VICODIN ES
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VICODIN ES (VICODIN ES).
Hydrocodone is a mu-opioid receptor agonist; acetaminophen inhibits cyclooxygenase (COX) and modulates descending serotonergic pathways.
| Metabolism | Hydrocodone: CYP2D6 and CYP3A4; acetaminophen: primarily glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1). |
| Excretion | Hydrocodone: primarily renal (urine) as unchanged drug and metabolites (O-demethylation and 6-keto-reduction products); ~26% excreted unchanged. Acetaminophen: renal (urine), ~85% as glucuronide and sulfate conjugates, ~2% unchanged. |
| Half-life | Hydrocodone: terminal half-life approximately 3.3-4.5 hours in adults, extended in hepatic or renal impairment. Acetaminophen: terminal half-life about 2-3 hours. |
| Protein binding | Hydrocodone: approximately 20-50% bound to plasma proteins. Acetaminophen: negligible (<10%) protein binding. |
| Volume of Distribution | Hydrocodone: Vd ~3.3-4.7 L/kg, indicating extensive tissue distribution. Acetaminophen: Vd ~0.9-1.0 L/kg. |
| Bioavailability | Hydrocodone: oral bioavailability ~50-70% (first-pass metabolism). Acetaminophen: oral bioavailability ~75-85%. |
| Onset of Action | Oral: hydrocodone onset 10-20 minutes; acetaminophen onset 30-60 minutes. |
| Duration of Action | Hydrocodone: 4-6 hours (analgesic effect). Acetaminophen: 4-6 hours. Clinical note: sustained-release formulations may extend duration. |
Oral: 1 tablet (7.5 mg hydrocodone/300 mg acetaminophen) every 4-6 hours as needed for pain; maximum 6 tablets per day due to acetaminophen limit.
| Dosage form | TABLET |
| Renal impairment | GFR 30-90 mL/min: No adjustment needed. GFR 10-29 mL/min: Administer every 6 hours; avoid use if GFR < 10 mL/min due to accumulation of acetaminophen metabolites and hydrocodone. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50% or extend dosing interval (e.g., every 6-8 hours). Class C: Contraindicated due to impaired acetaminophen metabolism and risk of hepatotoxicity. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. If used, weight-based dosing for hydrocodone: 0.1-0.2 mg/kg per dose every 4-6 hours as needed, with acetaminophen not exceeding 75 mg/kg/day. Use lowest effective dose and shortest duration. |
| Geriatric use | Initiate at lowest effective dose (e.g., 1 tablet every 6 hours) due to increased sensitivity, reduced renal/hepatic function, and risk of falls and cognitive impairment. Monitor for respiratory depression, constipation, and acetaminophen toxicity. Avoid in frail elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VICODIN ES (VICODIN ES).
| Breastfeeding | Hydrocodone is excreted into breast milk; M/P ratio approximately 2.5:1 (higher than morphine). Relative infant dose estimated at 2.1-3.7% of maternal weight-adjusted dose. Acetaminophen M/P ratio ~1.0. Risk of infant sedation and respiratory depression, especially in CYP2D6 ultra-rapid metabolizers. Avoid breastfeeding if mother is an ultra-rapid metabolizer or if infant is <2 months old. |
| Teratogenic Risk | VICODIN ES (hydrocodone/acetaminophen) is Pregnancy Category C prior to 30 weeks and Category D after 30 weeks gestation. First trimester: limited human data; animal studies show increased risk of neural tube defects at high doses. Second trimester: risk of spontaneous abortion and congenital anomalies not clearly increased. Third trimester (after 30 weeks): prolonged use can cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at delivery. Acetaminophen component associated with fetal liver toxicity in overdose. |
■ 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 due to acetaminophen.
| Serious Effects |
Significant respiratory depression; acute or severe bronchial asthma; gastrointestinal obstruction; known hypersensitivity to hydrocodone or acetaminophen.
| Precautions | Respiratory depression; serious allergic reactions; adrenal insufficiency; severe hypotension; risk of medication errors; interactions with drugs affecting CYP2D6; hepatic injury from acetaminophen. |
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| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, bowel function. Fetal monitoring: nonstress test (NST) and biophysical profile (BPP) weekly after 32 weeks if chronic use. Assess for NOWS after delivery using Finnegan scoring. Monitor liver function tests (LFTs) and acetaminophen levels if toxicity suspected. |
| Fertility Effects | Chronic opioid use may cause hypothalamic-pituitary-gonadal axis suppression leading to amenorrhea, oligomenorrhea, and decreased libido in women. In men, decreased testosterone and sperm motility. Effects are reversible upon discontinuation. Acetaminophen component not associated with fertility impairment. |