naproxen/diphenhydramine (OTC)

Brand and Other Names:Aleve PM
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Dosing & Uses


Dosing Forms & Strengths



  • 220mg/25mg

Sleeplessness due to Pain

2 tablets (440mg/50mg) PO at bedtime PRN

Dosage Forms & Strengths



  • 220mg/25mg

Sleeplessness due to Pain

<12 years: Safety and efficacy not established

≥12 years: 2 tablets (440mg/50mg) PO at bedtime PRN



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            Adverse Effects



            • Abdominal pain
            • GI bleeding
            • Nausea
            • Edema
            • Fluid retention


            • Sedation
            • Anticholinergic effects
            • Xerostomia
            • Blurred vision
            • Palpitations


            Black Box Warnings

            Cardiovascular risk

            • Nonsteroidal anti-inflammatory drugs (NSAIDs) may increase risk of serious cardiovascular thrombotic events, myocardial infarction (MI), and stroke, which can be fatal
            • Risk may increase with duration of use
            • Patients with existing cardiovascular disease or risk factors for such disease may be at greater risk
            • NSAIDs are contraindicated for perioperative pain in setting of coronary artery bypass graft (CABG) surgery

            Gastrointestinal risk

            • NSAIDs increase risk of serious GI adverse events, including bleeding, ulceration, and gastric or intestinal perforation, which can be fatal GI adverse events may occur at any time during use and without warning symptoms
            • Elderly patients are at greater risk for serious GI events




            • Absolute: Aspirin allergy; perioperative pain in setting of coronary artery bypass graft (CABG) surgery
            • Relative: Bleeding disorders, delayed esophageal transit, hepatic disease, peptic ulcer, renal impairment, stomatitis, late pregnancy (may cause premature closure of ductus arteriosus


            • Coadministration with MAOIs



            • Use caution in congestive heart failure (CHF), hypertension, renal/hepatic impairment, or aspirin sensitive asthma
            • May increase risk of aseptic meningitis, especially in patients with systemic lupus erythematosis and mixed connective tissue disorders
            • Prolonged use may increase risk of adverse cardiovascular events
            • May cause anaphylactoid reactions, even in patients with no prior exposure to NSAIDs
            • Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include elderly individuals, those with impaired renal function, hypovolemia, heart failure, liver dysfunction, or salt depletion, and those taking diuretics, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
            • May cause drowsiness, dizziness, and blurred vision
            • Platelet aggregation and adhesion may be decreased; may prolong bleeding time; monitor closely patients with coagulation disorders
            • May increase risk of hyperkalemia in the elderly, renal disease, or diabetics, especially when used concomitantly with drugs that increase hyperkalemia
            • May cause serious skin reactions including exfoliative dermatitis, toxic epidermal syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue therapy at first sign of skin rash


            • Driving or operating machinery
            • May potentiate effects of sedatives such as alcohol
            • Narrow-angle glaucoma
            • Prostatic hypertrophy
            • Stenosing peptic ulcer, pyloroduodenal obstruction
            • Bladder neck obstruction
            • Elderly patients: Considered high-risk medication for this age group because it may increase risk of falls and has high incidence of anticholinergic effects; may exacerbate existing lower urinary tract conditions or benign prostatic hyperplasia; use in special situations may be appropriate; not recommended for treatment of insomnia, because tolerance develops and risk of anticholinergic effects increases
            • Debilitated patients

            Pregnancy & Lactation

            Pregnancy category (naproxen): C; D if used for prolonged periods or after 31-32 weeks gestation; may cause premature closure of ductus arteriosus

            Naproxen: Quebec Pregnancy Registry identified 4705 women who had spontaneous abortions by 20 weeks' gestation; each case was matched to 10 control subjects (n=47,050) who had not had spontaneous abortions; exposure to nonaspirin NSAIDs during pregnancy was documented in approximately 7.5% of cases of spontaneous abortions and approximately 2.6% of controls

            Lactation: Naproxen and diphenhydramine are excreted in human breast milk; effect on infant unknown; not recommended

            Pregnant or breastfeeding patients should seek advice of health professional before using OTC drugs

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Naproxen: Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclooxygenase (COX) isoenzymes, COX-1 and COX-2

            Diphenhydramine: Histamine H1-receptor antagonist that elicits sedative effects



            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.