Adverse events associated with single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews

Cochrane Database Syst Rev. 2015 Oct 13;2015(10):CD011407. doi: 10.1002/14651858.CD011407.pub2.


Background: This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews.

Objectives: To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults.

Methods: We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews.

Main results: Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 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.

Authors' conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Acute Pain / drug therapy*
  • Acute Pain / etiology
  • Administration, Oral
  • Adult
  • Analgesics / administration & dosage
  • Analgesics / adverse effects*
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Drug Therapy, Combination / adverse effects
  • Humans
  • Pain, Postoperative / drug therapy*
  • Randomized Controlled Trials as Topic
  • Review Literature as Topic*


  • Analgesics
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal