ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Acetaminophen: cyclooxygenase (COX) inhibitor, primarily in the CNS, reducing prostaglandin synthesis; analgesic and antipyretic. Oxycodone: mu-opioid receptor agonist, inhibiting ascending pain pathways and altering pain perception.
| Metabolism | Acetaminophen: primarily hepatic via glucuronidation (UGT1A1, UGT1A6, UGT1A9), sulfation (SULT1A1), and minor CYP450 (CYP2E1, CYP3A4) to toxic NAPQI. Oxycodone: hepatic via CYP3A4 (major) and CYP2D6 (minor) to active metabolites (noroxycodone, oxymorphone). |
| Excretion | Acetaminophen: renal excretion of metabolites (glucuronide 45-55%, sulfate 20-30%, cysteine and mercapturate conjugates 5-10%) and unchanged drug (<5%); Oxycodone: renal excretion of unchanged drug (approximately 10-19%) and metabolites (noroxycodone, oxymorphone, and their glucuronides) (total renal elimination ~60-87%); fecal elimination of Oxycodone is minimal (<10%). |
| Half-life | Acetaminophen: 2-3 hours (prolonged in hepatic impairment or overdose); Oxycodone: 3-5 hours (immediate-release), 4.5-8 hours (extended-release); Clinical context: Terminal half-life of oxycodone may be prolonged in elderly or patients with renal/hepatic impairment. |
| Protein binding | Acetaminophen: 20-30% (albumin); Oxycodone: 45-50% (albumin). |
| Volume of Distribution | Acetaminophen: 0.9-1.0 L/kg (suggests distribution into total body water); Oxycodone: 2.6-4.0 L/kg (suggests extensive tissue distribution). |
| Bioavailability | Acetaminophen: Oral 85-90%; Oxycodone: Oral 60-87% (first-pass metabolism), Rectal (oxycodone suppository) ~60-80%. |
| Onset of Action | Acetaminophen: Oral 30-60 minutes; Oxycodone: Oral immediate-release 15-30 minutes, extended-release 1-2 hours. |
| Duration of Action | Acetaminophen: 4-6 hours; Oxycodone: Immediate-release 4-6 hours, extended-release 12 hours; Clinical note: Duration may be prolonged in hepatic insufficiency. |
| Molecular Weight | 351.83 |
1-2 tablets (equivalent to 325-650 mg acetaminophen / 5-10 mg oxycodone) every 4-6 hours as needed for pain; maximum 12 tablets per day (acetaminophen limit 3900 mg/day or lower if hepatic risk).
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | eGFR 30-60 mL/min: start with 50% of usual dose, increase cautiously; eGFR <30 mL/min: start with 25% of usual dose, extend dosing interval to every 8-12 hours; avoid in dialysis due to oxycodone accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: start with 50% of usual dose, maximum acetaminophen 2000 mg/day; Child-Pugh C: contraindicated. |
| Pediatric use | Weight-based: oxycodone 0.05-0.15 mg/kg/dose (max 5 mg/dose) with acetaminophen 10-15 mg/kg/dose every 4-6 hours; maximum acetaminophen 75 mg/kg/day (not to exceed 4000 mg/day). |
| Geriatric use | Start with lowest dose (e.g., half of adult dose), titrate slowly; avoid in patients with impaired renal/hepatic function or those at risk for falls; monitor for respiratory depression and constipation. |
| 1st trimester | Limited human data; animal studies not sufficient. Use only if benefits outweigh risks. |
| 2nd trimester | Assess for possible harm; use with caution. |
| 3rd trimester | Prolonged use may cause neonatal withdrawal; avoid high doses 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 agents cross the placenta. Oxycodone has moderate transfer; acetaminophen crosses readily. |
| Breastfeeding | Oxycodone is excreted into breast milk; monitor infant for respiratory depression and sedation. Acetaminophen is safe. The American Academy of Pediatrics considers acetaminophen compatible with breastfeeding; oxycodone use should be limited and monitored. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion of acetaminophen may cause hepatotoxicity; neonatal opioid withdrawal syndrome; CYP3A4 interaction with benzodiazepines or other CNS depressants.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to acetaminophen or oxycodoneSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusKnown or suspected gastrointestinal obstruction
| Precautions | Addiction, abuse, misuse; respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; hepatotoxicity (acetaminophen); interactions with CNS depressants; elderly or debilitated patients; renal impairment; severe hypotension; adrenal insufficiency; use in patients with head injury. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) for oxycodone; L1 (Safe) for acetaminophen. |
| Teratogenic Risk | Acetaminophen: Generally considered low risk; no consistent association with major malformations. Oxycodone: First trimester: No increased risk of major malformations in human studies. Second and third trimesters: Risk of neonatal opioid withdrawal syndrome (NOWS) with chronic use; respiratory depression at delivery. No specific human data for combination; extrapolated from individual components. |
| Fetal Monitoring | Maternal: Respiratory rate, sedation level, blood pressure, pain control. Fetal/neonatal: For chronic oxycodone use near term: fetal heart rate monitoring, assessment for NOWS (e.g., Finnegan scoring). Consider umbilical cord drug testing if opioid use disorder suspected. |
| Fertility Effects | Acetaminophen: No known effect on human fertility. Oxycodone: Can disrupt hypothalamic-pituitary-gonadal axis, leading to menstrual irregularities and reduced fertility in women; may decrease libido and cause erectile dysfunction in men. Effects usually reversible upon discontinuation. |
| Avoid alcohol. Grapefruit juice may increase oxycodone levels; limit or avoid grapefruit products. High-fat meals may delay absorption of oxycodone. Maintain adequate hydration to prevent constipation. |
| Clinical Pearls | Monitor for acetaminophen hepatotoxicity; maximum daily acetaminophen intake should not exceed 4000 mg. Oxycodone has high abuse potential; consider prescribing naloxone for patients at risk of opioid overdose. Avoid concurrent use of other CNS depressants. Use with caution in elderly or renally impaired patients. |
| Patient Advice | Do not exceed 4000 mg of acetaminophen per day from all sources. · This medication can cause drowsiness; avoid driving or operating machinery until you know how it affects you. · Do not consume alcohol while taking this medication. · Take exactly as prescribed; do not crush, chew, or break extended-release tablets. · Store securely out of reach of children and dispose of unused medication properly. · Seek emergency medical attention if you experience difficulty breathing, severe drowsiness, or signs of an allergic reaction. |