ALEVE PM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALEVE PM (ALEVE PM).
Diphenhydramine is a histamine H1 receptor antagonist that competes with histamine for binding at H1 receptor sites, reducing symptoms of allergic reactions and causing sedation. Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, decreasing synthesis of prostaglandins, which reduces pain and inflammation.
| Metabolism | Naproxen is extensively metabolized in the liver via CYP1A2 and CYP2C9 enzymes, primarily to 6-desmethylnaproxen. Diphenhydramine is metabolized in the liver via CYP2D6 to diphenylmethoxyacetic acid and other metabolites; undergoes extensive first-pass metabolism. |
| Excretion | Naproxen: renal (95% as unchanged drug and metabolites, primarily as naproxen and 6-O-desmethyl naproxen). Diphenhydramine: renal (50-60% as unchanged drug and metabolites, primarily as diphenhydramine and nor diphenhydramine); small amounts in feces. |
| Half-life | Naproxen: 12-17 hours (mean 13.6 hours); sufficient for twice-daily dosing; prolonged in renal impairment. Diphenhydramine: 2.4-9.3 hours (mean 5.5 hours); longer in elderly, hepatic impairment. |
| Protein binding | Naproxen: >99% bound to albumin. Diphenhydramine: 80-85% bound to albumin, alpha-1-acid glycoprotein. |
| Volume of Distribution | Naproxen: 0.16 L/kg (low, indicates limited tissue distribution). Diphenhydramine: 3-5 L/kg (large, extensive tissue binding). |
| Bioavailability | Naproxen: ~95% (oral). Diphenhydramine: 40-60% (oral, first-pass metabolism). |
| Onset of Action | Naproxen: 30-60 minutes (oral). Diphenhydramine: 15-60 minutes (oral). |
| Duration of Action | Naproxen: up to 12 hours (pain relief). Diphenhydramine: 4-6 hours (sedation). |
1 tablet (220 mg naproxen sodium / 25 mg diphenhydramine HCl) orally at bedtime as needed. Maximum: 2 tablets in 24 hours.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <30 mL/min. For CrCl 30-59 mL/min, reduce naproxen dose or avoid use. No specific dose adjustment for diphenhydramine, but use with caution. |
| Liver impairment | Child-Pugh Class A: No adjustment needed. Child-Pugh Class B or C: Avoid use of naproxen. Diphenhydramine: Use with caution and consider dose reduction. |
| Pediatric use | Not recommended for children under 12 years. For ages 12-17: Limit to 1 tablet at bedtime, not to exceed 1 tablet in 24 hours. Use under medical supervision. |
| Geriatric use | Initiate at the lowest effective dose (1 tablet at bedtime). Monitor for gastrointestinal bleeding, renal function, hypotension, and anticholinergic effects. Avoid in patients with significant renal impairment or dementia. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ALEVE PM (ALEVE PM).
| Breastfeeding | Naproxen and diphenhydramine are excreted into breast milk. Naproxen M/P ratio ~0.01; low oral bioavailability to infant. Diphenhydramine M/P ratio ~0.80; may cause drowsiness or fussiness in infant. Use with caution, especially in premature or high-risk infants. |
| Teratogenic Risk | First trimester: NSAID use associated with increased risk of spontaneous abortion and congenital malformations (e.g., cardiac defects). Avoid. Second trimester: Use only if clearly needed; potential for decreased fetal renal function and oligohydramnios. Third trimester: Contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and fetal renal impairment. |
■ FDA Black Box Warning
NSAIDs may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. Risk may increase with duration of use and in patients with cardiovascular risk factors. NSAIDs are contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
["Hypersensitivity to naproxen, diphenhydramine, or any component","History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in the setting of CABG surgery","Advanced renal disease","Concurrent use with other NSAIDs or aspirin","Pregnancy (especially third trimester) as it may cause premature closure of ductus arteriosus"]
| Precautions | ["Cardiovascular risk: increased risk of thrombotic events, MI, stroke, particularly with prolonged use and in patients with risk factors","Gastrointestinal risk: increased risk of GI bleeding, ulceration, and perforation; caution in patients with history of GI disease","Renal toxicity: NSAIDs may cause renal impairment; avoid in patients with advanced renal disease","Hepatic effects: elevated liver enzymes; discontinue if liver disease develops","Sedation: diphenhydramine may cause marked drowsiness; avoid driving or operating machinery","Anticholinergic effects: caution in patients with glaucoma, prostatic hypertrophy, or urinary retention"] |
Loading safety data…
| Fetal Monitoring | Monitor fetal ultrasound for oligohydramnios and ductus arteriosus flow if used beyond 28 weeks. Assess maternal renal function, blood pressure, and signs of bleeding. Consider fetal echocardiography if prolonged use. |
| Fertility Effects | NSAIDs may reversibly impair female fertility by inhibiting prostaglandin synthesis, affecting ovulation. Diphenhydramine has no known significant impact on fertility. |
| Food/Dietary | Avoid alcohol. Taking with food may decrease GI irritation. Avoid grapefruit juice? No known interaction; however, naproxen is metabolized by CYP2C9 and CYP1A2, and grapefruit affects CYP3A4, so interaction unlikely. Still, caution with high-fat meals may delay absorption but not clinically significant. |
| Clinical Pearls | ALEVE PM contains naproxen (NSAID) and diphenhydramine (antihistamine/sedative). Avoid concurrent use of other NSAIDs, anticoagulants, or CNS depressants. Use with caution in elderly, renal impairment, or history of GI bleeding. Max naproxen dose 440 mg/day; diphenhydramine may cause anticholinergic effects. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not exceed 2 tablets in 24 hours. · Do not use with other NSAIDs or pain relievers. · May cause drowsiness; avoid driving or operating machinery. · Avoid alcohol while taking this medication. · Do not use for more than 10 days for pain or 3 days for fever. · Stop and consult doctor if allergic reaction, chest pain, or bleeding occurs. |