Naproxen Dosing Interval
Naproxen should be dosed every 12 hours (twice daily) for most indications, with standard prescription doses of 375-500 mg twice daily. 1, 2
Standard Dosing Intervals by Indication
Chronic Inflammatory Conditions (Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis)
- Standard regimen: 250-500 mg every 12 hours (twice daily) 2
- The morning and evening doses do not need to be equal in size 2
- For patients requiring higher anti-inflammatory activity, doses up to 1500 mg/day may be used for limited periods (up to 6 months), still divided into twice-daily dosing 2
Acute Pain Conditions
- Initial dose: 500 mg, followed by 500 mg every 12 hours OR 250 mg every 6-8 hours 2
- The every 12-hour interval is preferred for convenience and equivalent efficacy 2
- Maximum initial daily dose: 1250 mg on day 1, then 1000 mg/day thereafter 2
- For acute migraine: 275-550 mg every 2-6 hours (maximum initial dose 825 mg, avoid exceeding 1.5 g/day) 3
Acute Gout
- Initial dose: 750 mg, followed by 250 mg every 8 hours until attack subsides 2
- This is the only indication where an 8-hour interval is specifically recommended 2
Key Pharmacokinetic Rationale
The twice-daily (every 12 hours) dosing is based on naproxen's relatively long half-life, which permits convenient dosing without compromising efficacy. 4, 5
- Naproxen has complete and rapid absorption with a long elimination half-life that supports 12-hour intervals 4
- Once-daily dosing has shown equivalent efficacy in some rheumatoid arthritis studies, though twice-daily remains standard 5, 6
Important Clinical Considerations
Formulation Differences
- Naproxen sodium (e.g., Aleve) is more rapidly absorbed than naproxen base and is preferred for acute pain when rapid onset is desired 2
- Over-the-counter naproxen sodium: 220-440 mg every 12 hours 1
- Different formulations are not bioequivalent; consider this when switching 2
Special Populations
- Elderly patients and those with renal/hepatic impairment should start with lower doses, but the 12-hour interval remains appropriate 2
- The unbound plasma fraction increases in elderly patients despite unchanged total concentration 2
Common Pitfalls to Avoid
- Do not dose more frequently than twice daily for chronic conditions - administration more frequently than every 12 hours is generally unnecessary and does not improve response 2
- Do not exceed maximum daily doses: 1250 mg on day 1 for acute pain, then 1000 mg/day; 1500 mg/day only for limited periods in chronic inflammatory disease 2
- The every 6-8 hour interval for acute pain is an option but offers no advantage over the more convenient 12-hour schedule 2