Naproxen Dosing for a Healthy Adult
For a healthy adult, take naproxen 220–440 mg (1–2 tablets of over-the-counter naproxen sodium) every 12 hours, not exceeding 660 mg in 24 hours for OTC use, or 500 mg twice daily (1000 mg/day) for prescription naproxen. 1
Standard Dosing by Formulation
Over-the-Counter Naproxen Sodium (Aleve)
- Initial dose: 220 mg (1 tablet), followed by 220 mg every 8–12 hours as needed 2
- For more severe pain: 440 mg (2 tablets) every 12 hours 2
- Maximum daily dose: 660 mg (3 tablets) in 24 hours for OTC use 1, 3
Prescription Naproxen
- Standard dose: 250–500 mg twice daily (every 12 hours) 2, 1
- Maximum routine daily dose: 1000 mg/day for long-term use 2, 1
- Short-term higher dosing: Up to 1250 mg on day 1 (500 mg initial dose, then 500 mg after 12 hours or 250 mg every 6–8 hours), followed by maximum 1000 mg/day thereafter 1
Dosing by Clinical Indication
Acute Pain (injury, dental pain, postoperative)
- Start with: 500 mg naproxen, then 500 mg every 12 hours or 250 mg every 6–8 hours 1
- Day 1 maximum: 1250 mg 1
- Subsequent days: Do not exceed 1000 mg/day 1
Migraine
- Initial dose: 275–550 mg, with maximum initial dose of 825 mg 2
- Maintenance: Avoid exceeding 1500 mg/day 2
- Trial period: Use for 2–3 migraine episodes before deciding efficacy 2
Chronic Inflammatory Conditions (arthritis)
- Standard: 375–500 mg twice daily 2, 1
- Higher doses: May increase to 1500 mg/day for up to 6 months in patients who tolerate lower doses well and require higher anti-inflammatory activity 1
- Titration: Morning and evening doses do not need to be equal 1
Critical Timing and Administration
- Take with food to minimize gastrointestinal irritation 2
- Onset of pain relief: Begins within 1 hour, with naproxen sodium absorbed more rapidly than naproxen base 1
- Dosing interval: Every 12 hours is standard; more frequent dosing does not improve response 1
Duration of Treatment
- Acute pain: 2–4 weeks at maximum tolerated dose, then reassess 2
- If continuing beyond 2–4 weeks: Evaluate response and consider tapering after 12 weeks of sustained response 2
- Long-term use: Requires monitoring every 3 months (blood pressure, renal function, liver enzymes, CBC, fecal occult blood) 2
Safety Monitoring and Discontinuation Criteria
Mandatory Monitoring for Extended Use (>2–4 weeks)
- Blood pressure (discontinue if hypertension develops or worsens) 2
- BUN and creatinine (discontinue if values double) 2
- Liver function tests (discontinue if >3× upper limit of normal) 2
- CBC and fecal occult blood 2
Immediate Discontinuation Required If:
- Gastrointestinal bleeding occurs 2
- Renal function deteriorates (BUN or creatinine doubles) 2
- New or worsening hypertension 2
- Liver enzymes rise to 3× normal 2
High-Risk Populations Requiring Caution or Avoidance
Use Lower Doses or Avoid Entirely
- Age ≥65 years: Start at lowest effective dose due to increased unbound drug fraction 1, 2
- Renal impairment (CrCl <30 mL/min): Not recommended 1
- History of peptic ulcer disease: Add proton pump inhibitor or H2 blocker 2
- Cardiovascular disease: Use with extreme caution 2
- Concurrent anticoagulants: Significantly increases bleeding risk; requires close monitoring 2
Gastroprotection Recommendations
- High-risk patients (≥75 years, peptic ulcer history, GI bleeding history, anticoagulant/antiplatelet/SSRI/glucocorticoid use): Add proton pump inhibitor or misoprostol 2
- Risk is dose-dependent across all NSAIDs 2
Common Pitfalls to Avoid
- Do not combine multiple NSAIDs (e.g., naproxen with ibuprofen) without physician direction, as this increases adverse effects without added benefit 2
- Do not exceed 1000 mg/day for routine long-term use 2, 1
- Do not take on an empty stomach 2
- Avoid in moderate-to-severe renal impairment (CrCl <30 mL/min) 1
- Check for "hidden NSAIDs" in combination medications to avoid excessive total NSAID exposure 2
Pharmacokinetic Considerations
- Linear pharmacokinetics up to 500 mg: AUC is proportional to dose 4, 5
- Above 500 mg: Increased unbound fraction leads to increased renal clearance of total drug while unbound clearance remains constant 4
- Higher doses (440 mg, 550 mg) are more effective than lower doses and maintain linear efficacy 5
- Extensive protein binding: Concentration-dependent binding to albumin 4
Safety Profile
- Adverse event rate comparable to placebo at OTC doses (220–750 mg/day) for 7–10 days 6, 3
- Most common side effect: Dyspepsia and GI discomfort (10–20% of patients) 2
- No dose effect on adverse events in short-term use 6
- No difference in adverse events between younger (<65) and older (≥65) adults in short-term trials 6
- Well-established safety profile over decades of clinical use 7