Straube C, Derry S, Jackson Cancer pain due to Various measures of Single or multiple Cochrane review of None of the included studies KC, Wiffen PJ, Bell RF, diverse types of efficacy and adverse doses of codeine RDBCTs compared codeine Strassels S, Straube S. (2014) malignancy in adults (no events with and without containing combinations 15 studies with 721 Codeine, alone and with studies in children paracetamol with the non-opiate in the Only two studies participants with cancer paracetamol identified) compared to combination. reported the pain. (acetaminophen), for cancer preferred responder placebo One included study (Chen pain. Cochrane Database of Most studies used codeine outcome of 2003) was a three arm Systematic Reviews Issue 9. or at doses of 30mg to 120mg with at crossover study in 18 people “participants Art. No.: CD006601. least 50% reduction with moderate to severe alternative actives The authors noted that in pain” and two cancer pain. The study reported compared single dose “participants Any formulation, all but one of the studies • with no worse than codeine 30mg (C), placebo dosage regimen and demonstrated mild pain (P) and codeine 13mg + route of superiority of codeine ibuprofen 200mg (CI). administration. over placebo in at trial Partial or complete pain one outcome measure relief was achieved in 18/18 there were insufficient • with C and 17/18 with CI. data for any pooled Time to showing effect was analysis less with CI than with C adverse event reporting • (48mins vs 60mins) and was was poor main-tained for longer (6.8 the literature was • hours vs 5.4 hours). disappointing - studies were of short the Chen study gives duration, and most had some limited low quality significant shortcomings evidence for analgesic in reporting. effectiveness of low dose codeine in combination with Authors’ conclusion: The ibuprofen, it did not include available evidence an ibuprofen only arm and indicates that codeine is the incremental analgesic more effective against effectiveness of the codeine cancer pain than placebo, in this combination could but with increased risk of not be assessed. nausea, vomiting, and constipation.
Straube C, Derry S, Jackson KC, Wiffen PJ, Bell RF, Strassels S, Straube S. (2014) Codeine, alone and with paracetamol (acetaminophen), for cancer pain. Cochrane Database of Systematic Reviews Issue 9. Art. No.: CD006601. Cancer pain due to diverse types of malignancy in adults (no studies in children identified) Various measures of efficacy and adverse events Only two studies reported the preferred responder outcome of “participants with at least 50% reduction in pain” and two reported “participants with no worse than mild pain Single or multiple doses of codeine with and without paracetamol compared to placebo or alternative actives Any formulation, dosage regimen and route of administration. Cochrane review of RDBCTs 15 studies with 721 participants with cancer pain. Most studies used codeine at doses of 30mg to 120mg The authors noted that • all but one of the studies demonstrated superiority of codeine over placebo in at one outcome measure • there were insufficient data for any pooled analysis • adverse event reporting was poor • the literature was disappointing - studies were of short duration, and most had significant shortcomings in reporting. Authors’ conclusion: The available evidence indicates that codeine is more effective against cancer pain than placebo, but with increased risk of nausea, vomiting, and constipation. None of the included studies compared codeine containing combinations with the non-opiate in the combination. One included study (Chen 2003) was a three arm crossover study in 18 people with moderate to severe cancer pain. The study compared single dose codeine 30mg (C), placebo (P) and codeine 13mg + ibuprofen 200mg (CI). Partial or complete pain relief was achieved in 18/18 with C and 17/18 with CI. Time to showing effect was less with CI than with C (48mins vs 60mins) and was main-tained for longer (6.8 hours vs 5.4 hours). the Chen study gives some limited low quality evidence for analgesic effectiveness of low dose codeine in combination with ibuprofen, it did not include an ibuprofen only arm and the incremental analgesic effectiveness of the codeine in this combination could not be assessed. trial
update-codeine-safety-and-efficacy-review.docx