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. |
| Molecular Weight | Oxycodone HCl: 351.82 Da; Acetaminophen: 151.16 Da |
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 | Associated with risk of neural tube defects and congenital anomalies; avoid use if possible. |
| 2nd trimester | May cause fetal opioid dependence and neonatal abstinence syndrome; use only if clearly needed. |
| 3rd trimester | Risk of neonatal respiratory depression and withdrawal; avoid chronic use 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 oxycodone and acetaminophen cross the placenta. Oxycodone transfer is significant and can lead to fetal opioid dependence and neonatal withdrawal. Acetaminophen readily crosses but is not associated with neonatal toxicity at therapeutic doses. |
■ 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 |
Severe respiratory depressionAcute or severe bronchial asthmaParalytic ileusKnown hypersensitivity to oxycodone or acetaminophenSevere hepatic impairment (acetaminophen 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. |
| Food/Dietary |
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| Breastfeeding |
| Oxycodone and acetaminophen are excreted into breast milk in low amounts. Oxycodone may cause infant sedation, respiratory depression, or withdrawal. Monitor infant for drowsiness and feeding difficulties. Acetaminophen is considered compatible with breastfeeding. |
| Lactation Rating | L3 (Moderately Safe) - Oxycodone; L1 (Safest) - Acetaminophen |
| Teratogenic Risk | 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. |
| Avoid alcohol consumption while taking this medication, as alcohol can increase the risk of hepatotoxicity from acetaminophen and enhance the sedative effects of oxycodone. Grapefruit and grapefruit juice may inhibit CYP3A4 and increase oxycodone levels; avoid concurrent use. High-fat meals may delay absorption of oxycodone. |
| Clinical Pearls | Maximum acetaminophen dose from all sources should not exceed 4 g/day (3 g/day in patients with hepatic impairment or alcohol use). Avoid in severe hepatic impairment. Use with caution in elderly, opioid-naïve, or patients with respiratory compromise. Monitor for signs of abuse, dependence, or withdrawal. Coadministration with CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) can alter oxycodone metabolism. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · May cause drowsiness, dizziness, or constipation; avoid driving or operating machinery until effects are known. · Avoid alcohol and other central nervous system depressants (e.g., sedatives, tranquilizers). · Do not exceed 4,000 mg of acetaminophen per day from all products; check labels of OTC medications. · Store securely out of reach of children; dispose of unused medication via drug take-back programs. · Seek immediate medical help if you experience signs of allergic reaction (rash, difficulty breathing) or symptoms of serotonin syndrome (agitation, hallucinations, rapid heart rate). · Do not stop abruptly; tapering may be needed to avoid withdrawal symptoms. |