What is the recommended dose of naproxen (nonsteroidal anti-inflammatory drug (NSAID)) for pain relief?

Naproxen Dosing for Pain

For acute pain relief, start with naproxen 500 mg (or naproxen sodium 550 mg) initially, followed by 500 mg every 12 hours or 250 mg every 6-8 hours, with a maximum initial daily dose of 1250 mg and subsequent daily doses not exceeding 1000 mg. 1

Standard Dosing Regimens

Acute Pain Management

• Initial dose: 500 mg naproxen (or 550 mg naproxen sodium for faster onset), followed by 500 mg every 12 hours or 250 mg every 6-8 hours 1
• Maximum dosing: Do not exceed 1250 mg on the first day; thereafter, limit to 1000 mg daily 1
• Onset of action: Pain relief typically begins within 1 hour, with naproxen sodium providing more rapid absorption when prompt pain relief is desired 1
• The maximum recommended dose from guidelines is 2 × 500 mg daily (1000 mg total) 2

Chronic Pain Conditions

• For rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: 250 mg, 375 mg, or 500 mg twice daily 1
• Doses do not need to be equal in size between morning and evening 1
• For limited periods (up to 6 months), doses may be increased to 1500 mg/day when higher anti-inflammatory activity is required, though this increases risk 1

Acute Gout

• Initial dose: 750 mg followed by 250 mg every 8 hours until the attack subsides 1

Important Clinical Considerations

Formulation Differences

• Naproxen sodium is preferred for acute pain due to faster absorption and more rapid onset of action 1
• Different formulations (tablets, suspension, delayed-release tablets) are not bioequivalent and have different pharmacokinetic profiles that affect onset of action 1
• When changing formulations, account for these differences in absorption characteristics 1

Dose-Response Relationship

• Naproxen demonstrates linear pharmacokinetics, meaning plasma levels increase proportionately with dose 3
• Higher doses (440-550 mg) provide greater therapeutic efficacy than lower doses (220 mg) 3
• All doses are significantly more effective than placebo, with higher strengths being at least as effective or superior to lower doses 3
• Research shows naproxen 500/550 mg provides at least 50% pain relief in approximately half of treated patients, with a number needed to treat (NNT) of 2.7 4, 5

Duration of Action

• Median time to use of rescue medication is approximately 8.9 hours with naproxen 500/550 mg compared to 2.0 hours with placebo 4
• Naproxen 500/550 mg provides long duration of action (eight hours or greater) 5

Special Populations and Dose Adjustments

Elderly Patients

• Start with lower doses as the unbound plasma fraction of naproxen increases with age 1
• Use the lowest effective dose and titrate upwards cautiously 1, 6
• Some adjustment of dosage may be required; it is prudent to use the lowest effective dose in elderly patients 1

Renal Impairment

• Naproxen is not recommended in patients with moderate to severe renal impairment (creatinine clearance <30 mL/min) 1
• Consider lower doses in patients with mild renal impairment 1

Hepatic Impairment

• Consider lower doses in patients with hepatic impairment 1

Critical Safety Warnings

Cardiovascular Risk

• Use the lowest effective dose for the shortest duration to minimize cardiovascular risk 2
• In post-MI patients, naproxen showed lower cardiovascular risk compared to other NSAIDs, with a hazard ratio of 1.29 for death, which was lower than rofecoxib (2.80), celecoxib (2.57), ibuprofen (1.50), and diclofenac (2.40) 2
• Naproxen is the preferred NSAID when NSAID therapy is necessary in patients with cardiovascular disease, if initial therapy with acetaminophen or small doses of narcotics is insufficient 2

Gastrointestinal Risk

• Monitor for GI toxicity, particularly in patients with risk factors 2
• Consider gastroprotection with proton pump inhibitors if GI symptoms develop 2
• Avoid in patients with active peptic ulcer disease 7

Renal Toxicity

• Exercise caution in patients with compromised fluid status or taking concomitant nephrotoxic drugs 7
• NSAIDs should be used cautiously with nephrotoxic chemotherapy such as cisplatin 2

Common Pitfalls to Avoid

• Do not combine with other NSAIDs (including aspirin at anti-inflammatory doses) as this increases risk without additional benefit 2
• Do not use methotrexate concurrently with naproxen 2
• Avoid prolonged use without reassessing benefits and risks 7
• Do not exceed maximum daily doses: 1250 mg on day 1, then 1000 mg daily thereafter 1
• For patients on low-dose aspirin for cardioprotection, timing of administration matters, though specific guidance for naproxen interaction with aspirin is less established than for ibuprofen 7

Stepped-Care Approach

When treating chronic musculoskeletal pain, particularly in patients with cardiovascular disease:

1. First-line: Acetaminophen, small doses of narcotics, or nonacetylated salicylates 2
2. Second-line: Nonselective NSAIDs such as naproxen if initial therapy is insufficient 2
3. Avoid: COX-2 selective inhibitors should not be used as first-line due to increased cardiovascular risk 2