Generic Name

Vicodin

Mechanism

• Acetaminophen: Inhibits central prostaglandin synthesis (COX‑1/COX‑2) with limited peripheral activity, providing antipyretic and analgesic effects without significant anti‑inflammatory action.
• Hydrocodone: Acts as a potent μ‑opioid receptor agonist in the brainstem and spinal cord, producing analgesia, sedation, and euphoria. It undergoes metabolic conversion to hydromorphone via CYP2D6/CYP3A4, enhancing analgesic potency.

The synergistic combination reduces required opioid dose and exploits additive analgesic effects.

Pharmacokinetics

• Absorption: Rapid oral uptake; peak plasma concentrations in ~1‑2 h.
• Bioavailability: ~80 % for hydrocodone; ~75 % for acetaminophen.
• Distribution: Hydrocodone crosses the blood‑brain barrier; acetaminophen distributes widely, predominantly to the liver.
• Metabolism:
• *Hydrocodone*: CYP2D6 & CYP3A4 → hydromorphone, 4‑hydroxy‑hydrocodone.
• *Acetaminophen*: Glucuronidation & sulfation; small proportion to N‑acetyl‑p‑benzoquinone imine (NAPQI) via CYP2E1.
• Elimination:
• Hydrocodone half‑life: 4‑6 h (with dependence on CYP profile).
• Acetaminophen half‑life: 1.5‑3 h; hepatic clearance dominates.
• Drug–Drug Interactions: CYP3A4 inhibitors (e.g., ketoconazole) elevate hydrocodone levels; CYP2D6 polymorphisms alter hydromorphone formation.

Indications

• Post‑operative or procedural acute pain (moderate to severe).
• Moderate‑to‑severe musculoskeletal trauma.
• Chronic pain settings (requires careful monitoring for dependence).

Contraindications

• Contraindications:
• Severe hepatic disease or elevated hepatic enzymes.
• Known hypersensitivity to acetaminophen or hydrocodone.
• Concomitant use of other CNS depressants (opioids, benzodiazepines, alcohol).
• Warnings:
• Opioid‑related: Respiratory depression, sedation, risk of dependence, tolerance, and withdrawal.
• Hepatic: Potential acetaminophen‑induced hepatotoxicity; monitor liver function.
• CNS: Potential for overlapping neurologic side effects when combined with other analgesics.

Dosing

• Typical adult dosing: 5 mg hydrocodone + 300 mg acetaminophen (1 tablet) every 4–6 h as needed.
• Maximum: Not exceed 4 g of acetaminophen per 24 h (≈ 12 tablets).
• For stronger pain, 15 mg/975 mg combination may be prescribed, but again monitor acetaminophen limits.
• Special populations:
• *Renal impairment*: Reduce frequency; consider lower hydrocodone dose.
• *Hepatic impairment*: Avoid or use lower hydrocodone dose; strict acetaminophen limit.
• Administration route: Oral, typically standing tablets; may be chewed if swallowing difficult.

Adverse Effects

• Common:
• Nausea, vomiting, dizziness, pruritus, constipation, dry mouth.
• Somnolence and mild sedation.
• Serious:
• Respiratory depression (especially with concomitant CNS depressants).
• Hepatotoxicity (especially in high‑dose or prolonged use).
• Seizure activity in overdose.
• QTc interval prolongation (rare).

Monitoring

• Pain scores and functional status.
• Respiratory rate (RR) and oxygen saturation in patients at risk.
• Liver function tests (ALT/AST, bilirubin) at baseline and periodically when >2 weeks of therapy or high‑dose use.
• Kidney function (serum creatinine) for dosage adjustments.
• Signs of opioid misuse: requests for extra doses, early refill, or non‑medical use.

Clinical Pearls

• Limit acetaminophen to ≤4 g/day—the primary hepatotoxic risk point.
• Use the lowest effective opioid dose: Start with 5 mg hydrocodone; adjust based on analgesic response.
• Avoid combining with SSRIs/WX (e.g., fluoxetine, fluvoxamine) that inhibit CYP2D6, increasing hydrocodone levels.
• Naloxone availability: For patients with opioid‑related risks or existing overdose, naloxone kits should be accessible.
• Patient education: Emphasize a “take‑home” strategy to prevent diversion; instruct on storage and disposal.
• Consider abuse‑deterrent formulations (if available) or alternative analgesics in patients with substance‑use disorder history.

Key references:

1. Clinical Pharmacology, 2025; 2. FDA drug label for Hydrocodone/Acetaminophen.

--
• This drug card provides a concise, reference‑friendly overview of Vicodin, ideal for medical students, residents, and practicing clinicians seeking quick, accurate pharmacological guidance.