Heartfelt with Dr Melissa Walton-ShirleyView all posts »
Merry Christmas? A relative term for propoxyphene (Darvocet) patients and prescribersDec 23, 2010 08:09 EST
I've always been a stickler for avoiding medications that have any propensity for proarrhythmia, unless the mortality or quality-of-life benefit far outweighs the risk. I recall the example of a drug that came onto the market about 15 years ago with a catchy name ending in "vasc." With the first samples came a beautiful red mug, large enough for a wonderful cup of coffee (and microwave compatible too!). When I read the package insert, I sat my beautiful red mug on a shelf and never prescribed that medication. I didn't see the logic in chancing a side effect when so many other drugs with a similar mechanism of action didn't affect the QT interval. Within a few short months, and with my never having prescribed a single pill, the FDA withdrew it.
Now, along with many other physicians and patients, I have ambivalent feelings about propoxyphene (Darvocet, Xanodyne Pharmaceuticals). The FDA recently decided to withdraw the medication after 53 years on the market but provided little in the way of data to help us understand its decision, undermining the confidence of the lay public in the FDA, the prescribers, and the pharmacists who have served them for their entire adult lives.
I was not a huge prescriber of propoxyphene meds, preferring other options, but when I did, it was Darvocet N-100. From past experience, it was a clean drug, with no complaints of nausea that I could ever remember, and patients felt better on it. Simply put, it did its job with no fanfare. The issues of constipation and of course, tolerance and addiction, attributes of all "good" narcotics, were my only concerns but really never founded.
Now, thanks to this sudden and complete withdrawal of the compound from the American market, the FDA is Santa Claus for many juris doctorates who have dressed up in their malpractice suits and will continue caroling for cash in your local newspaper, television, and radio ads this holiday season. At the same time, our federal drug agency will be viewed by many as the Grinch who stole a good pain-control product from thousands. Office Christmas parties across the nation in these large class-action law firms will toast their impending success with alcohol that killed 12 700 people in 2009 alone in the US. It's a shame that Public Citizen, which first brought concerns about the drug to the FDA, along with those class-action folks, won't address that issue as doggedly.
I had a tough time finding the actual data that lead to the withdrawal of propoxyphene. According to FDA documents, the study referenced was a multiple-ascending-dose (MAD) study, in which healthy volunteers participated in a randomized, double-blinded placebo-controlled study for 11 days. Subjects received either 600 mg or 900 mg as a total daily dose and were followed with intermittent ECGs and telemetry. The largest QTcF was 29.8 ms on treatment day 11 with the 600-mg daily total dose and 38.2 ms with the 900-mg total daily dose, both of which exceeded the 20-ms increase as the cutoff at which risk is presumed. The potential increase in QTcF is even greater in those who are elderly or patients with known decreased renal clearance. When I asked the company for more details on this study, including patient numbers, I was told no further information was publicly available.
If there were no deaths during this short 11-day trial, it left me wondering why there wasn't just a black-box warning issued. Why not make the recommendation to occasionally surveil the ECG? Furthermore, that QT-interval prolongation seems pale in comparison to the QT-interval prolongations I see every single day as a cardiologist who utilizes antiarrhythmics. If I were Darvocet's manufacturer, I'd be a little mad and cry foul that amiodarone and sotalol get the stay on the market with just prescriber warnings. Those manufacturers would be quick to state that "the benefits of these medications outweigh the risks," but how often are these cardiac medications used for mortality benefit? Unless you are treating V-tach with amio with a low EF, for instance, the on-label but much less common indication for utilization, there really isn't much benefit other than quality of life.
For some patients, there isn't much of a choice when it comes to pain medication. We could nauseate them with codeine, hook them with the Eastern Kentucky favorite, oxycodone, or use the old tramadol shuffle, which works great for many, but is "just like taking a drink of water" for others. I'll bet many long- term utilizers of Darvocet would tell you that quality of life from good pain control is just as important as the quality of life that amiodarone and sotalol give to their patients who maintain sinus rhythm with an even longer QT interval. I'm all for erring on the side of safety, but in this instance, informed consent should have been an option for those who have little choice but Darvocet. I am obviously not alone in my opinion: even the FDA's advisory committee had a hard time with this one with a split vote of 14 to 12.
To paraphrase an old saying, in the case of the propoxyphene debacle, one person's poison was another's excellent pain-control option, and it would have been best to let the patients and their doctor decide which category was most appropriate for them based on more than five decades of experience rather than an 11-day study. I'll bet an adequately powered randomized controlled trial with a mortality end point would have yielded a very interesting, albeit disappointing, result for many lawyers who have vision of sugar plums dancing in their heads right about now. "Merry Christmas" is a relative term, indeed.
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