Makindo Medical Notes

Naproxen is a non-steroidal anti-inflammatory drug (NSAID) used for pain and inflammation in musculoskeletal and rheumatic diseases. It is one of the most cardiovascularly safe traditional NSAIDs and is often preferred in UK practice for long-term rheumatology use. Always 🔗 check the BNF entry here for up-to-date dosing and cautions.

⚙️ Mode of Action

• Reversibly inhibits cyclo-oxygenase (COX-1 and COX-2) enzymes → decreased synthesis of prostaglandins and thromboxanes.
• ↓ Prostaglandin production leads to reduced vasodilation, oedema, and pain sensitisation at inflamed sites.
• Loss of protective gastric and renal prostaglandins explains major adverse effects (ulceration, renal impairment).
• Longer half-life (≈14 hours) gives sustained anti-inflammatory effect with twice-daily dosing.

🩺 Indications / Typical Dosing

• Rheumatic disease / MSK pain: 250–500 mg twice daily (max 1 g/day).
• Acute gout: 750 mg initially, then 250 mg every 8 hours as needed.
• Dysmenorrhoea: 500 mg initially, then 250 mg every 6–8 hours.
• Acute migraine: 750 mg at onset ± 250 mg after 4–6 hours if required.
• Always use the lowest effective dose for the shortest possible duration.
• Take with or after food to reduce gastric irritation.

🔄 Pharmacology

• Onset: 1 hour (analgesic), maximal anti-inflammatory effect after several days.
• Half-life: ~14 hours → twice-daily dosing sufficient.
• Metabolism: hepatic (CYP2C9); excretion: renal.
• Protein binding: >99% → displacement interactions possible (e.g., warfarin).

⚠️ Interactions

• Anticoagulants / antiplatelets (warfarin, clopidogrel, DOACs): ↑ bleeding risk.
• ACE inhibitors / ARBs / diuretics: may precipitate acute kidney injury (the “triple whammy”).
• SSRIs: ↑ risk of GI bleeding (consider gastroprotection).
• Lithium / methotrexate: reduced clearance → ↑ toxicity risk.
• Always verify interactions in the BNF.

⚖️ Cautions

• Renal impairment: reduce dose or avoid; prostaglandin inhibition may precipitate renal failure.
• Older adults: high risk of GI bleed, renal injury, and fluid retention — always use gastroprotection.
• Hypertension / heart failure: may cause sodium and fluid retention, raising BP or precipitating decompensation.
• Asthma: may provoke bronchospasm in aspirin-sensitive patients.
• Peptic ulcer disease: use PPI cover (omeprazole/lansoprazole) if any GI risk factor.
• Monitor renal function and BP in long-term users.

⛔ Contraindications

• Active or previous peptic ulcer / GI bleed.
• Severe heart failure or uncontrolled hypertension.
• Severe renal or hepatic impairment.
• Hypersensitivity to NSAIDs (including aspirin-induced asthma or urticaria).
• Third trimester of pregnancy (risk of premature ductus arteriosus closure).

💢 Side Effects

• Common: dyspepsia, nausea, headache, dizziness, oedema.
• GI: ulceration, perforation, haematemesis, or melaena — can occur at any time, often without warning.
• Renal: AKI, hyperkalaemia, papillary necrosis, worsening CKD.
• CV: hypertension, oedema; lowest CV risk among NSAIDs but not zero.
• Dermatological: photosensitivity, rash (rarely SJS/TEN).

🧠 Clinical Pearls (UK Practice)

• Among non-selective NSAIDs, naproxen and ibuprofen have the best evidence for lower cardiovascular risk — hence preferred in chronic use.
• Co-prescribe a PPI in all patients ≥65 years or with any GI risk factor (history of ulcer, anticoagulant/antiplatelet, steroids, SSRIs).
• Re-check U&Es and BP within 2 weeks of initiation in CKD, hypertension, or heart failure.
• In acute gout, naproxen 750 mg stat then 250 mg every 8 h is often better tolerated than indometacin.
• Educate patients on warning signs: black stools, vomiting blood, ankle swelling, shortness of breath.
• For chronic inflammatory disease, reassess need at every review — “no NSAID is forever.”

📚 References

• BNF: Naproxen
• NICE NG100: Rheumatoid arthritis – management.
• NICE NG136: Headaches in over-12s (use of naproxen for migraine).
• MHRA Drug Safety Update (2023): NSAID renal and CV risks.