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. |
| Molecular Weight | Oxycodone: 351.82 Da; Acetaminophen: 151.16 Da |
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 | Risk of neural tube defects and congenital malformations with first-trimester exposure; avoid unless no safer alternative available. |
| 2nd trimester | May cause fetal dependence and withdrawal; use lowest effective dose for shortest duration. |
| 3rd trimester | Prolonged use carries risk of neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery; avoid near term. |
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. Oxycodone: extensive placental transfer, with fetal concentrations similar to maternal. Acetaminophen: readily crosses placenta, fetal levels approximate maternal levels. |
■ 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 componentSignificant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or without resuscitative equipmentKnown or suspected gastrointestinal obstruction (e.g., paralytic ileus)Severe hepatic impairment (Child-Pugh C)Severe renal impairment (eGFR < 30 mL/min/1.73 m²)
| Precautions | Respiratory depression, hepatic injury, adrenal insufficiency, hypotension, seizures, severe hypotension, GI obstruction, use in elderly and debilitated patients, renal impairment, drug dependence. |
| Food/Dietary |
Loading safety data…
| Breastfeeding |
| Oxycodone and acetaminophen are excreted into breast milk in low concentrations. Monitor infant for sedation and respiratory depression. Acetaminophen is considered compatible; oxycodone may cause CNS depression in nursing infants. Use lowest effective dose and avoid in mothers with CYP2D6 ultra-rapid metabolizer phenotype. |
| Lactation Rating | L3 (Moderately Safe): Limited data suggest risk; consider risk-benefit. |
| Teratogenic Risk | 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. |
| Avoid alcohol entirely. High-fat meals may delay absorption, but no specific food restrictions. Maintain adequate fluid and fiber intake to prevent constipation. |
| Clinical Pearls | Oxycodone/APAP is a fixed-dose combination; titration is limited by acetaminophen ceiling (max 4000 mg/day, lower in hepatic impairment or alcohol use). Use with caution in elderly, renal impairment, and respiratory compromise. Avoid in severe asthma or ileus. Prescribe the lowest effective dose for the shortest duration. Consider naloxone co-prescription if risk factors for opioid overdose. Not recommended for chronic pain without nonopioid alternatives. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush, chew, or break tablets; swallow whole. · Avoid alcohol and other sedatives (benzodiazepines, muscle relaxants) as they increase risk of severe drowsiness, respiratory depression, and death. · Do not drive or operate machinery until you know how this medication affects you. · Keep out of reach of children and pets; dispose of unused medication via drug take-back programs. · Report any signs of allergic reaction (rash, difficulty breathing), severe constipation, nausea/vomiting, or confusion. · Do not stop abruptly; taper under medical supervision to avoid withdrawal symptoms. · Inform all healthcare providers that you are taking this medication. |