Contrave (bupropion/naltrexone) narrowly recommended for approval

The day job and an illness have kept me away from the blog this week. However, I did want to share with you a very nice article by Jane E. Allen of ABC News on the recent FDA advisory panel recommendation for approval (with a vote of 13-8) of the anti-obesity drug, Contrave (Oxrigen®). A sustained-release combination of the antidepressant bupropion and the orally-active opioid antagonist naltrexone, Contrave acts in the brain on the pro-opiomelanocortin (POMC) axis of appetite regulation. The FDA is not obligated to follow the recommendations of their advisory panels but most often do so.

Allen included a brief quote from me as I am often contacted by the ABC News Medical Unit for commentary on drug safety and pharmacotherapy. The biggest concern with the drug combination has been cardiovascular side effects, especially since such a drug will be much more widely used than the ~4,500 patients who participated in the clinical trials to date, patients who will often have complicating health issues and/or on many other potentially-interacting drugs.

The report published in The Lancet in August 2010 from 1742 patients is the only efficacy and safety data to which I am privy. In that study the drug combination causes an impressive 6-8% weight loss after 56 weeks, 8-13% drop in triglycerides, and a 12-17% in fasting insulin (suggesting improved insulin sensitivity) with very minimal effects on blood pressure.

With that as the only data I can see, I’m surprised that the vote was so equivocal – I suspect that the panel was privy to other data that I cannot access. This makes me worry that there are other concerns from other studies. Moreover, the panel may be concerned that the drug is likely to be quite popular and that any rare side effect not seen in the reported ~4,500 patients tested will be amplified when hundreds of thousands or a couple of million patients take the drug for long periods.

Interestingly, I saw no discussion of seizure risk which has been a low incidence issue with bupropion monotherapy.

With the limited amount of data available to me, my enthusiasm is mixed based on the published efficacy of the combination and the clear concerns reflected in the advisory committee vote. My greatest concern will be the indiscriminant use of the drug among large populations where diet and exercise would be more appropriate. The drug is primarily intended for obese patients with complicating issues such as cardiovascular disease or diabetes whose weight cannot be managed by diet and exercise alone.

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