Generic Name

Naprosyn

Mechanism

• Selective COX inhibition: Naproxen preferentially blocks cyclo‑oxygenase‑1 (COX‑1) and COX‑2 enzymes, reducing prostaglandin synthesis.
• Reduced prostaglandin‑mediated effects: Lowered prostaglandins → ↓ pain, ↓ inflammation, ↓ fever, but also ↓ gastric mucosal protection and platelet aggregation.

Pharmacokinetics

• Absorption: ~80 % oral bioavailability; peak plasma concentrations (Tmax) in 2–4 h.
• Distribution: Highly protein‑bound (≈ 99 % to albumin).
• Metabolism: Hepatic via CYP2C9 to inactive metabolites.
• Elimination: Renal excretion; terminal half‑life 12–17 h (longer than many NSAIDs).
• Drug interactions: Inhibits CYP2C9 → ↑ levels of warfarin, phenytoin, and some antiepileptics.

Indications

• Osteoarthritis & rheumatoid arthritis pain
• Acute musculoskeletal injury pain
• Dysmenorrhea and menstrual pain
• Low‑grade fever
• Acute gouty arthritis (short‑term)

Contraindications

• Active or history of peptic ulcer disease, GI bleeding
• Severe hepatic or renal dysfunction (CrCl < 30 mL/min)
• Known hypersensitivity to naproxen, other NSAIDs, or sulfonamides
• Pregnancy (especially 3rd trimester) and lactation (minimal data)
• History of hypersensitivity to aspirin (cross‑reactivity risk)

Warnings
• Increased risk of GI ulcers, bleeding, and perforation
• Cardiovascular events: hypertension, heart failure, myocardial infarction, stroke (especially with long‑term use)
• Renal impairment: potential acute interstitial nephritis or acute renal failure
• Platelet dysfunction → bleeding tendency, especially with concurrent antiplatelet agents

Dosing

• Adults:
• *Pain/arthritis*: 250–500 mg PO twice daily (BID) or 500 mg PO once daily (QD) after 7 days.
• *Acute pain*: 500 mg PO initially, then 250 mg BID.
• *Dysmenorrhea*: 500 mg PO BID during menstruation.
• Children: 5 mg/kg PO BID (max 500 mg).
• Administration tips: Take with food or milk to reduce GI upset; avoid alcohol.

Adverse Effects

• Common (≤ 10 %): nausea, dyspepsia, headache, dizziness, rash.
• Serious (> 10 % in high‑risk groups):
• GI bleeding or perforation
• Cardiovascular events (MI, stroke)
• Renal failure, acute interstitial nephritis
• Severe hypersensitivity (angioedema, anaphylaxis)

Monitoring

• Baseline: CBC, CMP (renal & hepatic panels), urinalysis, blood pressure, EKG if CV risk.
• During therapy:
• CBC & CMP every 2–4 weeks for first 3 months, then every 3–6 months if stable.
• Monitor for signs of GI bleeding (hematemesis, melena).
• Blood pressure weekly for first month.
• Drug‑specific: Evaluate for interaction with anticoagulants and antiplatelets.

Clinical Pearls

• Long half‑life advantage: Naproxen’s 12–17 h half‑life allows BID dosing, which may improve patient adherence compared to shorter‑acting NSAIDs.
• Food synergy: Taking naproxen with a fatty meal not only blunts GI irritation but also improves absorption, providing smoother analgesic curves.
• Pregnancy caution: Avoid naproxen in the 3rd trimester because of its potent COX‑2 inhibition, which can precipitate premature ductus arteriosus closure.
• Cardiovascular balancing: Use the lowest effective dose for the shortest duration; co‑prescribe proton pump inhibitor (PPI) or misoprostol in high‑GI‑risk patients to mitigate ulcer risk.
• Bleeding risk with antiplatelets: Naproxen can antagonize the antiplatelet effect of low‑dose aspirin (due to reversible COX‑1 blockade) and may increase bleeding when combined with clopidogrel. Consider alternative NSAIDs or temporary discontinuation in patients on dual antiplatelet therapy.
• Renal monitoring in elderly: Age‑related decline in renal function necessitates dose adjustment; start at 250 mg BID and titrate cautiously.
• Drug–drug interaction insight: Since naproxen is a moderate CYP2C9 inhibitor, concurrent use with warfarin can raise INR; monitor INR closely for at least 2–3 weeks after initiation.

Key Takeaway: Naproxen is a reliable, twice‑daily NSAID for moderate pain and inflammation when used with vigilant GI protection, cardiovascular surveillance, and renal monitoring.