Paracetamol plus dextropropoxyphene in postoperative pain
Clinical bottom line:
Paracetamol 650 mg plus dextropropoxyphene is an effective analgesic in postoperative pain. A single oral dose had an NNT of 4.4 (3.5-5.6) for at least 50% pain relief over 4 to 6 hours compared with placebo in pain of moderate to severe intensity. This is equivalent to 1000 mg of paracetamol alone.
Adverse effects were transient and of mild to moderate severity, mainly dizziness and drowsiness.
Paracetamol plus dextropropoxyphene
Paracetamol (Acetaminophen) is an important non-opiate analgesic. It accounts for over 5 million prescriptions in England alone (1995), and is widely available, alone and in combination, without prescription. Dextropropoxyphene is a relatively weak opioid analgesic usually prepared in combination with paracetamol or aspirin. Paracetamol/dextropropoxyphene combinations accounted for over 10 million prescriptions in England (1996).
Collins SL, Edwards JE, Moore RA, McQuay HJ Single dose dextropropoxyphene in postoperative pain: a quantitative systematic review. European Journal of Clinical Pharmacology 1998; 54:107-112.
- Date review completed: November 1996
- Number of trials included: 4 plus 1 meta-analysis of 18 trials
- Number of patients: 963 (478 paracetamol plus dextropropoxyphene / 485 placebo)
- Control group: oral placebo
- Main outcomes: pain relief at 4-6 hrs (TOTPAR / SPID), Number-needed-to-treat (NNT) (with 95% confidence intervals), relative benefit and relative risk (with 95% confidence intervals).
Inclusion criteria were full journal publication, single oral dose, randomised, placebo-controlled, double-blind trials of paracetamol plus dextropropoxyphene in acute postoperative pain, baseline pain moderate to severe. Mean TOTPAR and SPID values for each trial were converted to %maxTOTPAR and %maxSPID, and then the proportion of patients achieving at least 50%maxTOTPAR were calculated. This information was used to calculate the NNT and relative benefit. Adverse effects frequency data were used to calculate numbers-needed-to-harm and relative risk.
Trials of dextropropoxyphene hydrochloride 65 mg and napsylate 100 mg were analysed together.
Four reports compared dextropropoxyphene napsylate 100 mg plus paracetamol 650 mg with placebo, and one used dextropropoxyphene hydrochloride 65 mg plus paracetamol 650 mg.
Figure: Dextropropoxyphene with and without paracetamol versus placebo
Paracetamol 650 mg plus dextropropoxyphene had an NNT of 4.4 (3.5-5.6) for at least 50% pain relief over 4-6 hours compared with placebo for pain of moderate to severe intensity. The analgesic response was significantly more effective than placebo.
No patient withdrew as a result of adverse effects, and all reported were transient and of mild to moderate severity. Dizziness and drowsiness were the most commonly reported adverse effects. Both were significantly higher in comparison to placebo.
Table: Adverse effects with dextropropoxyphene 65 mg plus paracetamol 650 mg compared with placebo
|Number of trials||Adverse effect||No. of patients with adverse effects: drug||No. of patients with adverse effects: placebo||Relative risk (95%CI)||NNH (95%CI)|
|3||Nausea||12 / 405||33 / 799||0.7 (0.4 to 1.4)||not calculated|
|1||Vomiting||2 / 323||6 / 714||1.4 (0.3 to 6.7)||not calculated|
|4||Dizziness||17 / 435||16 / 829||2.2 (1.1 to 4.3)||43 (22 to 607)|
|3||Drowsiness/ somnolence||57 / 405||55 / 799||2.2 (2.0 to 2.4)||14 (9.1 to 30)|
|4||Headache||14 / 435||51 / 829||0.5 (0.4 to 0.6)||-33 (-170 to -19)|
|Negative NNTs indicate that fewer headaches occur with dextropropoxyphene plus paracetamol than with placebo|