NAPROXEN
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), thereby reducing the synthesis of prostaglandins involved in inflammation, pain, and fever.
| Metabolism | Primarily hepatic metabolism via CYP1A2 and CYP2C9; also undergoes glucuronidation and other conjugation reactions. |
| Excretion | Primarily renal (95% as unchanged naproxen and 6-O-desmethylnaproxen); <5% fecal via biliary excretion. |
| Half-life | Terminal elimination half-life 12-17 hours (mean 14 hours); permits twice-daily dosing. Half-life prolonged in elderly and hepatic impairment. |
| Protein binding | >99% bound to albumin. |
| Volume of Distribution | 0.16 L/kg; low Vd indicates extensive protein binding and limited tissue distribution. |
| Bioavailability | Oral: 95% (naproxen base); rectal: 80% (suppository). |
| Onset of Action | Oral: 1 hour for analgesic effect; rectal: 30-60 minutes; no parenteral form available. |
| Duration of Action | Analgesic: up to 12 hours; anti-inflammatory: up to 24 hours with regular dosing. |
250-500 mg orally twice daily; maximum 1.5 g/day. For extended-release: 750-1000 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose to 500 mg twice daily maximum. GFR <30 mL/min: contraindicated. Avoid in patients with creatinine clearance <20 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%; maximum 500 mg/day. Child-Pugh C: contraindicated. |
| Pediatric use | Children ≥2 years: 5-10 mg/kg/dose orally every 8-12 hours; maximum total daily dose 20 mg/kg/day. For juvenile idiopathic arthritis: 10-15 mg/kg/day in 2 divided doses. |
| Geriatric use | Initiate at lowest effective dose, typically 250 mg twice daily. Monitor renal function and gastrointestinal bleeding risk. Avoid doses >1 g/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| Breastfeeding | Small amounts excreted in milk (M/P ratio ~0.01); relative infant dose ~0.1-0.3% of weight-adjusted maternal dose. Considered compatible with breastfeeding; observe infant for gastrointestinal effects and rash. Prefer short-term use. |
| Teratogenic Risk | First trimester: Increased risk of spontaneous abortion and congenital malformations (cardiac defects, gastroschisis) in some studies, though data conflicting. Second trimester: Use only if clearly needed; avoid premature ductus arteriosus closure. Third trimester (after 30 weeks): Avoid; irreversible oligohydramnios (due to fetal renal effects) and premature closure of ductus arteriosus with persistent pulmonary hypertension. Use >48 hours before delivery increases risk of maternal and fetal hemorrhage and prolongs labor. |
■ FDA Black Box Warning
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. Naproxen is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | inflammation |
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs; perioperative pain in the setting of CABG surgery; patients with known hypersensitivity to naproxen; patients with severe uncontrolled heart failure; active gastrointestinal bleeding or ulceration.
| Precautions | Cardiovascular thrombotic events; gastrointestinal bleeding, ulceration, and perforation; renal toxicity; hypertension; heart failure; anaphylactoid reactions; serious skin reactions; hematologic toxicity; masking of infection; ophthalmic effects; hepatic effects; asthma; use with corticosteroids; use in patients with prior ulcer disease; pregnancy (avoid in third trimester). |
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| Fetal Monitoring | Fetal: Ultrasound for oligohydramnios and ductus arteriosus if used after 20 weeks GA; Doppler studies if oligohydramnios detected. Maternal: Renal function, blood pressure, and signs of bleeding (PPH risk). Monitor for NSAID-related adverse effects (GI, renal). |
| Fertility Effects | Reversible inhibition of prostaglandin synthesis may impair follicle rupture and ovulation, delaying conception. Use may increase risk of luteinized unruptured follicle syndrome. Effects resolve upon discontinuation. |