VICODIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VICODIN (VICODIN).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VICODIN (VICODIN).

Breastfeeding	Hydrocodone and acetaminophen are excreted into breast milk. M/P ratio not well established for hydrocodone; relative infant dose estimated <3% of weight-adjusted maternal dose. Caution advised, especially in breastfeeding mothers who are CYP2D6 ultra-rapid metabolizers, as hydrocodone is metabolized to hydromorphone. Monitor infant for sedation, respiratory depression, and poor feeding.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction; hypersensitivity to hydrocodone, acetaminophen, or any component; concomitant use with MAOIs or within 14 days of such therapy.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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VICODIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for VICODIN (VICODIN).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for VICODIN (VICODIN).

Breastfeeding	Hydrocodone and acetaminophen are excreted into breast milk. M/P ratio not well established for hydrocodone; relative infant dose estimated <3% of weight-adjusted maternal dose. Caution advised, especially in breastfeeding mothers who are CYP2D6 ultra-rapid metabolizers, as hydrocodone is metabolized to hydromorphone. Monitor infant for sedation, respiratory depression, and poor feeding.
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.