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New Drugs Update: FDA Approvals for 2013-14

T. Aaron Jones, PharmD, BCPS Director of Pharmacy Marquette General Hospital MPA Fall Meeting (October 4, 2014)

Disclosure

I will discuss off label use or investigational use in my presentation.

I have no financial relationships to disclose.

Goals & Objectives

GOAL: To review selected new molecular entities approved by the Food &

Drug Administration in 2013-14 OBJECTIVES: List the name, mechanism of action, pharmacological properties,

route of administration, dosing schedule, and dosage forms for the new drugs reviewed

Discuss cautions, side effects, potential drug interactions, and primary points of patient education for these medications

Review the disease states where these medications are being used

Compare and contrast their role in practice with existing medications prescribed for similar indications

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New Application Approvals

Number Meaning

1 New molecular entity

2 New active ingredient

3 New dosage form

4 New combination

5 New formulation or new manufacturer

6 New indication

7 Drug already marketed without an approved NDA

8 OTC switch

10 New indication submitted as distinct NDA

Letter Meaning

P Priority review drug

S Standard review drug

O Orphan drug

NME/BLA Approvals

NME/BLAs of 2013 Alogliptin benzoate (Nesina)

Alogliptin benzoate, metformin HCl (Kazano)

Mipomersen Na (Kynamro)REMS

Pomalidomide (Pomalyst)REMS

Ado-trastuzumab emtansine (Kadcyla)

Ospemifene (Osphena)

Technetium TC-99M tilmanocept (Lymphoseek kit)

Gadoterate meglumine (Dotarem)

Dimethyl fumarate (Tecfidera)

Canagliflozin (Invokana)

Fluticasone furoate, vilanterol trifenatate (Breo Ellipta)

Radium RA-223 dichloride (Xofigo)

Dabrafenib mesylate (Tafinlar)

Trametinib dimethyl sulfoxide (Mekinist)

Telavancin (Vibativ)REMS

Afatinib dimaleate (Gilotrif)

Ferric carboxymaltose (Injectafer)

Levomilnacipran (Fetzima)

Golimumab (Simponi Aria)

Dolutegravir (Tivicay)

Vortioxetine (Brintellix)

Bazedoxifene/estrogens (Duavee)

Riociguat (Adempas)REMS

Macitentan (Opsumit)REMS

Flutemetamol F-18 (Vizamyl)

Obinutuzumab (Gazyva)

Eslicarbazepine (Aptiom)

Ibrutinib (Imbruvica)

Simeprevir (Olysio)

Sofosbuvir (Sovaldi)

Umeclidinium/vilanterol (Anoro Ellipta)

REMS information available at:

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSaf

etyInformationforPatientsandProviders/ucm111350.htm

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NME/BLAs of 2014 Dapagliflozin (Farxiga)

Tasimelteon (Hetlioz)

Elosulfase alfa (Vimizim)

Droxidopa (Northera)

Metreleptin (Myalept)REMS

Florbetaben F-18 (Neuraceq)

Miltefosine (Impavido)

Apremilast (Otezla)

Albiglutide (Tanzeum)REMS

Ramucirumab (Cyramza)

Siltuximab (Sylvant)

Certinib (Zykadia)

Vorapaxar (Zontivity)

Vedolizumab (Entyvio)

Dalbavancin (Dalvance)

Efinaconazole (Jublia)

Tedizolid (Sivextro)

Belinostat (Beleodaq)

Tavaborole (Kerydin)

Idelalisib (Zydelig) REMS

Olodaterol (Striverdi Respimat)

Empagliflozin (Jardiance)

Oritavancin (Orbactiv)

Suvorexant (Belsomra)

Peginterferon beta-1A (Plegridy)

Insulin glargine (Basaglar)

Eliglustat (Cerdelga)

Amino acids/electrolytes/dextrose/lipid (Kabiven and Perikabiven)

Pembrolizumab (Keytruda)

Updated 9/16/14. REMS information available at:

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSaf

etyInformationforPatientsandProviders/ucm111350.htm

Topics for Todays Presentation

Hepatitis C Virus Agents

Gram Positive Antimicrobials

COPD agents

SGLT2 inhibitors

Inhaled insulin

Newer opioid formulations

Pollen extracts for oral administration

Biosimilars update

Monoclonal antibodies and tyrosine kinase inhibitors update

Newer Anti-Hepatitis C Virus Agents Available

Generic Sofosbuvir Simeprevir Boceprevir Telaprevir

Trade Sovaldi Olysio Victrelis Incivek

Manufacturer/ FDA Approval

Gilead Sciences,

December 2013; 1P

Janssen,

November 2013; 1P

Merck,

May 2011; 1P

Vertex,

May 2011; 1P

Mechanism of Action

NS5B polymerase

inhibitor

NS3/4A protease

inhibitor (second-

generation)

NS3/4A protease

inhibitor (first-

generation)

NS3/4A protease

inhibitor (first-

generation)

Treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen (peginterferon and ribavirin)?

Yes

Genotype 1, 2, 3,

or 4 including hepatocellular

carcinoma meeting

Milan criteria

(awaiting liver

transplantation) and those with

HCV/HIV-1 co-

infection

Yes

Genotype 1 with

compensated liver disease (alternative

recommended for

genotype 1a

containing the

Q80K polymorphism)

Yes

Genotype 1 with

compensated liver disease

Yes

Genotype 1 with

compensated liver disease

Dose 400 mg once daily with or without

food

150 mg once daily

with food

800 mg three times

daily with food

1125 mg twice

daily with food (not

low fat)

Availability 400 mg tablets 150 mg capsules 200 mg capsules 375 mg tablets

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Older HCV Agents

Peginterferon

CHC with compensated liver disease in combination with ribavirin

Alfa-2a (Pegasys) 180 mcg SQ weekly

Alfa-2b (PegIntron) 1.5 mcg/kg SQ weekly

Ribavirin (Copegus)

CHC with compensated liver disease in combination with peginterferon

Genotype 1, 4:

75 kg: 600 mg orally twice daily

Genotype 2, 3: 400 mg orally twice daily

HCV Agents Sofosbuvir Simeprevir Boceprevir Telaprevir Peg-

interferon Ribavirin

Trade Sovaldi Olysio Victrelis Incivek Pegasys Copegus

Dose 400 mg orally once daily with or without food

150 mg orally once daily with food

800 mg orally three times daily with food

1125 mg orally twice daily with food (not low fat)

180 mcg SQ weekly

400-600 mg orally twice daily

Duration Genotype 1 or 4: SOF + PEG/RIB x 12 weeks Genotype 2: SOF + RIB x 12 weeks Genotype 3: SOF + RIB x 24 weeks

SMV + PEG/RIB x 12 weeks followed by either 12 or 36 additional weeks of PEG/RIB depending on prior response status

PEG/RIB x 4 weeks followed by adding BOC (duration based on viral response, prior response status and presence of cirrhosis)

TEL + PEG/RIB x 12 weeks followed by either 12 or 36 additional weeks of PEG/RIB depending on prior response status

Genotype 1 or 4: PEG + RIB x48 weeks Genotype 2 or 3: PEG + RIB x48 weeks

Availability 400 mg tablet 150 mg capsule

200 mg capsule

375 mg tablet 180 mcg pen injector

200 mg tablet/capsule

Monthly Cost

$33,600 (28 tablets)

$26,544 (28 capsules)

$4,400 (336 capsules)

$26,462 (168 tablets)

$3,961 (4 pens)

$1,670 (168 tablets)

Adverse Effects

Ribavirin: fatigue, headache, fever, depression, alopecia, leukopenia, myalgia, anemia, pregnancy category X

Peginterferon: bone marrow suppression, flu-like symptoms, neuropsychiatric exacerbation*, autoimmune disease exacerbation*, infectious disease*, ischemic heart disease*, pregnancy category C

Boceprevir: fatigue, anemia, nausea, headache, dysgeusia, acute hypersensitivity reactions, pregnancy category B

Telaprevir: rash*, fatigue, pruritis, anemia, nausea, hemorrhoids, diarrhea, anorectal discomfort, anal pruritus, pregnancy category B

Simeprevir: elevated bilirubin, photosensitivity, rash, pruritis, nausea, pregnancy category C

Sofosbuvir: fatigue, headache, nausea, insomnia, anemia, pregnancy category B

*Black Box Warning.

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Drug Interactions

Ribavirin: didanosine (CI)

Peginterferon: 1A2 (alfa-2a), caution with CYP2C8/9 or 2D6 (alfa-2b)

Boceprevir: numerous, some with CI; 3A4 and Pgp substrate, 3A4/5 and Ppg inhibitor*

Telaprevir: numerous, some with CI; 3A4 and Pgp substrate, 3A4, Pgp, and OAT-P1B1 and P2B1 inhibitor*

Simeprevir: 3A4 and Pgp substrate, 1A2, Pgp, OAT-P1B1/3 inhibitor

Sofosbuvir: Pgp and BCRP substrate

*Contraindications.

Initial Therapy Recommendations

Genotype

Treatment Nave or Experienced Relapse after prior PEG/RBV Therapy (Level of Evidence)

Retreatment for Patients in Whom PEG/RBV Failed (Level of Evidence)

1 IFN eligible: SOF + PEG/RBV x 12 weeks IFN ineligible: SOF + SMV RBV x 12 weeks

IFN eligible: SMV x 12 weeks + PEG/RBV x 24 weeks IFN ineligible: SOF + RBV x 24 weeks

2 SOF + RBV x 12 weeks None

3 SOF + RBV x 24 weeks SOF + PEG/RBV x 12 weeks

4 IFN eligible: SOF + PEG/RBV x 12 weeks IFN ineligible: SOF + RBV x 24 weeks

SMV x 12 weeks + PEG/RBV x 24-48 weeks

Source: http://www.hcvguidelines.org/. Accessed September 2014.

Pipeline Agents

NS5a inhibitors Daclatasvir (BMS, marketed in EU)

ACH-3102 (Achillion, phase II)

Protease inhibitors Asunaprevir (BMS, marketed in EU)

ACH-2684 (Achillion, phase I)

Danoprevir (Genentech, phase II)

Sovaprevir (Achillion, phase II)

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Gram Positive Antimicrobials for Acute Bacterial Skin and Skin Structure Infections (abSSSI)

2010 FDA Draft Guidance for Industry

Revision from 1998 draft

Re-characterized categories of skin and skin structures

Noninferiority clinical trial designs

Study endpoints

Qualified Infectious Disease Product (QIDP)

Generating Antibiotic Incentives Now (GAIN) Act, part of the 2012 FDA Safety and Innovation Act

QIDP designation provides incentives including priority review, eligibility for FDAs fast track program, and 5 year extension of exclusivity under Hatch-Waxman Act

2014 Update IDSA Guidelines for Skin and Soft Tissue Infections

Gram Positive Antimicrobials for Acute Bacterial Skin and Skin Structure Infections (abSSSI)

Generic Tedizolid phosphate

Oritavancin diphosphate

Dalbavancin hydrochloride

Telavancin hydrochloride

Trade Sivextro Orbactiv Dalvance Vibativ

Manufacturer/ FDA Approval

Cubist,

June 2014; 1P

QIDP

Medicines Co,

August 2014; 1P

(not yet marketed)

QIDP

Durata Therap,

May 2014; 1P

QIDP

Theravance,

September 2009;

1S (reintroduced in

2013)

Mechanism of Action

Oxazolidinone Lipoglycopeptide Lipoglycopeptide Lipoglycopeptide

Indication Acute skin and skin structure infections

Acute skin and skin

structure infections

Acute skin and skin

structure infections

Complicated skin

and skin structure

infections

Hospital-acquired

and ventilator-

associated bacterial

pneumonia

Dose IV infusion and oral: 200 mg daily for 6

days

IV infusion:

Single 1,200 mg

dose

2-dose IV infusion:

1,000 mg followed

by 500 mg one

week later

IV infusion:

cSSSI: 10 mg/kg

daily for 7-14 days

HABP/VABP: 10 mg/kg daily for 7-

21 days

Gram Positive Antimicrobials

Randomized, multicenter, double-blind, non-inferiority Noninferiority margin of 10% (vs. 15% in earlier trials)

Primary outcomes Pre-2010: Clinical response at 7-14 days following end of antibiotic treatment

Post-2010: Early clinical response rate (48-72 hours) with no increase in lesion surface area from baseline and oral temperature 37.6 C

Comparative efficacy data for SSSI Tedizolid 6 day vs. linezolid 10 day

Oritavancin SD vs. vancomycin 7-10 day

Dalbavancin TD vs. vancomycin/linezolid 14 day

Telavancin 7-14 day vs. vancomycin 7-14 day

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Clinical Response Rates

Source: Package inserts for Sivextro, Orbactiv, Dalvance, and Vibativ. Accessed September 2014.

Other Clinical Trials

NCT02019420: tedizolid vs. linezolid for nosocomial pneumonia

NCT02127970: dalbavancin single vs. two dose regimen for abSSSI

NCT00057369: dalbavancin vs. vancomycin for catheter-related bloodstream infections

Contraindications/Warnings/ Precautions

Tedizolid (no CI or BBW), reversible MAO inhibitor (pregnancy category C)

Oritavancin (IV UFH CI for 48 hours after oritavancin administration), increase warfarin exposure, hypersensitivity/infusion-related reactions (pregnancy category C)

Dalbavancin (no CI or BBW), hypersensitivity/infusion-related reactions, ALT elevations (pregnancy category C)

Telavancin (BBW on fetal risk), nephrotoxicity, hypersensitivity/infusion-related reactions, QTc prolongation, coagulation test interference (pregnancy category C)

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Infusion Issues

Tedizolid: 200 mg powder vial, reconstitute with SWI and dilute with 250 mL NS;

administer as IV infusion over 1 hour

Incompatible with divalent cation solutions (including LR)

Oritavancin: 1200 mg powder vial, reconstitute with SWI and dilute with 1000 mL D5W;

administer as IV infusion over 3 hours

Incompatible with saline-based solutions

Dalbavancin: 500 mg powder vial, reconstitute with SWI and dilute with D5W (1-5

mg/mL); administer as IV infusion over 30 minutes

Incompatible with saline-based solutions

Telavancin: 250 mg and 750 mg powder vials, reconstitute with 15 mL and 45 mL

D5W/SWI/NS and dilute with D5W/NS/LR; administer as IV infusion over 60 minutes (final volume dependent on total dose)

Chronic Obstructive Pulmonary Disease (COPD)

2007 FDA Draft Guidance for Industry Assessment of NMEs in phase 3 studies

Study endpoints

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

2004 GOLD report

2014 update

COPD Foundation

Pharmacologic Therapy for Stable COPD

Beta2-agonists (short- and long-acting)

Anticholinergics (short- and long-acting)

Combination beta2-agonist plus anticholinergic

beta2-agonist plus corticosteroid

Methylxanthines

Inhaled corticosteroids

Systemic corticosteroids

Phosphodiesterase-4 inhibitors

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Available Long-Acting Beta2-Agonists

Agent FDA Approval

Salmeterol (Serevent MDI) February 1994

Salmeterol (Serevent Diskus) September 1997

Salmeterol/fluticasone (Advair Diskus) August 2000

Formoterol (Foradil Aerolizer) February 2001

Salmeterol/fluticasone (Advair HFA) June 2006

Formoterol/budesonide (Symbicort) July 2006

Arformoterol (Brovana) October 2006

Formoterol (Foradil Certihaler) December 2006

Formoterol (Perforomist) May 2007

Vilanterol/fluticasone (Breo Ellipta) May 2013

Available Anticholinergics

Agent FDA Approval

Ipratropium (Atrovent MDI) December 1986

Ipratropium/albuterol (Combivent) October 1996

Tiotropium (Spiriva HandiHaler) January 2004

Ipratropium (Atrovent HFA) November 2004

Ipratropium/albuterol (Combivent Respimat)

October 2011

Aclidinium (Tudorza Pressair) July 2012

Tiotropium (Spiriva Respimat) 2014??

Newer COPD Agents

Olodaterol (Striverdi Respimat)

Boehringer Ingelheim, 7/31/2014 (1S)

Long-acting beta2-adrenergic agonist for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease, including bronchitis and/or emphysema

Umeclidinium (Incruse Ellipta)

GlaxoSmithKline, 4/30/2014 (5S)

Anticholinergic for long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease

Umeclidinium/vilanterol (Anoro Ellipta) GlaxoSmithKline, 12/18/2013 (1S)

Anticholinergic and long-acting beta2-adrenergic agonist for long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease

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Confirmatory Trials

Incruse: placebo controlled

Striverdi: placebo and active control (formoterol, tiotropium)

Anoro: placebo and individual agents

Primary endpoint = lung function (change from baseline in trough FEV1) at 24 weeks

Contraindications/Warnings/ Precautions: Olodaterol (Striverdi)

LABA increase risk of asthma-related death (BBW)

LABA contraindicated in asthma without use of long-term asthma control medication

Not indicated for treatment of asthma

Do not initiate in acutely deteriorating COPD patients

Do not use for relief of acute symptoms

Do not exceed recommended dose

Life-threatening paradoxical bronchospasm can occur

Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, or sensitivity to sympathomimetic drugs

Adverse reactions (incidence 2%): nasopharyngitis, upper respiratory tract infections, bronchitis, urinary tract infections, cough, dizziness, rash, diarrhea, back pain, and arthralgia

Contraindications/Warnings/ Precautions: Umeclidinium (Incruse)

Severe hypersensitivity to milk proteins or any other ingredient

Do not initiate in acutely deteriorating COPD patients or to treat acute symptoms

Life-threatening paradoxical bronchospasm can occur

Worsening of narrow-angle glaucoma or urinary retention may occur

Adverse reactions (incidence 2%): nasopharyngitis, upper respiratory tract infection, cough, arthralgia

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Contraindications/Warnings/ Precautions: Umeclidinium/vilanterol (Anoro)

LABA increase risk of asthma-related death (BBW)

Severe hypersensitivity to milk proteins or any ingredients

Do not initiate in acutely deteriorating COPD patients or to treat acute symptoms

Do not use in combination with an additional LABA

Life-threatening paradoxical bronchospasm can occur

Use with caution in patients with cardiovascular or convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis

Worsening of narrow-angle glaucoma or urinary retention may occur

Hypokalemia and hyperglycemia

Adverse reactions (incidence 1%): pharyngitis, sinusitis, lower respiratory tract infection, constipation, diarrhea, pain in extremity, muscle spasms, neck pain, chest pain

Dosing/How Supplied

Olodaterol (Striverdi) Two inhalations once daily

Respimat cartridge and inhaler 60 metered actuations

28 metered actuations (institutional pack)

Umeclidinium (Incruse) One inhalation once daily

Ellipta inhaler containing double-foil blister strip with: 30 blisters

7 blisters (institutional pack)

Umeclidinium/vilanterol (Anoro Ellipta) One inhalation once daily

Ellipta inhaler containing 2 double-foil blister strip with: 30 blisters each

7 blisters each (institutional pack)

Pipeline Agents

Olodaterol/tiotropium via Respimat

Aclidinium/formoterol via Pressair?

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Managing Type 2 Diabetes

Biguanides

Sulfonylureas

Meglitinides

Thiazolidinediones

Alfa-glucosidase inhibitors

DPP-4 inhibitors

Sodium glucose cotransporter 2 inhibitors

Bile acid sequestrants

Dopamine-2 agonists

GLP-1 receptor agonists

Amylin mimetics

Insulins

Refs: Position Statement of ADA/EASD. Diabetes Care 2012;35:1364-79. Editors Expert Forum Follow Up. Diabetes Care 2014;37:2647-59.

SGLT2 Inhibitors Generic Dapagliflozin Empagliflozin Canagliflozin

Trade Farxiga Jardiance Invokana Invokamet

Manufacturer/ FDA Approval

AstraZeneca,

January 2014; 1S

Boehringer Ingelheim,

August 2014; 1S

Janssen,

March 2013; 1S

Mechanism of Action

Sodium-glucose cotransporter 2 inhibitor

Indication Adjunct to diet and exercise to improve glycemic control in adults with type 2 DM

Not for treatment of type 1 DM or diabetic ketoacidosis.

Availability 5 mg, 10 mg tablets 10 mg, 25 mg tablets 100 mg, 300 mg tablets

Combination with metformin

(Invokamet): 50/500 mg, 150/500 mg,

50/1000 mg, 150/1000 mg

SGLT2 Inhibitor Comparison Dapagliflozin Empagliflozin Canagliflozin

Bioavailability 78% N/A 65%

Protein Binding 91% 86.2% 99%

Food effect None None None

Metabolism Glucuronidation (minimal 3A4)

Glucuronidation Glucuronidation (minimal 3A4)

Elimination half-life

12.9 hours 12.4 hours 10.6-13.1 hours

Usual Adult Dosage

5 mg once daily, taken

in the morning with or

without food

(max: 10 mg/day)

10 mg once daily, taken

in the morning, with or

without food

(max: 25 mg/day)

100 mg once daily,

taken before the first

meal of the day

(max: 300 mg/day)

Dosage adjustment in renal impairment?

Do not initiate/continue if eGFR

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SGLT2 Inhibitor Comparison Dapagliflozin Empagliflozin Canagliflozin

Contraindications History of hypersensitivity Severe renal impairment, end-stage renal disease,

dialysis

Warnings/ Precautions

Hypotension Impairment in renal function Hypoglycemia (with insulin/insulin secretagogues) Genital mycotic infections Increased LDL-C Macrovascular outcomes

Bladder cancer Urinary tract infections

Hypersensitivity Hyperkalemia

Drug Interactions Insulin/insulin secretagogues Urine glucose tests

UGT enzyme inducers Digoxin

Pipeline Agents

Ipragliflozin (Astellas, phase III)

Ertugliflozin (Merck/Pfizer, phase III)

Inhaled Insulin

Afrezza Mannkind Corp. (partner with Sanofi)

FDA approved June 2014

Not yet available in US pharmacies (8/27/14)

Exubera Pfizer

FDA approved January 2006

Discontinued in October 2007

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Insulin human for inhalation (Afrezza)

Indicated for type 1 and 2 DM Must use long-acting insulin in type 1

Not recommended for diabetic ketoacidosis

Not recommended in patients who smoke

Contraindications Episodes of hypoglycemia

Chronic lung disease such as asthma, COPD (Black Box Warning)

Hypersensitivity to regular human insulin

Insulin human for inhalation (Afrezza)

Administer at the beginning of a meal Starting mealtime dose

Mealtime dose adjustment

Administration of doses exceeding 8 units

Dose adjustments due to drug interactions

Lung function assessment prior to therapy initiation

Single inhalation per single-use cartridge 4 units (blue)

8 units (green)

Biosimilars

FDA webpage on biosimilars

Draft guidance for industry

Purple Book

FDA-approved biosimilars

Enoxaparin (7/23/2010)??

TBO-filgrastim (Granix) by Teva: 8/29/2012

Insulin glargine (Basaglar) by Eli Lilly and Co.: 8/18/2014 (tentative approval)

On the horizon

Epoetin alpha/beta, darbepoetin

mAbs (rituximab, infliximab)

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Newer Opioid Formulations

Hydrocodone (Zohydro ER) Zogenix Inc.

October 25, 2013 (available)

Schedule II*

Oxycodone/naloxone (Targiniq) Purdue Pharma

July 23, 2014 (not yet marketed)

Schedule II

Sufentanil sublingual tablet system (Zalviso) AcelRx Pharma

Denied by FDA July 2014

*All hydrocodone-containing products going to schedule II (October 6, 2014).

Naloxone (Evzio)

FDA approval: April 3, 2014 New Dosage Form

Priority review drug

Marketed by: Kaleo Inc.

Website information: http://www.evzio.com/hcp/

Allergen Extract Sublingual Tablets

Ragwitek July 16, 2014 (Merck)

Short ragweed pollen

Oralair April 1, 2014 (Stallergenes)

Grass pollen

Grastek April 11, 2014 (Merck)

Grass pollen Source: http://www.fda.gov/BiologicsBloodVaccines/Allergenics/ucm391505.htm. Accessed August 2014.

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Monoclonal Antibodies: Elements of a Name

Prefix (1-2 syllables)

Infix (target/disease) tu/t = tumors

li/l = immunomodulator

ba/b = bacterial

Infix (source) zu = humanized

o = mouse

u = fully human

xi = chimeric

Suffix -mab or -pab

Ref: AMA website, Physician Resources. Accessed September 2012.

Monoclonal Antibodies: Example

Pertuzumab (Perjeta) per = unique syllable

tu = tumor (HER2-positive metastatic breast cancer)

zu = humanized (from mouse)

mab = monoclonal antibody

Newer mAbs of 2013-14

Ado-trastuzumab emtansine (Kadcyla) Genentech, 2/22/2013

HER2-positive, metastatic breast cancer

Golimumab (Simponi Aria) Janssen, 7/18/2013

Moderate to severe Rheumatoid Arthritis

Obinutuzumab (Gazyva) Genentech, 11/1/2013

Previously untreated chronic lymphocytic leukemia

Ramucirumab (Cyramza) Eli Lilly, 4/21/2014

Advanced gastric cancer or gastro-esophageal junction adenocarcinoma

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Newer mAbs of 2013-14

Siltuximab (Sylvant) Janssen, 4/22/2014

Multicentric Castlemans disease

Vedolizumab (Entyvio) Takeda, 5/20/2014

Adult ulcerative colitis, Crohns disease

Pembrolizumab (Keytruda) Merck, 9/4/2014

Unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor

Kinase Inhibitors

Inhibition of enzymes responsible for the activation of signal transduction cascades

No standardized nomenclature, typically end with inib or anib or enib

20+ kinase inhibitors BRAF inhibitor

Janus-Associated kinase inhibitor

Multikinase inhibitor

Tyrosine kinase inhibitor

Newer NIBs of 2013-14

Dabrafenib mesylate (Tafinlar) GlaxoSmithKline, 5/29/2013

Unresectable or metastatic melanoma with BRAF V600E mutation

Trametinib dimethyl sulfoxide (Mekinist) GlaxoSmithKline, 5/29/2013

Unresectable or metastatic melanoma with BRAF V600E or V600K mutations

Afatinib dimaleate (Gilotrif) Boehringer Ingelheim, 7/12/2013

Metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 substitution mutations

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Newer NIBs of 2013-14

Ibrutinib (Imbruvica) Pharmacyclics, 2/12/2014

Mantle cell lymphoma

Chronic lymphocytic leukemia

Chronic lymphocytic leukemia with 17p deletion

Certinib (Zykadia) Novartis, 4/29/2014

Anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer who have progressed on or are intolerant to crizotinib

Idelalisib (Zydelig) Gilead Sciences, 7/23/2014

Relapsed chronic lymphocytic leukemia in combination with rituximab

Relapsed follicular B-cell non-Hodgkin lymphoma

Relapsed small lymphocytic lymphoma

mAbs and NIBs

NIOSH 2014 hazardous drug list?

REMS

Specialty pharmacies

Patient assistance programs

Initiation or continuation of outpatient therapy during inpatient stays

Question #1

Sofosbuvir, the newest NS3/4A protease inhibitor, is FDA approved for HCV treatment.

a. True

b. False

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Question #2

What is the recommended dosing regimen for oritavancin?

a. 200 mg once daily x 6 days

b. Single 1,200 mg infusion

c. 1,000 mg followed by 500 mg one week later

d. 10 mg/kg daily for 7-14 days

Question #3

Oritavancin and dalbavancin are stable in saline-based solutions.

a. True

b. False

Question #4

Umeclidinium is a novel entity of which therapeutic class?

a. Long-acting beta2-agonist

b. Short-acting anticholinergic

c. Long-acting anticholinergic

d. Inhaled corticosteroid

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Question #5

The SGLT2 agents, dapagliflozin, empagliflozin, and canagliflozin are predominantly metabolized through CYP450 3A4.

a. True

b. False

Questions?