Naprosyn - Drug Monograph

Introduction

Naprosyn (naproxen) is a nonsteroidal anti-inflammatory drug (NSAID) widely used for its analgesic, anti-inflammatory, and antipyretic properties. First approved by the FDA in 1976, it remains a cornerstone therapy for various inflammatory conditions. Naprosyn is available in both prescription and over-the-counter formulations, with the prescription version typically providing higher doses and additional indications.

Mechanism of Action

Naproxen exerts its therapeutic effects through reversible inhibition of cyclooxygenase (COX) enzymes, primarily COX-1 and COX-2. This inhibition prevents the conversion of arachidonic acid to prostaglandin precursors, resulting in:

• Reduced synthesis of prostaglandins involved in pain and inflammation
• Decreased production of prostacyclin and thromboxane
• Inhibition of inflammatory mediators at sites of tissue injury

The drug's anti-inflammatory effects are primarily mediated through COX-2 inhibition, while its adverse effects on the gastrointestinal tract are largely attributed to COX-1 inhibition.

Indications

FDA-approved indications include:

• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Tendinitis
• Bursitis
• Acute gout
• Primary dysmenorrhea
• Mild to moderate pain
• Fever reduction (over-the-counter formulation)

Off-label uses may include:

• Juvenile idiopathic arthritis (using appropriate formulations)
• Migraine prophylaxis
• Acute migraine attacks

Dosage and Administration

• Rheumatoid arthritis, osteoarthritis, ankylosing spondylitis: 250-500 mg twice daily
• Acute gout: 750 mg initially, then 250 mg every 8 hours until attack subsides
• Mild to moderate pain: 500 mg initially, then 250 mg every 6-8 hours
• Primary dysmenorrhea: 500 mg initially, then 250 mg every 6-8 hours

• Geriatric patients: Use lowest effective dose
• Renal impairment: Avoid in severe renal impairment (CrCl <30 mL/min)
• Hepatic impairment: Use with caution; consider dose reduction
• Pediatric patients: 5-10 mg/kg/dose every 8-12 hours (maximum 15 mg/kg/day)

• Should be taken with food or milk to minimize gastrointestinal upset
• Immediate-release tablets: May be crushed if needed
• Delayed-release tablets: Should be swallowed whole
• Suspension: Shake well before use

Pharmacokinetics

• Rapid and complete oral absorption
• Peak plasma concentrations: 2-4 hours for immediate-release
• Food delays absorption but does not affect extent
• Bioavailability: Approximately 95%

• Volume of distribution: 0.16 L/kg
• Protein binding: >99% (primarily albumin)
• Crosses placenta and enters breast milk

• Primarily hepatic via cytochrome P450 system (CYP1A2, CYP2C9)
• Demethylation and conjugation reactions
• No active metabolites

• Half-life: 12-17 hours
• Renal excretion: 95% as unchanged drug and metabolites
• Fecal excretion: <5%
• Dialysis: Not significantly removed

Contraindications

• Hypersensitivity to naproxen or other NSAIDs
• History of asthma, urticaria, or allergic-type reactions after aspirin or other NSAIDs
• Perioperative pain in coronary artery bypass graft (CABG) surgery
• Third trimester of pregnancy

Warnings and Precautions

• Increased risk of serious cardiovascular thrombotic events, including MI and stroke
• Risk may increase with duration of use
• Contraindicated in CABG surgery

• Increased risk of GI bleeding, ulceration, and perforation
• Risk factors: advanced age, history of GI events, concomitant anticoagulant use

• May cause renal papillary necrosis and other renal injury
• Risk increased in patients with renal impairment, heart failure, or volume depletion

• May cause hepatic injury, including fulminant hepatitis
• Monitor liver function tests periodically

• Anaphylactoid reactions possible
• May cause fluid retention and edema
• May inhibit platelet aggregation

Drug Interactions

• Anticoagulants (warfarin): Increased bleeding risk
• Aspirin: Decreased naproxen efficacy, increased GI toxicity
• ACE inhibitors/ARBs: Reduced antihypertensive effect
• Diuretics: Reduced diuretic efficacy
• Lithium: Increased lithium levels
• Methotrexate: Increased methotrexate toxicity
• Cyclosporine: Increased nephrotoxicity
• SSRIs/SNRIs: Increased bleeding risk
• Corticosteroids: Increased GI toxicity

Adverse Effects

• Dyspepsia
• Heartburn
• Nausea
• Headache
• Dizziness

• Constipation
• Diarrhea
• Rash
• Tinnitus
• Edema

• GI bleeding/perforation
• Myocardial infarction
• Stroke
• Renal failure
• Hepatic failure
• Stevens-Johnson syndrome
• Anaphylaxis

Monitoring Parameters

• Complete blood count
• Renal function tests (BUN, creatinine)
• Liver function tests
• Blood pressure
• Assessment of cardiovascular risk factors

• Signs/symptoms of GI bleeding
• Renal function (periodically)
• Liver function (periodically)
• Blood pressure
• Signs of fluid retention
• Efficacy assessment

• Not routinely required
• Therapeutic range: 30-50 mcg/mL

Patient Education

• Take with food or milk to reduce stomach upset
• Do not crush or chew delayed-release tablets
• Report any signs of GI bleeding (black stools, abdominal pain)
• Monitor for signs of cardiovascular events (chest pain, shortness of breath)
• Avoid alcohol consumption during therapy
• Inform all healthcare providers about NSAID use
• Use lowest effective dose for shortest duration
• Do not use during third trimester of pregnancy
• Report any skin rash or allergic symptoms immediately

• Store at room temperature (15-30°C)
• Keep container tightly closed
• Protect from moisture

References

1. FDA Prescribing Information: Naprosyn (naproxen). 2023 2. American College of Rheumatology Guidelines for NSAID Use. Arthritis Care Res. 2020 3. UpToDate: Naproxen drug information. Wolters Kluwer, 2023 4. Micromedex Solutions: Naproxen monograph. IBM Watson Health, 2023 5. AHFS Drug Information: Naproxen. American Society of Health-System Pharmacists, 2023 6. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw Hill; 2017 7. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023