PERCOCET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PERCOCET (PERCOCET).
Oxycodone is a mu-opioid receptor agonist, inhibiting ascending pain pathways and altering pain perception and emotional response. Acetaminophen inhibits cyclooxygenase (COX) in the CNS, reducing prostaglandin synthesis and exerting analgesic and antipyretic effects.
| Metabolism | Oxycodone: primarily hepatic via CYP3A4 and CYP2D6 to active metabolites (noroxycodone, oxymorphone). Acetaminophen: hepatic via glucuronidation (UGT1A1/1A6), sulfation, and minor CYP2E1 oxidation. |
| Excretion | Oxycodone: primarily renal (up to 19% as unchanged drug, 50% as noroxycodone and oxymorphone metabolites); about 10% biliary/fecal. Acetaminophen: renal (majority as glucuronide and sulfate conjugates, about 5% unchanged). |
| Half-life | Oxycodone: 3.5–4.5 hours (terminal) in normal renal function; prolonged in hepatic/renal impairment (up to 6–12 hours). Acetaminophen: 2–3 hours (terminal) in overdose, extended with hepatic injury. |
| Protein binding | Oxycodone: 38–45% bound to albumin and alpha-1-acid glycoprotein. Acetaminophen: 10–25% bound to albumin (minimal). |
| Volume of Distribution | Oxycodone: Vd approximately 2.6 L/kg (extensive tissue distribution). Acetaminophen: Vd approximately 0.9 L/kg (total body water). |
| Bioavailability | Oxycodone: oral bioavailability 60–87% (immediate-release). Acetaminophen: oral bioavailability 85–98% (first-pass metabolism minimal). |
| Onset of Action | Oral: oxycodone immediate-release: 10–15 minutes; acetaminophen: 30–60 minutes. |
| Duration of Action | Oxycodone immediate-release: 4–6 hours (analgesic); acetaminophen: 4–6 hours (antipyretic/analgesic). Clinical note: Duration may be shorter with initial doses; extended-release formulations last 12 hours. |
One tablet (5 mg oxycodone/325 mg acetaminophen) every 6 hours as needed for pain; maximum 12 tablets per day.
| Dosage form | TABLET |
| Renal impairment | GFR >60 mL/min: no adjustment; GFR 30-60 mL/min: dose every 8 hours; GFR <30 mL/min: avoid use or use with extreme caution, consider reducing dose to 50% or extending interval to every 12 hours; not recommended in ESRD. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce total daily dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not FDA-approved for children <18 years; off-label: 0.1-0.2 mg/kg oxycodone (max 5 mg) plus 5-10 mg/kg acetaminophen every 4-6 hours; total acetaminophen not to exceed 75 mg/kg/day or 4 g/day. |
| Geriatric use | Start with low end of dosing, e.g., 2.5 mg oxycodone/325 mg acetaminophen every 6 hours; monitor renal function and avoid >4 g/day acetaminophen; titrate cautiously due to increased sensitivity and fall risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PERCOCET (PERCOCET).
| Breastfeeding | Oxycodone is excreted into breast milk; relative infant dose is approximately 1-2% of maternal weight-adjusted dose. M/P ratio (milk/plasma) is about 3.2:1 for oxycodone. Acetaminophen M/P ratio ~1.0. Low levels expected, but monitor infant for sedation and poor feeding. Caution with maternal high doses or prolonged use; avoid if mother is ultra-rapid CYP2D6 metabolizer due to risk of toxicity. |
| Teratogenic Risk | Percocet (oxycodone/acetaminophen) is pregnancy category C prior to 30 weeks gestation and category D after 30 weeks. First trimester: No clear evidence of major malformations, but opioid use may be associated with neural tube defects and gastroschisis. Second trimester: Risk of miscarriage, intrauterine growth restriction. Third trimester: Prolonged use can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Acetaminophen is considered safe in therapeutic doses but overdose is hepatotoxic to fetus. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of any dosage (especially in children) can be fatal; neonatal opioid withdrawal syndrome with prolonged use during pregnancy; CYP3A4 inhibitors or discontinuation of CYP3A4 inducers may cause fatal respiratory depression; concomitant use with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma, and death.
| Serious Effects |
Hypersensitivity to oxycodone, acetaminophen, or any component; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; severe hepatic impairment (acetaminophen hepatotoxicity risk).
| Precautions | Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; severe hypotension; seizures; serotonin syndrome; adrenal insufficiency; hepatotoxicity (acetaminophen); increased risk of pancreatitis (if combined with alcohol); risk of overuse for acetaminophen. |
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| Fetal Monitoring | Monitor maternal vital signs, pain scores, bowel function, and signs of respiratory depression. Fetal monitoring: Nonstress test or biophysical profile if prolonged use (>7 days) near term. Assess for NOWS after delivery using standardized scoring tools (e.g., Finnegan score). Monitor liver function tests if high-dose acetaminophen (>4 g/day). |
| Fertility Effects | Chronic opioid use may cause menstrual irregularities, anovulation, and reduced fertility due to hypothalamic-pituitary-gonadal axis suppression (decreased LH, FSH, testosterone). Effects are reversible upon cessation. Acetaminophen has no known significant effect on fertility. |