ROXICET 5/500
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ROXICET 5/500 (ROXICET 5/500).
Oxycodone is a full opioid agonist that binds to mu-opioid receptors in the CNS, inhibiting ascending pain pathways and altering pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and producing analgesic and antipyretic effects.
| Metabolism | Oxycodone is metabolized primarily via CYP3A4 and CYP2D6 to noroxycodone and oxymorphone. Acetaminophen is metabolized mainly via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation, with minor oxidation by CYP2E1 and CYP1A2 producing N-acetyl-p-benzoquinone imine (NAPQI). |
| Excretion | Oxycodone: primarily hepatic metabolism to noroxycodone, oxymorphone, and conjugates; renal elimination of metabolites (about 60-87% as unchanged and metabolites), fecal < 10%. Acetaminophen: renal elimination of conjugates (90-100%), <5% unchanged. |
| Half-life | Oxycodone: 3-5 hours (immediate-release); Acetaminophen: 2-3 hours. In hepatic impairment, oxycodone half-life prolonged (up to 12-15 hours). |
| Protein binding | Oxycodone: ~45% bound to albumin; Acetaminophen: 10-25% bound to albumin. |
| Volume of Distribution | Oxycodone: 2-3 L/kg (extensive tissue distribution); Acetaminophen: 0.8-1.0 L/kg (distribution throughout body water). |
| Bioavailability | Oxycodone oral: 60-87% (high first-pass metabolism varies); Acetaminophen oral: 80-90%. |
| Onset of Action | Oral: oxycodone 10-15 minutes; acetaminophen 15-30 minutes. |
| Duration of Action | Oxycodone IR: 4-6 hours; acetaminophen: 4-6 hours. Clinical duration limited by oxycodone in fixed combination. |
1-2 tablets (5-10 mg oxycodone / 325-650 mg acetaminophen) orally every 4-6 hours as needed for pain; maximum 12 tablets per day (60 mg oxycodone / 6000 mg acetaminophen) in 24 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: administer every 6 hours. CrCl 10-29 mL/min: administer every 8 hours. CrCl <10 mL/min: use not recommended due to oxycodone accumulation; consider alternative. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and extend dosing interval to every 8 hours. Child-Pugh Class C: contraindicated due to acetaminophen hepatotoxicity. |
| Pediatric use | Not typically recommended; use weight-based dosing of oxycodone 0.1-0.2 mg/kg/dose (max 5 mg/dose) every 4-6 hours as needed, with acetaminophen component not to exceed 75 mg/kg/day. Not approved for children <12 years. |
| Geriatric use | Initiate at lowest dose (one tablet every 6 hours) and titrate cautiously. Monitor for respiratory depression, sedation, and constipation. Avoid doses >4 tablets per day unless tolerated. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ROXICET 5/500 (ROXICET 5/500).
| Breastfeeding | Oxycodone is excreted into breast milk with relative infant dose (RID) of 1.7-6.2% of maternal weight-adjusted dose; M/P ratio not well established (estimated ~1.3-3.7). Acetaminophen RID ~1-2%, M/P ratio ~0.91-1.0. Caution: Monitor infant for somnolence, respiratory depression, poor feeding. Avoid in breastfeeding women with CYP2D6 ultra-rapid metabolizer status due to increased morphine production. |
| Teratogenic Risk | Pregnancy Category C (oxycodone) and D (acetaminophen at high doses). Oxycodone: Risk of neonatal opioid withdrawal syndrome (NOWS) with prolonged use in third trimester; risk of respiratory depression near term. Acetaminophen: Epidemiologic data not conclusively linked to major malformations at therapeutic doses, but high doses may be associated with fetal hepatotoxicity. FDA warns against chronic use during pregnancy due to NOWS. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of even one dose of oxycodone, especially by children, can cause fatal overdose; neonatal opioid withdrawal syndrome; cytochrome P450 3A4 interaction with concurrent use of benzodiazepines or other CNS depressants; hepatotoxicity due to acetaminophen (dose-related).
| Serious Effects |
Hypersensitivity to oxycodone, acetaminophen, or any component of the formulation; 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 (for acetaminophen component).
| Precautions | Risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression; risk of accidental ingestion; neonatal opioid withdrawal syndrome if used during pregnancy; risk of severe hypotension; risk of hepatotoxicity due to acetaminophen; risk of serotonin syndrome if co-administered with serotonergic drugs; adrenal insufficiency; risk of seizures; risk of increased intracranial pressure; severe renal or hepatic impairment; drug interactions with CNS depressants and CYP3A4 inhibitors/inducers. |
Loading safety data…
| Fetal Monitoring | Maternal: Pain score, respiratory rate, sedation level, bowel function, liver function tests (acetaminophen). Fetal/Neonatal: Fetal heart rate monitoring if prolonged use near term; assess for NOWS (Neonatal Abstinence Score) in newborns. Consider umbilical cord drug testing if chronic use. |
| Fertility Effects | Oxycodone may impair fertility in females by disrupting menstrual cycles and ovulation via opioid receptor-mediated hypothalamic-pituitary-gonadal axis suppression. Acetaminophen: Limited evidence suggests possible prolongation of time to pregnancy with chronic use; mechanism unclear. Both may affect sperm parameters in males (decreased motility, count). |