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. |
| Molecular Weight | 351.4 |
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 | Avoid due to risk of fetal malformations, particularly cardiac defects and gastroschisis, associated with aspirin. Oxycodone may cause neural tube defects. |
| 2nd trimester | Use only if clearly needed. Aspirin may impair fetal renal function and cause oligohydramnios; oxycodone may lead to fetal dependence. |
| 3rd trimester | Contraindicated: Aspirin increases risk of premature closure of ductus arteriosus and bleeding; oxycodone can cause neonatal opioid withdrawal syndrome. |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Placental transfer | Both components cross the placenta. Aspirin is detected in fetal plasma; oxycodone achieves fetal concentrations 50-100% of maternal levels. |
■ 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 NSAIDsSevere asthmaActive peptic ulcer diseaseBleeding disordersChildren with viral infections (Reye's syndrome risk)Third trimester pregnancy
| 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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| Breastfeeding |
| Aspirin and oxycodone are excreted into breast milk. Aspirin may cause Reye's syndrome in infants; oxycodone may cause infant CNS depression. Use with caution, monitor for sedation and poor feeding. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | 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. |
| Food/Dietary | 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. |
| Clinical Pearls | 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. |
| Patient Advice | 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). |