Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACTAHIST vs ACETAMINOPHEN AND IBUPROFEN
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Antihistamine; binds to histamine H1 receptors, blocking the effects of histamine; also exhibits anticholinergic and mild sedative properties.
Acetaminophen is a centrally acting analgesic and antipyretic whose exact mechanism is not fully understood, but is thought to involve inhibition of cyclooxygenase (COX) in the brain and modulation of cannabinoid receptors. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that non-selectively inhibits COX-1 and COX-2, reducing prostaglandin synthesis.
Symptomatic relief of allergic rhinitis,Urticaria,Off-label: motion sickness,Off-label: insomnia
Temporary relief of minor aches and pains,Reduction of fever,Off-label: Management of osteoarthritis pain, headache, dysmenorrhea
1.34 mg (one capsule) orally twice daily.
Oral: Acetaminophen 325 mg and ibuprofen 200 mg, 1-2 tablets every 6 hours as needed, not exceeding 6 tablets/24 hours.
6.9 ± 1.7 hours in adults; prolonged to 12-18 hours in elderly or patients with hepatic impairment, requiring dosing interval adjustment.
Acetaminophen: 2-3 hours (normal hepatic function). Ibuprofen: 2-4 hours (immediate-release); prolonged in overdose or hepatic impairment.
Hepatic metabolism via CYP450 enzymes (primarily CYP3A4 and CYP2D6); major metabolite is inactive.
Acetaminophen is primarily metabolized via glucuronidation and sulfation; a minor pathway via CYP2E1 produces a toxic metabolite, NAPQI. Ibuprofen is metabolized primarily by CYP2C9 and to a lesser extent by CYP2C8.
Primarily renal (approximately 85% as unchanged drug and metabolites) and fecal (15%) via biliary elimination.
Acetaminophen: renal excretion of metabolites (glucuronide 55%, sulfate 30%, cysteine/mercapturate <10%); <5% unchanged. Ibuprofen: renal excretion of metabolites (conjugates) 90%; <10% unchanged; minor biliary/fecal.
92% bound to albumin.
Acetaminophen: 10-25% (albumin). Ibuprofen: >99% (albumin).
0.9 ± 0.3 L/kg, indicating extensive extravascular distribution.
Acetaminophen: 0.9 L/kg; Ibuprofen: 0.15 L/kg (highly protein-bound, low Vd).
Oral: 68% ± 12% due to first-pass metabolism.
Acetaminophen: 75-85% oral. Ibuprofen: 80-100% oral.
No dose adjustment required for mild to moderate renal impairment. Safety not established for severe impairment (GFR <30 m L/min).
GFR 30-59: Caution, use lowest effective dose; GFR <30: Contraindicated due to ibuprofen component.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C).
Child-Pugh A: No adjustment; Child-Pugh B: Caution, reduce acetaminophen dose; Child-Pugh C: Contraindicated.
Not indicated for pediatric patients under 12 years of age. Safety and efficacy not established.
Weight-based: 10-15 mg/kg acetaminophen + 5-10 mg/kg ibuprofen per dose, every 6-8 hours, max 4 doses/day.
No specific dose adjustment recommended; monitor for increased anticholinergic effects and cognitive impairment.
Use lowest effective dose; monitor renal function due to ibuprofen; avoid durations >10 days.
None.
Acetaminophen may cause severe liver injury, including acute liver failure, at doses exceeding 4,000 mg/day. Ibuprofen: NSAIDs 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. NSAIDs also increase risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of stomach or intestines.
May cause drowsiness; caution when driving or operating machinery. Avoid alcohol. Use with caution in patients with narrow-angle glaucoma, prostatic hyperplasia, or urinary retention. Geriatric patients more sensitive to anticholinergic effects. Pediatric patients <6 years: not recommended.
Acetaminophen: Hepatotoxicity risk with excessive doses, use with caution in hepatic impairment, avoid with alcohol use >3 drinks/day. Ibuprofen: Cardiovascular risk, gastrointestinal bleeding, renal toxicity, hypertension, fluid retention, avoid late pregnancy.
Hypersensitivity to any component. Newborns or premature infants. Breastfeeding (contraindicated due to risk of adverse effects in infants). Concomitant use with MAOIs.
Acetaminophen: Severe hepatic impairment, allergy to acetaminophen. Ibuprofen: Hypersensitivity to ibuprofen or other NSAIDs, history of asthma/urticaria after NSAIDs, perioperative pain in CABG surgery, severe heart failure, active GI bleeding, late pregnancy.
Avoid high-tyramine foods (aged cheese, cured meats, fermented products) if taking MAOIs. Grapefruit juice may increase phenylephrine absorption; limit intake.
Avoid alcohol; take with food or milk to minimize GI irritation. No specific food restrictions.
ACTAHIST (brompheniramine/phenylephrine) pregnancy category C. Inadequate human data; animal studies show no malformations at therapeutic doses. First trimester: theoretical risk from vasoconstrictive effects (phenylephrine) possibly reducing uterine blood flow; avoid if possible. Second/third trimester: phenylephrine may cause fetal hypoxia via placental vasoconstriction; use only if benefit outweighs risk. No known structural teratogenicity.
First trimester: Acetaminophen is considered low risk; ibuprofen is associated with increased risk of miscarriage and cardiac defects. Second trimester: Acetaminophen is safe; ibuprofen is relatively safe but may cause oligohydramnios. Third trimester: Acetaminophen is safe; ibuprofen is contraindicated due to risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment.
Brompheniramine is excreted in breast milk in small amounts; M/P ratio not established. Phenylephrine has minimal excretion. Due to anticholinergic effects, may reduce milk production or cause sedation in infants. Use caution; prefer non-sedating alternatives if possible.
Acetaminophen: low levels in breast milk, M/P ratio ~0.9; considered compatible with breastfeeding. Ibuprofen: minimal excretion, M/P ratio ~0.01; considered compatible. Combination: low risk with recommended doses.
No specific pharmacokinetic studies. Increased plasma volume and renal clearance in pregnancy may reduce drug levels, but efficacy threshold remains. No dose adjustment recommended; use the lowest effective dose for shortest duration due to potential risks.
No standard adjustment for acetaminophen; ibuprofen dosing unchanged in pregnancy but avoid in third trimester; consider increased clearance of acetaminophen in pregnancy but no dose adjustment recommended.
Actahist is a combination antihistamine-decongestant (chlorpheniramine/phenylephrine). Avoid in patients with hypertension, severe coronary artery disease, or MAOI use. Monitor for sedation and urinary retention, especially in elderly males with BPH.
Combination product for acute pain; fixed-dose may exceed recommended daily acetaminophen limit if other acetaminophen-containing products are used. Onset of ibuprofen is 30-60 min, acetaminophen 15-30 min; duration 4-6 hours. Caution in renal impairment (ibuprofen) and hepatic impairment (acetaminophen). Avoid in third trimester of pregnancy.
Take with food or milk to reduce stomach upset.,Avoid alcohol and CNS depressants as they can increase drowsiness.,Do not drive or operate machinery until you know how this medication affects you.,Contact your doctor if you experience chest pain, rapid heartbeat, or difficulty urinating.
Do not exceed 10 tablets (500 mg acetaminophen/200 mg ibuprofen) per day.,Do not take with other products containing acetaminophen or NSAIDs.,Take with food or milk to reduce stomach upset.,Avoid alcohol while taking this medication.,Seek medical help if pain persists >10 days or fever >3 days.,Store at room temperature, away from moisture.
No interactions on record
"Concomitant use of Ibuprofen (a nonsteroidal anti-inflammatory drug, NSAID) and Methylprednisolone (a systemic corticosteroid) synergistically increases the risk of gastrointestinal (GI) ulceration, bleeding, and perforation due to additive inhibition of prostaglandin synthesis and mucosal protection. Additionally, Ibuprofen may potentiate the immunosuppressive effects of Methylprednisolone, elevating infection risk. This interaction can lead to serious clinical outcomes, including acute GI hemorrhage, perforation, and impaired wound healing."
"The combination of olopatadine, an antihistamine with sedative properties, and ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), may result in additive central nervous system (CNS) depression, leading to increased sedation, dizziness, and impaired psychomotor function. Ibuprofen can inhibit the metabolism of olopatadine via competition for hepatic CYP450 enzymes, potentially elevating olopatadine plasma concentrations and prolonging its systemic effects. Clinically, patients may experience exacerbated drowsiness, reduced alertness, and increased risk of falls or accidents, especially in the elderly or those with compromised hepatic function."
"Ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID), can decrease the metabolism of pioglitazone, a thiazolidinedione antidiabetic agent, by inhibiting cytochrome P450 2C8 (CYP2C8) enzyme activity. This inhibition elevates plasma concentrations of pioglitazone, potentially enhancing its hypoglycemic effects and increasing the risk of adverse reactions such as edema, weight gain, and heart failure exacerbation. Clinically, concomitant use may lead to improved glycemic control but also raises concerns for dose-dependent toxicities, necessitating careful monitoring and possible dose adjustment of pioglitazone."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACTAHIST vs ACETAMINOPHEN AND IBUPROFEN, answered by our medical review team.
ACTAHIST is a Antihistamine that works by Antihistamine; binds to histamine H1 receptors, blocking the effects of histamine; also exhibits anticholinergic and mild sedative properties.. ACETAMINOPHEN AND IBUPROFEN is a NSAID that works by Acetaminophen is a centrally acting analgesic and antipyretic whose exact mechanism is not fully understood, but is thought to involve inhibition of cyclooxygenase (COX) in the brain and modulation of cannabinoid receptors. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that non-selectively inhibits COX-1 and COX-2, reducing prostaglandin synthesis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACTAHIST and ACETAMINOPHEN AND IBUPROFEN 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 ACTAHIST is: 1.34 mg (one capsule) orally twice daily.. The standard adult dose of ACETAMINOPHEN AND IBUPROFEN is: Oral: Acetaminophen 325 mg and ibuprofen 200 mg, 1-2 tablets every 6 hours as needed, not exceeding 6 tablets/24 hours.. 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 ACTAHIST and ACETAMINOPHEN AND IBUPROFEN 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. ACTAHIST is classified as Category C. ACTAHIST (brompheniramine/phenylephrine) pregnancy category C. Inadequate human data; animal studies show no malformations at therapeutic doses. First trimester: theoretical risk f. ACETAMINOPHEN AND IBUPROFEN is classified as Category D/X. First trimester: Acetaminophen is considered low risk; ibuprofen is associated with increased risk of miscarriage and cardiac defects. Second trimester: Acetaminophen is safe; ibup. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.