• In all people, consider using:
• An alternative to an oral nonsteroidal anti-inflammatory drug (NSAID), for example:
• For pain: paracetamol, with or without codeine.
• For gout: colchicine.
• For osteoarthritis: other analgesics, physical treatments (including exercise), surgery.
• For rheumatoid arthritis: optimization of disease modifying drugs (DMARDs). (Usually requires referral.)
• Only one NSAID at a time:
• When possible, avoid concomitant use of an NSAID with low-dose aspirin. Low-dose aspirin for cardiovascular protection almost always has priority over an NSAID.
• Avoid using an oral NSAID and a topical NSAID at the same time.
• The lowest NSAID dose that is compatible with symptom relief.
• In people who are at increased risk of gastrointestinal (GI) adverse effects and require an oral NSAID, prescribing options are:
• A standard NSAID with a proton pump inhibitor (PPI) prescribed at a dose licensed for gastroprotection (see Table 1).
• A coxib with a PPI.

• For people who have an NSAID-associated peptic ulcer, see the CKS topic on Dyspepsia - proven peptic ulcer.

• People younger than 45 years of age and at low risk of GI adverse events (e.g. no history of GI bleeding or Helicobacter pylori infection and not on aspirin, warfarin, or oral corticosteroids) may not need the concomitant use of a gastroprotective drug with a nonsteroidal anti-inflammatory drug (NSAID).
• Options for gastroprotective drugs to prescribe with standard NSAIDs also include misoprostol or a histamine₂–receptor antagonist, but a PPI is the preferred choice.
• For detailed information on the use of low-dose aspirin, including advice on how to minimize the risk of GI adverse events, see the CKS topic on Antiplatelet treatment.

These recommendations are largely based on National Institute for Health and Clinical Excellence (NICE) guidelines [NICE, 2004; National Collaborating Centre for Chronic Conditions, 2008]. The approach to safe and effective prescribing is also based on the opinion of experts and on advice from the Commission on Human Medicines and the Medicines and Healthcare products Regulatory Agency [CHM, 2006; MHRA, 2007; BNF 55, 2008].

Alternative simple analgesia:

• A questionnaire study of 1799 people with osteoarthritis (OA), rheumatoid arthritis (RA), or fibromyalgia asked people to rate their overall satisfaction with their drug treatment [Wolfe et al, 2000]:
• Of the responses, about 40% of those who had taken paracetamol found it moderately or very effective, 25% found it equally effective as NSAIDs, and 12% preferred paracetamol to NSAIDs.
• When effectiveness and adverse effects were considered together, these percentages increased slightly in favour of paracetamol.
• Although there was a definite preference for NSAIDs over paracetamol, many people with OA and RA were still satisfied with paracetamol.
• A systematic review and meta-analysis of 10 RCTs (n = 1712) investigated whether paracetamol reduced the pain of OA [Zhang et al, 2004]. Although NSAIDs were found to be better for pain relief than paracetamol, paracetamol was effective for pain relief due to OA. For safety reasons, it was concluded that paracetamol should be the first-line treatment.
• A Cochrane review of 15 RCTs (n = 5986) investigated the efficacy of paracetamol in OA [Towheed et al, 2006]. Seven RCTs compared paracetamol with placebo, and 10 RCTs compared paracetamol with NSAIDs. From the limited number of well-controlled studies available, there was little difference between paracetamol and NSAIDs, at least for people with mild pain.

Avoiding concomitant use of two or more NSAIDs:

• This recommendation is based on criteria for the safe use of NSAIDs advised by the Commission on Human Medicines (formerly the Committee on Safety of Medicines) [CSM, 2002].

Gastroprotection:

• An individual person's baseline risk of GI complications is a key factor in determining how beneficial gastroprotection will be [MeReC, 2007].
• Coxibs are associated with a reduction in the risk of GI symptoms and complications compared with standard NSAIDs, but they do not eliminate the risk of GI adverse effects [Rostom et al, 2007].
• PPIs are effective at reducing the GI risks associated with NSAIDs and reduce the risks to a similar level as use of a coxib alone [Chan et al, 2002]. PPIs are also well tolerated, unlike misoprostol.
• NICE based their recommendation to add a PPI with a coxib on two papers reporting three RCTs (n = 1870) [Scheiman et al, 2006; Chan et al, 2007]. For more information, see Prevention of GI adverse effects.