Minimizing undue risks

In the news today, the latest analysis of FDA reports of serious drug reactions has just been released by the Institute for Safe Medication Practice. For the second quarter in a row, one drug was responsible for more serious injuries in the United States than any other prescription drug.

The Institute for Safe Medication Practices* just issued its Quarter Watch for the first quarter of 2008, reporting the number of deaths and serious injuries associated with medicines reported to the U.S. Food and Drug Administration. A total of 1,001 new injuries and 50 more deaths were attributed to varenicline (Chantix, Champix), more than any other prescription drug prescribed in the country. This is a drug made by Pfizer and marketed to help smokers quit.

Caution is warranted in interpreting the increase in reports to the FDA, of course, because some could be due to heightened awareness of safety concerns with this drug among the public and healthcare professionals since the FDA issued an Early Communication last November, warning that it was investigating serious adverse events from the drug. This warning was followed on February 1^st by a formal FDA Public Health Advisory and a Medwatch alert, which was updated on May 16^th. Since September 2007, the Public Citizen has also been warning the public not to use Chantix. More information on the serious reactions being reported is here. While the reporting system for adverse reactions connected with drugs after they’ve gone to market is voluntary and not evidence of causation, several published scientific reports have estimated that only 1-10% of adverse events are ever reported to the FDA, according to ISMP.

What is especially disconcerting about these escalating reports and the concerns raised by the medical community for more than a year questioning the strength of the evidence, is that just months ago, the Health and Human Services issued the new smoking cessation Clinical Practice Guidelines, “Treating Tobacco Use and Dependence, 2008 Update” which specifically recommends Chantix. This 2008 clinical practice guideline, followed by our nation’s doctors, was written by an expert panel in which nine members disclosed extensive pharmaceutical financial interests. Regardless of the clinical issue, having experts writing clinical guidelines with direct connections to the companies whose products they are recommending raises ethical concerns. But even more prominent was that 15 of the 18 members of the expert committee had extensive ties and funding from the drug maker’s nonprofit foundation. Those connections, however, weren’t disclosed because they aren’t required to be under current federal disclosure regulations from the Office of Research Integrity. Yet, this lapse has received little reaction from the medical community.

According to the ISMP quarterly report, the other drugs accounting for the largest numbers of serious adverse events in the first quarter of 2008 also included: heparin (notably attributed to a contamination problem of heparin made by a foreign supplier), fentanyl, interferon beta, infliximab, etanercept, clipidogrel, pregabalin, acetaminophen and oxycodone (which was associated with the most deaths).

Every medicine is a matter of balancing desirable effects with potential adverse effects, which is why the soundest and most objective science is so important for consumers and healthcare professionals alike. ISMP highlighted that their report isn’t meant to downplay the great benefits to millions of patients from prescription drugs and that most are used safely, but that “these data show the need for additional progress to better manage the risks to patients.” Specifically related to varenicline, their report recommended:

[A]dditional action is needed to make all patients aware of the potential accident risks. We recommend that the FDA and the manufacturer add a prominent warning about accident risks to the patient Medication Guide and prescribing information for doctors. This warning should be similar to the new warnings about psychiatric side effects. While we commend the federal government for prompt action in banning varenicline in the most sensitive occupations such as for airline pilots, air controllers and military missile crews, a broader warning is still needed. Also, additional investigation and action may be needed regarding other adverse effects of varenicline, and prescribers should consider alternative treatments.

* For those unfamiliar with the ISMP, since 1975, it’s been the country’s only nonprofit organization devoted solely to medication error prevention and safe medication use, and is funded only by charitable donations.