Few adverse events with single dose oral analgesics for acute postoperative pain

The Cochrane Collaboration has completed a large number of systematic reviews of individual oral analgesics versus placebo in acute postoperative pain. The aim was to provide an overview of adverse event rates associated with single dose oral analgesics, compared with placebo, for acute postoperative pain in adults.


All Cochrane reviews of RCTs of single dose oral analgesics for acute postoperative pain in adults (aged 15 years and over) were considered. Two reviewers independently selected reviews, assessed methodological quality and extracted data. Methodological quality was assessed using criteria adapted from AMSTAR (Assessing the Methodological Quality of Systematic Reviews).


  • 39 Cochrane reviews investigating 41 analgesics or analgesic combinations were included.
  • The number of unique studies is around 350 with 35,000 unique participants.
  • Most studies involved younger participants with pain following removal of molar teeth.
  • For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo.
  • For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo.
  • Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.
  • Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.
  • Most reviews did not report specific adverse events.


The authors concluded:

Despite ongoing problems with the measurement, recording, and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.


Currently there are 93 reviews on the Cochrane library related to oral analgesics of these 39 met the criteria for this overview. The review authors comment that the results are not unexpected for single dose studies although they do suggest some caution in interpreting the results as adverse event reporting rates are heavily influenced by the capture methods employed e.g. patient diaries are known to yield significantly more adverse events than other methods. Most of the studies included in the reviews were conducted on patients undergoing third molar removal who a relatively young and fit. Consequently adverse events rates may be different in patients who are older, less well, or who take analgesics for several days or longer.


Moore RA, Derry S, Aldington D, Wiffen PJ. Adverse events associated with single dose oral analgesics for acute postoperative pain in adults – an overview of Cochrane reviews. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No.: CD011407. DOI: 10.1002/14651858.CD011407.pub2.


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