NAPROXEN SODIUM
Clinical safety rating: avoid
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
Non-selective cyclooxygenase (COX-1 and COX-2) inhibitor, reducing prostaglandin synthesis.
| Metabolism | Primarily hepatic metabolism via CYP1A2 and CYP2C9; minor pathways include glucuronidation. |
| Excretion | Renal: 95% (as unchanged drug, conjugated naproxen, and 6-O-desmethyl naproxen); Fecal: <5% |
| Half-life | 12–17 hours (terminal); allows twice-daily dosing; prolonged in elderly and renal impairment |
| Protein binding | >99% bound to albumin |
| Volume of Distribution | 0.16 L/kg (approx 11 L/70 kg); indicates limited extravascular distribution |
| Bioavailability | Oral: 95% (naproxen sodium); rectal suppository: >80% |
| Onset of Action | Oral: 1 hour for analgesic effect; peak effect 2–4 hours |
| Duration of Action | 7–12 hours (analgesic); 12–14 hours (anti-inflammatory) |
220-550 mg orally twice daily; maximum 1375 mg/day.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-89 mL/min: no adjustment needed. eGFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B or C: use with caution; reduce dose by 50% or avoid. |
| Pediatric use | ≥2 years: 2.5-10 mg/kg/dose every 8-12 hours; maximum 15 mg/kg/day. |
| Geriatric use | Consider lower starting dose (e.g., 220 mg twice daily); monitor renal function and GI bleeding risk; maximum 1100 mg/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.
| FDA category | Positive |
| Breastfeeding | Naproxen sodium excreted into breast milk in low amounts (M/P ratio approximately 0.01). Relative infant dose <1% of maternal weight-adjusted dose. Considered compatible with breastfeeding, but avoid in preterm infants or those with thrombocytopenia, renal impairment, or ductal-dependent cardiac lesions. Monitor for gastrointestinal effects or drowsiness in infants. |
| Teratogenic Risk |
■ 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. NSAIDs are contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Common Effects | inflammation |
| Serious Effects |
["Hypersensitivity to naproxen or any NSAID","History of asthma, urticaria, or allergic reaction after taking aspirin or other NSAIDs","Perioperative pain in CABG surgery","Advanced renal disease","Active peptic ulcer disease or gastrointestinal bleeding"]
| Precautions | ["Cardiovascular thrombotic events","Gastrointestinal bleeding, ulceration, and perforation","Hypertension","Heart failure exacerbation","Renal toxicity","Anaphylactoid reactions","Serious skin reactions (e.g., Stevens-Johnson syndrome)","Hematologic effects (anemia, bleeding)","Hepatic effects (elevated liver enzymes)","Asthma exacerbation in aspirin-sensitive patients","Use in pregnancy (avoid in third trimester)"] |
Loading safety data…
| First trimester: Limited data suggest a small increased risk of oral clefts and cardiac malformations. Second trimester: No specific fetal risks documented beyond general NSAID effects. Third trimester: Avoid after 30 weeks gestation due to risk of premature closure of ductus arteriosus (hazard ratio 2.12 for closure) and oligohydramnios; associated with neonatal renal impairment and pulmonary hypertension. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and signs of gastrointestinal bleeding during chronic use. In third trimester, assess amniotic fluid volume (ultrasound for oligohydramnios), fetal ductus arteriosus patency (echocardiography if indicated), and fetal growth. Monitor neonatal end-organ perfusion and renal function if used near delivery. |
| Fertility Effects | Naproxen sodium may impair fertility in females by interfering with ovulation via inhibition of prostaglandin synthesis. This effect is reversible upon discontinuation. Male fertility: Potential reduction in semen quality (decreased sperm motility and count) based on NSAID class effects; data for naproxen alone are limited. |