A Cochrane review [Abstract] 1 included 26 studies with a total of 2 295 subjects comparing paracetamol plus codeine with placebo. The proportion of participants experiencing at least 50% pain relief over four to six hours with 800 mg to 1000 mg of paracetamol plus 60 mg codeine was 53% compared with 7% treated with placebo. Significant dose response was seen for the outcome of at least 50% pain relief over four-to-six hours, with NNTs of 2.2 (95% CI 1.8 to 2.9) for 800 to 1000 mg paracetamol plus 60 mg codeine, 3.9 (95% CI 2.9 to 4.5) for 600 to 650 mg paracetamol plus 60 mg codeine, and 6.9 (95% CI 4.8 to 12) for 300 mg paracetamol plus 30 mg codeine. Time to use of rescue medication was over 4 hours with paracetamol plus codeine and 2 hours with placebo. The NNT to prevent remedication was 5.6 (95% CI 4.0 to 9.0) for 600 mg paracetamol plus 60 mg codeine over four to six hours. For all doses together, the NNH for any adverse event for paracetamol plus codeine compared to placebo was 8.9 (6.6 to 14).
14 studies (n= 926) were included in the comparison of paracetamol plus codeine with the same dose of paracetamol alone. The proportion of patients experiencing at least 50% pain relief over four to six hours with 800 mg to 1000 mg paracetamol plus 60 mg codeine was 59% compared with 42% treated with 1000 mg paracetamol alone. Addition of codeine increased proportion of participants achieving at least 50% pain relief over four-to-six hours by 10 to 15%, increased time to use of rescue medication by about one hour, and reduced proportion of participants needing rescue medication by about 15% (NNT to prevent remedication 6.9 (95% CI 4.2 to 19). Adverse events were mainly mild to moderate in severity and incidence did not differ between groups.
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