Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ADVIL PM vs ACTRON
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Acetaminophen (paracetamol) is a non-opioid analgesic and antipyretic. Its mechanism is not fully understood but involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. It also modulates the endocannabinoid system and serotonergic pathways.
Temporary relief of occasional sleeplessness associated with minor aches and pains
Mild to moderate pain,Fever
Two caplets (ibuprofen 200 mg, diphenhydramine citrate 38 mg) orally at bedtime as needed for insomnia. Maximum: 2 caplets in 24 hours.
Oral: 400 mg every 4-6 hours as needed for pain; maximum 1200 mg/day.
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.
Terminal elimination half-life 2-4 hours; prolonged to 6-12 hours in elderly or renal impairment (Cr Cl <30 m L/min).
Ibuprofen is primarily metabolized via hepatic oxidation by CYP2C9. Diphenhydramine is metabolized via hepatic N-demethylation and oxidation, primarily by CYP2D6.
Primarily metabolized in the liver via glucuronidation (UGT1A1, UGT1A6, UGT1A9), sulfation (SULT1A1, SULT1A3), and oxidation (CYP2E1, CYP3A4) to form the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by glutathione.
Ibuprofen: Renal (90% as metabolites and conjugates, <10% unchanged); Diphenhydramine: Renal (primarily as metabolites, ~1% unchanged). Fecal excretion is negligible for both.
Renal: 90% as unchanged drug; biliary/fecal: 10% as metabolites.
Ibuprofen: >99% bound to albumin; Diphenhydramine: 78-85% bound to albumin.
>99% bound to albumin.
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.
0.1-0.2 L/kg; indicates limited extravascular distribution.
Ibuprofen: 80-100% (oral); Diphenhydramine: 50-70% (oral) due to first-pass metabolism.
Oral: 70-90% (first-pass metabolism minimal); IV: 100%.
Avoid use in GFR <30 m L/min. For GFR 30-59 m L/min, limit to single dose and avoid chronic use. No adjustment needed for GFR ≥60 m L/min.
GFR <30 m L/min: Avoid use. GFR 30-50 m L/min: Reduce dose to 50% of normal, maximum 600 mg/day.
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.
Child-Pugh Class B: Reduce dose by 50%; maximum 600 mg/day. Child-Pugh Class C: Contraindicated.
Not recommended for children under 12 years. For age ≥12 years, same adult dose: 2 caplets at bedtime.
Children ≥12 years: 400 mg orally every 6-8 hours as needed; maximum 1200 mg/day. Children <12 years: Not recommended.
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.
Initiate at 200 mg every 6-8 hours; maximum 600 mg/day due to increased risk of gastrointestinal bleeding and renal impairment.
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.
Acetaminophen has been associated with cases of acute liver failure, sometimes resulting in liver transplant and death. Most cases involve use of acetaminophen at doses exceeding 4000 mg per day, often involving more than one acetaminophen-containing product.
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
Hepatotoxicity: risk increased with chronic alcohol use, liver disease, or use of other acetaminophen-containing products. Avoid exceeding 4000 mg/day. Severe skin reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis. Hypersensitivity reactions: anaphylaxis.
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
Severe hepatic impairment or active liver disease. Known hypersensitivity to acetaminophen or any component of the formulation.
Take with food or milk to reduce GI upset. Avoid alcohol and grapefruit juice. Caffeine may enhance CNS stimulation and should be limited.
Avoid alcohol; may increase risk of GI bleeding. No specific food restrictions, but taking with food can reduce gastrointestinal irritation. Maintain adequate hydration to prevent renal impairment.
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.
First trimester: Based on animal studies and limited human data, possible increased risk of cardiovascular and neural tube defects. Second/third trimester: Risk of premature closure of ductus arteriosus and oligohydramnios with prolonged use. Avoid after 30 weeks gestation.
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.
Excreted in breast milk; M/P ratio 0.15. Low oral bioavailability to infant; considered compatible with breastfeeding. Monitor infant for sedation or feeding problems.
No specific dose adjustment recommended for ibuprofen or diphenhydramine in pregnancy. However, due to altered pharmacokinetics (increased volume of distribution, renal clearance), standard doses may be less effective. Avoid use if possible, especially after 30 weeks. Use lowest effective dose for shortest duration.
Dose adjustment not typically required; however, due to increased renal clearance and volume of distribution in pregnancy, higher doses may be needed to achieve therapeutic effect. Use lowest effective dose for shortest duration.
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.
ACTRON (ketorolac tromethamine) is a nonsteroidal anti-inflammatory drug (NSAID) for short-term management of moderate to severe acute pain, typically not exceeding 5 days due to risk of GI bleeding, renal impairment, and cardiovascular events. Avoid in patients with active peptic ulcer disease, bleeding diathesis, or advanced renal disease. Monitor renal function and signs of bleeding. Use lowest effective dose for shortest duration. May cause bronchospasm in aspirin-sensitive asthma.
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).
Take with food or milk to reduce stomach upset.,Do not take for more than 5 days as prescribed; longer use increases risk of serious side effects.,Avoid alcohol while taking this medication to lower risk of stomach bleeding.,Report any signs of bleeding (e.g., black stools, vomiting blood), unusual bruising, or decreased urination.,Do not take with other NSAIDs (e.g., ibuprofen, naproxen) or aspirin without consulting your doctor.,Inform your doctor about all medications, especially blood thinners (e.g., warfarin) and diuretics.,If you have asthma, be aware of potential bronchospasm; seek immediate help if you have breathing trouble.,Not recommended during pregnancy, especially in the third trimester.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ADVIL PM vs ACTRON, answered by our medical review team.
ADVIL PM is a NSAID/Sedative Combination that works by 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.. ACTRON is a NSAID that works by Acetaminophen (paracetamol) is a non-opioid analgesic and antipyretic. Its mechanism is not fully understood but involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. It also modulates the endocannabinoid system and serotonergic pathways.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ADVIL PM and ACTRON depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ADVIL PM is: Two caplets (ibuprofen 200 mg, diphenhydramine citrate 38 mg) orally at bedtime as needed for insomnia. Maximum: 2 caplets in 24 hours.. The standard adult dose of ACTRON is: Oral: 400 mg every 4-6 hours as needed for pain; maximum 1200 mg/day.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ADVIL PM and ACTRON in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ADVIL PM is classified as Category C. 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 neede. ACTRON is classified as Category C. First trimester: Based on animal studies and limited human data, possible increased risk of cardiovascular and neural tube defects. Second/third trimester: Risk of premature closur. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.