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. |
| Molecular Weight | 230.26 |
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 | Avoid; associated with increased risk of miscarriage and congenital malformations (e.g., cardiac defects, gastroschisis). NSAIDs should be avoided during first trimester unless absolutely necessary. |
| 2nd trimester | Caution; may cause oligohydramnios and fetal renal dysfunction. Use only if potential benefit outweighs risk, at lowest effective dose and shortest duration. |
| 3rd trimester | Avoid; risk of premature closure of ductus arteriosus, persistent pulmonary hypertension, oligohydramnios, and impaired platelet function. Contraindicated after 30 weeks gestation. |
Clinical note
Comprehensive clinical and safety monograph for ANAPROX (ANAPROX).
| Placental transfer | Naproxen crosses the placenta; measurable levels in fetal plasma. Higher degree of transfer in third trimester due to increased placental surface area. |
| Breastfeeding | Naproxen passes into breast milk in low amounts. The relative infant dose (RID) is approximately 1-3% of the maternal weight-adjusted dose. No reports of adverse effects in breastfed infants, but caution is advised due to potential for infant gastrointestinal or renal effects. Consider using an alternative with a shorter half-life, such as ibuprofen, if available. |
■ 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 formulationHistory of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDsActive peptic ulcer disease or gastrointestinal bleedingSevere heart failure (NYHA class III-IV)Coronary artery bypass graft (CABG) surgery perioperative painThird trimester of pregnancy (after 30 weeks gestation)Severe renal impairment (CrCl <30 mL/min)History of significant gastrointestinal bleeding or perforation related to previous NSAID therapy
| 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) |
Loading safety data…
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |