What is the adult dosing regimen, contraindications, and precautions for naproxen?

Naproxen: Adult Dosing, Contraindications, and Precautions

For most adult indications, naproxen should be initiated at 250-500 mg orally twice daily (every 12 hours), with a maximum daily dose of 1000 mg for routine long-term use, though acute conditions may require up to 1250 mg on day one followed by 1000 mg daily thereafter. 1

Standard Adult Dosing Regimens

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

• Start with 250 mg, 375 mg, or 500 mg twice daily 1
• Maximum routine dose: 1000 mg/day (500 mg twice daily) 2, 3
• For refractory cases requiring higher anti-inflammatory activity: up to 1500 mg/day may be used for limited periods up to 6 months, but only when increased clinical benefit clearly outweighs increased risk 1
• Morning and evening doses need not be equal 1

Acute Pain, Primary Dysmenorrhea, Acute Tendonitis/Bursitis

• Initial dose: 500 mg, followed by 500 mg every 12 hours OR 250 mg every 6-8 hours 1
• Day 1 maximum: 1250 mg 1
• Subsequent days maximum: 1000 mg/day 1
• Naproxen sodium formulation preferred for acute conditions due to more rapid absorption 1

Acute Gout

• Initial dose: 750 mg, followed by 250 mg every 8 hours until attack subsides 1
• Full anti-inflammatory dosing should be continued without interruption of any established urate-lowering therapy 4

Migraine (Acute Treatment)

• Initial dose: 275-550 mg, may repeat every 2-6 hours as needed 3
• Maximum initial dose: 825 mg 3
• Maximum daily dose: 1500 mg 3
• Trial for 2-3 migraine episodes before discontinuing 3

Absolute Contraindications

Naproxen is absolutely contraindicated in the following situations: 1

• Known hypersensitivity to naproxen 1
• History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs (risk of severe, rarely fatal anaphylactic-like reactions) 1
• Treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery 1
• Active peptic ulcer disease or history of gastrointestinal bleeding 2
• Current use of anticoagulants (3-6 fold increased GI bleeding risk, INR increases up to 15%) 4
• Moderate to severe renal impairment (creatinine clearance <30 mL/min) 5, 1

Critical Precautions and High-Risk Populations

Age-Related Considerations

• Patients ≥60 years have substantially increased risk of NSAID complications 2
• The one-year risk of serious GI bleeding increases from 1 in 2,100 in adults <45 years to 1 in 110 in adults >75 years 2, 5
• Use lowest effective dose in elderly patients; dose adjustment may be required at higher doses 5, 1
• Unbound plasma fraction of naproxen increases in elderly despite unchanged total plasma concentration 1

Gastrointestinal Risk Management

• 10-20% of patients experience dyspepsia or GI discomfort 5, 3
• Add proton pump inhibitor (PPI), double-dose H2 blocker, or misoprostol for gastroprotection in high-risk patients: 4
  • Age ≥60 years 2
  • History of peptic ulcer disease 4, 2
  • Concurrent use of anticoagulants, antiplatelet agents, SSRIs, or corticosteroids 3
  • Alcohol use 2
• For patients with prior NSAID-associated ulcer who must take NSAIDs, gastroprotection is mandatory 4
• Risk of recurrent bleeding in patients with ulcer history: as high as 5% in 6 months even with COX-2 inhibitors or nonselective NSAIDs plus PPI 4

Cardiovascular Precautions

• NSAIDs cause 3.5 excess cardiac ischemic events per 1,000 persons compared to placebo 5
• Use with extreme caution in patients with cardiovascular disease or congestive heart failure 5, 3
• Mean blood pressure increase of 5 mmHg; avoid in uncontrolled hypertension 5
• If patient takes low-dose aspirin for cardioprotection: naproxen must be taken at least 30 minutes AFTER immediate-release aspirin or at least 8 hours BEFORE aspirin to avoid interfering with aspirin's antiplatelet effect 2

Renal Precautions

• Avoid in patients with preexisting renal disease, congestive heart failure, or cirrhosis 4
• Use with extreme caution when combining with ACE inhibitors, ARBs, or beta blockers (additive renal effects) 5
• Avoid in patients with compromised fluid status or taking concurrent nephrotoxic drugs 3

Hematologic Precautions

• Avoid in patients with preexisting platelet defects or thrombocytopenia 4
• When NSAIDs combined with anticoagulants: 3-6 fold increased GI bleeding risk plus INR increases up to 15% 4
• If concurrent NSAID and anticoagulant use is unavoidable: anticipate INR increase, monitor closely, adjust warfarin dose, and initiate GI prophylaxis 4

Perioperative Management

• Stop naproxen 2-3 days before surgery (five elimination half-lives) 4
• For high-risk cardiovascular patients on aspirin: aspirin should generally be continued perioperatively; if withheld, stop 7-10 days preoperatively 4

Respiratory Precautions

• Aspirin-exacerbated respiratory disease prevalence: 0.07% in general population, up to 21% in adults with asthma 4
• Higher suspicion warranted in patients with asthma plus nasal polyps or recurrent sinusitis 4
• High cross-reactivity with other NSAIDs due to shared COX-1 inhibition 4
• Patients requiring NSAIDs despite aspirin-exacerbated respiratory disease should be considered for aspirin desensitization 4

Central Nervous System Effects (More Common in Elderly)

• Tinnitus (reversible, may indicate high drug levels) 4
• Psychosis and cognitive changes (most often with indomethacin, but possible with naproxen) 4
• Aseptic meningitis occurs more often in patients with lupus taking naproxen; consider in any adult with meningitis on NSAIDs 4
• Other potential effects: confusion, depression, dizziness, somnolence 4

Mandatory Baseline Assessment Before Prescribing

Obtain the following before initiating naproxen: 2

• Blood pressure measurement
• BUN and creatinine
• Liver function tests
• Complete blood count
• Fecal occult blood test

Monitoring During Treatment

For treatment extending beyond 2-4 weeks, repeat monitoring every 3 months: 2, 3

• Blood pressure
• BUN and creatinine
• Liver function tests
• Complete blood count
• Fecal occult blood

Immediate Discontinuation Criteria

Stop naproxen immediately if any of the following occur: 2, 3

• BUN or creatinine doubles from baseline 2, 3
• Liver function tests increase to ≥3 times upper limit of normal 2, 3
• Development or worsening of hypertension 2, 3
• Any signs of GI bleeding (black stools, hematemesis, severe abdominal pain) 2, 3

Treatment Duration and Response Assessment

• Evaluate treatment response at 2-4 weeks 3
• If two different NSAIDs fail sequentially, switch to an alternative analgesic approach rather than trying additional NSAIDs 2, 5, 3
• For acute conditions (e.g., sciatica): limit treatment to 10 days; if pain persists beyond 2-4 weeks, reassess diagnosis and consider multimodal approaches 2
• For chronic inflammatory conditions: if sufficient response achieved, consider tapering after 12 weeks of sustained response 3

Critical Drug Interactions

• Never combine naproxen with other NSAIDs (including ibuprofen or ketorolac) - toxicities are additive without additional analgesic benefit 2
• Anticoagulants: Avoid combination; if unavoidable, requires intensive INR monitoring and gastroprotection 4, 5
• Probenecid: Significantly alters naproxen disposition 6
• Lithium and methotrexate: Significant drug interactions demonstrated 6

Special Populations

Hepatic Impairment

• Lower starting dose recommended; titrate cautiously 1
• Hepatic disease significantly alters naproxen disposition kinetics 6

Breastfeeding

• Naproxen is safe to use in breastfeeding women 4
• Drug is excreted into breast milk but amount transferred comprises only small fraction of maternal exposure 6

Juvenile Arthritis

• Recommended total daily dose: approximately 10 mg/kg in 2 divided doses (5 mg/kg twice daily) 1
• Naproxen oral suspension recommended over tablets for this indication 1

Safer Alternatives When Naproxen Is Contraindicated or Fails

• Acetaminophen up to 3000 mg daily (safer in high-risk patients, though potentially less effective for inflammatory pain) 4, 2
• Topical NSAIDs to minimize systemic exposure for localized pain 2, 3
• Celecoxib (COX-2 inhibitor) as option in patients with GI contraindications or intolerance to NSAIDs, though cardiovascular risk-benefit ratio must be carefully considered 4

Key Prescribing Principles

• Use the lowest effective dose for the shortest duration consistent with treatment goals 2, 3
• Provide clear written instructions about discontinuation criteria and when to seek immediate medical attention 2
• Take with food to minimize GI upset 4
• Different formulations (tablets, suspension, delayed-release tablets, naproxen sodium) are not bioequivalent; consider this when changing formulations 1
• Onset of pain relief can begin within 1 hour 1