EC-NAPROSYN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, thereby reducing prostaglandin synthesis, which mediates inflammation, pain, and fever.
| Metabolism | Naproxen is extensively metabolized in the liver via cytochrome P450 (CYP) enzymes, primarily CYP2C9, to 6-O-desmethyl naproxen, and undergoes glucuronidation. |
| Excretion | Renal (95%) as unchanged drug (10%) and conjugated metabolites (60%) and other metabolites (25%); biliary/fecal (5%) |
| Half-life | Terminal elimination half-life 12-17 hours (mean 14 hours); prolonged in elderly and renal impairment |
| Protein binding | >99.7% bound, primarily to albumin |
| Volume of Distribution | 0.16-0.2 L/kg (low, consistent with extensive plasma protein binding) |
| Bioavailability | Oral: 95% (enteric-coated formulation similar to immediate-release) |
| Onset of Action | Oral: 1-2 hours for analgesic effect; 2-4 hours for anti-inflammatory effect |
| Duration of Action | Analgesic: 6-8 hours; anti-inflammatory: up to 12 hours with twice-daily dosing (enteric-coated formulation provides sustained release) |
| Molecular Weight | 230.26 |
500-1000 mg orally twice daily; maximum 1500 mg/day.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: contraindicated. |
| Pediatric use | ≥2 years: 10-20 mg/kg orally twice daily; maximum 1000 mg/day. |
| Geriatric use | Start at lowest effective dose; maximum 1000 mg/day due to increased risk of GI and renal adverse effects. |
| 1st trimester | Avoid. NSAIDs are associated with increased risk of miscarriage and cardiac malformations. Naproxen crosses placenta. Use only if clearly needed. |
| 2nd trimester | Avoid if possible. May cause oligohydramnios and premature closure of ductus arteriosus. Use only for short-term, low-dose if necessary. |
| 3rd trimester | Contraindicated. Risk of premature closure of ductus arteriosus, oligohydramnios, necrotizing enterocolitis, intracranial hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).
| Placental transfer | Naproxen crosses the placenta. Transfer is significant, with cord blood concentrations approximately 50% of maternal plasma levels. In animal studies, naproxen is distributed to fetal tissues. |
| Breastfeeding | Naproxen is excreted into breast milk in low amounts. The relative infant dose is approximately 1% of maternal weight-adjusted dose. While generally considered compatible, avoid in breastfeeding infants with known NSAID sensitivity or bleeding risk. Prolonged use may affect infant platelet function. |
■ 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 occur early in treatment and 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.
| Serious Effects |
History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsPerioperative pain in the setting of coronary artery bypass graft surgeryActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA class III–IV)Third trimester of pregnancy
| Precautions | Cardiovascular thrombotic events, Gastrointestinal bleeding, ulceration, and perforation, Renal toxicity, including renal papillary necrosis, Hypertension, Anaphylactic reactions, Serious skin reactions (e.g., Stevens-Johnson syndrome), Hematologic toxicity (e.g., anemia), Fluid retention and edema, Hepatic toxicity, Asthma exacerbation |
| Food/Dietary |
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| Lactation Rating | L2 (Safer) |
| Teratogenic Risk | First trimester: Risk of cardiac malformations and gastroschisis; avoid use. Second trimester: Use only if clearly needed; may cause oligohydramnios. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus and persistent pulmonary hypertension in the neonate. |
| Fetal Monitoring | Monitor maternal blood pressure, renal function, and signs of gastrointestinal bleeding. In third trimester, fetal echocardiography for ductal patency and amniotic fluid volume assessment is recommended. |
| Fertility Effects | Reversible inhibition of ovulation, implantation, and luteolysis due to prostaglandin synthesis inhibition. May delay or prevent pregnancy; discontinue if fertility desired. |
| Avoid alcohol; may increase risk of GI bleeding. Take with food or milk to minimize GI irritation. Avoid high-potassium foods if renal impairment is a concern (concurrent ACE inhibitors/ARBs). No other specific food restrictions. |
| Clinical Pearls | EC-NAPROSYN is an enteric-coated formulation of naproxen designed to reduce gastric irritation. Onset of action is delayed due to enteric coating; not suitable for acute pain where rapid absorption is needed. Do not crush or chew tablets. Monitor renal function in elderly and patients with creatinine clearance <30 mL/min. Avoid concurrent use of other NSAIDs, including OTC naproxen. Use lowest effective dose for shortest duration. Significant drug interaction with methotrexate, lithium, and anticoagulants. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Swallow tablet whole; do not crush, chew, or break. · Avoid alcohol while taking this medication. · Do not take with other NSAIDs or aspirin. · Contact your doctor if you experience black/tarry stools, vomiting blood, or severe abdominal pain. · May cause dizziness or drowsiness; avoid driving until you know how it affects you. · Stay hydrated; report swelling or weight gain. · Do not take within 2 hours of antacids. |