OXYCODONE AND ASPIRIN (HALF-STRENGTH)
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
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.
| Metabolism | 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. |
| Excretion | 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. |
| Half-life | 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. |
| Protein binding | Aspirin: 80-90% (primarily to albumin, saturable). Oxycodone: 38-45% (primarily to albumin). |
| Volume of Distribution | Aspirin: 0.15-0.2 L/kg. Oxycodone: 2.0-3.7 L/kg; extensive tissue distribution. |
| Bioavailability | Oral: Aspirin: 80-100% (first-pass hydrolysis to salicylate). Oxycodone: 60-87% (oral); rectal: similar to oral; intravenous: 100%. |
| Onset of Action | Oral: Aspirin: 30 minutes for analgesia; Oxycodone: 10-30 minutes. Peak effects: Aspirin 1-2 hours; Oxycodone 30-60 minutes. |
| Duration of Action | Aspirin: 4-6 hours for analgesia. Oxycodone: Immediate release: 4-6 hours; controlled release: 12 hours. Clinical note: Duration may be prolonged in hepatic impairment. |
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.
| Dosage form | TABLET |
| Renal impairment | For GFR 10-50 mL/min: Administer 75% of usual dose at extended intervals (every 8-12 hours). For GFR <10 mL/min: Avoid use due to risk of aspirin accumulation and oxycodone toxicity. |
| Liver impairment | 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. |
| Pediatric use | 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. |
| Geriatric use | 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. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | 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. |
| Teratogenic Risk |
■ FDA Black Box Warning
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.
| Common Effects | Constipation |
| Serious Effects |
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.
| Precautions | 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). |
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| 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. |
| Fetal Monitoring | Maternal: Liver function tests (aspirin hepatotoxicity), renal function, blood pressure, bleeding time, urine toxicology screens for opioid compliance. Fetal: Ultrasound for growth and amniotic fluid volume (oligohydramnios risk with aspirin), fetal echocardiography (aspirin-associated ductus closure), nonstress test or biophysical profile in third trimester. Neonatal: Monitoring for signs of opioid withdrawal (Finnegan scores) and bleeding diathesis. |
| Fertility Effects | Oxycodone: Chronic use may reduce fertility by altering gonadotropin secretion (hypogonadotropic hypogonadism) and causing amenorrhea in women. Aspirin: No direct toxicity, but NSAIDs including aspirin can inhibit prostaglandin synthesis, potentially impairing ovulation and implantation; effect is reversible upon discontinuation. |