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) |
| Molecular Weight | 252.3 |
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 | Avoid; associated with increased risk of spontaneous abortion and cardiac defects. |
| 2nd trimester | Use with caution; may cause oligohydramnios and premature ductus arteriosus constriction. |
| 3rd trimester | Avoid; risk of premature ductus arteriosus closure, oligohydramnios, and neonatal renal impairment. |
Clinical note
ACE inhibitors and ARBs may have diminished antihypertensive effect Increases risk of serious cardiovascular thrombotic events and GI bleeding.
| FDA category | Positive |
| Placental transfer | Crosses placenta; fetal concentrations approximately 1% of maternal levels. |
| Breastfeeding |
■ 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 |
History of hypersensitivity to naproxen or other NSAIDsHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsCoronary artery bypass graft surgery
| 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) |
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| Minimal excretion into breast milk; considered compatible with breastfeeding due to low infant dose. |
| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | 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. |
| Food/Dietary | Avoid alcohol consumption; both alcohol and naproxen can increase the risk of GI bleeding. No specific food restrictions, but taking with food may reduce GI irritation. High-sodium foods should be limited in patients with hypertension or heart failure due to the sodium content of the drug. |
| Clinical Pearls | Naproxen sodium, a propionic acid derivative and nonselective COX inhibitor, has a longer half-life (12-17 h) than other NSAIDs, allowing twice-daily dosing. Due to its sodium content (20 mg per 220 mg tablet), use cautiously in hypertension, heart failure, or renal impairment. Onset of analgesia is ~1 h with peak at 2-4 h. Consider gastroprotection with a PPI or misoprostol in high-risk patients (age >65, prior GI bleed, concurrent corticosteroids or anticoagulants). Avoid in patients with CrCl <30 mL/min, severe heart failure, or perioperative pain in CABG surgery. Naproxen can reduce the antihypertensive effect of ACE inhibitors, ARBs, and beta-blockers, and decrease loop diuretic efficacy. It may also potentiate lithium and methotrexate toxicity. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not take more than 2 tablets (440 mg) in 24 hours for OTC use without consulting a doctor. · Report signs of stomach bleeding: black/tarry stools, vomit that looks like coffee grounds, or severe abdominal pain. · Avoid alcohol consumption while taking this medication. · Do not use with other NSAIDs or pain relievers (e.g., ibuprofen, aspirin) unless directed by a healthcare provider. · Stay hydrated and monitor for swelling of ankles/feet, especially if you have high blood pressure or heart disease. · Naproxen sodium contains sodium; check with your doctor if you are on a low-sodium diet. · If you are pregnant or planning to become pregnant, avoid use in the third trimester (can harm the fetal cardiovascular system). · Do not use for more than 10 days for pain or 3 days for fever unless directed by a doctor. |