Key Facts

NSAIDs are among the most widely prescribed and OTC-available analgesics. They are highly effective for pain and inflammation but carry significant GI, CV, and renal risks. Safe prescribing requires careful patient selection, lowest effective dose, and shortest duration.

Epidemiology

• Among the most commonly prescribed drugs worldwide
• ~15–20 million NSAID prescriptions/year in England
• NSAIDs account for ~30% of drug-related hospital admissions (mainly GI bleeding)

Pharmacology

• COX-1: constitutive — produces prostaglandins for gastric mucosal protection, platelet aggregation (thromboxane A2), renal blood flow
• COX-2: primarily inducible — mediates inflammation, pain, fever; also constitutive in kidneys
• Non-selective NSAIDs: inhibit both COX-1 and COX-2 (ibuprofen, naproxen, diclofenac)
• COX-2 selective (coxibs): celecoxib, etoricoxib — reduced GI risk but increased CV risk

Pathophysiology of ADRs

• GI: reduced gastric prostaglandin → ↓ mucus/bicarbonate secretion → mucosal damage → ulceration/bleeding
• CV: COX-2 inhibition → ↓ prostacyclin (vasodilator/antithrombotic) → prothrombotic state → MI/stroke
• Renal: ↓ renal prostaglandin → afferent arteriolar constriction → ↓ GFR → AKI, Na/water retention, hyperkalaemia
• Platelet: COX-1 inhibition → ↓ thromboxane A2 → impaired platelet aggregation → bleeding risk

Indications

• Musculoskeletal pain (osteoarthritis, rheumatoid arthritis, back pain)
• Post-operative pain (multimodal analgesia)
• Dysmenorrhoea
• Gout (anti-inflammatory, not urate-lowering)
• Headache, dental pain, renal colic
• Inflammatory conditions (pleurisy, pericarditis)

GI Complications

• Dyspepsia, nausea
• Gastric/duodenal ulceration
• Upper GI bleeding (haematemesis, melaena)
• Perforation

CV Complications

• Increased risk of MI and stroke (all NSAIDs)
• Fluid retention → worsening heart failure
• Hypertension

Renal Complications

• AKI (especially with 'triple whammy')
• Sodium and water retention → oedema
• Hyperkalaemia
• Chronic interstitial nephritis, analgesic nephropathy (long-term)

Red Flags

• GI bleeding: haematemesis, melaena — stop NSAID, PPI, endoscopy
• AKI: rising creatinine, oliguria — stop NSAID, IV fluids
• Chest pain/stroke symptoms — NSAID may have contributed
• Severe asthma exacerbation — aspirin/NSAID hypersensitivity (COX-1 inhibition → leukotriene shunting)

Before Prescribing

• GI risk assessment: age >65, prior GI bleed/ulcer, concurrent anticoagulant/antiplatelet/corticosteroid, H. pylori
• CV risk assessment: existing CVD, hypertension, heart failure
• Renal function: U&Es — avoid if eGFR <30; caution if <60
• Blood pressure: baseline

Monitoring

• U&Es: check within 1–2 weeks of starting, especially if on ACE-i/diuretic
• FBC: if on long-term NSAIDs — monitor for anaemia (occult GI bleeding)
• BP monitoring: NSAIDs may elevate BP
• Symptom review: GI symptoms, fluid retention

Special Tests

• H. pylori test: eradicate before starting NSAIDs in patients with GI risk factors
• OGD: if GI symptoms develop or suspected ulcer

Prescribing Principles

• Lowest effective dose for shortest duration: fundamental principle
• Ibuprofen 200–400 mg TDS: first-choice NSAID (good safety profile)
• Naproxen 250–500 mg BD: preferred if CV risk (lowest CV risk — NICE CG177)
• Diclofenac 50 mg TDS: effective but HIGHEST CV risk — MHRA restricted to short-term use; avoid in CVD
• Celecoxib 100–200 mg BD: COX-2 selective — lower GI risk; still need PPI if GI risk factors; CV risk similar to diclofenac

GI Protection

• Co-prescribe PPI (lansoprazole 15–30 mg OD or omeprazole 20 mg OD) if:
  • Age >65
  • Prior GI bleed/ulcer
  • Concurrent anticoagulant, antiplatelet, or corticosteroid
  • H. pylori positive (eradicate first)
• H. pylori eradication: test and treat before long-term NSAID

Topical NSAIDs

• Topical ibuprofen, diclofenac, ketoprofen: for localised musculoskeletal pain
• Significantly lower systemic absorption → reduced GI/CV/renal risk
• NICE recommends topical NSAID before oral for osteoarthritis of knee/hand

Contraindications

• Active GI bleeding or peptic ulceration
• Severe heart failure (NYHA III–IV)
• Severe renal impairment (eGFR <30)
• Third trimester of pregnancy
• Previous NSAID hypersensitivity (including aspirin-exacerbated respiratory disease)
• Concurrent anticoagulant use (unless benefit clearly outweighs risk + PPI)

Referral Criteria

• Gastroenterology: GI bleeding, refractory dyspepsia
• Rheumatology: alternative anti-inflammatory strategies for chronic inflammatory disease
• Nephrology: NSAID-induced renal impairment

• GI bleeding: ~2–4% annual risk with regular NSAID use; reduced by ~60% with PPI co-prescription
• CV events: diclofenac increases MI risk by ~40% (similar to coxibs); naproxen has lowest additional CV risk
• AKI: usually reversible on drug withdrawal; chronic use may cause irreversible renal damage
• Topical NSAIDs: significantly safer; effective for localised musculoskeletal pain
• NSAID-related morbidity and mortality are largely preventable with appropriate prescribing

NSAID Comparison

NSAID Risk Factor Checklist