ADVIL PM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADVIL PM (ADVIL PM).
Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis. Diphenhydramine is a first-generation antihistamine that antagonizes histamine H1 receptors, causing sedation.
| Metabolism | Ibuprofen is primarily metabolized via hepatic oxidation by CYP2C9. Diphenhydramine is metabolized via hepatic N-demethylation and oxidation, primarily by CYP2D6. |
| Excretion | Ibuprofen: Renal (90% as metabolites and conjugates, <10% unchanged); Diphenhydramine: Renal (primarily as metabolites, ~1% unchanged). Fecal excretion is negligible for both. |
| Half-life | Ibuprofen: 2-4 hours (terminal); clinical context: steady state achieved in 1 day, not affected by renal impairment. Diphenhydramine: 4-8 hours (terminal); clinical context: prolonged in hepatic impairment. |
| Protein binding | Ibuprofen: >99% bound to albumin; Diphenhydramine: 78-85% bound to albumin. |
| Volume of Distribution | Ibuprofen: 0.1-0.2 L/kg; small Vd consistent with high protein binding. Diphenhydramine: 4.5-8.5 L/kg; large Vd indicating extensive tissue distribution. |
| Bioavailability | Ibuprofen: 80-100% (oral); Diphenhydramine: 50-70% (oral) due to first-pass metabolism. |
| Onset of Action | Ibuprofen: 30-60 minutes (oral); Diphenhydramine: 30-60 minutes (oral). |
| Duration of Action | Ibuprofen: 4-6 hours (analgesic/antipyretic); Diphenhydramine: 4-8 hours (sedative). Clinical note: diphenhydramine's sedative effect may outlast analgesic effect of ibuprofen. |
Two caplets (ibuprofen 200 mg, diphenhydramine citrate 38 mg) orally at bedtime as needed for insomnia. Maximum: 2 caplets in 24 hours.
| Dosage form | CAPSULE |
| Renal impairment | Avoid use in GFR <30 mL/min. For GFR 30-59 mL/min, limit to single dose and avoid chronic use. No adjustment needed for GFR ≥60 mL/min. |
| Liver impairment | Contraindicated in Child-Pugh Class C. In Child-Pugh Class B, reduce dose by 50% (max 1 caplet) and monitor for toxicity. No adjustment for Child-Pugh Class A. |
| Pediatric use | Not recommended for children under 12 years. For age ≥12 years, same adult dose: 2 caplets at bedtime. |
| Geriatric use | Start with lowest effective dose (1 caplet) at bedtime to minimize anticholinergic and GI adverse effects. Avoid in elderly with cognitive impairment or high fall risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADVIL PM (ADVIL PM).
| Breastfeeding | Diphenhydramine and ibuprofen are excreted into breast milk. M/P ratio not established. Both drugs are considered compatible with breastfeeding in low doses, but theoretical risk of infant sedation (diphenhydramine) and gastrointestinal effects (ibuprofen). Max daily dose for mother should not exceed recommended limits. Monitor infant for drowsiness and poor feeding. |
| Teratogenic Risk | Pregnancy Category C/D (after 30 weeks). First trimester: Potential risk of miscarriage and cardiac defects (limited data with NSAIDs). Second trimester: Avoid unless clearly needed; possible oligohydramnios, premature closure of ductus arteriosus, and fetal renal impairment. Third trimester: Contraindicated after 30 weeks due to risk of premature ductus arteriosus closure and persistent pulmonary hypertension. |
■ FDA Black Box Warning
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. NSAIDs are contraindicated in the setting of coronary artery bypass graft (CABG) surgery.
| Serious Effects |
["Hypersensitivity to ibuprofen, diphenhydramine, or any component of the formulation","History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs","Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery","Neonates and premature infants (due to diphenhydramine)","Concurrent use with other diphenhydramine products or sedatives"]
| Precautions | ["Cardiovascular thrombotic events","Gastrointestinal bleeding, ulceration, and perforation","Renal toxicity","Sedation and impaired cognitive function","Anticholinergic effects","Avoid use with other NSAIDs or antihistamines","Use caution in elderly, renal impairment, hepatic impairment, and pregnancy"] |
| Food/Dietary |
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| Fetal Monitoring | Monitor fetal well-being via ultrasound if used beyond 48 hours; assess amniotic fluid volume (risk of oligohydramnios). In third trimester, avoid use; if used inadvertently, monitor fetal ductus arteriosus and pulmonary artery pressure via echocardiography. Maternal monitoring: renal function, hepatic function, and bleeding time if used long-term. |
| Fertility Effects | Ibuprofen may reversibly impair female fertility by inhibiting prostaglandin synthesis affecting ovulation. Effects are reversible upon discontinuation. Diphenhydramine has no known direct fertility effects. Use in women trying to conceive is not recommended. |
| Take with food or milk to reduce GI upset. Avoid alcohol and grapefruit juice. Caffeine may enhance CNS stimulation and should be limited. |
| Clinical Pearls | Advil PM combines ibuprofen (NSAID) and diphenhydramine (antihistamine). Avoid concomitant use with other NSAIDs or CNS depressants (including alcohol). Use lowest effective dose for shortest duration. Contraindicated in severe hepatic/renal impairment, active GI bleeding, or during third trimester of pregnancy. May cause morning drowsiness due to antihistamine. |
| Patient Advice | Take only one tablet before bedtime; do not exceed recommended dose. · Avoid alcohol and other sedatives while using this medication. · Do not use for more than 10 days for pain or 3 days for fever unless directed by a doctor. · May cause drowsiness; avoid driving or operating machinery until you know how the drug affects you. · Not for use in children under 12 years of age or during pregnancy/breastfeeding without consulting a healthcare provider. · Report signs of stomach bleeding (e.g., black/tarry stools, vomiting blood) or allergic reactions (e.g., facial swelling, difficulty breathing). |