Recent Pharmacological and Therapeutic Developments Affecting

Recent Pharmacological and Therapeutic Developments Affecting Public Health

Tennessee Department of Public HealthSeptember 16, 2011

2011 TPHA Annual Conference 1

Recent Pharmacological and Therapeutic Developments Affecting

Public Health Practitioners

Glen E. Farr, Pharm.D.Professor of Clinical Pharmacy

University of Tennessee College of Pharmacy

[email protected]

PresentedSeptember 16, 2011

Tennessee Department of Public Health Annual Conference

Franklin, TN

Disclosure

I have the following financial relationship to disclose: Speaker’s Bureau for Abbott Laboratories

I will discuss off-label use of quinine and terbutaline in my presentation.

I will discuss investigational drugs for diabetes.




Educational Objectives

At the conclusion of this session, the participant should be able to:

Compare and contrast recently introduced drugs with existing drugs of the same classification.

Evaluate recent drug-related studies, controversies, and developments, particularly those related to public health practitioners.

Counsel patients/clients on the latest developments with pharmacological agents and supplements.

FDA New Drug Approvals

The number of new drugs approved by FDA in 2010 was just below pace with 2009.

Drugs approved:2010: 20

2009: 26

2008: 25 Through August, 2011, FDA has approved 22 drugs

Pharmacist’s Activists, January, 2011




Chronic Medicine Use Reaches Record in U.S.

The US CDC reported that almost half of Americans took at least one prescription drug per month in 2008, marking an increase of 10% since 1999. Across the same period, spending on

prescription drugs more than doubled to $234.1 billion.

People 65 and older were most likely to be on chronic medicines.

http://www.cdc.gov/nchs/data/databriefs/db42.pdf, September 2, 2010

CDC: Half of US Adults Take Vitamins, Supplements

About half of U.S. adults take vitamins and other dietary supplements. The use of dietary supplements has grown

since the early 1990s when it was about 42%.

The biggest change was for calcium. Two-thirds of women 60 and older take it, up

from 28% in the early 1990s.

http://www.cdc.gov/nchs, April 13, 2011




America's Most Medicated StatesRetail prescriptions filled per capita for 2009

1. West Virginia 18.42. Tennessee 16.9

3. Alabama 16.7

4. Kentucky 16.5

5. Arkansas 16.4

6. South Carolina 16.3

7. Mississippi 15.9

8. Iowa 15.3

9. Missouri 15.0

10.Vermont 15.0

Forbes.com, August 16, 2010

Tennessee Climbs Back to 2nd from 4th

Top 15 Drugs in # of Rxs for 2010

Drug # millions of Rxs1. Hydrocodone 131.22. Simvastatin 94.13. Lisinopril 87.44. Levothyroxine 70.55. Amlodipine 57.26. Omeprazole 54.47. Azithromycin 52.68. Amoxicillin 52.39. Metformin 48.310.Hydrochlorothiazide 47.811.Alprazolam 46.312.Lipitor® 45.313.Furosemide 44.414.Metoprolol 38.915.Zolpidem 38.0

http://www.imshealth.com/ April 2011

Note: No branded drug in the top 10. Lipitor fell from #7 in 2009 to #12 for 2010




Top 15 Drugs for 2010 by Sales (in Billions of US$ & Percent change from 2009)

1. Lipitor 10.7 -6%

2. Plavix 9.43 -4%

3. Remicade 7.99 N/A

4. Advair 7.94 2%

5. Enbrel 7.23 N/A

6. Abilify 6.78 N/A

7. Humira 6.55 19%

8. Avastin 6.22 8%

9. Rituxan 6.11 9%

10. Diovan 6.05 1%

11. Crestor 5.69 26%

12. Seroquel 5.3 9%

13. Herceptin 5.22 7%

14. Zyprexa 5.03 2%

15. Singulair 4.99 7%

http://www.bloomberg.com/news/2011-02-10

Top 15 Therapeutic Classes by Rxs for 2010

Class of Drug # millions of Rxs1. Lipid regulators 255.42. Antidepressants 253.63. Narcotic analgesics 244.34. Beta-blockers 191.55. ACE inhibitors 168.76. Antidiabetes 165.07. Respiratory agents 153.38. Anti-Ulcerants 147.19. Diuretics 131.010.Anti-Epileptics 121.711.Anti-psychotic agents 108.612.Thyroid agents 107.213.Calcium antagonists 97.914.Antirheumatics 95.015.Contraceptives 92.3





Top 15 Therapeutic Classes by Spending for 2010

Class of Drug In billions of $1. Oncologics 22.32. Respiratory agents 19.33. Lipid regulators 18.84. Antidiabetes 16.95. Antipsychotics 16.16. Anti-ulcerants 11.97. Antidepressants 11.68. Autoimmune diseases 10.69. HIV Antivirals 9.210.ARBs 8.711.Narcotic analgesics 8.412.ADHD 7.213.Platelet inhibitors 7.114.Erythropoietins 6.115.Multiple Sclerosis 5.7


Generic Drugs Continue to Grow

Generics now account for 78% of the total US pharmaceutical market volume, reaching an all-time high in 2010. However, brand name

drugs made up about 80% of dollars spent on prescription drugs.





Generic Drugs Continue to Grow


0%

10%

20%

30%

40%

50%

60%

70%

80%

2006 2007 2008 2009 2010

Generic MarketShare

Branded Products That Became Available Generic in 2010

Cozaar®/Hyzaar®

(losartan/losartan & HCTZ)

Arimidex® (anastrozole)

Effexor XR® (venlafaxine)

Aricept® (donepezil)

Flomax® (tamsulosin)

http://www.fool.com/investing/high-growth/2009/12/29/09




Branded Products Going Generic in 2011 & 2012

2011 Lipitor® (atorvastatin)

Generic atorvastatin became available in Canada in May 2010

Plavix® (clopidogrel)

Actos® (pioglitazone)

Zyprexa® (olanzapine)

2012

Lexapro® (escitalopram)

Avandia® (rosiglitazone)

Advair® (salmeterol/fluticasone)

Diovan® (valsartan)

Zometa® (zoledronic acid)

Viagra® (sildenafil) Pfizer will make the generic

brand and call it Avigra®

http://www.onemedplace.com/blog/archives/5021, May 3, 2010

“Are Generic Drugs the Same?” Medical Letter CONCLUSION The continuing claims of pharmaceutical

manufacturers and others that generic drugs are inferior to brand-name originals still lack convincing documentation.

Nevertheless, with levothyroxine and antiepilepticdrugs, Medical Letter consultants recommend using one formulation (brand name or generic) consistently or, if consistency is not possible with generics, prescribing the brand name routinely.

The Medical Letter, October 19, 2009




Drug Shortages Reach Record High in 2011

Drug shortages in the US are poised to hit a record number in 2011, with 82% of hospitals reporting to the American Hospital Association that they have been forced to delay care for patients as a result.

The FDA currently lists 246 drugs in short supply, up from around 200 in 2010 and 56 in 2006.

First Word, August 16, 2011

Tennessee Controlled Substance Database The Tennessee Controlled Substance

Monitoring Database began in 2007.

The database includes data on controlled substance prescription of schedule II-V drugs.

The database includes: who the prescribing practitioner is

who filled the prescription

basic patient information

the name and form of medication that the patient received




Top 10 Controlled Substances in Tennessee1. Hydrocodone (Vicodin, Lorcet, Lortab)

2. Alprazolam (Xanax)

3. Oxycodone (OxyContin®, Percocet®)

4. Codeine (Tylenol #3, various cough syrups)

5. Clonazepam (Klonopin®)

6. Zolpidem (Ambien®)

7. Lorazepam (Ativan®)

8. Diazepam (Valium®)

9. Propoxyphene (Darvocet N-100)

10. Pregabalin (Lyrica®)Tennessee Department of Health data reported in the News Sentinel, August 7, 2011

Source for Opiates Used for Non-Medical Use

1. From a friend: 56%

2. From one doctor: 18%

3. Bought from a friend or relative: 9%

4. Other sources: 8%

5. Took from a friend or relative without asking: 5%

6. Bought from a drug dealer: 4%

Tennessee Department of Health data reported in the News Sentinel, August 7, 2011




Drugs Used in Mental Health, Drug Abuse and Pain Management

New Atypical Antipsychotic:Lurasidone (Latuda®)

The 10th atypical is a dopamine type 2 (D2) AND serotonin type 2 (5-HT2A) antagonist approved for schizophrenia. Marketed as “less metabolic effects and once-a-day.”

Cost is ~$15-20/day.

Prescriber’s Letter, February 2011




New Atypical Antipsychotic:Asenapine (Saphris®) Approved 2009 for schizophrenia and bi-polar.

Sublingual tablet that is inactive if swallowed. Patients who may “cheek” other antipsychotics

to avoid therapy, can just swallow this one.

Cost ~$500/month.

Prescriber’s Letter, October 2009

"Substantial" Weight Gain in Children Treated with Atypical Antipsychotics

Treatment-naive children who took atypical antipsychotics for 11 weeks had mean weight gain ranging from 4.4 kg to 8.5 kg, depending on the drug prescribed. Lead author Christoph Correll commented that "weight

gain was pervasive even in medications usually considered to be weight neutral in adults."

The study involved 272 children aged 4 years to 19 years of age with bipolar disorder, schizophrenia or other behavioral disorders.

JAMA. 2009;302(16):1811-1812




"Substantial" Weight Gain in Children Treated with Atypical Antipsychotics

Specifically, weight gain was reported as follows: Zyprexa® (olanzapine) = 8.5 kg (18.7 pounds)

Seroquel® (quetiapine) = 6.1 kg (13.4 pounds)

Risperdal® (risperidone) = 5.3 kg (11.7 pounds)

Abilify® (aripiprazole) = 4.4 kg (9.7 pounds)

JAMA. 2009;302(16):1811-1812

Quetiapine (Seroquel®) Abuse

Some people are abusing quetiapine (Seroquel®) for its sedating and antianxiety effects. It's known on the street as

"quell" or "baby heroin."

It is especially popular among jail inmates or substance abusers.

Prescriber’s Letter, October 2007




New Antidepressant: Vilazodone (Viibryd®)

Approved 2011, vilazodone (Viibryd®) is the first and only SSRI and 5HT1A receptor partial agonist. Claims to be “dual-action.”

Cost ~$150/month.

The marketing niche is that it may not interfere with sexual desire.

http://www.viibryd.com/

Antidepressant Benefits May Vary Depending on Severity of Symptoms

A meta-analysis of 6 placebo-controlled studies of antidepressants.

Those with severe symptoms derived the most benefit, while those with less-severe symptoms experienced minimal or no benefit. Conclusion: “There is little evidence to

suggest that [antidepressants] produce specific pharmacological benefit for the majority of patients with less severe acute depression."

JAMA. 2010;303(1):47-53




Benzodiazepine Abuse

The most abused today is alprazolam (Xanax®) The 2 mg scored

4-way tablets are known on the street as:

“Totem Poles”

“Bars” or “3-Bars”

“Bricks”

“Tombstones”

“Ladders”

Buspar® 15 mg looks similar

Abuse of Carisoprodol (Soma®)

Meprobamate (Equanil®, Miltown®) was a popular “nerve pill” in the 1960’s. Meprobamate is a C-IV controlled

substance that is seldom used today.

As of April 2011, carisoprodol is also a C-IV in Tennessee.

The muscle relaxant carisoprodol (Soma®) is metabolized to meprobamate, thus the abuse potential of Soma®.




Intuniv® (Guanfacine) For ADHD

In September 2009, the FDA approved Intuniv® (guanfacine) to treat ADHD in children and adolescents aged 6 to 17 years. The approval makes the

once-daily product the first selective alpha-2A adrenergic receptor agonist authorized in the country for use in ADHD.

FDA.gov, September 3, 2009

Clonidine (Kapvay®) Approved for ADHD

In October 2010, the FDA approved the non-stimulant medication Kapvay® (clonidine hydrochloride) in an extended-release, twice daily oral formulation as add-on therapy to stimulants for the treatment of ADHD in children and adolescents ages 6-17 years.

FDA.gov, October 4, 2010




Clonidine Abuse

Clonidine is often used in opioid detox programs to reduce withdrawal symptoms such as anxiety, restlessness, insomnia.

But some people are abusing it for its sedative effects or to ease withdrawal symptoms when they can't afford street drugs.

Pharmacist’s Letter, March 2010

New ‘Old’ Drug for Restless Legs Syndrome (RLS) In 2011, gabapentin enacarbil (Horizant®)

was approved for RLS It forms gabapentin (Neurontin®)

This makes 3 drugs approved for RLS

ropinirole (Requip®)

pramipexole (Mirapex®)




“Abuse-resistant” Formulation of OxyContin® Approved

April 2010 FDA approved an “abuse-resistant” formulation of oxycodone ER OxyContin®.

The reformulated “new” OxyContin® is a hard plastic polymer rendering the tablet difficult to crush or dissolve.

It is intended to prevent the opioid medication from being cut, broken, chewed, crushed or dissolved to release more medication.

FDA.gov, April 5, 2010

“Abuse-resistant” Formulation of OxyContin®: “OP”

The original OxyContin® is "OC," while the newer abuse-resistant formulation is "OP."

Some claim the new "OP" tablets don't work as well as, or cause more side effects than, the original "OC" tablets.

Pharmacist’s Letter, December 2010




Oxecta®: Abuse-Resistant Immediate-release Oxycodone In June 2011, the FDA approved Oxecta®

brand of immediate-release oxycodone "designed to discourage common methods of tampering associated with opioid abuse and misuse." This technology, known as Aversion

Technology, cause the active ingredient to gel to prevent injection if one tries to extract the oxycodone, or to irritate nasal passages if crushed and inhaled.

FDA.gov, June 20, 2011

Codeine/Promethazine Syrup Abuse In the past few years, there has been an

increase in the abuse of syrups containing codeine + promethazine, especially in the professional athletes and rap artists.

Known on the street as: “Pimp juice”

“Lean”

“Texas tea”

“Purple drank”




Pain Management and Recent Analgesic & Anti-inflammatory Drug Developments

FDA Limits Acetaminophen Amount in Combination Products

In January 2011, the FDA asked manufacturers of prescription combination products that contain acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule. These products include (Tylenol with Codeine®),

oxycodone (Percocet®), and hydrocodone (Vicodin®, Lortab®).

OTC acetaminophen products are not affected by this action.

FDA.gov, January 13, 2011




Max Daily Dose of Acetaminophen: 3000 mg/day In July 2011, McNeil Consumer Healthcare

has announced that the maximum daily dose for single-ingredient Extra Strength Tylenol® products sold in the U.S. will be lowered from eight dosage forms per day (4,000 mg) to six per day (3,000 mg).

Medscape.com 8-1-11

Injectable Acetaminophen (OFIRMEV®) Approved In U.S.

In November 2010, the FDA approved the first injectable acetaminophen in the U.S. An injectable acetaminophen has been

available for several years in Europe and certain other countries, where it is marketed under the brand name Perfalgan® for the treatment of post-operative pain.

FDA.gov, November 2, 2010




All Liquid Acetaminophen Discontinued Except 160 mg/5 ml

May 2011, the FDA and the Consumer Healthcare Products Association agreed to discontinue the 80 mg/0.8 ml and 80 mg/1 ml strengths of acetaminophen infant drops and market only one strength: 160 mg/5 ml.

This move is expected to reduce medication errors and overdose.

FDA Asks Manufacturers to Include Medication Delivery Devices

Figuring out how much liquid medication to give your baby or toddler should be a little easier.

In May 2011 FDA asked manufacturers to provide clearly and consistently marked delivery devices (syringes, cups, droppers or spoons), which will provide accurate doses of the liquid medication.

FDA.gov, May 9, 2011




Colchicine: New Formulation of an Old Drug: Colcrys® Colchicine, available generically for several

years, is now available only as Colcrys®. Price is ~$170/30 tablets or $5.60/tablet.

Are seeing increased use of the old formulation ColBenemid®.

Dosing is a bit different from the old dosing regimen. It used to be given as two 0.6 mg tablets, followed by one tablet every hour until relief or intolerable side effects (vomiting, cramps, etc.).

Colchicine: New Formulation of an Old Drug: Colcrys® The new regimen is to follow the two initial

tablets by just one tablet one hour later for a gout flare.

More than 3 tablets total is not more effective.

The I.V. form of colchicine and older oral forms of generic colchicine are no longer available.




7-Day Pain Patch: Buprenorphine (Butrans®) In July 2010, the FDA approved a once-

weekly buprenorphine transdermal system (Butrans®) for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period. It is a Schedule III Controlled Substance

The patches are available in cartons of 4 patches at 5, 10, and 20 μg/hour strengths and cost $126, $189, and $334 respectively.

Medscape, July 13, 2010

Tramadol (Ultram®, Ultracet®, Ryzolt®) Now C-IV in Tennessee

In April 2011 Governor Haslam signed into law the scheduling of tramadol (Ultram®, Ultracet®, Ryzolt®) as a C-IV in Tennessee. At the same time, carisoprodol (Soma®) was

made a C-IV also.




Drugs Used in Cardiovascular Health

Oral Direct Thrombin Inhibitor (DTI): Dabigatran (Pradaxa®)

Boehringer is marketing an oral DTI called dabigatran (Pradaxa®), which was approved in 2010.

It was marketed in the U.K and Germany in 2008.




How Does Dabigatran Compare to Warfarin?

In contrast to warfarin, dabigatran is given in a fixed dose twice daily independent of body weight, sex, food, fewer drug interactions than warfarin and no need to monitor the coagulation system.

Dabigatran prevents more strokes, including hemorrhagic strokes.

In fact, dabigatran prevents about 5 more strokes for every 1000 atrial fib patients treated for one year compared to warfarin.

Pharmacist’s Letter, November 1, 2010


But don't forget about warfarin yet.

Dabigatran costs about $8/day, which is more than the cost of warfarin PLUS monitoring.

Dabigatran must be given twice a day, it is not reversible, and it causes more dyspepsia than warfarin.

It is not currently FDA approved for prophylaxis or treatment of VTE, but may be used off-label.






Both drugs have a similar overall bleeding risk, but warfarin causes more intracranial bleeding; and dabigatran more GI bleeding.

There is no antidote for dabigatran, whereas vitamin K can reverse warfarin’s effects.


Rivaroxaban (Xarelto®) Approved for DVT Prevention Rivaroxaban (Xarelto®), the second oral

direct thrombin inhibitor (DTI), was approved in July 2011 for the prevention of DVT in patients undergoing knee or hip replacement surgery. Data that showed Xarelto® was more effective

in both a head-to-head comparison with Lovenox® (enoxaparin).

In the trials, Xarelto® demonstrated a similar safety profile to enoxaparin, including lower rates of major bleeding.

FDA.gov, July 2, 2011




Ticagrelor (Brilinta®) Approved for ACS

The antiplatelet agent ticagrelor (Brilinta®) was approved in July 2011 to treat ACS.

Brilinta® contains two boxed warnings: Aspirin doses above 100 mg/day decrease the

effectiveness of the medication

It increases the rate of bleeding and can cause significant, sometimes fatal, bleeding.


Ticagrelor (Brilinta®) Approved for ACS

In clinical trials, Brilinta® was more effective than Plavix® in preventing heart attacks and death, but that advantage was seen with aspirin maintenance doses of 75 to 100 mg/day.





Does Aspirin Reduce Deaths?

Experts agree that aspirin is worth taking for people who have already had one heart attack (secondary prevention).

But whether and when healthy people (primary prevention) might benefit is a hotly debated question.

The American Journal of Medicine, online May 18, 2011

Does Aspirin Reduce Deaths?

A meta-analysis involving more than 100,000 men and women, some healthy and some with diabetes, but none with cardiac risk factors, was conducted. 3.65% of those on low-dose aspirin died

during the trials, compared to 3.74% of people not taking the drug.

According to the author: "If the patient has no risk factors for heart disease, I see no reason to put them on aspirin."

The American Journal of Medicine, online May 18, 2011




Lipitor® Approved for Children in Europe

In July 2010, the European Union approved a chewable form of atorvastatin (Lipitor®) for children 10 years of age and older with familial hypercholesterolemia.

Associated Press, July 6, 2010

The Medical Letter Review of Pitavastatin (Livalo®) Recommended doses of pitavastatin (Livalo®) have

not been shown to decrease LDL cholesterol more than recommended doses of other statins with longer safety records and, unlike other statins, no data are available on clinical outcomes with pitavastatin.

In addition, pitavastatin has a worrisome potential for clinically significant drug interactions.

There is no good reason to use it.

The Medical Letter, July 26, 2010




FDA: Do Not Use 80 mg Simvastatin (Zocor®) In 2011, the FDA recommended that due to

an increased risk of muscle damage, providers should restrict prescribing high-dose (80 mg) simvastatin.

The 80-mg dose should not be used unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.


Azilsartan (Edarbi®)

In 2011, the FDA approved the 8th

ARB azilsartan (Edarbi) tablets for treatment of hypertension.

It might be more effective than some others in lowering blood pressure.

Having to store the tablets in their original container may be a problem for some patients.

The Medical Letter, May 16, 2011




Diabetes: The story has changed…Diabetes in the 1920’s

Diabetes in the 21st century

A meta-analysis of 140 studies by the Agency for Healthcare Research and Quality (AHRQ) of the comparative safety and efficacy of oral hypoglycemic agents was conducted.

The analysis showed that the drugs have similar hypoglycemic effects but show marked differences in adverse events.

The analysis also finds that the long-term benefits and harms of diabetes medications remain unclear.

Meta-analysis of Medications for Type 2 Diabetes

Ann Intern Med. Published online March 14, 2011




The evidence supports the choice of metformin as first-line therapy.

Meta-analysis of Medications for Type 2 Diabetes


Metformin was more effective than the DPP-4 inhibitors at reducing A1c.

All drugs also were associated with weight gain, with the exception of metformin, which was consistently associated with weight reduction or neutrality.

Sulfonylureas were associated with a 4-fold increased risk for hypoglycemia vs metformin alone.

Meta-analysis: Comparisons with Metformin





Sulfonylureas + metformin increased hypoglycemia risk more than 5-fold vs metformin + thiazolidinediones.

Thiazolidinediones increased the risk for congestive heart failure vs sulfonylureas, and the risk for bone fractures relative to metformin.

Metformin carried a risk for GI tract adverse effects, particularly diarrhea, vs the thiazolidinediones.

Meta-analysis: Comparisons with Metformin


Rosiglitazone (Avandia®) Restricted in U.S., Suspended in Europe In September 2010, the FDA ruled that

Avandia® will stay on the market for use only by special order (if will not be on the pharmacy shelf), and will carry several restrictions. The European Medicines Agency (EMA)

recommended the suspension of marketing this product.

FDA.gov, September 23, 2010




Actos® (pioglitazone) Withdrawn in Europe; Warning in U.S. In June 2011, regulators in France and

Germany announced that Actos® (pioglitazone) will be withdrawn from the market. A few days later, the U.S. FDA issued a warning on the product. The withdrawal was not related to

cardiovascular events; it was related to an increased risk of bladder cancer.

First Word, June 9, 2011

Incretin-Based Treatments: DPP-4 Inhibitors Dipeptidyl Peptidase (DPP) IV Inhibitors

Sitagliptin (Januvia®)

Saxagliptin (Onglyza™)

Linagliptin (Tradjenta™) It was marketed in 2011 as “only one strength” which does not require a

dosage decrease in impaired renal function.




Incretin-Based Treatments: GLP-1 Agonists Glucagon-Like Peptide-1 (GLP-1) Receptor

Agonists Exenatide (Byetta®)

Clinical trials of a long-acting exenatide (Bydureon®)

Liraglutide (Victoza®)

Recent Developments in Women’s Health




“The Pill” Turns 50

May 2010 marked the 50th anniversary of the sexual revolution sparked by a little white tablet known as “The Pill.”

U.S. FDA approved it in 1960 as Enovid® and a year later, German drugmaker Bayer AG introduced it in Europe.

Business Week, April 15, 2010

Oral Contraceptives May Reduce Death Rate From Any Cause Data from a prospective cohort

study published in the March 11, 2010 issue of the British Medical Journal showed that women who use oral contraceptives have a significantly lower rate of death from any cause, including heart disease and all cancers, compared with women who have never used the products.

BMJ 2010;340:c927




Natazia®: First Four-phasic OC

Natazia® (17-β estradiol/dienogest), approved in May 2010, is the first four-phasic oral contraceptive to be marketed in the US. The drug has been marketed in Europe since

May 2009 where it is sold under the brand name Qlaira®.

FDA.gov, May 6, 2010

Beyaz®: First Oral Contraceptive + Folate Combo Approved

In September 2010, the FDA approved Beyaz®. It is the first of its kind and is intended both to

prevent pregnancy and reduce the risk for neural tube defects in their offspring if and when they give birth.

Medscape.com, September 24, 2010




Safyral®: Second OC + Folate

Approved in December 2010, Safyral® is the second oral contraceptive that contains folate.

It contains drospirenone 3 mg, ethinyl estradiol 30 mcg, levomefolate calcium 451 mcg, and levomefolate calcium 451 mcg.

Bayer Press Release, December 17, 2010

5 Day Post Emergency Contraceptive: Ulipristal (ella®) In 2010, the FDA approved ulipristal (ella®)

as an emergency contraceptive for use up to 120 hours (5 days) following unprotected sexual intercourse or contraceptive failure.

ella® is a progesterone agonist/antagonist whose likely main effect is to inhibit or delay ovulation.

FDA.gov, August 13, 2010




New Risedronate Formulation: Atelvia® Atelvia®, approved in 2010, is a 35 mg

delayed release (enteric-coated) tablet of risedronate that is taken once per week. It is the only oral bisphosphonate that

eliminates the waiting time to eat or drink.

RANK Ligand Inhibitor for Osteoporosis: Denosumab (Prolia®)

On June 1, 2010, FDA approved denosumab (Prolia®), the first and only RANK Ligand inhibitor.

It works to decrease the destruction of bone and increase bone mass and strength by inhibiting proteins that activate bone-destroying cells.





RANK Ligand Inhibitor for Osteoporosis: Denosumab (Prolia®)

It is an every six month 60 mg subcutaneous injection administered by a health care professional.

Cost is ~$825 per injection.


Denosumab (Xgeva®) for Fracture Risk with Bone Metastases

In 2011, denosumab was approved with a different brand name Xgeva® and dosage for prevention of skeletal-related events (such as pathologic fracture, spinal cord compression or radiation to bone) in patients with bone metastases from solid tumors.




Makena® Injection Approved to Reduce Premature Births In February 2011, the FDA gave priority

approval to Makena® (hydroxyprogesterone caproate) injection to reduce the risk of preterm delivery before 37 weeks of pregnancy, in pregnant women with a history of at least one spontaneous preterm birth. This is the only drug FDA approved for

tocolysis.

FDA.gov, February 4, 2011

Makena® Injection Approved to Reduce Premature Births It initially cost ~$1500/dose as manufactured,

but pressure lead to a reduction to $690. It was compounded in a pharmacy at ~$10 - $20/dose. 3-30-11 FDA announced that pharmacies can still compound

the product, despite the letter sent by K-V Pharmaceuticals.

It is administered once a week by injection into the hip. Treatment should begin at 16 weeks and no later

than 21 weeks of pregnancy. The FDA originally approved hydroxyprogesterone caproate under

the trade name Delaluti® in 1956 for threatened miscarriage. It was withdrawn in 2000 for reasons unrelated to safety.

FDA.gov, February 4, 2011 and March 30, 2011




Black Box: FDA Says Don’t Use Terbutaline off-label for Tocolysis February 2011, the FDA warned that

injectable terbutaline should not be used to prevent preterm labor or to treat it beyond 48 to 72 hours because of a potential for cardiac problems or death. The agency is requiring that a boxed warning

and contraindication be added to the terbutaline label for both the injectable and tablet form of the drug.

FDA.gov, February 17, 2010

Drugs Used in Miscellaneous Conditions




WHO Calls for 'Urgent' Action to Tackle Drug Resistance

In April 2011, the World Health Organization called for "urgent and concerted" efforts to combat the growing global threat of drug resistance.

WHO Director-General Margaret Chan warned that "in the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure."

http://www.firstwordplus.com/ April 7, 2011

Last Line of Defense for Treating Gonorrhea is Crumbling

Cephalosporins, the last class of antibiotics that treat gonorrhea, seem to be losing their effectiveness as the pathogen quickly evolves to bypass the antibiotic. "We are at an impasse, with no new drugs in

development," said Dr. Bolan. "We want to sound the alarm."

Morbidity and Mortality Weekly Report, 2011:60;873-877, July 8, 2011




Last Line of Defense for Treating Gonorrhea is Crumbling

Although Dr. Bolan said she was not aware of any new drug development in the pipeline, the CDC and the NIH are running a treatment trial on existing drugs: gentamicin, azithromycin, and gemifloxacin.

However, the development of new antibiotics is unlikely. The article characterized the next several decades as "a very barren period of time" in terms of antibiotics development.

Morbidity and Mortality Weekly Report, 2011:60;873-877, July 8, 2011

OK To Treat OM with Antibiotics in Children <3 For the last few years, the trend was NOT

give antibiotics right away and see if the ear infection resolves by itself.

New evidence shows antibiotics ARE beneficial for kids under 3 years with a definite case of acute otitis media.

Pharmacist’s Letter, March 2011




OK To Treat OM with Antibiotics in Children <3 The use of amoxicillin/clavulanate instead of

waiting spares one out of every 4 kids from a more prolonged or severe infection.

A cephalosporin (cefdinir, etc) is useful if resistance is a concern due to recent antibiotic use and day care attendance or under age 2...or if symptoms don't improve within 72 hours.

Advise parents to treat ear pain with analgesic ear drops or oral acetaminophen or ibuprofen. Pharmacist’s Letter, March 2011

Fidaxomicin (Dificid®) Approved for C. diff Diarrhea

In May 2011, the FDA approved fidaxomicin (Dificid®) for the treatment of Clostridium difficile-associated diarrhea (CDAD).

Clinical trial data showed that a greater number of patients treated with Dificid® had a sustained cure three weeks after treatment compared to those given vancomycin. Cost is $2,800 for a 10-day course compared

to $1,000–$1,800 for vancomycin.

Firstwordplus.com May 31, 2011




New Use for Nitroglycerin Ointment: Rectiv® for Anal Fissures

In June 2011, the FDA approved a 0.4% nitroglycerin ointment (Rectiv®) for the treatment of moderate to severe pain associated with chronic anal fissures. It is known as Rectogesic® in other parts of the

world.


Two New Drugs for Hepatitis C

In 2011, the FDA approved the protease inhibitors boceprevir (Victrelis®) andtelaprevir (Incivek®) for the treatment of hepatitis C, making them the first in a new class of drugs approved to treat the disease. They are approved to be used in combination

with standard therapy of peginterferon alfa and ribavirin.




Potential Name/Ingredients Confusion with Maalox® Products

Name Formulation Active Ingredients

Maalox Total Relief® Liquid Bismuth subsalicylate

Maalox Regular Strength®

Chewable tablets Calcium carbonate

Maalox Advanced®Regular Strength and Maximum Strength

Liquid Calcium carbonate, magnesium hydroxide

Maalox Advanced®Maximum Strength

Chewable tablets Calcium carbonate, simethicone

The Medical Letter, June 28, 2010

Potential Name/Ingredients Confusion with Mylanta® Products

Name Formulation Active Ingredients

Mylanta Classic® Liquid Aluminum hydroxide, magnesium hydroxide, simethicone

Mylanta Gas® Soft gels chewable tablets

Simethicone

Mylanta Supreme® Liquid Calcium carbonate, magnesium hydroxide

Mylanta Ultimate Strength®

Liquid Aluminum hydroxide, magnesium hydroxide

Mylanta Ultimate Strength®

Chewable tablets Calcium carbonate, magnesium hydroxide

The Medical Letter, June 28, 2010




What’s in Kaopectate®?

Sometimes the brand name is the same but the active ingredient is different.

Kaopectate® bismuth subsalicylate in

the U.S.

attapulgite in Canada

kaolin/pectin in Mexico

Pharmacist’s Letter, July 2008

First Underarm Testosterone: Axiron® Gel In December 2010, the FDA approved

testosterone 2% topical solution (Axiron®) as the first testosterone replacement therapy to be applied to the underarm, in much the same way as deodorant.




FDA Issues Second Warning Against Treating Leg Cramps With Quinine

On July 8, 2010, the FDA stated: Physicians should not prescribe the malaria drug

quinine (Qualaquin®) for nocturnal leg cramps — an off-label use — because it may result in serious and life-threatening hematologic adverse effects. The FDA issued a similar warning in 2006, but the

agency noted that the majority of quinine used in the U.S. is still for the prevention of leg cramps.



Quinine therapy may result in thrombocytopenia, which can cause serious bleeding, or thrombotic thrombocytopenic purpura (TPP), which may lead to permanent kidney damage.






The FDA said that it has received 38 reports of serious adverse events associated with quinine between April 2005 and October 1, 2008, in the United States through its Adverse Event Reporting System. Only 1 patient was taking quinine to treat malaria.

Two patients died.



Under a REMS plan approved by the FDA, the drug's manufacturer will issue a letter to prescribers warning of the risk for hematologic reactions to the drug.

In addition, patients must be given a medication guide explaining what quinine is and is not approved for, and its potential adverse effects.





American Academy of Neurology (ANN) Guidelines for Treatment of Muscle Cramps

The AAN recommends that patients with idiopathic muscle cramps be treated with agents such as vitamin B complex or diltiazem as initial therapies.

However, if cramps are still disabling, then a trial of quinine may be warranted as long as patients clearly understand the risks associated with the drug.

Neurology, February 23, 2010 (2010;74:691-696)

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