OXYCODONE 2.5/APAP 500
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Oxycodone is a mu-opioid receptor agonist that inhibits ascending pain pathways and alters pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis.
| Metabolism | Oxycodone is metabolized primarily by CYP3A4 and CYP2D6 to noroxycodone, oxymorphone, and glucuronides. Acetaminophen is metabolized via glucuronidation, sulfation, and CYP2E1-mediated oxidation to N-acetyl-p-benzoquinone imine (NAPQI). |
| Excretion | Oxycodone: primarily renal (87% as metabolites, 10% unchanged). Acetaminophen: primarily renal (90-100% as glucuronide and sulfate conjugates, 2-5% unchanged). Fecal elimination <10% |
| Half-life | Oxycodone: 3.5-5.5 hours in healthy adults; steady state reached within 24 hours. Acetaminophen: 2-3 hours; prolonged in hepatic impairment. |
| Protein binding | Oxycodone: 38-45% (primarily albumin). Acetaminophen: 10-20% (albumin). |
| Volume of Distribution | Oxycodone: 2-3 L/kg (large Vd indicates extensive tissue distribution). Acetaminophen: 0.9-1.0 L/kg (distributes uniformly throughout body water). |
| Bioavailability | Oxycodone: oral 60-87% (first-pass metabolism). Acetaminophen: oral 70-90% (minimal first-pass). Rectal: variable for both. |
| Onset of Action | Oral: oxycodone onset 10-15 minutes; acetaminophen onset 15-30 minutes. Peak effect: oxycodone 30-60 minutes; acetaminophen 30-60 minutes. |
| Duration of Action | Oxycodone: 3-6 hours (immediate-release). Acetaminophen: 4-6 hours. Clinical duration limited by opioid tolerance; analgesic duration may be shorter than half-life. |
1-2 tablets (oxycodone 2.5-5 mg/APAP 500-1000 mg) orally every 4-6 hours as needed for pain; maximum APAP 4000 mg/day (consider lower APAP limit per institutional guidelines).
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min: no adjustment initially, monitor for adverse effects; eGFR <30 mL/min: reduce starting dose by 50% or extend dosing interval (e.g., every 6-8 hours); avoid in dialysis unless benefits outweigh risks. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce starting dose by 50% and monitor; Child-Pugh C: avoid use due to risk of APAP toxicity and opioid accumulation. |
| Pediatric use | Weight-based: oxycodone 0.05-0.15 mg/kg/dose (max 5 mg/dose) orally every 4-6 hours as needed; APAP component: 10-15 mg/kg/dose (max 500 mg/dose) every 4-6 hours, not to exceed 5 doses (75 mg/kg/day) in 24 hours. Not recommended for children < 2 years. |
| Geriatric use | Start at lowest effective dose (e.g., 0.5-1 tablet) every 4-6 hours; increase cautiously; avoid APAP doses >3000 mg/day; monitor for sedation, constipation, and respiratory depression; consider alternative if renal or hepatic impairment. |
| 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; M/P ratio approximately 3.4:1. Acetaminophen M/P ratio ~0.91. American Academy of Pediatrics recommends caution; monitor infant for sedation and respiratory depression. Maximum daily oxycodone dose in milk ~7% of maternal weight-adjusted dose. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction; risk of hepatotoxicity from acetaminophen overdose.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to oxycodone, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma; GI obstruction; suspected surgical abdomen; acetaminophen poisoning.
| Precautions | Respiratory depression, hepatic injury, adrenal insufficiency, hypotension, seizures, severe hypotension, GI obstruction, use in elderly and debilitated patients, renal impairment, drug dependence. |
Loading safety data…
| First trimester: Limited human data; animal studies show no teratogenicity at therapeutic doses. Second and third trimesters: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS). High doses near term may cause neonatal respiratory depression. |
| Fetal Monitoring | Maternal: Respiratory rate, sedation level, bowel function, signs of abuse or diversion. Fetal: Heart rate monitoring during labor if oxycodone used; assessment for NOWS in neonate after prolonged maternal use. Ultrasound for growth if chronic use. |
| Fertility Effects | Oxycodone may suppress gonadotropin-releasing hormone, leading to reduced libido and anovulation in females; oligospermia in males. Acetaminophen has minimal direct effect on fertility at therapeutic doses. |