Paracetamol 1000 mg plus codeine 60 mg

Clinical bottom line:
The combination of paracetamol (acetaminophen) 1000 mg and codeine 60 mg has a NNT of 2.2 (1.7 to 2.9) for at least 50% pain relief over four to six hours compared with placebo.Combining data from active and placebo controlled trials, 150 of 229 patients, or 66% (59% to 72%), had at least 50% pain relief with paracetamol 1000 mg plus codeine 60 mg.

Combinations of simple analgesics and often used in acute and chronic pain. The efficacy of these combinations has been challenged. A new review of the combination of paracetamol 1000 mg and codeine 60 mg updates a previous review .

Systematic review

Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg Lesley A Smith , Andrew R Moore , Henry J McQuay , David Gavaghan BMC Medical Research Methodology 2001, 1:1 (10-Jan-2001).

Date review completed: 2000

Number of trials included: 3 placebo controlled trials, plus trials of other dose combinations, trials with active controls, and six trials with different designs

Number of patients: 197 in placebo controlled trials of paracetamol 1000 mg plus codeine 60 mg, 1195 patients with trials of other dose combinations, 117 patients in trials lacking a placebo.

Control groups: placebo and active controls

Main outcomes: 4-6 hr TOTPAR (predominantly); number-needed-to-treat (NNT) for 50% pain relief (with 95% confidence intervals); relative benefit (with 95% confidence intervals).

Inclusion criteria were full journal publication of trials of paracetamol and paracetamol plus codeine in acute postoperative pain; single oral dose; randomised; placebo-controlled; double-blind; moderate to severe baseline pain; adult populations; group sizes at least 10; sufficient data to calculate the area under the curve for pain relief (TOTPAR).

Results

The combination of paracetamol (acetaminophen) 1000 mg and codeine 60 mg has a NNT of 2.2 (1.7 to 2.9) for at least 50% pain relief over four to six hours compared with placebo. Mathematical modelling showed that confidence in this result was 94%.

Other combinations

Information for all combinations where there were at least two studies is summarised in the Table. Higher doses of paracetamol and codeine produced lower (better) NNTs. Combining data from active and placebo controlled trials, 150 of 229 patients, or 66% (59% to 72%), had at least 50% pain relief with paracetamol 1000 mg plus codeine 60 mg.

Summary results for efficacy of paracetamol/codeine combinations from randomised, double-blind, placebo-controlled trials in acute pain
		At least 50% pain relief with paracetamol and codeine		At least 50% pain relief with placebo
Paracetamol + codeine dose	Number of trials	Number /total	Percent (95%CI)	Number /total	Percent (95%CI)	Relative benefit (95% CI)	NNT (95% CI)
1000 mg + 60 mg	3	65/114	57 (48-66)	9/83	11(4-18)	4.8 (2.6 to 8.8)	2.2 (1.7 to 2.9)
600/650 mg + 60 mg	13	191/398	48 (43-53)	78/418	19 (15-22)	2.5 (2.0 to 3.1)	3.4 (2.8 to 4.3)
300 mg + 30 mg	4	56/215	26 (20-32)	14/164	9 (4-13)	3.2 (1.8 to 5.6)	5.6 (4.0 to 9.8)
For inclusion there had to be at least two studies.

Six other studies whose design would not allow inclusion into the meta-analysis because of different pain measures, or time, or with multiple rather than single doses, but with otherwise good quality scores (3 out of 5) and with 907 patients were better than placebo or comparator for at least one measure.

Comment

This paper not only give information about paracetamol and codeine combinations, but also has an interesting discussion about how different types of information can be combined to give a fuller picture of efficacy and effectiveness.