Local advice on choosing a nonsteroidal anti-inflammatory drug (and see Appendix 2):
The CSM and MHRA have issued safety advice on the use of NSAIDs; this advice has been incorporated into these notes.
In single dose NSAIDs have analgesic activity comparable to that of paracetamol, but paracetamol is preferred, particularly in the elderly.
The lowest effective dose of NSAID should be used for the shortest necessary time. The need for therapy should be re-evaluated periodically. Patients should be advised that PRN dosing is appropriate if the pain syndrome is intermittent, eg in patient with osteoarthritis.
NSAIDs may enhance the effect of warfarin and other coumarin anticoagulants and co-prescription should be avoided if at all posiible.
About 60% of patients will respond to any NSAID; the remaining 40% may need to try several different drugs before finding the most suitable agent.
NSAIDs should be started at the lowest recommended dose. Where appropriate, first line NSAIDs include ibuprofen 400mg TDS and naproxen 250mg BD. An increased anti-inflammatory effect may be acheived by increasing the dose (ibuprofen 800mg TDS, naproxen 500mg BD). Naproxen is particularly useful where a sustained effect is required because it has a half-life of 14 hours.
Relative safety of NSAIDs:
Adverse effects of NSAIDs are frequently reported to the Committee on Safety of Medicines. These effects fall into the following categories:
Upper gastro-intestinal
Gastro-intestinal damage is a systemic effect of NSAIDs and is not prevented by the use of enteric-coated tablets or suppositories. The following patient groups should be considered at high risk of developing serious gastrointestinal adverse events:
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65 years of age or over.
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Those with serious co-morbidity
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Those currently using systemic steroids
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Those with prior history of gastroduodenal ulcer, gastrointestinal bleeding or perforation.
Piroxicam, ketoprofen and ketorolac are associoated with the highest risk of gastrointestinal adverse events. Of the traditional NSAIDs, low dose ibuprofen offers the lowest risk.
Cox-2 inhibitors are associated with reduced gastrointestinal risk relative to most NSAIDs at equivalent doses. However, Cox-2 inhibiotors may vary in their effects, and evidence is weak for a reduction in clinically important gastrointestinal risks with etoricoxib.
Proton pump inhibitors reduce the gastrointestinal risks associated with NSAIDs, and may reduce the risks to a similar level as use of a Cox-2 inhibitor alone.
The combination of a NSAID and low dose aspirin can increase the risk of gastrointestinal adverse events; the combination should be used only if absolutely necessary and the patient monitored closely.
Cardiovascular
All NSAID use (including Cox-2 inhibitors) can, to varying degrees, be associated with a small increased risk of thrombotic events (eg MI and stroke) independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those receiving high doses long term. The absolute increase in risk for ‘healthy’ users is very low. Cox-2 inhibitors, diclofenac (150mg daily) and ibuprofen (2.4g daily) are associated with an increased risk of thrombotic events. The increased risk for diclofenac is similar to that of licensed doses of etoricoxib. Naproxen (1g daily) is associated with a lower thrombotic risk, and low doses of ibuprofen (1.2g daily or less) have not been asscoiated with an increased risk of MI. Caution is required in patients with cardiac impairment as NSAIDs may impair renal function. Cox-2 inhibitors are contraindicated in ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and mild to severe heart failure. The balance of CV and GI risk should be considered before prescribing a COX-2 inhibitor, particularly if patients have risk factors for heart disease or are taking low dose aspirin - the GI benefit of Cox-2 inhibitors has not been conclusively demonstrated when aspirin is taken concomitantly.
Renal
NSAIDs may provoke renal failure, especially in patients with pre-existing renal impairment. Therefore NSAIDs should be avoided if possible or used with caution in patients with renal impairment, or who are at risk of renal impairment (particularly elderly patients). Sodium and water retention may occur and renal fucntion may deteriorate. Renal function should be monitored in patients prescribed an NSAID who are renally impaired. It is important to consider other concomitant disease states, conditions, or medicines that may precipitate reduced renal function when prescribing NSAIDs.
Asthma
The CSM warns that any degree of worsening of asthma may be related to the ingestion of NSAIDs. NSAIDS are therefore contraindicated in patients with a history of hypersensitivity to aspirin.
Skin reactions including rashes, photosensitivity and rarely Stevens-Johnson syndrome or toxic epidermal necrolysis.
CNS reactions include headache, dizziness, drowsiness, vertigo, hearing disturbances, visual disturbances.
Dysmenorrhoea, menorrhagia and premenstrual syndrome
Mefenamic acid has not been included in the formulary because of increasing evidence that ibuprofen and naproxen are as effective analgesics for dysmenorrhoea and menorrhagia. Both are available OTC.
Primary dysmenorrhoea - Evidence from two systematic reviews supports the use of standard NSAIDs (eg ibuprofen, naproxen) for the management of primary dysmenorrhoea. There is insufficient evidence to indicate whether any one NSAID is more effective than another for the treatment of dysmenorrhoea.
Menorrhagia - NSAIDs significantly reduce menstrual blood loss compared with placebo. There is no significant difference between mefenamic acid and naproxen. NSAIDs are preferred over oral progestogen by NICE Clinical Guideline No 44 (Jan 2007). If there is no improvement, stop oral NSAIDs after 3 cycles.
Premenstrual syndrome - RCTs have found benefit from NSAIDs compared to placebo for a range of premenstrual symptoms. No systematic reviews have been found, but small RCTs show naproxen (and mefenamic acid) to significantly reduce pain and physical symptoms of premenstrual syndrome.