsFor locations, visit conference.thoracic.org/2015

Calendar of Special Events OPENING CEREMONY Continued from page 1

journals, become principal investigators, and mentored junior faculty,” Dr. Ferkol said.

On global health, Dr. Ferkol noted that the ATS’s 15,000 members hail from 122 coun-tries, and the Society maintains relationships with sister societies around the world and is a founding member of the Forum of Interna-tional Respiratory Societies, a collaborative to promote lung health. He also nodded to the Methods in Epidemiologic, Clinical, and Op-erations Research (MECOR) program, which strengthens capacity related to respiratory conditions, critical care, and sleep medicine in middle- and low-income countries. Afterward, ATS President-Elect Atul Malhotra, MD, was invited to describe the Global Scholars Program, a new distance-learning initiative to better improve medical education worldwide.

Lastly, Dr. Ferkol discussed the importance of advocacy on legislative and regulatory issues important to the organization, acknowledging the staff in Washington, DC. He also noted the importance of advocacy journalism, which provided a segue to introducing Mr. Mandvi, satirical humorist and senior correspondent on Comedy Central’s The Daily Show.

He joked about interviews he has done for the show and showed videos of several of his favorite segments. When technical difficulties stopped the first video, Mr. Mandvi drew loud laughs by looking at the audio-visual crew and saying, “People keep pointing at people … just like doctors. ‘Hey, I’m just a pulmonary guy … he’s the heart guy.’”

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 2015 27

Juan Celedón, MD, DrPHDaniel Weiner, MDJonathan Spahr, MD

Affiliated with the University of Pittsburgh School of Medicine and ranked among the nation’s best children’s hospitals by U.S. News & World Report.

Challenging conventional treatments for cystic fibrosis and asthma.

At Children’s Hospital of Pittsburgh of UPMC, our research and clinical teams are investigating every possibility to improve the quality of life for our patients with cystic fibrosis (CF) and asthma. As a longstanding Therapeutics Development Network center, we are testing novel drug therapies and other interventions to find better ways to treat CF. And our Pediatric Asthma Center conducts NIH- and privately funded research on the role of genetics, epigenetics, immunology, diet, obesity, and stress on childhood asthma, taking care to include underserved minority children such as Puerto Ricans and African-Americans. To learn more about how we’re helping children with cystic fibrosis and asthma, visit UPMCPhysicianResources.com/PedsPulm.

Stephen Walczak, RRT

HONOR ROLL2014-15

HOSPITALSCHILDREN’SBEST

Hands-on Skills in the Practical Workshops

P articipate in 90 minutes of hands-on demonstrations and skill-building presentations with a

different exhibiting company each day in the Practical Workshop located at the end of the 100 aisle.

TODAY12:30 to 2 p.m.Bronchial Thermoplasty (BT): Emerging Data and Real World ExperienceBronchial Thermoplasty (BT), delivered

by the Alair™ System, is a safe and effective outpatient procedure clinically proven to last at least five years for adult patients with severe asthma. Hear from physicians about their real-world experience, patients who can benefit from BT, emerging data, and participate in a hands-on work-shop. Includes boxed lunch.Company: Boston Scientific Corporation* Vermont law imposes additional restric-tions when Vermont licensed HCPs are in attendance. If you are licensed in Vermont, please notify BSC immediately.

Rory Williams, DirectorLisa K. Brown, Manager

ATS Communications and Marketing

The ATS Daily Bulletin is published by Ascend Integrated Media, LLC

for the ATS.

Photography by Steve Schneider and R.C. Photographic Productions.

©2015 by the American Thoracic Society25 Broadway, 18th Floor

New York, New York 10004(212) 315-8600

thoracic.org

ATS Daily Bulletin

pluripotent cells can be created from cells anywhere in a patient’s body, so they can be gathered with minimal discomfort to the patient. And, unlike ES cells, they are genetically identical to the patient, mini-mizing the possibility of being rejected when reintroduced into the body.

“Lung Regeneration: An Achievable Mis-sion” is supported by an educational grant from Lung Biotechnology.

TWO BILLION AND COUNTING: REINVIGORATING THE BATTLE AGAINST OUR OLD FOE, TBBellco Theatre Section 2 (Street Level), Colorado Convention Center

Trevor Mundel, MD, PhD, president of the global health program at the Bill and Melinda Gates Foundation, will describe the important progress the world has made against tuberculosis over the past 20 years and the work that must continue. TB remains a leading cause of death in both developing and middle-income countries. Current drugs, diagnostics, vaccines, and delivery approaches are not sufficient to sustain, let alone accelerate, reductions in global incidence.

To bend the curve on tuberculosis pre-vention, diagnosis, and treatment, funda-mental questions about the basic biology of tuberculosis infection and disease must be answered. For example, there is a need to better understand TB transmission, the different stages of the disease in the human body, and its response or failure to respond to treatment. There is also need to develop and advance strategies that accelerate access to existing and new solutions.

The Bill and Melinda Gates Founda-tion is working with a wide range of partners in the public and private sectors to ensure the development and delivery of better tools for TB control. It is also seeking to create partnerships and ex-pand existing collaborations to develop improved host-directed therapies and other transformational tools that can shorten treatment and reduce the risk of relapse and reinfection.

DISCOVERIES Continued from page 1

PAR Continued from page 8

The physicians also gained insights from patients, including first-time presenter Rebecca Keith, MD, assistant professor of medicine at the University of Colorado School of Medicine, Aurora.

“It’s exciting because it allows me as a physician to understand what my patients are learning and what they are interested in,” Dr. Keith says. “I spent some time having lunch with patients who have pulmonary fibrosis and learning from them about what it’s like to deal with this disease and how they get through every day. How resilient they are and how they manage to make the best out of each situation and get involved in advocacy groups is really impressive.”

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 201528

W ith increasing popularity of Indus-try Theaters, ATS 2015 will deliver more offerings than ever before.

Professionals will lead a total of 19 Industry Theater and Mini Industry Theater discussions in the Exhibit Hall. Have lunch while learning about new product launches and treatment options. Complimentary boxed lunch will be provided by the ATS while supplies last.

TODAY11:45 a.m. to 12:30 p.m.Industry Theater 1The Role of Bronchodilators in the Long-Term Maintenance Treatment of Patients with COPD: A Review of the DataDiscover the mist. A dynamic presentation of the role of bronchodilators in the long-term maintenance treatment of patients with COPD. An expert speaker will review the efficacy and safety data of bronchodilator maintenance treatments as well as the features of the inhaler.Company: Boehringer Ingelheim Pharmaceuticals, Inc.

1 to 1:45 p.m.Industry Theater 1Are We Gaining the Maximum Benefit from Bronchodilators in COPD?(Open to non-U.S. based physicians only)During this industry theater supported by Novartis, Chairman Ken Chapman will pose pertinent clinical questions on COPD thera-pies to a faculty of world-renowned experts. The program will highlight the fundamental role of bronchodilators in COPD manage-ment, and will discuss key data on indacaterol

and glycopyrronium, as well as the efficacy and safety profile of the dual bronchodilation combination indacaterol/glycopyrronium. Inhaled corticosteroids (ICS) have been used in COPD management for many years but their use in practice is often contrary to guideline recommendations. New and recent evidence— demonstrating that, for many patients, effective bronchodilation may be a better option than ICS-containing regimens—will be shown. The appropriate ICS patient, data from recent ICS withdrawal trials, and use of alternative agents will be discussed.Speakers: Chair: Professor Ken Chapman, University of Toronto, Canada; Effective Use of Bronchodilators in COPD; Professor José Jardim, Federal University of São Paulo, Brazil; Re-thinking the Use of ICS in COPD; and Professor Marc Miravitlles, Hospital Universitari Vall d’Hebron, Barcelona, SpainCompany: Novartis Pharma AG

11:45 a.m. to 12:30 p.m.Industry Theater 2Want to Add More to Your PAH Treatment Strategy?Join a panel of experts for a poster-themed discussion on disease progression in pulmo-nary arterial hypertension, adding prostacy-clin class therapy in appropriate patients, and how an inhaled prostacyclin-class therapy may help. Topics include diagnosis, clinical trial study design, efficacy, side effects, dosing, and therapy management. Lunch provided.Speakers: Steven Nathan, MD, FCCP, Medical Director, Advanced Lung Disease and Lung Transplant Programs, Inova Fairfax Hospital, Falls Church, VA; Lynette Brown,

MD, PhD, Associate Director, Pulmonary Hypertension Program, Intermountain Medical Center, Murray, UT; and Glenna Traiger, RN, MSN, CNS-BC, Pulmonary Hypertension CNS, David Geffen School of Medicine at UCLA, Los Angeles, CA.Company: United Therapeutics Corporation

1 to 1:45 p.m.Industry Theater 2The Role of Nitric Oxide (NO) in the Pathology of PAH (WHO Group 1) and CTEPH (WHO Group 4)Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two different forms of pulmonary hypertension, character-ized by elevated pulmonary artery pressures and increased pulmonary vascular resistance. Impaired synthesis of endogenous nitric oxide contributes to the pathology of both diseases. PH experts will present and discuss a CTEPH case and a PAH case that are typical of pa-tients who may be encountered in practice.Speakers: Nicholas S. Hill, MD, Professor of Medicine, Chief, Pulmonary, Critical Care and Sleep Division, Tufts University School of Medicine, Boston, MA, and Nick H. Kim, MD, Clinical Professor of Medicine, Director, Pulmonary Vascular Medicine, University of California San Diego School of Medicine San Diego, CACompany: Bayer HealthCare Pharmaceuticals

11:30 a.m. to NoonMini Industry TheaterPattern Recognition and Identification of Idiopathic Pulmonary Fibrosis (IPF)Come explore a hands-on learning adventure, presented by thought-leader experts on IPF. This program features a uniquely designed, high-impact visual exploration of IPF. Par-ticipants will also be invited to test their new knowledge via polling questions interspersed throughout the program.Company: Genentech, Inc.

12:30 to 1 p.m.Mini Industry TheaterPattern Recognition and Identification of Idiopathic Pulmonary Fibrosis (IPF)Come explore a hands-on learning adventure, presented by thought-leader experts on IPF. This program features a uniquely designed, high-impact visual exploration of IPF. Par-ticipants will also be invited to test their new knowledge via polling questions interspersed throughout the program.Company: Genentech, Inc.

1:30 to 2 p.m.Mini Industry TheaterPattern Recognition and Identification of Idiopathic Pulmonary Fibrosis (IPF)Come explore a hands-on learning adventure, presented by thought-leader experts on IPF. This program features a uniquely designed, high-impact visual exploration of IPF. Par-ticipants will also be invited to test their new knowledge via polling questions interspersed throughout the program.Company: Genentech, Inc.

Be Sure to Attend Industry Theaters and Mini Theaters

T he ATS Fellows Track Symposium, Resident Boot Camp, and Student Scholars Program have become a huge

draw for early career professionals, with this year’s attendance at 405, representing a 61 percent increase from last year.

So many residents applied for the 70 spots in the Friday and Saturday Resident Boot Camp that the program’s capacity was doubled to 140, to satisfy the demand.

“The leadership felt it would not be appropri-ate to turn them down since one of our mis-sions is to train the next generation of pulmo-nary care physicians. We doubled the program

and added a pediatric track,” says Resident Boot Camp Course Chair and ATS Training Com-mittee Vice Chair Laura Crotty Alexander, MD, assistant clinical professor of medicine at the University of California, San Diego.

Now in its second year, the Resident Boot Camp prepares residents who are entering pulmonary, critical care, and sleep fellowships with small breakout sessions and skills-based workshops with 85 faculty members.

“We know the best way to teach is in very small groups with this generation of learners, so we minimized the lectures to two hours a day and the other six hours to small group sessions,”

Dr. Crotty Alexander says.Planners set aside four hours each day to

show the groups how to perform bronchoso-copy, intubation, heart and chest ultrasound, spirometry, and mechanical ventilation.

“I think this is important for residents because they will not have been exposed to a lot of these things going into fellowship. Our hope is that this will build their confidence for their first day of fellowship,” says Brendan Clark, MD, a member of the Resident Boot Camp Planning Committee and an assistant profes-sor of medicine at the University of Colorado School of Medicine, Aurora.

The skills-based learning has been rewarding for April McDonald, MD, a third-year resident at the University of Tennessee, Knoxville.

“We’ve been doing ultrasound, bronchosco-py, and all kinds of things that will be pertinent to when we begin [our fellowships]. It gives us a leg up before we get started. It’s been a wonder-ful opportunity, and I’m thankful to be here,” Dr. McDonald says.

This year, 200 fellows took part in the Fellows Track Symposium. Faculty discussed clinical issues related to the diagnosis and treatment of a variety of pulmonary, critical care, and sleep disorders, including sepsis, COPD, lung cancer, asthma, and interventional pulmonology. It also included four breakout sessions and an ultrasonography dinner symposium.

“I’m going to take the pulmonary boards this year, so I thought this was good fit,” says Hrishikesh Kulkarni, MD, a second-year fellow

at Washington University, St. Louis. “There was a wide spectrum of topics covered, and I think the faculty did a great job covering them and answering questions.”

Also this year, the Medical Student Scholar Program was renamed the ATS Student Schol-ars Program to reflect the inclusion of attendees from various professional backgrounds. That program has grown from 31 to 65 attendees, organizers note.

Sarah Haeger, an MD/PhD student study-ing acute lung injury for her thesis project at the University of Colorado, is mindful of the educational benefit, especially the opportunity to talk with her fellow mentor.

“I’m excited to talk about how he got into pulmonary and critical care medicine and the path he has taken because I’m interested in pulmonary critical care medicine,” Ms. Haeger says.

The Resident Boot Camp is supported by an educational grant from Olympus Corporation of the Americas. In-kind support is provided by Bryan Corporation; FUJIFILM SonoSite, Inc.; Hamilton Medical, Inc.; Micro Direct, Inc.; Olympus Corporation of the Americas; Richard Wolf Medical Instruments Corp.; Smiths Medi-cal; and Verathon.

The FTS is supported by educational grants from Actelion Pharmaceuticals US, Inc.; Astra-Zeneca LP; Boehringer Ingelheim Pharmaceu-ticals, Inc.; Genentech; and Sunovion Phar-maceuticals, Inc. In-kind support is provided by FUJIFILM SonoSite, Inc.

Programs for Early Career Professionals Grow

During the ATS Resident Boot Camp, which attracted 140 residents, participants practice hands-on skills.

Come Join Us at the Industry Theater Presentation

TREATMENT of the RESPIRATORY MANIFESTATIONS

of SYMPTOMATICSARCOIDOSIS

This program will discuss sarcoidosis and an FDA-approved treatment option.

TUESDAY, MAY 19

11:30 AM–12:00 PM

Speaker 1

Robert P. Baughman, MD University of Cincinnati Medical Center

12:30 PM–1:00 PM

Speaker 2

Daniel Culver, DO Cleveland Clinic

Location

ATS 2015 International Conference Mini Industry Theater

Box lunches will be provided.

Sponsored by

An Industry Theater Presentation at the ATS 2015 International Conference. This presentation is sponsored by Mallinckrodt Pharmaceuticals and is open to all ATS 2015 International Conference attendees.

Please Note: Attendance is restricted to US healthcare providers (HCPs) only. Spouses and guests are not permitted to attend. Additionally, Federal employees and HCPs licensed to practice in Minnesota and Vermont are not permitted to attend this event. Mallinckrodt Pharmaceuticals, Inc., is required to report all payments or exchanges of value (eg, meals) in compliance with the Sunshine Act and state laws. Please keep in mind that HCPs may only attend 1 Mallinckrodt event per conference.This event is not CME accredited.

© 2015 Mallinckrodt. PM-01-13-1769 04/15 Printed in USA

KJob Number: 21248Revision No: 0Date: 4/22/15

YMC554-42845

ATS Daily Bulletin • ATS 2015 International Conference • Monday May 18, 201530

ATS 2015: Here’s Looking at You

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