naproxen (Aleve, EC Naprosyn, Anaprox, Anaprox DS, Naprosyn, Midol Extended Relief, Naprox Sodium, Naproxen EC, Naproxen SR, Naprelan, Pamprin All Day)
Classes: NSAIDs
Dosing and uses of Aleve, Anaprox (naproxen)
Adult dosage forms and strengths
tablet
- 220mg (OTC)
- 250mg
- 275mg
- 375mg
- 500mg
- 550mg
tablet delayed release
- 375mg
- 500mg
tablet extended release
- 375mg
- 500mg
- 750mg
capsule
- 220mg
oral suspension
- 25mg/mL
Pain
500 mg PO initially, then 250 mg PO q6-8hr or 500 mg PO q12hr PRN; not to exceed 1250 mg/day naproxen base on day 1; subsequent daily doses should not exceed 1000 mg naproxen base
Extended release: 750-1000 mg PO qDay; may temporarily increase to 1500 mg/day if tolerated well and clinically indicated
Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis
500-1000 mg/day PO divided q12hr; may increase to 1500 mg/day if tolerated well for limited time
Extended release: 750-1000 mg PO qDay; may temporarily increase to 1500 mg/day if tolerated well and clinically indicated
Dysmenorrhea
500 mg PO initially, then 250 mg PO q6-8hr or 500 mg PO q12hr (long-acting formula); not to exceed 1250 mg/day on first day; subsequent doses should not exceed 1000 mg/day naproxen base
Gout, Acute
750 mg PO initially, followed by 250 mg q8hr until attack subsides
Extended release: 1000-1500 mg qDay, followed by 1000 mg qDay until attack subsides
Migraine (Off-label)
750 mg PO initially, may give additional 250-500 mg if necessary; not to exceed 1250 mg in 24 hr
Dosing Considerations
220 mg of naproxen sodium contains 200 mg of naproxen
Delayed-release formulation not recommended for acute pain
Take with food or 8-12 oz of water to avoid gastrointestinal (GI) effects
Dosing Modifications
CrCl <30 mL/min: Use not recommended
Pediatric dosage forms and strengths
tablet
- 220mg (OTC)
- 250mg
- 275mg
- 375mg
- 500mg
- 550mg
tablet delayed release
- 375mg
- 500mg
tablet extended release
- 375mg
- 500mg
- 750mg
capsule
- 220mg
oral suspension
- 25mg/mL
Pain
>2 years
- Cancer pain (off-label): 5-7 mg/kg PO q8-12hr; not to exceed 1000 mg/day
>12 years
- 500 mg PO initially, then 250 mg PO q6-8hr or 500 mg PO q12hr PRN; not to exceed 1250 mg/day naproxen base on day 1; subsequent daily doses should not exceed 1000 mg naproxen base
- Extended release: 750-1000 mg PO qDay; may temporarily increase to 1500 mg/day if tolerated well and clinically indicated
Juvenile Idiopathic Arthritis
>2 years: 10 mg/kg/day oral suspension PO divided q12hr; not to exceed 15 mg/kg/day
Aleve, Anaprox (naproxen) adverse (side) effects
1-10%
Abdominal pain (3-9%)
Constipation (3-9%)
Dizziness (3-9%)
Drowsiness (3-9%)
Headache (3-9%)
Heartburn (3-9%)
Nausea (3-9%)
Edema (3-9%)
GI bleeding (1-4%)
GI perforation (1-4%)
Lightneadedness (<3%)
GI ulcers (1-4%)
Fluid retention (3-9%)
Diarrhea (1-3%)
Stomatitis (<3%)
Diverticulitis (1-3%)
Dyspnea (3-9%)
Hearing disturbances (<3%)
<1%
Meaningful (3 × upper limit of normal) elevation of serum alanine aminotransferase or aspartate aminotransferase
Warnings
Black box warnings
Cardiovascular risk
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
- Risk may increase with duration of use
- Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
- NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery
Gastrointestinal risk
- NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal
- GI adverse events may occur at any time during use and without warning symptoms
- Elderly patients are at greater risk for serious GI events
Contraindications
Absolute: Aspirin allergy; perioperative pain in setting of coronary artery bypass graft (CABG) surgery
Relative: Bleeding disorders, delayed esophageal transit, hepatic disease, peptic ulcer, renal impairment, stomatitis, late pregnancy (may cause premature closure of ductus arteriosus)
Cautions
Use caution in congestive heart failure (CHF), hypertension, renal/hepatic impairment, or aspirin sensitive asthma
May increase risk of aseptic meningitis, especially in patients with systemic lupus erythematosis and mixed connective tissue disorders
Prolonged use may increase risk of adverse cardiovascular events
May cause anaphylactoid reactions, even in patients with no prior exposure to NSAIDs
Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
May cause drowsiness, dizziness, and blurred vision
Platelet aggregation and adhesion may be decreased; may prolong bleeding time; monitor closely patients with coagulation disorders
May increase risk of hyperkalemia in the elderly, renal disease, or diabetics, especially when used concomitantly with drugs that increase hyperkalemia
May cause serious skin reactions including exfoliative dermatitis, toxic epidermal syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue therapy at first sign of skin rash
May cause new-onset of hypertension; monitor blood pressure closely throughout therapy
OTC use not for children <12 years
Withhold for at least 4-6 half-lives prior to surgery or dental procedure
Heart Failure (HF) risk
- NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
- NSAIDS should be avoided or withdrawn whenever possible
- AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134
Pregnancy and lactation
Pregnancy category: C; D if used for prolonged periods or after 31-32 weeks gestation
Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and approximately 2.6% of controls
Lactation: Drug excreted in breast milk; effect on infant unknown; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aleve, Anaprox (naproxen)
Mechanism of action
Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2
May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity
Absorption
Bioavailability: 95%
Onset: 30-60 min
Duration: < 12 hr
Peak serum time: 1-4 hr (tablets); 2-12 hr (delayed release empty stomach); 4-24 hr (delayed relase with food)
Peak plasma concentration: 62-96 mcg/mL
Distribution
Protein bound: <99%
Vd: 0.16 L/kg
Metabolism
Metabolized in liver via conjugation
Metabolites: 6-Desmethylnaproxen, glucuronide conjugates
Enzymes inhibited: COX-1, COX-2
Elimination
Half-life: 12-17 hr
Dialyzable: No value
Clearance: 0.13 mL/min/kg
Excretion: Urine (95%), feces (<3%)
