What are the recommended adult dosing guidelines for naproxen, including acute and chronic use, maximum daily dose, and contraindications?

Naproxen Adult Dosing Guidelines

For most adult indications, naproxen should be dosed at 500 mg twice daily (every 12 hours), with a maximum daily dose of 1000 mg for chronic use, though acute conditions may require up to 1250 mg on the first day followed by 1000 mg daily thereafter. 1

Standard Dosing by Indication

Chronic Inflammatory Conditions (Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis)

• Start with 250-500 mg twice daily (every 12 hours) 1
• Maximum daily dose for routine long-term use: 1000 mg/day (500 mg twice daily) 2, 1
• For patients requiring higher anti-inflammatory activity, the dose may be increased to 1500 mg/day for limited periods up to 6 months, though this carries increased risk and requires close monitoring 1
• Morning and evening doses do not need to be equal, and dosing more than twice daily provides no additional benefit 1

Acute Pain Management

• Initial dose: 500 mg, followed by 500 mg every 12 hours OR 250 mg every 6-8 hours 1
• Maximum first-day dose: 1250 mg 1
• Maximum subsequent daily dose: 1000 mg 1
• For acute migraine: 275-550 mg every 2-6 hours, with a maximum initial dose of 825 mg and not exceeding 1.5 g/day 2

Acute Gout

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

Primary Dysmenorrhea and Acute Tendonitis/Bursitis

• Use the acute pain dosing regimen above 1
• Naproxen sodium formulations are preferred for these conditions due to more rapid absorption and faster onset of pain relief 1

Maximum Daily Doses by Clinical Context

• Chronic inflammatory conditions (standard): 1000 mg/day 2, 1
• Chronic inflammatory conditions (high-activity periods): 1500 mg/day for up to 6 months only 1
• Acute pain (first day): 1250 mg 1
• Acute pain (subsequent days): 1000 mg 1
• Over-the-counter naproxen sodium: 660 mg/day (equivalent to 440 mg naproxen sodium twice daily) 2

Formulation Considerations

• Different formulations are NOT bioequivalent and have pharmacokinetic differences affecting onset of action 1
• Naproxen sodium is absorbed more rapidly than naproxen base and should be used when prompt pain relief is desired (acute pain, dysmenorrhea, acute tendonitis) 1
• Onset of pain relief typically begins within 1 hour 1
• When switching formulations, account for these differences 1

Treatment Duration and Monitoring

Short-Term Use (7-10 days)

• At non-prescription doses (220-750 mg/day), naproxen has a safety profile similar to placebo with no increased risk of adverse events 3
• No dose-dependent increase in adverse events at these doses 3

Long-Term Use

• Evaluate treatment response at 2-4 weeks 2
• If insufficient response after 2-4 weeks at maximum tolerated dose, switch to another NSAID or add second-line treatments 2
• Consider tapering after 12 weeks of sustained response 2
• Monitor every 3 months: blood pressure, BUN, creatinine, liver function tests, CBC, and fecal occult blood 2

Special Populations

Elderly Patients (≥65 years)

• Use the lowest effective dose 1
• Although total plasma naproxen concentration is unchanged, the unbound fraction increases in elderly patients 1
• Caution is advised when high doses are required; dose adjustment may be necessary 1
• Mandatory gastroprotection with a proton pump inhibitor regardless of GI history 2

Renal Impairment

• Naproxen is NOT recommended in moderate to severe renal impairment (creatinine clearance <30 mL/min) 1
• Use with extreme caution in patients with compromised fluid status or taking nephrotoxic drugs 2
• Discontinue if BUN or creatinine doubles during treatment 2

Hepatic Impairment

• Consider a lower starting dose 1
• Discontinue if liver function tests increase to 3× upper limit of normal 2

Major Contraindications

Absolute Contraindications

• Active peptic ulcer disease 2
• Severe heart failure 2
• Liver failure 2
• History of GI bleeding 2
• Pregnancy (third trimester) 2
• Moderate to severe renal impairment (CrCl <30 mL/min) 1

Use with Extreme Caution

• History of peptic ulcer disease 2
• Age >60 years (requires gastroprotection) 2
• Cardiovascular disease or congestive heart failure 2
• Concomitant anticoagulant use (increases bleeding risk 3-6 fold) 2
• Concomitant use of antiplatelets, SSRIs, or glucocorticoids 2

Gastroprotection Strategy

• Patients <65 years without GI risk factors: naproxen alone is appropriate 2
• Patients ≥65 years OR with prior GI events: mandatory co-administration of a proton pump inhibitor 2
• High-risk patients (≥75 years, peptic ulcer disease, history of GI bleeding, anticoagulants, antiplatelets, SSRIs, or glucocorticoids): require concomitant misoprostol or PPI at any dose 2
• Risk of GI bleeding is dose-dependent across all NSAIDs 2

Common Adverse Effects

• Gastrointestinal effects (10-20% of patients): dyspepsia, GI discomfort, nausea, vomiting, diarrhea 4, 3
• Most adverse events are mild to moderate 3
• Discontinue immediately if GI bleeding occurs 2

Drug Interactions

• Anticoagulants: significantly increase bleeding risk; avoid combination or monitor closely 2
• Antiplatelets, SSRIs, glucocorticoids: increase GI bleeding risk 2
• Avoid combining multiple NSAIDs, as many patients inadvertently do this without physician direction 2

Clinical Pearls

• Try naproxen for 2-3 headache episodes before abandoning therapy (for migraine management) 4
• If one NSAID fails, switching to a different NSAID may be effective 2
• If two different NSAIDs fail sequentially, switch to an alternative analgesic approach rather than continuing to trial additional NSAIDs 2
• Naproxen has been used effectively for decades and can be considered first-line treatment for rheumatic diseases and pain states 5, 6
• For localized pain, consider topical NSAIDs to minimize systemic exposure 2