NIHR Signal A single dose of diclofenac potassium is more effective for postoperative pain than the more commonly used diclofenac sodium

Published on 10 September 2015

This Cochrane systematic review found that the same single dose of fast-acting diclofenac potassium tablets is more effective for moderate to severe short-term postoperative pain relief than coated diclofenac sodium tablets. Both versions were compared with a placebo, rather than each other. On average, only two people need to be treated with a single dose of the fast acting pill instead of the dummy pill for one to experience adequate pain relief. The rate of adverse effects after a single dose was low and there was no difference between the two drugs. Across all uses, diclofenac sodium is much more commonly prescribed in the NHS. Because this is usually in a coated formulation its absorption is slowed and blood levels are lower than with the uncoated diclofenac potassium.  This evidence suggests diclofenac potassium (50mg) is the better option for acute postoperative pain relief in adults.

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Why was this study needed?

Diclofenac, a widely used pain-killer, belongs to the group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). It is available in two tablet forms: fast-acting diclofenac potassium and slower-acting (enteric coated) diclofenac sodium. In 2013 diclofenac sodium accounted for 98% of diclofenac prescriptions in England.  Diclofenac potassium used to be available without prescription but was withdrawn after concerns over long term use and risks to the heart and vascular system. A 2009 Cochrane systematic review identified 15 trials comparing the two forms of diclofenac for the treatment of postoperative pain. The current review (2015) is an update and includes three new trials on top of the original 15.

What did this study do?

A total of 3,714 adults were included in this review of 18 randomised controlled trials in which a single dose of diclofenac taken by mouth was compared with a placebo in the relief of moderate to severe postoperative pain. The main measure of success was participants self-reporting at least 50% relief from postoperative pain over four to six hours after taking a single dose of diclofenac or placebo. Trials used standard pain scoring systems, such as visual analogue pain scales (see definitions). Most of the evidence available was for a single dose of 50mg diclofenac potassium.

What did it find?

  • The pooled results of seven trials showed that about two people would need to be treated with a single 50mg dose of diclofenac potassium in order for one person to achieve at least 50% pain relief compared with a placebo. There was gradual improvement in the effectiveness of diclofenac potassium as the dose increased from 25mg to 50mg to 100mg.
  • By comparison, three studies examining single dose 50mg diclofenac sodium found that around seven people would need to be treated for one person to achieve at least 50% pain relief compared with inactive placebo. These trials of the slower-acting preparation were conducted in similar populations to the trials of the fast-acting version.
  • The rate of adverse effects with either type of diclofenac was low and no different from placebo. No serious side effects were reported. However, few trials reported on adverse effects – seven studies for diclofenac potassium and only one for diclofenac sodium. Therefore we can have less confidence in this finding.

What does current guidance say on this issue?

There is no guidance on the broad issue of postoperative pain relief. NICE does issue advice on the well-recognised potential adverse effects in continued use of all NSAIDs on the digestive system (for example, irritation and bleeding) and kidney function. NICE also highlights the possible risks of several NSAIDs, including diclofenac, on the heart and vascular system, for example increased risk of blood clots. However, these risks are more likely to be linked to long-term use rather than the short-term use which was the focus of this review.

What are the implications?

This review found that fast-acting diclofenac potassium provided more effective relief from postoperative pain than placebo. While the studies didn’t directly compare fast-release diclofenac potassium with slow-release diclofenac sodium, comparing both against a placebo suggested the fast-acting preparation was more effective. We know diclofenac sodium is currently much more commonly prescribed in the NHS as a whole. The review findings suggest that diclofenac is more effective for severe to moderate short-term postoperative pain.  

Most of the evidence was for 50mg diclofenac potassium, far fewer trials looked at 25mg and 100mg resulting in a weaker evidence base around these doses.

Doctors may be reluctant to prescribe diclofenac for postoperative pain because of historical concerns over the potential risk of harms to the digestive system, kidneys or heart and vascular system. The limited evidence on adverse effects available in this review suggests that a single dose of diclofenac is very safe for the relief of postoperative pain. This high quality review may encourage more use of fast-acting diclofenac potassium.

Citation

Derry S, Wiffen PJ, Moore RA. Single dose oral diclofenac for acute postoperative pain in adults. Cochrane Database Syst Rev. 2015;(7):CD004768.

Bibliography

NICE. Non-steroidal anti-inflammatory drugs. Key Therapeutic Topic 13. London: National Institute for Health and Care Excellence; 2015.

Why was this study needed?

Diclofenac, a widely used pain-killer, belongs to the group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). It is available in two tablet forms: fast-acting diclofenac potassium and slower-acting (enteric coated) diclofenac sodium. In 2013 diclofenac sodium accounted for 98% of diclofenac prescriptions in England.  Diclofenac potassium used to be available without prescription but was withdrawn after concerns over long term use and risks to the heart and vascular system. A 2009 Cochrane systematic review identified 15 trials comparing the two forms of diclofenac for the treatment of postoperative pain. The current review (2015) is an update and includes three new trials on top of the original 15.

What did this study do?

A total of 3,714 adults were included in this review of 18 randomised controlled trials in which a single dose of diclofenac taken by mouth was compared with a placebo in the relief of moderate to severe postoperative pain. The main measure of success was participants self-reporting at least 50% relief from postoperative pain over four to six hours after taking a single dose of diclofenac or placebo. Trials used standard pain scoring systems, such as visual analogue pain scales (see definitions). Most of the evidence available was for a single dose of 50mg diclofenac potassium.

What did it find?

  • The pooled results of seven trials showed that about two people would need to be treated with a single 50mg dose of diclofenac potassium in order for one person to achieve at least 50% pain relief compared with a placebo. There was gradual improvement in the effectiveness of diclofenac potassium as the dose increased from 25mg to 50mg to 100mg.
  • By comparison, three studies examining single dose 50mg diclofenac sodium found that around seven people would need to be treated for one person to achieve at least 50% pain relief compared with inactive placebo. These trials of the slower-acting preparation were conducted in similar populations to the trials of the fast-acting version.
  • The rate of adverse effects with either type of diclofenac was low and no different from placebo. No serious side effects were reported. However, few trials reported on adverse effects – seven studies for diclofenac potassium and only one for diclofenac sodium. Therefore we can have less confidence in this finding.

What does current guidance say on this issue?

There is no guidance on the broad issue of postoperative pain relief. NICE does issue advice on the well-recognised potential adverse effects in continued use of all NSAIDs on the digestive system (for example, irritation and bleeding) and kidney function. NICE also highlights the possible risks of several NSAIDs, including diclofenac, on the heart and vascular system, for example increased risk of blood clots. However, these risks are more likely to be linked to long-term use rather than the short-term use which was the focus of this review.

What are the implications?

This review found that fast-acting diclofenac potassium provided more effective relief from postoperative pain than placebo. While the studies didn’t directly compare fast-release diclofenac potassium with slow-release diclofenac sodium, comparing both against a placebo suggested the fast-acting preparation was more effective. We know diclofenac sodium is currently much more commonly prescribed in the NHS as a whole. The review findings suggest that diclofenac is more effective for severe to moderate short-term postoperative pain.  

Most of the evidence was for 50mg diclofenac potassium, far fewer trials looked at 25mg and 100mg resulting in a weaker evidence base around these doses.

Doctors may be reluctant to prescribe diclofenac for postoperative pain because of historical concerns over the potential risk of harms to the digestive system, kidneys or heart and vascular system. The limited evidence on adverse effects available in this review suggests that a single dose of diclofenac is very safe for the relief of postoperative pain. This high quality review may encourage more use of fast-acting diclofenac potassium.

Citation

Derry S, Wiffen PJ, Moore RA. Single dose oral diclofenac for acute postoperative pain in adults. Cochrane Database Syst Rev. 2015;(7):CD004768.

Bibliography

NICE. Non-steroidal anti-inflammatory drugs. Key Therapeutic Topic 13. London: National Institute for Health and Care Excellence; 2015.

Single dose oral diclofenac for acute postoperative pain in adults

Published on 8 July 2015

Derry, S.,Wiffen, P. J.,Moore, R. A.

Cochrane Database Syst Rev Volume 7 , 2015

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.

Visual analogue pain scale (VAS) is an example of a standardised pain measure to help people show the level of pain they are experiencing. The scale, a 10cm line, has a “no pain” labelled on the far left and “extreme pain” on the right. The person is asked to mark the line at a position corresponding to the amount of pain they feel.

Expert commentary

This updated review on single dose oral diclofenac for acute postoperative pain in adults includes significantly more patients and has allowed stronger conclusions to be made with regard to formulation.  Fast acting formulations, predominantly diclofenac potassium, had clear advantages over diclofenac sodium (enteric coated).

Diclofenac potassium 50 mg has a number needed to treat (NNT) for at least 50% maximum pain relief of about 2 with a low rate of adverse events no different from placebo.

This evidence strongly supports the routine use of diclofenac potassium 50mg for acute postoperative pain in adults, unless there are strong contraindications.

Dr John Goddard, Consultant in paediatric anaesthesia and pain medicine, Sheffield Children's Hospital

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