EC-NAPROSYN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).

How it works

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.

What the body does with it

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)

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).

Breastfeeding	Naproxen is excreted in breast milk in small amounts (M/P ratio approximately 0.01). Use with caution, especially in infants with compromised renal function or bleeding risk. Short-term use is likely compatible; avoid prolonged use.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to naproxen or any component of the formulation","History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery","Advanced renal disease","Active peptic ulcer disease or GI bleeding"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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EC-NAPROSYN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).

How it works

What the body does with it

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)

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EC-NAPROSYN (EC-NAPROSYN).

Breastfeeding	Naproxen is excreted in breast milk in small amounts (M/P ratio approximately 0.01). Use with caution, especially in infants with compromised renal function or bleeding risk. Short-term use is likely compatible; avoid prolonged use.
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.