Non-steroidal anti-inflammatory drugs (NSAIDs)

Summary of recommendations: NSAIDs

Indications and effectiveness

Oral NSAIDs

Generally:

• 60% of people will respond to any NSAID. Others will respond to one NSAID more than another
• Analgesic effect starts with the first dose and full analgesic effect occurs after one week, whereas anti-inflammatory effect is evident after three weeks
• If there is no response within the expected timeframe, there should be a change of NSAID⁵⁰
• NNTs vary from 2.4 (ibuprofen 400mg) to 3.0 (naproxen 550mg) to obtain 50% pain relief in acute pain, based on dental abscess pain,⁵¹ over four to six hours
• Fibromyalgia:⁵² NSAIDs cannot be considered as useful in the management of fibromyalgia due to very low-quality evidence
• NSAIDs (non-selective and selective) should be considered for short term (less than six months) use in those with osteoarthritis and inflammatory arthritis⁴⁶
• Osteoarthritis: NSAIDs should be considered in the management of pain in individuals with hip or knee osteoarthritis with paracetamol (1,000-4,000mg/day) in addition to non-pharmacological treatments^47,53
• Low back pain and sciatica (lumbar radiculopathy):
  • SIGN 2025 notes that evidence for the use of NSAIDs for chronic lower back pain is inconsistent and the certainty of evidence was insufficient and therefore could not make a recommendation for or against use of NSAIDs in chronic low back pain⁴⁶
  • There is low certainty of evidence that NSAIDs may provide small effect on chronic low back pain⁵⁴
  • NICE states there is insufficient evidence for and against the use of NSAIDs in sciatica (lumbar radiculopathy), but there is increased risk of harm⁴⁵
• Neuropathic pain (including post herpetic neuralgia): NSAIDs should not be used

Topical NSAIDs

• There was no difference in efficacy in a direct comparison of a topical NSAID with an oral NSAID⁵⁵
• Topical NSAIDs could be considered in chronic musculoskeletal conditions, particularly in individuals who cannot tolerate oral NSAIDs
• Osteoarthritis:
  • Offer a topical NSAID to people with knee osteoarthritis^46,53 and hand osteoarthritis⁵⁵ although evidence is limited to six to 12 weeks follow up.
  • Consider a topical NSAID for people with osteoarthritis that affects other joints⁴⁷

Risks and harms of oral NSAIDs

• Gastrointestinal (GI):
  • There are risks associated with long-term use
  • These effects are systemic rather than local. Therefore, use of enteric-coated preparations are generally not beneficial⁵⁰
  • GI adverse effects are variable between different NSAIDs:
    • highest risk: piroxicam, ketoprofen
    • intermediate risk: indomethacin, diclofenac, naproxen
    • lowest risk: ibuprofen⁵⁰
  • COX-2 inhibitors (e.g. etoricoxib, celecoxib) have lower risk of upper GI events, but these are negated if low dose aspirin is taken
    • If NSAIDs are required in those at risk (e.g. history of peptic ulcer disease or gastrointestinal bleeding, aged over 65 years, dual antiplatelet, with concurrent corticosteroids, combination with selective serotonin reuptake inhibitors (SSRI)) GI protection should be considered
• Renal impairment: NSAIDs should be avoided as the risk of renal failure is highest in those with existing renal impairment⁵⁶. If necessary, use with caution for the shortest time period and at the lowest effective Note that the risk is higher when individuals are prescribed any three of metformin, NSAIDs, ACE inhibitors/ angiotensin-II receptor blocker (ARB), or diuretics (triple whammy).
• Bleeding
  • high-risk combinations – gastrointestinal bleeding concomitant use of NSAIDs and SSRIs
  • high-risk combinations - Use of combination antiplatelets/anticoagulants

 

Cardiovascular risk 

Individuals treated with COX-2 inhibitors may be at an increased risk of cardiovascular issues, such as angina pectoris, myocardial infarction, cerebral infarction, embolism and thrombosis. COX-2 inhibitors are estimated to be associated with approximately three additional thrombotic events per 1000 individuals per year in the general population. 

Diclofenac is associated with cardiovascular risks that are higher than the other non-selective NSAIDs and are similar to the selective COX-2 inhibitors. 

Naproxen and low-dose ibuprofen (less than 2400mg daily) are considered to have the most favourable cardiovascular safety profiles of all non-selective NSAIDs.

• Do not prescribe COX-2 inhibitors, diclofenac, aceclofenac, or high-dose ibuprofen (more than 2400mg daily) to individuals with:
  • ischaemic heart disease
  • congestive heart failure (New York Heart Association [NYHA] classification II–IV)
  • cerebrovascular disease
  • peripheral arterial disease
  • inflammatory bowel disease (COX-2 inhibitors only)
• Do not prescribe etoricoxib or high-dose ibuprofen to individuals with uncontrolled hypertension (persistently above 140/90 mmHg).
• Prescribe NSAIDs with caution to people with:
  • cardiac impairment or heart failure  
  • impaired renal function
  • cerebrovascular disease
  • hypertension — NSAIDs may impair renal function
  • ischaemic heart disease
  • peripheral arterial disease
  • risk factors for cardiovascular events — for example, hypertension, hyperlipidaemia, diabetes mellitus, and smoking
• Elderly/frailty: avoid use of NSAIDs wherever possible due to increased risks of adverse effects⁵⁶
• NSAIDs are cautioned or contra-indicated in people with asthma, depending on their previous history of NSAID use, as they may worsen asthma symptoms⁵⁷

Risks and harms of topical NSAIDs

• Local adverse effects (mostly mild skin reactions) were more common with topical NSAIDs compared with placebo or oral NSAIDs. There was no increase in serious adverse events
• GI adverse effects with topical NSAIDs did not differ from placebo but were less frequent than with oral NSAIDs⁵⁵
• Topical NSAIDs can be used in renal impairment, although deterioration of renal function has been reported after topical use