Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
OXYCODONE AND ASPIRIN (HALF-STRENGTH) vs ACTAHIST
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, resulting in analgesia through supraspinal and spinal pathways. Aspirin irreversibly acetylates cyclooxygenase-1 and -2 (COX-1/2), inhibiting prostaglandin synthesis and providing anti-inflammatory and analgesic effects.
Antihistamine; binds to histamine H1 receptors, blocking the effects of histamine; also exhibits anticholinergic and mild sedative properties.
Moderate to moderately severe pain (when combination therapy is appropriate),Off-label: acute pain, chronic pain
Symptomatic relief of allergic rhinitis,Urticaria,Off-label: motion sickness,Off-label: insomnia
Adults: One to two tablets (325 mg aspirin/2.5 mg oxycodone per tablet) orally every 6 hours as needed for pain. Maximum dose: 12 tablets per day.
1.34 mg (one capsule) orally twice daily.
Aspirin: 2-3 hours for low doses, 15-30 hours for anti-inflammatory doses; increased half-life with dose due to saturable metabolism. Oxycodone: Immediate release: 3-4 hours; controlled release: 4.5-5 hours with biphasic absorption.
6.9 ± 1.7 hours in adults; prolonged to 12-18 hours in elderly or patients with hepatic impairment, requiring dosing interval adjustment.
Oxycodone is extensively metabolized in the liver via CYP3A4 (N-demethylation to noroxycodone) and CYP2D6 (O-demethylation to oxymorphone). Aspirin is rapidly hydrolyzed to salicylic acid by esterases in the liver and plasma; salicylic acid is conjugated primarily with glycine (salicyluric acid) and glucuronic acid.
Hepatic metabolism via CYP450 enzymes (primarily CYP3A4 and CYP2D6); major metabolite is inactive.
Aspirin: Renal (primarily as salicyluric acid, salicyl glucuronides, and free salicylate); 10% excreted as unchanged salicylate. Oxycodone: Renal (primarily as noroxycodone, oxymorphone, and conjugates); approximately 87% eliminated in urine, 10-14% in feces.
Primarily renal (approximately 85% as unchanged drug and metabolites) and fecal (15%) via biliary elimination.
Aspirin: 80-90% (primarily to albumin, saturable). Oxycodone: 38-45% (primarily to albumin).
92% bound to albumin.
Aspirin: 0.15-0.2 L/kg. Oxycodone: 2.0-3.7 L/kg; extensive tissue distribution.
0.9 ± 0.3 L/kg, indicating extensive extravascular distribution.
Oral: Aspirin: 80-100% (first-pass hydrolysis to salicylate). Oxycodone: 60-87% (oral); rectal: similar to oral; intravenous: 100%.
Oral: 68% ± 12% due to first-pass metabolism.
For GFR 10-50 m L/min: Administer 75% of usual dose at extended intervals (every 8-12 hours). For GFR <10 m L/min: Avoid use due to risk of aspirin accumulation and oxycodone toxicity.
No dose adjustment required for mild to moderate renal impairment. Safety not established for severe impairment (GFR <30 m L/min).
Child-Pugh Class A: No adjustment necessary. Child-Pugh Class B: Initiate at 50-75% of usual dose and titrate cautiously. Child-Pugh Class C: Avoid use due to risk of oxycodone accumulation and aspirin-induced bleeding.
No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not recommended for severe hepatic impairment (Child-Pugh C).
Not recommended for pediatric use due to risk of Reye's syndrome from aspirin and lack of safety data for oxycodone in children <18 years.
Not indicated for pediatric patients under 12 years of age. Safety and efficacy not established.
Initiate at the low end of dosing range (e.g., one tablet every 6 hours) due to increased sensitivity to opioid effects and risk of aspirin-induced gastrointestinal bleeding. Titrate slowly and monitor renal function.
No specific dose adjustment recommended; monitor for increased anticholinergic effects and cognitive impairment.
Addiction, abuse, and misuse risk; life-threatening respiratory depression; accidental ingestion (especially in children) can be fatal; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; cytochrome P450 3A4 interaction with concomitant CNS depressants; risk of Reye syndrome (aspirin) in children and teenagers with viral illnesses.
None.
Respiratory depression; drug dependence, abuse, and addiction; CNS depression (additive with other CNS depressants); head injury and increased intracranial pressure; hypotension; seizure disorders; biliary tract disease; impaired renal or hepatic function; history of gastrointestinal bleeding (aspirin); bleeding disorders (aspirin); concurrent use with anticoagulants; Reye syndrome; hypersensitivity to aspirin or NSAIDs; pregnant women (prolonged use may cause neonatal withdrawal).
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.
Hypersensitivity to oxycodone, aspirin, or any component; severe respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction; Reye syndrome (in children/teenagers with viral illness) (aspirin); pregnancy (prolonged use or high doses near term); breastfeeding (oxycodone); severe bleeding disorders (aspirin); concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy.
Hypersensitivity to any component. Newborns or premature infants. Breastfeeding (contraindicated due to risk of adverse effects in infants). Concomitant use with MAOIs.
Avoid alcohol; may increase risk of liver damage (not applicable) and gastric bleeding. Avoid high-tyramine foods (e.g., aged cheeses, cured meats) if taking MAOIs (unlikely but caution). Take with food to minimize GI irritation.
Avoid high-tyramine foods (aged cheese, cured meats, fermented products) if taking MAOIs. Grapefruit juice may increase phenylephrine absorption; limit intake.
Pregnancy Category D (oxycodone) and Category D (aspirin) prior to 2015 reclassification; current FDA labeling advises avoidance in pregnancy. First trimester: Aspirin associated with increased risk of neural tube defects and gastroschisis; oxycodone may cause neural tube defects. Second trimester: Aspirin may impair fetal renal function; oxycodone risk persists. Third trimester: Aspirin increases risk of premature closure of ductus arteriosus, oligohydramnios, and periventricular hemorrhage; oxycodone may cause neonatal withdrawal syndrome. Chronic use may lead to neonatal abstinence syndrome.
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.
Oxycodone: M/P ratio approximately 0.5; low levels in milk (0.3-6.9% of maternal weight-adjusted dose), but risk of neonatal sedation and withdrawal. Aspirin: Excreted in milk; M/P ratio ~0.03-0.1; risk of Reye's syndrome with high doses. Both drugs generally contraindicated during breastfeeding due to potential adverse effects in infants.
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.
Oxycodone: Increased clearance and volume of distribution in pregnancy may require higher doses for analgesia; dose adjustment should be individualized. Aspirin: No pharmacokinetic adjustments recommended; however, due to teratogenicity and fetal risks, use is contraindicated in pregnancy, especially during third trimester. Half-strength formulation not specifically studied; dosage should be based on oxycodone component (typically 2.25 mg) and aspirin component (325 mg) with caution.
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.
Monitor for respiratory depression, especially in elderly or debilitated patients. Avoid in patients with severe asthma or COPD. Assess renal function before use, as aspirin can worsen renal impairment. The half-strength formulation contains 325 mg aspirin and 2.25 mg oxycodone HCl per tablet.
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.
Take with food or milk to reduce stomach upset.,Do not exceed recommended dose; risk of liver damage with acetaminophen-containing products (not applicable here), but aspirin can cause gastrointestinal bleeding.,Avoid alcohol while taking this medication.,Do not crush or chew extended-release tablets (this formulation is immediate-release; advise to swallow whole).,May cause drowsiness or dizziness; avoid driving until you know how the medication affects you.,Seek medical help if you experience signs of allergic reaction (rash, difficulty breathing) or signs of bleeding (black stools, vomiting blood).
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.
"Phenobarbital, a potent inducer of cytochrome P450 (CYP) enzymes, particularly CYP3A4 and CYP2D6, significantly increases the hepatic metabolism of oxycodone, a prodrug that requires CYP3A4-mediated N-demethylation to noroxycodone and CYP2D6-mediated O-demethylation to oxymorphone for its analgesic effects. This induction reduces the systemic exposure and peak plasma concentration of active oxycodone and its active metabolite oxymorphone, leading to diminished analgesic efficacy and potential opioid withdrawal symptoms in patients on chronic opioid therapy. Clinically, patients may require substantially higher doses of oxycodone to achieve pain relief, increasing the risk of dose-related adverse effects if the interaction is not recognized."
"The co-administration of oxycodone, a mu-opioid receptor agonist, and gamma-hydroxybutyric acid (GHB), a central nervous system depressant with activity at GABA-B and GHB receptors, results in additive or synergistic respiratory depression and CNS depression. This interaction potentiates the risk of severe hypoventilation, coma, and fatal overdose, especially in non-tolerant users or at therapeutic doses. The combined sedation also increases the likelihood of hypotension, bradycardia, and impaired psychomotor function, necessitating extreme caution."
"The coadministration of oxycodone, a mu-opioid receptor agonist with central nervous system (CNS) depressant effects, and perampanel, a noncompetitive AMPA receptor antagonist that also causes CNS depression, produces additive sedative and respiratory depressant effects. This synergy increases the risk of excessive sedation, impaired cognitive function, and potentially life-threatening respiratory depression. Patients may experience profound somnolence, confusion, and an increased fall risk, necessitating dose adjustments or avoidance."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about OXYCODONE AND ASPIRIN (HALF-STRENGTH) vs ACTAHIST, answered by our medical review team.
OXYCODONE AND ASPIRIN (HALF-STRENGTH) is a Opioid Agonist that works by Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, resulting in analgesia through supraspinal and spinal pathways. Aspirin irreversibly acetylates cyclooxygenase-1 and -2 (COX-1/2), inhibiting prostaglandin synthesis and providing anti-inflammatory and analgesic effects.. 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.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between OXYCODONE AND ASPIRIN (HALF-STRENGTH) and ACTAHIST 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 OXYCODONE AND ASPIRIN (HALF-STRENGTH) is: Adults: One to two tablets (325 mg aspirin/2.5 mg oxycodone per tablet) orally every 6 hours as needed for pain. Maximum dose: 12 tablets per day.. The standard adult dose of ACTAHIST is: 1.34 mg (one capsule) orally twice daily.. 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 OXYCODONE AND ASPIRIN (HALF-STRENGTH) and ACTAHIST 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. OXYCODONE AND ASPIRIN (HALF-STRENGTH) is classified as Category D/X. Pregnancy Category D (oxycodone) and Category D (aspirin) prior to 2015 reclassification; current FDA labeling advises avoidance in pregnancy. First trimester: Aspirin associated w. 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. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.