Naproxen Sodium

Approved Indications:

• Pain Management:
• Mild to moderate acute pain (e.g., musculoskeletal, dental, post-operative)
• Primary dysmenorrhea (menstrual cramps)
• Inflammatory and Rheumatic Conditions:
• Osteoarthritis
• Rheumatoid arthritis (including juvenile idiopathic arthritis)
• Ankylosing spondylitis
• Acute Gout:
• Relief of signs and symptoms during gout flare-ups
• Fever Reduction:
• Short-term symptomatic relief of fever in both adults and children

Clinically Accepted Off-label Uses:

• Migraine (acute treatment)
• Post-episiotomy pain relief
• Pericarditis (as first-line NSAID)
• Post-traumatic inflammation (e.g., sprains, strains)

Route of Administration: Oral (tablet, capsule, suspension); rectal suppository (rare)

Adults:

• Pain or Dysmenorrhea:
• Initial dose: 550 mg
• Follow-up: 275 mg every 6–8 hours as needed
• Max: 1,375 mg/day on day 1, then 1,100 mg/day
• Rheumatic Diseases:
• 250–500 mg twice daily
• Max: 1,500 mg/day (short term only)
• Acute Gout:
• 825 mg initially, then 275 mg every 8 hours until symptoms resolve

Pediatrics (≥2 years):

• Juvenile Idiopathic Arthritis:
• 10–15 mg/kg/day in 2 divided doses
• Oral suspension preferred in younger children

Elderly:

• Start at the lower end of the dosing range
• Monitor renal function and GI tolerance closely

Renal Impairment:

• Contraindicated in severe impairment (CrCl <30 mL/min)
• Use lowest effective dose in mild to moderate impairment

Hepatic Impairment:

• Use with caution
• Periodic liver function monitoring recommended in long-term use

Naproxen sodium is a nonselective NSAID that inhibits both COX-1 and COX-2 enzymes, which are responsible for the conversion of arachidonic acid into prostaglandins. These prostaglandins mediate pain, inflammation, and fever. By suppressing their production, naproxen reduces peripheral and central sensitization of pain receptors, lowers fever by resetting the hypothalamic thermostat, and diminishes inflammation at sites of tissue damage. The sodium form ensures faster absorption and quicker onset compared to naproxen base.

• Absorption:
• Rapidly and almost completely absorbed
• Onset faster with sodium salt (within 30–60 minutes)
• Bioavailability:
• Approximately 95%
• Distribution:
• 99% bound to plasma proteins
• Crosses placenta and detectable in breast milk
• Metabolism:
• Extensively metabolized in the liver to 6-O-desmethyl naproxen (inactive)
• Elimination:
• Half-life: 12–17 hours (longer in elderly)
• Excreted mainly via urine (unchanged and as metabolites)

• Pregnancy:
• Category C (1st and 2nd trimesters): Use only if clearly needed
• Category D (3rd trimester): Contraindicated due to risk of premature closure of ductus arteriosus
• Lactation:
• Excreted in small amounts in breast milk
• Generally considered safe for short-term use in breastfeeding mothers
• Caution advised with prolonged use

• Primary Class: Nonsteroidal Anti-inflammatory Drug (NSAID)
• Subclass: Propionic acid derivative; nonselective COX inhibitor

• Hypersensitivity to naproxen or other NSAIDs
• History of asthma, urticaria, or allergic-type reactions after NSAID use
• Active peptic ulcer or GI bleeding
• Severe renal impairment (CrCl <30 mL/min)
• Advanced hepatic disease
• Perioperative pain in CABG surgery
• Third trimester of pregnancy

• Cardiovascular Risk:
• May increase risk of myocardial infarction and stroke
• Gastrointestinal Toxicity:
• GI bleeding, ulceration, and perforation can occur without warning
• Renal Effects:
• NSAIDs may cause renal impairment, especially with prolonged use
• Hepatic Effects:
• Rare cases of hepatitis and liver failure reported
• Fluid Retention and Hypertension:
• Use cautiously in heart failure or uncontrolled hypertension
• Anemia and Hematologic Effects:
• May cause or worsen anemia; monitor hemoglobin and hematocrit in long-term use
• Skin Reactions:
• Rare but serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis
• Elderly Caution:
• Higher risk of GI bleeding, renal dysfunction, and cardiovascular events

Common (≥1%):

• GI: Nausea, dyspepsia, heartburn, abdominal pain, constipation
• CNS: Headache, dizziness, drowsiness
• Dermatologic: Rash, pruritus
• Renal: Edema

Serious / Rare:

• GI bleeding, ulcers, perforation
• Acute renal failure, interstitial nephritis
• Hepatitis, elevated liver enzymes
• Cardiovascular events (MI, stroke)
• Hypersensitivity reactions (angioedema, anaphylaxis)
• Aseptic meningitis (especially in lupus patients)

• Anticoagulants (e.g., warfarin):
• Increased risk of GI bleeding
• Other NSAIDs or aspirin:
• Additive GI and renal toxicity
• ACE inhibitors / ARBs / Diuretics:
• Reduced antihypertensive efficacy and increased nephrotoxicity
• Lithium:
• Increased serum lithium levels and toxicity
• Methotrexate:
• May decrease clearance, increasing toxicity risk
• SSRIs / SNRIs:
• Additive risk of bleeding
• Enzyme Pathways:
• Metabolized via hepatic pathways; not a major CYP450 substrate

• FDA (2020):
• NSAID use during the second half of pregnancy may cause rare but serious kidney problems in unborn babies
• NICE & EMA (2023):
• Continued recommendation to use NSAIDs at the lowest effective dose for the shortest duration, especially in patients with cardiovascular or GI risk factors
• Updated Arthritis Guidelines:
• Emphasis on co-prescription of proton pump inhibitors (PPIs) for patients on chronic NSAIDs with GI risk

• Temperature:
• Store at 20°C to 25°C (68°F to 77°F)
• Humidity & Light:
• Protect from excessive heat, moisture, and direct sunlight
• Handling Instructions:
• Keep in original container
• Do not use if tablets are discolored or expired
• Store oral suspension tightly closed; shake well before use