OXYCODONE HYDROCHLORIDE AND ACETAMINOPHEN
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, inhibiting neurotransmitter release and pain signal transmission. Acetaminophen inhibits cyclooxygenase (COX) enzymes, particularly in the central nervous system, reducing prostaglandin synthesis and pain perception.
| Metabolism | Oxycodone: CYP3A4 and CYP2D6; Acetaminophen: Glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation; minor CYP2E1. |
| Excretion | Oxycodone: primarily renal (10-20% unchanged, metabolites conjugated); Acetaminophen: renal (85-90%, primarily as glucuronide and sulfate conjugates, <5% unchanged). |
| Half-life | Oxycodone: 3.5-5.5 hours (immediate-release); Acetaminophen: 1.5-3 hours. Clinical context: renal/hepatic impairment prolongs half-life. |
| Protein binding | Oxycodone: 45% bound primarily to albumin; Acetaminophen: 10-25% bound (albumin). |
| Volume of Distribution | Oxycodone: 2.6-3.3 L/kg; Acetaminophen: 0.75-1.0 L/kg. Clinical meaning: oxycodone distributes widely into tissues; acetaminophen distributes evenly into body water. |
| Bioavailability | Oxycodone: oral 60-87% (first-pass metabolism); Acetaminophen: oral 85-95%. |
| Onset of Action | Oral (immediate-release): 10-30 minutes; peak effect 30-60 minutes; Oral (extended-release): 1 hour; peak 3-4 hours. |
| Duration of Action | Immediate-release: 3-6 hours; Extended-release: 12 hours. Clinical notes: tolerance may shorten duration; adjust dosing in elderly/hepatic impairment. |
Adults: 1-2 tablets (each containing 5 mg oxycodone/325 mg acetaminophen) orally every 4-6 hours as needed for pain; maximum 12 tablets per day (60 mg oxycodone/3900 mg acetaminophen).
| Dosage form | SOLUTION |
| Renal impairment | GFR ≥60 mL/min: No adjustment. GFR 30-59 mL/min: Reduce dose to 50-75% of usual; avoid if possible due to metabolite accumulation. GFR 10-29 mL/min: Reduce to 50% of usual; monitor for toxicity. GFR <10 mL/min: Avoid use; consider alternative. |
| Liver impairment | Child-Pugh Class A: No adjustment recommended. Child-Pugh Class B: Reduce dose by 50%; start with lowest effective dose. Child-Pugh Class C: Avoid use; consider alternative due to risk of hepatic encephalopathy and acetaminophen toxicity. |
| Pediatric use | Children ≥11 years and >50 kg: Same as adult dosing. Children 6-10 years: 0.05-0.15 mg/kg oxycodone component every 4-6 hours; max acetaminophen 75 mg/kg/day. Children <6 years: Not recommended; use alternative. |
| Geriatric use | Start at lowest effective dose (e.g., 2.5 mg oxycodone/162.5 mg acetaminophen) every 6 hours; titrate cautiously. Monitor for respiratory depression, sedation, and falls. Avoid acetaminophen doses >3000 mg/day. Consider renal/hepatic function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
| FDA category | Positive |
| Breastfeeding | Oxycodone excreted into breast milk with relative infant dose of 1.7-8.8% of maternal weight-adjusted dose; M/P ratio approximately 3.7:1. Acetaminophen levels low (M/P ratio ~1.0). Use with caution; monitor infant for drowsiness, poor feeding, respiratory depression. Avoid in rapid metabolizers (CYP2D6) due to risk of morphine toxicity. |
| Teratogenic Risk |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risk with concomitant use of benzodiazepines or other CNS depressants; hepatotoxicity from acetaminophen.
| Common Effects | Constipation |
| Serious Effects |
Significant respiratory depression; acute or severe bronchial asthma; known or suspected gastrointestinal obstruction; hypersensitivity to oxycodone, acetaminophen, or any component.
| Precautions | Addiction, abuse, misuse; respiratory depression; neonatal opioid withdrawal syndrome; interactions with CNS depressants; hepatotoxicity; adrenal insufficiency; hypotension; seizures; serotonin syndrome; severe hypotension; head injury; gastrointestinal obstruction. |
Loading safety data…
| First trimester: Limited data, but acetaminophen generally considered safe; oxycodone associated with neural tube defects in some studies but risk low. Second and third trimesters: Chronic oxycodone use may cause fetal dependence and withdrawal; acetaminophen not teratogenic. Neonatal opioid withdrawal syndrome (NOWS) with third trimester use. Avoid long-term use; use lowest effective dose. |
| Fetal Monitoring | Maternal: respiratory rate, sedation, bowel function, blood pressure, liver function tests (acetaminophen). Fetal: ultrasound for growth restriction with chronic use; fetal heart rate monitoring in labor; assess for neonatal withdrawal (Finnegan score) after delivery. |
| Fertility Effects | Opioids may suppress gonadotropin-releasing hormone (GnRH), leading to hypogonadism, reduced libido, and menstrual irregularities. Acetaminophen: limited data, may be associated with prolonged time to pregnancy at high doses. Impact reversible upon discontinuation. |