Extended-Release Oxycodone/Acetaminophen Revisited

The most recent (July 21, 2014) issue of The Medical Letter included an article on a new formulation (Xartemis XR) of the popular combination of oxycodone and acetaminophen (Percocet, and others). The raison d’être for the new product is a new coating that delays the release of both acetaminophen and oxycodone long enough to justify giving it every 12 hours rather than every 6 hours.

FDA approval of Xartemis XR was based on a single clinical trial, which we described briefly in our issue. The new formulation was compared only to placebo, which is all that the law requires. Obviously, we would have been more interested in a study with an active comparator. Everybody knows that oxycodone and acetaminophen are more effective analgesics than placebo.

Nevertheless, there are some interesting things about the study that, for better or worse, we did not mention in our issue. Five of the 6 authors are employees of the manufacturer. In their discussion of the trial, the authors explain that they chose bunionectomy to test their drug because it offers an established model of acute pain, with well standardized surgical and anesthetic procedures and predictable levels of postoperative pain that persists for several days.

The primary endpoint was the summed pain intensity difference over the first 48 hours postoperatively between the active drug and placebo. (We reported the outcomes of 2 secondary endpoints, a ≥30% reduction in pain intensity scores and the mean time before use of rescue medication). Pain was assessed on a 10-point scale, and the pain intensity difference was calculated as the difference between the pain-intensity score before the first dose of active medication or placebo and the score at the various time-points. As would be expected, the active drug made more of a difference in the patients’ pain than placebo did.

We showed in our cost chart that the wholesale acquisition cost of Xartemis XR is lower than the WAC of Percocet, but more than twice as much as a generic q6h formulation of oxycodone/acetaminophen. What we would really like to know is whether a generic q6h formulation would provide equal or better pain relief than q12h Xartemis XR. That would seem to be more important for patients in pain than the convenience of taking fewer doses per day. But generic manufacturers generally do not sponsor elaborate clinical trials like this one.

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  1. Robert Schrock MD retired orthopaedic surgeon says:

    If I had just had a bunionectomy, I surely would not take the chance of receiving the placebo. What a stupid study!

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