OXYCODONE AND ACETAMINOPHEN
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Oxycodone is a full mu-opioid receptor agonist, producing analgesia via activation of descending inhibitory pathways, while acetaminophen is a centrally acting analgesic and antipyretic, likely through inhibition of cyclooxygenase (COX) in the CNS and modulation of serotonergic pathways.
| Metabolism | Oxycodone is extensively metabolized in the liver via CYP3A4 (primarily) and CYP2D6 (minor) to noroxycodone, oxymorphone, and other metabolites. Acetaminophen is metabolized in the liver mainly via glucuronidation and sulfation with a minor CYP2E1 pathway producing toxic NAPQI. |
| Excretion | Oxycodone: renal (primarily as noroxycodone, oxymorphone, and conjugated metabolites; <10% unchanged). Acetaminophen: renal (85-90% as sulfate and glucuronide conjugates; 2-4% unchanged; 8-10% as cysteine and mercapturate conjugates). Biliary/fecal excretion: minor (<5% for both). |
| Half-life | Oxycodone: 3-5 hours (immediate-release), 4.5-8 hours (extended-release). Acetaminophen: 1.5-3 hours. Clinical context: Half-life may be prolonged in hepatic impairment, elderly, and renal failure. |
| Protein binding | Oxycodone: 38-45% (primarily to albumin). Acetaminophen: 10-25% (minimal binding). |
| Volume of Distribution | Oxycodone: 2.6-3.0 L/kg (wide distribution into tissues). Acetaminophen: 0.9-1.0 L/kg (uniformly distributed in body fluids). |
| Bioavailability | Oral immediate-release: oxycodone 60-87%, acetaminophen 68-88%. Oral extended-release: oxycodone 60-87% (less variable). Rectal: variable (unspecified for this combination). |
| Onset of Action | Oral immediate-release: 10-15 minutes for analgesic effect; peak effect at 1 hour. Oral extended-release: 1-2 hours. Parenteral: 5-10 minutes (not a standard route for this combination). |
| Duration of Action | Immediate-release: 4-6 hours. Extended-release: 12 hours. Clinical notes: Duration is opioid-tolerance dependent. Hepatic impairment prolongs effect. |
| Molecular Weight | Oxycodone: 315.36 Da; Acetaminophen: 151.16 Da |
Oral: 5-10 mg oxycodone (with 325-650 mg acetaminophen) every 4-6 hours as needed; maximum oxycodone 60 mg/day (for immediate-release) or acetaminophen 4000 mg/day. Titrate to pain control.
| Dosage form | TABLET |
| Renal impairment | CrCl ≥60 mL/min: no adjustment; CrCl 30-59 mL/min: acetaminophen no change, oxycodone consider 75% of usual dose; CrCl 10-29 mL/min: acetaminophen extend interval to q6h, oxycodone consider 50% of usual dose; CrCl <10 mL/min: acetaminophen avoid or 650 mg q8h, oxycodone 50% of usual dose; hemodialysis: acetaminophen 650 mg q8h, oxycodone 25-50% of usual dose. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: oxycodone reduce dose by 50%, acetaminophen maximum 2000 mg/day; Child-Pugh C: oxycodone reduce dose by 75%, acetaminophen maximum 2000 mg/day; severe hepatic impairment: avoid acetaminophen component. |
| Pediatric use | Children ≥6 months: 0.05-0.15 mg/kg oxycodone (based on oxycodone component) every 4-6 hours, maximum single dose 5 mg; acetaminophen 10-15 mg/kg/dose, maximum 75 mg/kg/day (up to 4000 mg/day). Weight-based oxycodone not to exceed adult dose. |
| Geriatric use | Start at 50% of adult dose (oxycodone 2.5-5 mg every 6 hours), titrate cautiously; maximum acetaminophen 3000 mg/day due to decreased hepatic reserves; monitor for renal impairment and avoid if CrCl <30 mL/min. |
| 1st trimester | Use with caution; associated with increased risk of congenital malformations, particularly cardiac defects, with first-trimester exposure. |
| 2nd trimester | Use with caution; may cause fetal dependence and withdrawal. Avoid prolonged use. |
| 3rd trimester | Use with caution; may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression if used 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 oxycodone and acetaminophen cross the placenta. Oxycodone achieves fetal plasma concentrations 50-100% of maternal levels; acetaminophen crosses readily. |
| Breastfeeding |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; accidental ingestion may be fatal; risk of hepatotoxicity with acetaminophen overdose.
| Common Effects | Constipation |
| Serious Effects |
Known hypersensitivity to oxycodone or acetaminophenSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusSevere hepatic impairment (acetaminophen component)
| Precautions | Addiction, abuse, and misuse; respiratory depression; neonatal opioid withdrawal syndrome; interactions with CNS depressants; hepatotoxicity (acetaminophen); severe hypotension; adrenal insufficiency; seizures; increased risk of overdose in patients with head injury or COPD. |
| Food/Dietary | Avoid alcohol consumption; increases risk of hepatotoxicity from acetaminophen and potentiates CNS depression. Grapefruit juice may increase oxycodone absorption; avoid concurrent use. High-fat meals can delay oxycodone peak concentration, potentially reducing rapid pain relief. No specific restrictions with other foods. |
Loading safety data…
| Oxycodone and acetaminophen are excreted into breast milk in low amounts. Oxycodone may cause infant sedation or respiratory depression, particularly in CYP2D6 ultra-rapid metabolizers. Acetaminophen is considered compatible. Monitor infant for drowsiness and feeding difficulties. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Risk of neural tube defects not significantly increased with therapeutic use; opioid dependence may increase risk of congenital malformations (e.g., gastroschisis). Second/third trimester: Chronic use may cause fetal opioid dependence, leading to neonatal abstinence syndrome (NAS). Late third trimester: Risk of respiratory depression in neonate if used near delivery. |
| Fetal Monitoring | Assess maternal pain control, bowel function, sedation, and respiratory rate. Fetal monitoring: ultrasound for growth restriction with chronic use; nonstress test for near-term risk of NAS. Neonatal monitoring: observe for signs of NAS (irritability, poor feeding, respiratory distress) for 48-72 hours after delivery. |
| Fertility Effects | Data limited; chronic opioid use may disrupt hypothalamic-pituitary-gonadal axis, leading to amenorrhea, anovulation, and reduced fertility. Acetaminophen not associated with fertility impairment at therapeutic doses. |
| Clinical Pearls | Maximum daily acetaminophen dose is 4000 mg from all sources; prescribed combination tablets contribute to this limit. Oxycodone immediate-release duration is 3-6 hours; avoid crushing extended-release formulations. Both components have abuse potential; screen for opioid use disorder. In renal impairment, adjust dosing interval for oxycodone; avoid in CrCl <30 mL/min. In hepatic impairment, the acetaminophen component may be hepatotoxic; avoid in severe disease. Coadministration with serotonergic agents may precipitate serotonin syndrome. Naloxone is the reversal agent for oxycodone; acetylcysteine for acetaminophen overdose. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not take other products containing acetaminophen (e.g., Tylenol, cold medications) to avoid exceeding the maximum daily dose of 4000 mg. · Avoid alcohol while taking this medication; liver damage risk increases with alcohol use. · Do not crush, break, or chew tablets; swallow whole to avoid rapid release of oxycodone. · This medication can cause drowsiness or dizziness; avoid driving or operating machinery until you know how it affects you. · Store securely out of sight and reach of children; dispose of unused medication via a drug take-back program. · Take with food if nausea occurs; avoid high-fat meals as they may delay absorption. · Do not stop abruptly; withdrawal symptoms may occur. Consult your doctor for a tapering schedule. |