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October 2016 Newsletter

 Recent Project News

NEW! Two CME/CPE Modules on Opioids


The DC Center for Rational Prescribing in collaboration with the DC Department of Health, George Washington University, and Georgetown released two new video CME courses on the opioid epidemic: 

These modules are video interviews with Dr. Anna Lembke, Chief of Addiction Medicine at Stanford University, and Dr. Christina Prather, Associate Professor of Geriatrics at the George Washington University School of Medicine.

Anyone can view the modules. Free CME credit available for DC healthcare providers and $20 for healthcare providers licensed elsewhere. Get these (and many more) CME courses at doh.dc.gov/dcrx.

PharmedOut Conference: Call for Abstracts

Save the date: June 15-16, 2017. For our 2017 conference, we will be featuring abstracts of students, residents, and fellows. Selected abstracts will win free conference registration. Submission requirements and more information are available on our website.

PharmedOut Fodder

FDA Caves to Patient Pressure

by Alycia Hogenmiller


On Monday, September 19, the FDA approved eteplirsen (Exondys 51). Produced by Sarepta Therapeutics, eteplirsen is a drug for Duchenne Muscular Dystrophy (DMD), a genetic disorder that is characterized by progressive muscular degeneration.

From the beginning, this approval has been mired in controversy. During the FDA advisory committee meeting to evaluate the drug, the FDA expanded the time for the open public hearing and moved the location to a larger room to accommodate all of the people signed up to speak. Testimony was given by children with DMD, their parents, and lawmakers urging the FDA to approve the drug. Of the 52 people that testified, only 1 person (from National Center for Health Research) spoke out against approval of the drug.

The evidence for this drug was based on an open-label 12 person study, with a post hoc comparison with untreated patients used as a historical control group. The study found that there was a 1% increase in dystrophin (a muscle protein). AFter debating whether this increase in dystrophin conferred a clinically meaningful benefit, the committee voted 7-3 against the approval of the drug, with 3 members abstaining. Documents for the advisory committee hearing can be accessed here.

Although the decision was scheduled to be announced on May 26, controversy raged inside the FDA as the decision was delayed for months. Janet Woodcock, Director of the Center for Drug Evaluation and Research, approved eteplirsen against the recommendation of the review team. In an unusual move, two FDA reviewers, Dr. Ellis Unger and Dr. Luciana Borio, wrote an appeal letter to Robert Califf, the FDA commissioner. Commissioner Califf deferred to Janet Woodcock's decision to approve the drug. In the same memo, however, Califf also stated that the only published study of eteplirsen's efficacy should be retracted. This brings up the question of what basis the FDA thad for approving an ineffective drug. 

This controversial approval will open the doors for Pharma to use patient advocacy groups to pressure the FDA to approve more ineffective – or dangerous – drugs. That hardly creates an incentive left for pharmaceutical companies to create drugs that work.

Rx Files: Levalbuterol, Levying Risk vs. Benefit

by Ben Albrecht, PharmD


“The patient is tachycardic. Let’s switch to levalbuterol,” the resident says. The attending nods in approval. They are discussing a patient in his mid-fifties, barely 24 hours after a 3-vessel coronary bypass artery graft.

“If you are seriously worried about tachycardia, we should probably consider just discontinuing the beta-2 agonist altogether,” I say. 

A popular beta-agonist, levalbuterol, (XopenexR) is a bronchodilator that is the R-enantiomer of albuterol. Levalbuterol is often used off-label in mechanically ventilated patients despite a preponderance of evidence showing that neither levalbuterol nor albuterol affects the risk of aspiration pneumonia, tracheostomy, ventilator-free days, or mortality.1 Nonetheless, physicians and respiratory therapists commonly recommend these drugs. The attitude seems to be “It can’t hurt.” In fact, all medications are associated with adverse effects, and beta-agonists can induce cardiac arrhythmias in post-operative patients.

Levalbuterol has become a popular alternative to albuterol in tachycardic, intubated patients because, theoretically, it should be less likely to cause tachyarrhythmias than albuterol.1 Albuterol is a racemic mixture of the inactive L-enantiomer and the active bronchodilatory R-enantiomer. The S-enantiomer form found in albuterol has a 100-fold less B2-receptor activity (the receptor mainly responsible for bronchodilation), and can lead to more stimulation of the B1-receptor, the receptor associated with inotropic effects on the heart and thus tachycardia.

Levalbuterol is 13 times more expensive than albuterol.2 When these bronchodilators are used up to 6 times per day for the duration of a patient’s mechanical ventilation, the costs associated with their use can quickly add up. So does this “pure” form result in clinical benefit to the patient? Clinical trials do show that compared to albuterol, levalbuterol decreases associated tachycardia. However, that decrease has only been shown to be, at most, 1-2 beats per minute in adult ICU patients. This difference would have no effect on post-operative atrial fibrillation or other clinically significant tachyarrhythmic events. In fact, the only patient population that levalbuterol has shown any superiority over albuterol for tachyarrhythmias is in pediatric populations, and that was shown in only one randomized double-blind study.3,4,5,6

Lack of knowledge about pharmacology resulted in a number of ramifications for this patient:

  • The patient was subjected to one medication, albuterol, which has no documented clinical benefit, and may have caused tachycardia.
  • The solution was to switch to levalbuterol, a similar but more expensive, medication with no documented clinical benefit, and which also causes tachycardia.
  • Amiodarone was added to the patient’s regimen as prophylaxis against atrial fibrillation (essentially using a medication to treat a medication-related induced problem, the epitome of pharmaceutical inelegance).

I explained that levalbuterol is not advantageous over albuterol in adult ICU patients and that the use of any beta-agonist has not yet demonstrated any benefit. We discontinued the bronchodilators, and all of our heart rates returned to normal.

Benjamin Albrecht, PharmD, is a graduate of the University of Georgia College of Pharmacy. He is currently completing his Pharmacy Residency at Emory University Hospital. 

1. Cazzola, Mario, Maria G. Matera, and Claudio F. Donner. "Inhaled β2-adrenoceptor agonists." Drugs65.12 (2005): 1595-1610. 2. Albuterol. Lexi-Drugs Online [Internet]. Hudson, (OH): Lexicomp. 1978-2013 [cited 2016 March 8]. Available from http://online.lexi.com/crlsql/servlet/crlonline. 3. Salpeter, Shelley R., Thomas M. Ormiston, and Edwin E. Salpeter. "Cardiovascular effects of β-agonists in patients with asthma and COPD: a meta-analysis." CHEST Journal 125.6 (2004): 2309-2321. 4. Lam, Sum, and Julie Chen. "Changes in heart rate associated with nebulized racemic albuterol and levalbuterol in intensive care patients." American journal of health-system pharmacy 60.19 (2003): 1971-1975. 5. Qureshi, Faiqa, et al. "Clinical efficacy of racemic albuterol versus levalbuterol for the treatment of acute pediatric asthma." Annals of emergency medicine 46.1 (2005): 29-36. 6. Ralston, Mark E., et al. "Comparison of levalbuterol and racemic albuterol combined with ipratropium bromide in acute pediatric asthma: a randomized controlled trial." The Journal of emergency medicine 29.1 (2005): 29-35.

News Round-Up

(For more, follow @Pharmed_Out on Twitter!)

 

Sep 27

Furor Over Drug Prices Puts Patient Advocacy Groups in Bind by Katie Thomas (NY Times)

Sep 26

New Reports Reveal Aggressive Pharmaceutical Push For Opioids (WBUR)

Sep 23

How the FDA Manipulates the Media by Charles Seife (Scientific American)

Sep 22

Valeant avoids double-digit price hikes with 9.9 percent increases by Ed Silverman (STAT)

Patients, Docs Press for Federal 'Right To Try' Bill by Shannon Firth (MedPage Today)

Secret trove reveals bold ‘crusade’ to make OxyContin a blockbuster by David Armstrong (STAT)

Sep 21

Amid controversial Sarepta approval decision, FDA head calls for key study retraction by Dalmeet Singh Chawla (Retraction Watch)

Sep 20

Approving A Muscular Dystrophy Drug Ignites A Civil War At The FDA by Matthew Herper (The Forbes)

Sep 19

How Big Pharma Pressures States to Pay for Pricey Pills by Andrew Martin (BloombergMarkets)

Drama at FDA: 5 things to know about the Sarepta approval by Ned Pagliarulo and Lisa LaMotta (BioPharmaDIVE)

Introducing the EpiPencil by Dr. Mixael S. Laufer (Four Thieves Vinegar)

Behind the Sarepta drug approval was intense FDA bickering by Ed Silverman (STAT)

FDA Approves Sarepta’s Muscular Dystrophy Drug by Thomas M. Burton (The Wall Street Journal)

Sep 16

EpiPen Maker Lobbies to Shift High Costs to Others by Eric Lipton and Rachel Abrams (The New York Times)

Sep 12

FDA reviewers question Pfizer study about safety of its Chantix smoking cessation pill by Ed Silverman (STAT)

How the Sugar Industry Shifted Blame to Fat by Anahad O’Connor (The New York Times)

Sep 9

Food allergy group with ties to EpiPen maker says no to future donations by Ike Swetlitz and Ed Silverman (STAT)

Sep 8

A Push to Lower Drug Prices That Hit Insurers and Employers the Hardest by Katie Thomas (The New York Times)

The ‘Grassroots Campaign’ for ‘Female Viagra’ Was Actually Funded by Its Manufacturer Jennifer Block and Liz Canner by (The CUT)

5 Myths About the EpiPen Scandal by Zoe Carpenter (The Nation)

Sep 6

Drug Industry Group Starts Ad Campaign to Defend Pricing by Caroline Chen (Bloomberg)

The secretive system for vetting cancer drug use needs an urgent overhaul by Ed Silverman (STAT)

Sep 1

Long Island county sues opioid drug makers for misleading marketing by Ed Silverman (STAT)

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