Adverse events after single doses of oral analgesics for acute pain after operation in adults

Acute pain is often felt soon after injury. Most people who have surgery have moderate or severe pain afterwards. Painkillers (analgesics) are tested in people with pain, often following the removal of wisdom teeth. In all these studies, the participants have to have at least moderate pain in order for there to be a sensitive measure of pain-relieving properties. The pain is usually treated with painkillers taken by mouth. Results can be applied to other forms of acute pain.

In May 2015, we performed searches to update an overview review originally published in 2011. The Cochrane Library now has 39 reviews of oral analgesic interventions for pain immediately after operations, with 41 different painkillers at various doses. How well the drugs work is reported in a different overview.

In this overview, we used information from about 35,000 participants in about 350 studies to look specifically at the adverse events (unwanted effects) experienced with painkillers, and compared the results with those for placebo (dummy pill). Measuring adverse events is complicated because the particular method used to collect information influences how many adverse events are reported. Most people in the studies had wisdom teeth removed, were relatively young and fit, and were likely to take occasional painkillers. Adverse events may be different in people who are less well, older, or who take painkillers for several days or longer.

The results we have showed that for most nonsteroidal anti-inflammatory drugs (painkillers like aspirin, ibuprofen, or diclofenac), paracetamol, and combinations of different painkillers that do not contain opioids (drugs like codeine), adverse events happened to the same proportion of people with painkillers and placebo. With aspirin 1000 mg, opioids, or fixed dose combinations containing opioids, people typically experienced significantly more adverse events than with placebo. A combination of ibuprofen and paracetamol resulted in significantly fewer adverse events than placebo.

Serious adverse events were rare, occurring a rate of about 1 in 3200 people.

The results are not unexpected for single dose studies, which are likely to be different from the situation when analgesics are taken over the medium or longer term.

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.

Read the full abstract...

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.


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


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.