Analgesic Efficacy of Dextropropoxyphene and Dextropropoxyphene-containing Combinations: a Review

Abstract

<jats:p> Twenty years ago, as part of a review of the clinical pharmacology of mild analgesics (Beaver, 1965, 1966), I evaluated reports of those analgesic trials of dextropropoxyphene that appeared to satisfy the minimum methodologic requirements for a controlled clinical trial of analgesic efficacy. On reviewing reports of studies that have been published since then, I find little need to modify my evaluation of the efficacy of dextropropoxyphene that appeared in 1966, at least in respect to the effect of single oral doses: </jats:p><jats:p> In summary, dextropropoxyphene (hydrochloride) is a mild oral analgesic which has proven superior to placebo in doses of 65 mg or more but which is of questionable efficacy in doses lower than 65 mg. The drug is definitely less potent than codeine: the best available estimates of the relative potency of the two drugs indicating that dextropropoxyphene is approximately 1/2-2/3 as potent. Likewise, dextropropoxyphene in 32-65 mg doses is certainly no more, and possibly less, effective than the usually used doses of aspirin or A.P.C. (aspirin/phenacetin/caffeine). </jats:p><jats:p> In the interim, the efficacy of dextropropoxyphene has been the subject of a number of other critical reviews (Miller et al., 1970; Miller, 1977), commentaries (Kiplinger &amp; Nickander, 1971; Lasagna, 1976), and even congressional hearings (Beaver, 1979; Moertel, 1979). More importantly, new controlled clinical trials involving dextropropoxyphene hydrochloride or napsylate have been reported, and some of these use more sophisticated design and analysis than those available in 1966. I will therefore discuss the results of those newer studies of apparently suitable scientific design that meet at least the minimum criteria for a valid clinical assay of analgesic activity (Beaver, 1965; Houde et al., 1965,1966; Wallenstein &amp; Houde, 1975; Beaver, 1983), and I will comment on only a few of the studies included in my previous review (Beaver, 1966). </jats:p>

The cognitive and psychomotor effects of opioid analgesics

“…Dextropropoxyphene undergoes extensive first pass metabolism (Nickander et al 1984) so that systemic availability after single oral doses is poor. However, single dose studies have confirmed the analgesic effects of dextropropoxyphene in a variety of pain states (Beaver 1984) so this model should be valid. These data indicate that dextropropoxyphene in usual dosage does not produce significant impairment of coginitive or psychomotor function.…”

“…Its analgesic efficacy resides in the dextrorotatory isomer, dextropropoxyphene (Jaffe and Martin 1990). Dextropropoxyphene hydrochloride (65 mg and higher) or dextropropoxyphene napsylate (100 mg and higher) have analgesic activity in patients with many kinds of pain (Beaver 1984). Toxicity is as one would expect from an opioid analgesic: central nervous system and respiratory depression, nausea and constipation.…”

Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol

“…The salt forms, hydrochloride and napsylate, were assumed to have no effect on the systemic activity of the analgesic, and a dose of 65 mg of the hydrochloride was assumed to be equivalent to 100 mg of the napsylate, as previously described by Beaver. 10 For each of the studies we calculated a standardised baseline pain score index (BPS%) to enable an comparison between trials of the mean severity of pain of the patients at entry. This was calculated by taking the mean baseline score reported in any given trial divided by the maximum score possible on the scale used.…”