Abstract

Background

Diclofenac is a nonsteroidal anti‐inflammatory drug, available as a potassium salt (immediate release) or sodium salt (enteric coated to suppress dissolution in the stomach). This review updates an earlier review published in the Cochrane Database of Systematic Reviews (Issue 2, 2009) entitled 'Single dose oral diclofenac for acute postoperative pain in adults'.

Objectives

To assess the analgesic efficacy and adverse effects of a single oral dose of diclofenac for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 9 March 2015.

Selection criteria

Randomised, double‐blind, placebo‐controlled clinical trials of single dose, oral diclofenac (sodium or potassium) for acute postoperative pain in adults.

Data collection and analysis

Two review authors independently considered studies for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either diclofenac or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects.

Main results

This update included three new studies, providing a 26% increase in participants in comparisons between diclofenac and placebo. We included 18 studies involving 3714 participants, 1902 treated with diclofenac and 1007 with placebo. This update has also changed the focus of the review, examining the effects of formulation in more detail than previously. This is a result of increased understanding of the importance of speed of onset in determining analgesic efficacy in acute pain.

The largest body of information, for diclofenac potassium 50 mg, in seven studies, produced an NNT for at least 50% of maximum pain relief compared with placebo of 2.1 (95% confidence interval (CI) 1.9 to 2.5) (high quality evidence). There was a graded improvement in efficacy as doses rose from 25 mg to 100 mg, both for participants achieving at least 50% maximum pain relief, and for remedication within 6 to 8 hours. Fast‐acting formulations (dispersible products, solutions, and softgel formulations) had a similar efficacy for a 50 mg dose, with an NNT of 2.4 (2.0 to 3.0). Diclofenac sodium in a small number of studies produced a lesser effect, with an NNT of 6.6 (4.1 to 17) for the 50 mg dose.

Adverse event rates were low in these single dose studies, with no difference between diclofenac and placebo (moderate quality evidence).

Authors' conclusions

Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.

Author(s)

Sheena Derry, Philip J Wiffen, R Andrew Moore

Abstract

Plain language summary

Single dose oral diclofenac for acute postoperative pain in adults

Acute pain is often felt soon after injury. Most people who have surgery have moderate or severe pain afterwards. Painkillers are tested in people with pain, often following a painful condition such as the removal of wisdom teeth. This pain is usually treated with painkillers taken by mouth. We believe these results can be applied to other acute painful conditions.

A series of Cochrane reviews looks at how good painkillers are. We know that in some circumstances, fast‐dissolving and absorbed painkillers provide better pain relief than those that are absorbed slowly. This review examined how good different formulations of diclofenac were in relieving moderate or severe pain after surgery.

This is an update of a review published in 2009. New searches in March 2015 identified three new studies, making 18 studies with 3714 participants altogether, 1902 of whom were treated with diclofenac and 1007 with placebo. Diclofenac potassium is a rapidly absorbed formulation, and the 50 mg dose provided the largest amount on information. With this dose of this formulation, more than 6 in 10 (64%) participants had effective pain relief, compared with fewer than 2 in 10 (17%) with placebo (high quality evidence).

Adverse events occurred at similar rates with diclofenac and placebo in these single dose studies (moderate quality evidence). There were few serious adverse events or withdrawals due to adverse events.

Diclofenac potassium represents a useful option in controlling acute pain.

Author(s)

Sheena Derry, Philip J Wiffen, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For people with moderate to severe acute pain

Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Choice of dose may depend on the situation. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.

For clinicians

Diclofenac potassium provides good pain relief at 25 mg, 50 mg, and 100 mg doses. Choice of dose may depend on the situation. Diclofenac sodium has limited efficacy and should probably not be used in acute pain.

For policy makers

Diclofenac sodium has limited efficacy and should probably not be used in acute pain. It is not clear if this is widely recognised. Diclofenac potassium is among the most effective analgesics in acute pain.

For Funders

Diclofenac sodium has limited efficacy and should probably not be used in acute pain. Diclofenac potassium is among the most effective analgesics in acute pain.

Implications for research 

General

This review confirms other research indicating that rapidly dispersible and absorbed analgesics provide good pain relief, and that slow absorption results in poor pain relief in acute pain. Formulation is therefore of major consequence, and while the evidence on this is growing, there remain considerable gaps in our knowledge. These include direct linking of pharmacokinetics and pharmacodynamics in acute pain, something readily amenable to test in relatively inexpensive clinical trials.

Research could, and probably should, include effects of fasting and fed states for acute pain and headache, especially in situations where many over‐the‐counter drugs are taken. The effects of food on drug absorption and analgesics efficacy are not well understood, but they are significant.

Design

The current design of acute pain studies is well understood, and has proven to be robust.

Measurement (endpoints)

Endpoints in these studies have been extensively validated, as have standard pain scoring systems. The main outcome used is one valued by people with pain, and has economic benefits in most circumstances.

Comparison between active treatments

The standardised nature of the study design means that indirect comparisons with placebo are valid, as evidenced by independent research on the topic. There is, however, a very large body of information amenable to network meta‐analysis. While unlikely to provide much in the way of new insights, it could prove an invaluable tool for testing network meta‐analytical methods.

Reporting

The continued omission of details about methods, such as how the random sequence was generated and how its allocation was concealed, should be addressed.

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