OXYCODONE 5/APAP 500
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Oxycodone: mu-opioid receptor agonist; Acetaminophen: cyclooxygenase (COX) inhibition, analgesic and antipyretic via central action.
| Metabolism | Oxycodone: primarily hepatic via CYP3A4 and to a lesser extent CYP2D6; Acetaminophen: hepatic via glucuronidation, sulfation, and CYP2E1 (minor). |
| Excretion | Renal: Oxycodone ~87% (10% unchanged, 77% as metabolites); Acetaminophen ~85% (2-5% unchanged, rest as glucuronide and sulfate conjugates). Biliary/fecal: Minimal for both. |
| Half-life | Oxycodone: Terminal half-life 3.5-5.6 hours (mean 4.5 h); prolonged in renal/hepatic impairment. Acetaminophen: 2-3 hours. |
| Protein binding | Oxycodone: 38-45% (primarily albumin); Acetaminophen: 10-25% (albumin). |
| Volume of Distribution | Oxycodone: 2.6-3.0 L/kg (reflects moderate tissue distribution); Acetaminophen: 0.9-1.0 L/kg (mainly body water). |
| Bioavailability | Oxycodone oral: 60-87% (first-pass metabolism); Acetaminophen oral: 85-98% (minimal first-pass). |
| Onset of Action | Oral (immediate-release): Oxycodone 15-30 min; Acetaminophen 30-60 min. |
| Duration of Action | Oxycodone: 4-6 hours (analgesia); Acetaminophen: 4-6 hours (antipyretic/analgesic). Note: Combination may have shorter analgesic duration than oxycodone alone at higher doses. |
| Molecular Weight | Oxycodone: 315.36 Da; Acetaminophen: 151.16 Da |
1-2 tablets (oxycodone 5-10 mg/APAP 500-1000 mg) orally every 4-6 hours as needed for pain; maximum APAP dose 4000 mg/day from all sources.
| Dosage form | TABLET |
| Renal impairment | GFR 10-50 mL/min: extend dosing interval to every 6 hours; GFR <10 mL/min: use with caution, consider reducing dose or extending interval; not recommended in dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce starting dose by 50% and increase dosing interval; Child-Pugh Class C: avoid use. |
| Pediatric use | Not recommended for children <18 years due to safety concerns with codeine/oxycodone and APAP; for specific use, weight-based dosing of oxycodone 0.05-0.15 mg/kg/dose every 4-6 hours; APAP 10-15 mg/kg/dose every 4-6 hours; max APAP 75 mg/kg/day. |
| Geriatric use | Start at low end of dosing range (e.g., 2.5-5 mg oxycodone) due to increased sensitivity and risk of respiratory depression; monitor renal function; avoid in patients with significant hepatic impairment. |
| 1st trimester | Oxycodone/acetaminophen is not recommended in the first trimester due to potential teratogenic effects. Acetaminophen is generally considered safe but limited data on oxycodone; avoid if possible. |
| 2nd trimester | Use with caution in the second trimester. Risks include neonatal abstinence syndrome and potential for acetaminophen hepatotoxicity at high doses. Limited human data. |
| 3rd trimester | Avoid prolonged use in the third trimester due to risk of neonatal respiratory depression and neonatal opioid withdrawal syndrome. Acetaminophen at therapeutic doses is considered safe. |
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 has high placental transfer; acetaminophen crosses readily. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants; hepatotoxicity from acetaminophen overdose.
| Common Effects | Constipation |
| Serious Effects |
Hypersensitivity to oxycodone, acetaminophen, or any componentSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusSuspected or known gastrointestinal obstructionSevere hepatic impairmentUse within 14 days of MAO inhibitors
| Precautions | Respiratory depression; drug dependence; abuse potential; hepatotoxicity; hypersensitivity; adrenal insufficiency; hypotension; seizures; severe hypotension; head injury; gastrointestinal obstruction; severe hypertension; severe hepatic or renal impairment; elderly/debilitated patients; pregnancy/breastfeeding. |
| Food/Dietary |
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| Breastfeeding | Oxycodone is excreted into breast milk; relative infant dose is approximately 1.7-3.5%. Acetaminophen is safe in breastfeeding. Monitor infant for signs of sedation, respiratory depression, or poor feeding. Consider risk of neonatal opioid withdrawal if mother is dependent. |
| Lactation Rating | L3 (Moderately Safe, use with caution) |
| Teratogenic Risk | First trimester: Oxycodone is not associated with a significant increased risk of major congenital malformations in most studies, but data on the combination with acetaminophen are limited. Second and third trimesters: Chronic use or high doses near term may cause neonatal opioid withdrawal syndrome (NOWS). Use during labor may cause respiratory depression in the neonate. Acetaminophen is generally considered low risk, but overdose is hepatotoxic to fetus. |
| Fetal Monitoring | Maternal: Monitor for signs of opioid toxicity (respiratory depression, sedation, constipation), acetaminophen hepatotoxicity (liver enzymes, bilirubin), and development of opioid use disorder. Fetal/Neonatal: Monitor fetal heart rate patterns during labor; assess for NOWS (e.g., feeding difficulties, irritability, tremors) for at least 48-72 hours after delivery if maternal use near term. |
| Fertility Effects | Oxycodone may cause menstrual cycle irregularities (e.g., anovulation) due to opioid-induced hyperprolactinemia and suppression of GnRH, potentially impairing fertility. Acetaminophen at therapeutic doses has no known adverse effect on fertility. |
| Grapefruit and grapefruit juice may increase oxycodone levels by inhibiting CYP3A4; avoid concurrent intake. Alcohol potentiates CNS depression and increases hepatotoxicity risk; strict avoidance is recommended. High-fat meals may delay absorption of oxycodone but do not significantly alter overall exposure. No specific interactions with other foods; maintain adequate hydration and fiber to mitigate constipation. |
| Clinical Pearls | Oxycodone/APAP 5/500 mg combines a semi-synthetic opioid agonist (oxycodone) with a para-aminophenol derivative (acetaminophen). The acetaminophen component limits daily dosing to a maximum of 4 g (or 3 g in patients with hepatic impairment or chronic alcohol use) to avoid hepatotoxicity. Oxycodone is approximately 1.5 times more potent than oral morphine. Use with caution in patients with compromised respiratory function, sleep apnea, or CNS depression. Concomitant use with CYP3A4 inhibitors (e.g., macrolides, azole antifungals) can increase oxycodone exposure; CYP3A4 inducers (rifampin, carbamazepine) may reduce efficacy. Prescribe with a laxative regimen to prevent opioid-induced constipation. Assess for history of substance abuse; opioid use disorder risk is significant. Avoid concurrent use with benzodiazepines or CNS depressants due to additive sedation and respiratory depression risks. |
| Patient Advice | Take exactly as prescribed; do not crush, break, or chew tablets. · Do not exceed 8 tablets per day (4 g acetaminophen) due to risk of liver damage. · Avoid alcohol entirely while taking this medication. · May cause drowsiness, dizziness, or impaired judgment; do not drive or operate machinery until you know how you react. · Use a stool softener or laxative to prevent constipation; increase fluid and fiber intake. · Do not stop abruptly without consulting your doctor; withdrawal symptoms may occur. · Store securely out of reach of children and pets; dispose of unused medication via drug take-back programs. · Avoid other acetaminophen-containing products to prevent overdose. · Report difficulty breathing, severe sedation, or signs of allergic reaction immediately. · Do not share this medication with others; it can be habit-forming. |