HYDROCODONE BITARTRATE AND ACETAMINOPHEN
Clinical safety rating: avoid
CNS depressants including alcohol and benzodiazepines increase sedation risk Life-threatening respiratory depression may occur.
Hydrocodone is a mu-opioid receptor agonist that inhibits ascending pain pathways and alters pain perception. Acetaminophen inhibits cyclooxygenase (COX) enzymes, primarily in the CNS, reducing prostaglandin synthesis and providing analgesic and antipyretic effects.
| Metabolism | Hydrocodone: primarily CYP3A4 and CYP2D6 to hydromorphone (active). Acetaminophen: primarily glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3), with minor CYP2E1 oxidation to NAPQI (toxic). |
| Excretion | Renal excretion of metabolites (hydrocodone: ~60% as conjugates, <12% unchanged; acetaminophen: ~85-90% as glucuronide and sulfate conjugates, <5% unchanged). Biliary/fecal elimination of minor metabolites. |
| Half-life | Hydrocodone: 3.8-7.4 hours (terminal), prolonged in hepatic impairment. Acetaminophen: 1.5-2.5 hours (terminal). |
| Protein binding | Hydrocodone: ~20-50% bound to albumin and other proteins. Acetaminophen: 10-25% bound to albumin. |
| Volume of Distribution | Hydrocodone: 3.3-4.7 L/kg (extensive tissue distribution). Acetaminophen: 0.75-1.0 L/kg (primarily total body water). |
| Bioavailability | Oral: Hydrocodone ~70-80% (first-pass metabolism). Acetaminophen ~60-90% (product dependent). |
| Onset of Action | Oral: 30-60 minutes for analgesic effect. |
| Duration of Action | Oral: 4-6 hours (analgesic effect). Clinical note: Duration may vary with dose and patient factors; extended-release formulations not applicable. |
Oral: 1-2 tablets (5-10 mg hydrocodone/325-650 mg acetaminophen) every 4-6 hours as needed for pain; maximum daily doses: hydrocodone 40 mg, acetaminophen 3000 mg.
| Dosage form | CAPSULE |
| Renal impairment | eGFR 30-89 mL/min: No adjustment. eGFR <30 mL/min: Avoid use or reduce dose and frequency. Hemodialysis: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce total daily dose by 50% or extend dosing interval. Child-Pugh C: Avoid use. |
| Pediatric use | Not recommended for children <18 years due to safety concerns. For postoperative tonsillectomy/adenoidectomy: contraindicated. |
| Geriatric use | Initiate at lowest effective dose (e.g., 2.5 mg hydrocodone/325 mg acetaminophen) and titrate slowly; monitor for CNS depression and constipation. Avoid in renal impairment. |
| 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 | Hydrocodone is excreted into human breast milk, with an M/P ratio approximately 2.5. Postpartum use may lead to infant sedation and respiratory depression, especially in CYP2D6 ultra-rapid metabolizers. Acetaminophen is excreted in low levels. Use is generally avoided due to risks; if used, monitor infant for drowsiness and feeding difficulties. |
| Teratogenic Risk |
■ 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 | Cough |
| Serious Effects |
Significant respiratory depression, acute or severe bronchial asthma, GI obstruction (including paralytic ileus), hypersensitivity to hydrocodone or acetaminophen, severe hepatic impairment, and known or suspected gastrointestinal obstruction.
| Precautions | Respiratory depression, drug dependence, abuse potential, risks with CNS depressants, elderly/debilitated patients, hepatic impairment, renal impairment, severe hypotension, head injury, seizures, use in pregnancy, use in breastfeeding, adrenal insufficiency, anaphylaxis, withdrawal, and driving impairment. |
Loading safety data…
| First trimester: Limited human data; animal studies show no consistent teratogenicity. Second and third trimesters: Chronic use may cause fetal opioid dependence, neonatal withdrawal syndrome, and reduced fetal growth. Acetaminophen component: no known teratogenic risk at therapeutic doses. |
| Fetal Monitoring | Maternal: respiratory rate, oxygen saturation, sedation level, signs of abuse/dependence. Fetal: ultrasound for growth restriction in chronic use; nonstress test or biophysical profile if prolonged therapy near term. Neonatal: observe for signs of neonatal opioid withdrawal syndrome for 48-72 hours after delivery. |
| Fertility Effects | Opioids may disrupt the hypothalamic-pituitary-gonadal axis, potentially causing decreased libido, erectile dysfunction, and menstrual irregularities. Acetaminophen: no known direct effect on fertility. Reversible upon discontinuation. |