ANAPROX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ANAPROX (ANAPROX).
Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin synthesis, which mediates inflammation, pain, and fever.
| Metabolism | Primarily hepatic via CYP2C9 and CYP1A2; minor glucuronidation. Metabolites include 6-O-desmethylnaproxen and naproxen conjugates. |
| Excretion | Renal excretion of metabolites (95%) and unchanged drug (<5%); biliary/fecal elimination minor (<5%). |
| Half-life | Terminal elimination half-life 12-17 hours; prolonged in elderly (up to 20 hours) and in renal impairment. |
| Protein binding | >99%, primarily to albumin. |
| Volume of Distribution | 0.2-0.3 L/kg; low Vd indicates extensive protein binding with limited distribution into tissues. |
| Bioavailability | Oral: 95-100%; rectal: ~80%; intramuscular: ~100%. |
| Onset of Action | Oral: 30 minutes to 1 hour; rectal: 30-60 minutes; onset of analgesia within 1 hour. |
| Duration of Action | Analgesic: 4-6 hours; anti-inflammatory: up to 8 hours with sustained dosing. |
250-500 mg orally twice daily; maximum 1.5 g/day; for extended-release: 375-750 mg orally twice daily
| Dosage form | TABLET |
| Renal impairment | CrCl 30-60 mL/min: reduce dose to 250 mg twice daily; CrCl <30 mL/min: not recommended |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use |
| Pediatric use | For juvenile idiopathic arthritis: 5-10 mg/kg/dose orally twice daily; maximum 1 g/day |
| Geriatric use | Initiate at lowest effective dose; maximum 500 mg/day due to increased risk of gastrointestinal bleeding and renal impairment |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ANAPROX (ANAPROX).
| Breastfeeding | Naproxen is excreted into breast milk in low concentrations (M/P ratio approximately 0.01). American Academy of Pediatrics considers it compatible with breastfeeding, but caution is advised due to potential adverse effects on infant cardiovascular and renal systems. Preferable to use alternative analgesics with longer safety data. |
| Teratogenic Risk | First trimester: Avoid; NSAIDs associated with increased risk of miscarriage and cardiac defects. Second trimester: Use only if clearly needed; potential for oligohydramnios and fetal renal effects. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, pulmonary hypertension, and oligohydramnios. |
■ FDA Black Box Warning
Cardiovascular risk: NSAIDs may increase risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk increases with duration of use and in patients with cardiovascular risk factors or pre-existing disease. Gastrointestinal risk: NSAIDs increase risk of serious GI adverse events including bleeding, ulceration, and perforation of stomach or intestines, which can be fatal. Elderly patients and those with prior GI disease are at greater risk.
| Serious Effects |
["Hypersensitivity to naproxen or any component of formulation","History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in setting of coronary artery bypass graft (CABG) surgery","Active GI bleeding or ulcer disease","Severe heart failure","Severe renal impairment (CrCl <30 mL/min)","Third trimester of pregnancy"]
| Precautions | ["Cardiovascular thrombotic events (MI, stroke)","GI bleeding, ulceration, perforation","Renal toxicity (especially in elderly, renal impairment, heart failure, liver dysfunction, diuretic use, ACE inhibitor use)","Hypertension","Heart failure exacerbation","Anaphylactoid reactions","Serious skin reactions (e.g., Stevens-Johnson syndrome)","Hematologic effects (anemia, prolongation of bleeding time)","Hepatic toxicity","Asthma exacerbation (aspirin-sensitive patients)","Use in pregnancy (avoid in third trimester due to premature closure of ductus arteriosus)"] |
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| Fetal Monitoring | Monitor maternal renal function, blood pressure, and signs of fluid retention. In third trimester, assess fetal ductus arteriosus via echocardiography and amniotic fluid volume via ultrasound if used. Monitor infant for jaundice, bleeding, and renal function if exposed near delivery. |
| Fertility Effects | May impair female fertility via inhibition of prostaglandin synthesis affecting ovulation; reversible upon discontinuation. No direct male fertility effects reported. |
| Food/Dietary | Avoid alcohol. Take with food or milk to minimize GI irritation. No other significant food interactions. |
| Clinical Pearls | ANAPROX (naproxen sodium) has a faster onset than naproxen base due to enhanced absorption. Use with caution in patients with cardiovascular risk; may increase thromboembolic events. Reversible inhibition of platelet aggregation occurs; stop 2–3 days before surgery. Monitor renal function in elderly, dehydrated, or those on ACEi/diuretics. Not recommended for periprocedural pain in CABG. May cause pseudoporphyria in children with chronic use. |
| Patient Advice | Take with food or milk to reduce gastrointestinal upset. · Do not exceed prescribed dose; risk of bleeding or kidney injury increases with higher doses. · Avoid alcohol while taking this medication. · Report signs of stomach bleeding: black/tarry stools, vomit that looks like coffee grounds. · Consult doctor before taking other OTC NSAIDs or pain relievers. · If you have asthma, watch for breathing difficulty after taking. |