Single dose oral dextropropoxyphene, alone and with paracetamol (acetaminophen), for postoperative pain: Cochrane systematic review
This is an updated version of the original Cochrane review published in Issue 1, 1999. Patient surveys have shown that postoperative pain is often not managed well, and there is a need to assess the efficacy and safety of commonly used analgesics as newer treatments become available. Dextropropoxyphene is one example of an opioid analgesic that used to be widely prescribed for pain relief in combination with paracetamol under names such as Co-proxamol and Distalgesic. This drug is now only available on a named patient basis in the UK. For this group there is a provision for the supply of unlicensed co-proxamol on the responsibility of the prescriber.Objectives
To determine the analgesic efficacy and adverse effects of single dose oral dextropropoxyphene alone and in combination with paracetamol (acetaminophen) for moderate to severe postoperative pain.Search methods
Published studies were identified from: MEDLINE, EMBASE, Cochrane CENTRAL up to December 2007, and the Oxford Pain Relief Database (1954 to 1994).Selection criteria
The inclusion criteria used were: full journal publication, postoperative pain, postoperative oral administration, adult participants, baseline pain of moderate to severe intensity, double-blind design, and random allocation to treatment groups which included dextropropoxyphene and placebo or a combination of dextropropoxyphene plus paracetamol and placebo.Data collection and analysis
Data were extracted by two review authors, and studies were quality scored.
Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants with at least 50% pain relief. This was used to calculate the relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to achieve at least 50% pain relief.Main results
Eleven studies met the inclusion criteria. Six studies (440 participants) compared dextropropoxyphene with placebo, four studies (325 participants) and one individual patient meta-analysis (638 participant) compared dextropropoxyphene plus paracetamol 650 mg with placebo.
For a single dose of dextropropoxyphene 65 mg in postoperative pain the NNT for at least 50% pain relief was 7.7 (95% confidence interval (CI) 4.6 to 22) when compared with placebo over four to six hours. There was no significant difference between the proportion of participants remedicating within four to eight hours with dextroporpoxyphene 65 mg (35%) and placebo (43%), relative risk 0.8 (0.7 to 1.03).
For the equivalent dose of dextropropoxyphene combined with paracetamol 650 mg the NNT was 4.4 (3.5 to 5.6) when compared with placebo. These results were compared with those for other analgesics obtained from equivalent systematic reviews. Significantly fewer participants remedicated within four to eight hours with dextropropoxyphene 65 mg combined with paracetamol 650 mg (34%) than with placebo (57%), relative risk 0.7 (0.5 to 0.8).
Pooled data showed increased incidence of central nervous system adverse effects for dextropropoxyphene plus paracetamol compared with placebo.Authors' conclusions
Since the last version of this review no new relevant studies have been identified. The combination of dextropropoxyphene 65 mg with paracetamol 650 mg shows similar efficacy to tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of adverse effects. The same dose of paracetamol combined with 60 mg codeine appears more effective but, with the slight overlap in the 95% CI, this conclusion is not robust. Adverse effects of both combinations were similar.
Ibuprofen 400 mg has a lower (better) NNT than both dextropropoxyphene 65 mg plus paracetamol 650 mg and tramadol 100 mg.
Moore R Andrew, Collins Sally L, Edwards Jayne, Derry Sheena, McQuay Henry J
Dextropropoxyphene in a single dose taken on its own and also with paracetamol to treat postoperative pain
This review assessed the analgesic efficacy and adverse effects that single dose oral dextropropoxyphene taken alone or in combination with paracetamol had in treating moderate to severe postoperative pain. The combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to that of tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of side effects. This review also highlighted that Ibuprofen 400 mg was yet more effective than both tramadol 100 mg and dextropropoxyphene 65 mg.
Implications for practice
Dextropropoxyphene is not particularly effective on its own in single dose postoperative use. It is far more commonly used in combination with paracetamol and our results support the assertion that this provides more effective analgesia. However, evidence produced by the same methodology suggests that ibuprofen 400 mg provides better analgesia for postoperative pain than the paracetamol/dextropropoxyphene combination. In some parts of the world limitations on prescribing make dextropropoxyphene increasingly difficult to obtain.
Implications for research
Dextropropoxyphene alone and in combination with paracetamol was previously extensively used. One of the major problems with reviewing such well established interventions is that the original studies may predate the development of validated analgesic trial methodology. However, a quantitative assessment of these interventions is required as a comparison for novel analgesics. Potentially more evidence may be produced by using the combination as the 'gold standard' analgesic in RCTs of new interventions. It is unlikely that new studies in acute pain will feature dextropropoxyphene alone or in combination with paracetamol, and there does not appear to be any pressing need for new studies because there are many alternative analgesics now available.
The combination of dextropropoxyphene with paracetamol has been widely used in chronic pain. Although results from single dose studies usually translate reasonably well to multiple dose situations, a method needs to be developed to quantitatively assess both efficacy and adverse effects in prolonged usage.Get full text at The Cochrane Library
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