OXYCET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OXYCET (OXYCET).
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, though it can interact with other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Acetaminophen is believed to produce analgesia through central action, possibly mediated through inhibition of cyclooxygenase (COX) and activation of descending serotonergic pathways, though the exact mechanism is not fully understood.
| Metabolism | Oxycodone is extensively metabolized in the liver via cytochrome P450 3A4 (CYP3A4) and CYP2D6 to noroxycodone, oxymorphone, and noroxymorphone. Acetaminophen is primarily metabolized in the liver via conjugation (glucuronidation and sulfation) and, to a lesser extent, via CYP2E1 to a toxic metabolite (NAPQI) which is normally detoxified by glutathione. |
| Excretion | Oxycodone is primarily metabolized in the liver via CYP3A4 to noroxycodone and via CYP2D6 to oxymorphone. Renal excretion accounts for approximately 87% of the administered dose, with 8.1% as unchanged oxycodone, 22.8% as noroxycodone, 9.1% as noroxymorphone, 3.2% as oxymorphone, and others. Fecal excretion is about 10%. |
| Half-life | The terminal elimination half-life of oxycodone is approximately 3.5-4 hours for immediate-release formulations. For controlled-release formulations, the half-life is similar due to absorption-limited elimination, but the duration of action is extended due to the formulation. In elderly patients or those with hepatic impairment, half-life may be increased up to 2-fold. |
| Protein binding | Approximately 45% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 2.6-3.6 L/kg. This indicates extensive tissue distribution, with oxycodone widely distributed throughout body fluids and tissues, including the brain. |
| Bioavailability | Oral immediate-release: 60-87% due to first-pass metabolism. Extended-release: approximately the same as immediate-release when adjusted for dose. Intravenous: 100%. Rectal: similar to oral (60-87%). |
| Onset of Action | Immediate-release oral: onset within 15-30 minutes, peak effect at 1 hour. Extended-release oral: onset within 1 hour, peak at 3-4 hours. Intravenous: onset within minutes. Rectal: onset within 30-60 minutes. |
| Duration of Action | Immediate-release: 3-6 hours. Extended-release: 12 hours for 12-hour formulations (e.g., OxyContin). Analgesic effect correlates with plasma concentrations; tolerance may develop with prolonged use. |
| Action Class | H1 Antihistaminics (second Generation) |
| Brand Substitutes | L Dio 1 Tablet, LCZ Tablet, Lecope Tablet, 1-AL Tablet, L Hist Tablet |
1 tablet (325 mg acetaminophen and 5 mg oxycodone) orally every 4 to 6 hours as needed for pain; maximum 12 tablets per day.
| Dosage form | TABLET |
| Renal impairment | For CrCl 30-50 mL/min: administer every 6 hours; CrCl 10-29 mL/min: administer every 8 hours; CrCl < 10 mL/min: not recommended due to risk of oxycodone accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or extend dosing interval; Child-Pugh C: contraindicated or use with extreme caution, maximum 50% of normal dose. |
| Pediatric use | Not recommended for children under 18 years due to risk of respiratory depression; for older adolescents (≥18 years), adult dosing may be considered. |
| Geriatric use | Initiate at lowest effective dose, typically one-half of adult dose (one tablet every 6 hours) and titrate slowly; caution due to increased sensitivity and risk of falls and respiratory depression. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OXYCET (OXYCET).
| Breastfeeding | Oxycodone is excreted into breast milk; relative infant dose approximately 1.6-3.5% of maternal weight-adjusted dose. M/P ratio not firmly established. Use caution; monitor infant for sedation, respiratory depression, poor feeding. Paracetamol is safe; excreted in low levels. If prolonged maternal oxycodone use, risk of neonatal withdrawal. |
| Teratogenic Risk | Oxycodone/paracetamol (OXYCET). Oxycodone: FDA Category B (but Category D if prolonged use or near term). First trimester: Increased risk of neural tube defects, congenital heart defects; limited data, but avoid if possible. Second and third trimesters: Prolonged use may cause fetal dependence, withdrawal syndrome; near term, neonatal respiratory depression. Paracetamol: Category B; appears safe in standard doses but overdose causes fetal hepatotoxicity. |
■ FDA Black Box Warning
Addiction, Abuse, and Misuse: Oxycodone exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor regularly for development of these behaviors or conditions. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Accidental Ingestion: Accidental ingestion of even one dose of oxycodone, especially by children, can result in a fatal overdose of oxycodone. Neonatal Opioid Withdrawal Syndrome: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants may result in profound sedation, respiratory depression, coma, and death. Reserve for use in patients for whom alternative treatment options are inadequate. Hepatotoxicity: Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses exceeding 4000 mg per day, and often involve more than one acetaminophen-containing product.
| Serious Effects |
["Hypersensitivity to oxycodone or acetaminophen","Significant respiratory depression","Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment","Paralytic ileus","Severe hepatic impairment (for acetaminophen component)","Concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy"]
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| Fetal Monitoring | Maternal: Liver function tests (paracetamol overdose risk), respiratory status, signs of opioid dependence. Fetal: Ultrasound for growth restriction (if chronic use); fetal heart rate monitoring if near term due to risk of neonatal respiratory depression. Neonatal: Observe for withdrawal (irritability, tremors, poor feeding) if maternal use >1 week prior to delivery. |
| Fertility Effects | Oxycodone may impair female fertility (disrupted ovulation, menstrual cycle); effects likely reversible upon discontinuation. Paracetamol has no known significant effect on fertility in humans. |
| Precautions | ["Risk of addiction, abuse, and misuse","Life-threatening respiratory depression","Accidental ingestion (especially in children)","Neonatal opioid withdrawal syndrome","Risks from concomitant use with benzodiazepines or other CNS depressants","Hepatotoxicity from acetaminophen","Severe hypotension","Gastrointestinal effects (e.g., constipation, ileus)","Seizures in patients with seizure disorders","Serotonin syndrome with concomitant serotonergic drugs","Adrenal insufficiency","Use in patients with head injury or increased intracranial pressure","Use in patients with acute abdominal conditions"] |