OXYCODONE AND ASPIRIN
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Oxycodone: mu-opioid receptor agonist; Aspirin: irreversible cyclooxygenase (COX-1 and COX-2) inhibitor, reducing prostaglandin synthesis.
| Metabolism | Oxycodone: hepatic via CYP3A4 and CYP2D6 to active metabolites; Aspirin: hepatic hydrolysis to salicylate, further conjugated with glycine (salicyluric acid) or glucuronic acid. |
| Excretion | Oxycodone: renal (primarily as noroxycodone) 87%, fecal <10%. Aspirin (as salicylate): renal 50-80% (dose-dependent; alkaline urine increases excretion), with biliary elimination of metabolites. |
| Half-life | Oxycodone: 3-5 hours (immediate-release); 4.5-8 hours (extended-release). Aspirin (salicylate): 2-3 hours (low dose), 15-30 hours (high dose due to saturation of metabolic pathways). |
| Protein binding | Oxycodone: 45% bound to plasma proteins (primarily albumin). Aspirin (acetylsalicylic acid): 80-90% bound to albumin; salicylic acid: 50-80% bound. |
| Volume of Distribution | Oxycodone: 2.6-3.0 L/kg (indicating extensive tissue distribution). Aspirin (salicylate): 0.15-0.20 L/kg (low Vd, primarily restricted to extracellular fluid). |
| Bioavailability | Oxycodone: oral 60-87% (first-pass metabolism); rectal suppository ~50%. Aspirin: oral 40-50% (due to first-pass hydrolysis); rectal ~20-60%. |
| Onset of Action | Oral oxycodone: 10-15 minutes; oral aspirin: 5-30 minutes. Immediate-release combination: ~15-30 minutes. |
| Duration of Action | Oxycodone immediate-release: 4-6 hours; extended-release: 12 hours. Aspirin: 4-6 hours (analgesic/antipyretic), up to 7-10 days for antiplatelet effect. Duration may be longer in hepatic or renal impairment. |
1 tablet (oxycodone 4.5 mg/aspirin 325 mg) orally every 6 hours as needed for pain; maximum 4 tablets in 24 hours.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: use with caution, reduce dose or interval. GFR <30 mL/min: avoid use (accumulation of aspirin metabolites and oxycodone). |
| Liver impairment | Child-Pugh A: no adjustment recommended. Child-Pugh B: reduce oxycodone dose by 50% (e.g., start with 2.25 mg) and avoid aspirin if severe hepatic impairment. Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for children <18 years due to risk of Reye syndrome from aspirin and lack of safety data for oxycodone. |
| Geriatric use | Initiate at lowest dose (e.g., 1 tablet every 6 hours), monitor renal function and cognitive effects; avoid in patients with GFR <30 mL/min. |
| 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: Excreted into breast milk; relative infant dose (RID) 3-8% of maternal weight-adjusted dose. Monitor infant for drowsiness and poor feeding. Aspirin: Excreted into breast milk; high doses may cause Reye's syndrome risk in infant; generally avoid breastfeeding with high-dose aspirin. M/P ratio for oxycodone: ~3.2:1 (milk:plasma). |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion (especially in children); neonatal opioid withdrawal syndrome; CYP3A4 interaction with other drugs; risk of gastric mucosal injury and bleeding with aspirin.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to oxycodone or aspirin, significant respiratory depression, acute or severe bronchial asthma, suspected paralytic ileus, GI obstruction, bleeding disorders, children with viral illness (Reye's syndrome), third trimester pregnancy, concomitant use with MAOIs or within 14 days.
| Precautions | Respiratory depression, CNS depression, opioid-induced hyperalgesia, adrenal insufficiency, hypotension, seizures, gastrointestinal bleeding (aspirin), Reye's syndrome (aspirin in children), bleeding risk, renal impairment. |
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| First trimester: Aspirin is associated with increased risk of neural tube defects and cardiac malformations at high doses. Oxycodone use may be associated with neural tube defects but data are limited. Second trimester: Aspirin may impair fetal renal function and lead to oligohydramnios. Oxycodone crosses placenta; chronic use may cause fetal dependence. Third trimester: Aspirin near term increases risk of intracranial hemorrhage in neonate and premature closure of ductus arteriosus. Oxycodone may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. |
| Fetal Monitoring | Maternal: Liver function tests, renal function, complete blood count, coagulation profile due to aspirin. For opioid: respiratory rate, sedation level, bowel function. Fetal: Ultrasound for growth and amniotic fluid volume, fetal heart rate monitoring if chronic use. Neonatal: Monitor for NOWS; if aspirin near term, screen for bleeding. |
| Fertility Effects | Aspirin may inhibit ovulation via prostaglandin synthesis inhibition at high doses; low-dose aspirin may have minimal effect. Oxycodone can cause hyperprolactinemia and hypothalamic-pituitary-gonadal axis suppression leading to menstrual irregularities, anovulation, and reduced libido. Chronic use may impair fertility. |