VICODIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VICODIN (VICODIN).
VICODIN (hydrocodone/acetaminophen) is a combination opioid agonist and analgesic. Hydrocodone acts on mu-opioid receptors in the CNS to alter pain perception and response; acetaminophen inhibits cyclooxygenase (COX) activity, likely in the CNS, reducing prostaglandin synthesis and providing antipyretic effects.
| Metabolism | Hydrocodone: primarily hepatic, CYP3A4 and CYP2D6-mediated O-demethylation to hydromorphone; Acetaminophen: hepatic, primarily via glucuronidation and sulfation, with minor CYP2E1, CYP1A2, CYP3A4 oxidation to toxic NAPQI. |
| Excretion | Hydrocodone: primarily renal (~60% as metabolites, 12% unchanged); minor biliary. Acetaminophen: renal (90-100% as metabolites, 2-4% unchanged). |
| Half-life | Hydrocodone: 3.8-6.4 hours (terminal); Acetaminophen: 2-3 hours (terminal). Clinically, steady-state achieved in 1-2 days. |
| Protein binding | Hydrocodone: 36-50% (primarily albumin); Acetaminophen: 10-25% (minimal binding). |
| Volume of Distribution | Hydrocodone: ~3.3 L/kg (extensive tissue distribution); Acetaminophen: ~0.9-1.0 L/kg. |
| Bioavailability | Oral: Hydrocodone ~70-80% (first-pass metabolism); Acetaminophen ~90-95% (minimal first-pass). |
| Onset of Action | Hydrocodone (oral): 10-30 minutes; acetaminophen (oral): 30-60 minutes. |
| Duration of Action | Hydrocodone: 4-6 hours (analgesic); acetaminophen: 4-6 hours (antipyretic/analgesic). Note: tolerance may develop with prolonged use. |
| Molecular Weight | 592.67 |
1-2 tablets (hydrocodone 5-10 mg and acetaminophen 300-325 mg) orally every 4-6 hours as needed for pain; maximum daily acetaminophen dose 4 g.
| Dosage form | TABLET |
| Renal impairment | GFR 50-90 mL/min: no adjustment; GFR 10-49 mL/min: consider 50% dose reduction; GFR <10 mL/min: avoid use. |
| Liver impairment | Child-Pugh A: caution, consider 50% dose reduction; Child-Pugh B: use 25-50% of usual dose; Child-Pugh C: contraindicated. |
| Pediatric use | Hydrocodone component: 0.1-0.2 mg/kg/dose every 4-6 hours; acetaminophen component: 10-15 mg/kg/dose every 4-6 hours; maximum 5 doses/24 hours. Not recommended for children <2 years or with CYP2D6 ultrarapid metabolizer status. |
| Geriatric use | Initiate with 50% of usual adult dose; maximum single dose 5 mg hydrocodone; monitor for sedation, constipation, and respiratory depression. |
| 1st trimester | Avoid; associated with increased risk of congenital malformations, particularly neural tube defects and cardiac anomalies, especially with first-trimester exposure. |
| 2nd trimester | Avoid; chronic use may lead to fetal dependence and withdrawal; use only if clearly needed at lowest effective dose for shortest duration. |
| 3rd trimester | Avoid; risk of neonatal respiratory depression, withdrawal syndrome, and premature labor; prolonged use may cause persistent pulmonary hypertension of the newborn. |
Clinical note
Comprehensive clinical and safety monograph for VICODIN (VICODIN).
| Placental transfer | Hydrocodone and acetaminophen readily cross the placenta. Hydrocodone undergoes placental metabolism to hydromorphone and other active metabolites. Acetaminophen crosses the placenta easily. |
| Breastfeeding | Hydrocodone and acetaminophen are excreted into breast milk in low concentrations. However, infants of mothers taking hydrocodone may develop respiratory depression, sedation, and withdrawal symptoms. The American Academy of Pediatrics considers codeine (related) to be contraindicated; similar caution applies. Avoid breastfeeding if mother is a CYP2D6 ultra-rapid metabolizer due to increased morphine conversion. |
■ FDA Black Box Warning
Addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; interactions with CNS depressants; hepatotoxicity from acetaminophen overdose; risks from concomitant use with benzodiazepines or other CNS depressants; and risks associated with rapid tapering or abrupt discontinuation.
| Serious Effects |
Hypersensitivity to hydrocodone, acetaminophen, or any componentSignificant respiratory depression (especially in unmonitored settings)Acute or severe bronchial asthma or hypercarbiaParalytic ileus, suspected or known gastrointestinal obstructionConcurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapySevere hepatic impairment (Child-Pugh Class C) due to acetaminophen component
| Precautions | Respiratory depression; drug dependence and abuse; CNS depression; increased risk of seizures; adrenal insufficiency; severe hypotension; hepatotoxicity; use in patients with head injury; use in pregnancy; use in breastfeeding; concomitant use with CYP3A4 inhibitors/inducers; use in hepatic or renal impairment; use in elderly or debilitated patients. |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L3 - Possibly Hazardous (based on hydrocodone component; avoid if possible, especially in ultra-rapid metabolizers) |
| Teratogenic Risk | Pregnancy Category C prior to 32 weeks; Category D after 32 weeks due to risk of neonatal opioid withdrawal syndrome. First trimester: possible increased risk of neural tube defects, but data are limited. Second and third trimesters: prolonged use may lead to fetal dependence, preterm delivery, and low birth weight. Third trimester: risk of respiratory depression and withdrawal in neonate. |
| Fetal Monitoring | Monitor maternal respiratory status, level of sedation, and symptoms of withdrawal. Fetal monitoring: ultrasound for growth restriction if prolonged use; nonstress test or biophysical profile if signs of fetal distress. Neonatal monitoring for opioid withdrawal using Finnegan scoring if maternal use in third trimester. |
| Fertility Effects | Opioids may suppress gonadotropin-releasing hormone, leading to decreased libido, erectile dysfunction, or menstrual irregularities. Acetaminophen is not known to affect fertility. Reversible upon discontinuation. |
| Avoid alcohol; ethanol increases acetaminophen hepatotoxicity. High-fat meals may delay absorption but not significantly affect clinical response. Grapefruit juice may increase hydrocodone levels via CYP3A4 inhibition; avoid concurrent intake. |
| Clinical Pearls | VICODIN (hydrocodone/acetaminophen) is a Schedule II controlled substance; always check PDMP before prescribing. Acetaminophen ceiling: max 4 g/day from all sources; avoid co-formulations to prevent hepatotoxicity. Hydrocodone is a prodrug converted to hydromorphone via CYP2D6; ultra-rapid metabolizers may experience toxicity. Use with caution in elderly due to falls risk and in renal impairment (active metabolite accumulation). Constipation prophylaxis (e.g., senna, PEG) should be initiated concurrently. |
| Patient Advice | Take only as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and any medications containing acetaminophen (e.g., Tylenol, cold medicines) to prevent liver damage. · Do not drive or operate machinery until you know how this drug affects you; it may cause drowsiness or dizziness. · Store securely out of reach of others; dispose of unused tablets via a take-back program. · Notify your doctor immediately if you experience signs of liver injury (nausea, abdominal pain, dark urine) or respiratory difficulty. |