Vicodin - Drug Monograph

Introduction

Vicodin is a widely prescribed combination analgesic medication containing hydrocodone bitartrate, a semi-synthetic opioid agonist, and acetaminophen, a non-opioid analgesic and antipyretic. This Schedule II controlled substance is commonly used for the management of moderate to moderately severe pain. First approved by the FDA in 1984, Vicodin has become one of the most frequently prescribed opioid medications in the United States, though its use has declined in recent years due to increased awareness of opioid misuse risks.

Mechanism of Action

Vicodin exerts its analgesic effects through two distinct mechanisms:

• Hydrocodone: Binds primarily to mu-opioid receptors in the central nervous system, altering the perception of and response to pain through agonist activity at opioid receptors. It also produces cough suppression by direct action on the cough center in the medulla.
• Acetaminophen: Exact mechanism not fully established, but believed to involve central inhibition of prostaglandin synthesis with minimal peripheral effects. It may act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase (COX-1 and COX-2).

Indications

FDA-approved for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Dosage and Administration

• 1-2 tablets every 4-6 hours as needed for pain
• Maximum daily acetaminophen dose: 4,000 mg (reduced to 3,000 mg daily in certain populations)
• Maximum daily hydrocodone dose: Individualized based on pain severity and patient response

• Hydrocodone 5 mg/Acetaminophen 300 mg
• Hydrocodone 7.5 mg/Acetaminophen 300 mg
• Hydrocodone 10 mg/Acetaminophen 300 mg

• Renal impairment: Use with caution; consider reduced frequency
• Hepatic impairment: Contraindicated in severe hepatic impairment
• Geriatric patients: Start with lowest effective dose
• Pediatric patients: Not recommended for children under 6 years

Pharmacokinetics

• Hydrocodone: Volume of distribution ~4.6 L/kg; 36% protein bound
• Acetaminophen: Volume of distribution ~0.9 L/kg; 10-25% protein bound

• Hydrocodone: Extensive hepatic metabolism via CYP3A4 and CYP2D6 to active (hydromorphone) and inactive metabolites
• Acetaminophen: Primarily hepatic conjugation with glucuronide and sulfate; minor metabolism via CYP2E1 to toxic metabolite NAPQI

• Hydrocodone: Half-life ~4 hours; renal excretion (primarily as metabolites)
• Acetaminophen: Half-life ~2-3 hours; renal excretion (primarily as conjugates)

Contraindications

• Significant respiratory depression
• Acute or severe bronchial asthma in unmonitored settings or without resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Hypersensitivity to hydrocodone, acetaminophen, or any component
• Severe hepatic impairment

Warnings and Precautions

• Addiction, abuse, and misuse: Risk of opioid addiction, abuse, and misuse
• Life-threatening respiratory depression: Serious, life-threatening, or fatal respiratory depression
• Accidental ingestion: Accidental ingestion, especially in children, can be fatal
• Neonatal opioid withdrawal syndrome: Prolonged use during pregnancy
• Hepatotoxicity: Acetaminophen associated with acute liver failure

• Interactions with alcohol: Concomitant use may result in increased plasma levels and fatal overdose
• CYP3A4 and CYP2D6 inhibitors/inducers: May affect hydrocodone levels
• Head injury and increased intracranial pressure: May obscure clinical course
• Hypotensive effects: May cause severe hypotension
• Gastrointestinal conditions: May cause spasm of the sphincter of Oddi

Drug Interactions

• Benzodiazepines and other CNS depressants: Increased risk of respiratory depression
• CYP3A4 inhibitors (ketoconazole, clarithromycin): Increased hydrocodone levels
• CYP3A4 inducers (rifampin, carbamazepine): Decreased hydrocodone levels
• CYP2D6 inhibitors (paroxetine, fluoxetine): May decrease hydrocodone conversion to hydromorphone
• Anticholinergic drugs: Increased risk of urinary retention and constipation
• Warfarin: Acetaminophen may potentiate anticoagulant effect

Adverse Effects

• Nausea, constipation, vomiting
• Dizziness, drowsiness, lightheadedness
• Headache

• Pruritus, rash
• Dry mouth, sweating
• Mental clouding, dysphoria

• Respiratory depression
• Hypotension
• Adrenal insufficiency
• Anaphylaxis
• Serotonin syndrome (with serotonergic drugs)
• Severe skin reactions

Monitoring Parameters

• Pain assessment and relief using standardized scales
• Respiratory rate, depth, and rhythm
• Blood pressure and heart rate
• Mental status changes
• Bowel function (constipation management)
• Signs of misuse, abuse, or addiction
• Liver function tests (with prolonged use)
• Renal function in elderly or renally impaired

Patient Education

• Take exactly as prescribed; do not increase dose without consultation
• Avoid alcohol and other CNS depressants
• Do not crush, chew, or break tablets
• Recognize signs of overdose: extreme drowsiness, confusion, shallow breathing
• Report constipation, nausea, or dizziness to healthcare provider
• Store securely away from children and others
• Proper disposal of unused medication
• Inform all healthcare providers of Vicodin use
• Understand risks of dependence and addiction
• Do not drive or operate machinery until effects are known
• Acetaminophen content: Be aware of other medications containing acetaminophen

References

1. Vicodin [package insert]. North Chicago, IL: AbbVie Inc.; 2021. 2. Trescot AM, Datta S, Lee M, Hansen H. Opioid pharmacology. Pain Physician. 2008;11(2 Suppl):S133-S153. 3. US Food and Drug Administration. Acetaminophen information. FDA.gov. Updated July 2018. 4. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1-49. 5. Webster LR. Hydrocodone: a history of misuse and abuse. J Opioid Manag. 2007;3(3):115-117. 6. American Geriatrics Society. Pharmacological management of persistent pain in older persons. J Am Geriatr Soc. 2009;57(8):1331-1346. 7. National Institute on Drug Abuse. Opioid overdose crisis. NIDA.nih.gov. Updated March 2023.