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. |
| Molecular Weight | Hydrocodone: 299.36 Da; Acetaminophen: 151.16 Da |
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 | Not recommended; associated with increased risk of congenital malformations, including neural tube defects and gastroschisis, from opioid exposure. |
| 2nd trimester | Use with caution; chronic use may lead to fetal dependence and withdrawal; avoid if possible. |
| 3rd trimester | Avoid; prolonged use can cause neonatal opioid withdrawal syndrome (NOWS). High doses near term may increase risk of respiratory depression in neonate. |
Clinical note
Comprehensive clinical and safety monograph for VICODIN ES (VICODIN ES).
| Placental transfer | Both hydrocodone and acetaminophen cross the placenta. Hydrocodone reaches fetal concentrations up to 60% of maternal levels. |
| Breastfeeding | Hydrocodone is excreted into breast milk; levels are low but may accumulate in infants with impaired CYP2D6 activity. Monitor infant for sedation, respiratory depression, and poor feeding. Avoid use in breastfeeding mothers with ultra-rapid metabolizer status. |
■ 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 |
Hypersensitivity to hydrocodone, acetaminophen, or any componentSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileusConcurrent use of MAO inhibitors or within 14 days of such therapy
| Precautions | Respiratory depression; serious allergic reactions; adrenal insufficiency; severe hypotension; risk of medication errors; interactions with drugs affecting CYP2D6; hepatic injury from acetaminophen. |
| Food/Dietary | Avoid alcohol and beverages containing alcohol. High-fat meals may delay absorption but do not significantly alter overall exposure. No specific food restrictions, but maintain adequate hydration to prevent constipation. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls | VICODIN ES contains hydrocodone 7.5 mg and acetaminophen 750 mg. The maximum daily acetaminophen dose should not exceed 4 g from all sources. Use the lowest effective dose for the shortest duration. Risk of respiratory depression, especially in elderly or opioid-naïve patients. Avoid in severe asthma or paralytic ileus. Monitor for signs of misuse or abuse. Coadministration with other CNS depressants requires dose reduction. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not consume alcohol while taking VICODIN ES, as it increases the risk of liver damage and sedation. · Avoid driving or operating machinery until you know how this medication affects you. · Do not take other medications containing acetaminophen, including over-the-counter pain relievers, to avoid exceeding the maximum daily dose. · Store securely out of reach of children and others; dispose of unused medication properly at a drug take-back site. · Contact your doctor if you experience severe drowsiness, confusion, shallow breathing, or signs of allergic reaction. |