Hydrocodone

1. Drug Name

• Generic Name: Hydrocodone

• Brand Names: Vicodin (with acetaminophen), Norco, Lortab, Zohydro ER, Hysingla ER

2. Drug Classification

• Class: Opioid analgesic

• Subclass: Semisynthetic opioid

3. Mechanism of Action

• Primary Action: Hydrocodone acts primarily as an agonist at the μ-opioid receptor, resulting in analgesia, sedation, and euphoria. By binding to these receptors, it inhibits the transmission of pain signals in the central nervous system.

• Secondary Effects: Like other opioids, hydrocodone also affects the medullary respiratory centers, which can lead to respiratory depression in higher doses or with misuse.

4. Pharmacokinetics

• Absorption: Oral bioavailability ranges from 50-70%, affected by formulation (immediate or extended-release).

• Distribution: Volume of distribution (Vd) is approximately 4 L/kg; highly protein-bound (20-50%).

• Metabolism: Primarily metabolized in the liver through CYP3A4 and CYP2D6 to hydromorphone (active) and norhydrocodone (inactive). Hydromorphone has a more potent analgesic effect, though present in lower concentrations.

• Excretion: Half-life (t½) is approximately 4-8 hours for immediate-release and 8-12 hours for extended-release; elimination is primarily renal (urinary excretion).

• Special Considerations: Liver impairment can affect metabolism and necessitate dosage adjustments.

5. Indications

• Primary Indications:

  • Management of moderate to severe pain where alternative treatments are inadequate.

• Off-label Uses:

  • Sometimes used for chronic cough suppression, though less commonly.

• Beneficial Populations: Patients with acute injury, post-surgical pain, or certain chronic pain conditions that respond to opioid therapy.

6. Dosage and Administration

• Adult Dosing:

  • Pain Management (Immediate-Release): 2.5-10 mg every 4-6 hours as needed, often in combination with acetaminophen or ibuprofen.

  • Extended-Release Formulation: Start with 10 mg every 12 hours, with adjustments based on patient response and tolerance.

• Pediatric Dosing: Generally not recommended for children under 18, though specific formulations may be used in select cases with careful monitoring.

• Routes: Oral tablets or oral liquid formulations.

• Renal/Hepatic Adjustments: Caution advised in patients with severe hepatic or renal impairment; dosing adjustments and extended monitoring may be required.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to hydrocodone or any components of the formulation.

  • Severe respiratory depression or asthma in an unmonitored setting.

  • Gastrointestinal obstruction, including paralytic ileus.

• Relative Contraindications:

  • Moderate-to-severe hepatic or renal impairment; avoid in cases of severe impairment unless closely monitored.

8. Warnings and Precautions

• Black Box Warnings: High risk of addiction, abuse, and misuse; serious risk of life-threatening respiratory depression; accidental ingestion can be fatal, especially in children; neonatal opioid withdrawal syndrome may occur with prolonged use in pregnancy.

• Pregnancy and Lactation: Can cause neonatal withdrawal syndrome if used long-term during pregnancy; hydrocodone passes into breast milk and may affect the infant.

• Monitoring Parameters: Respiratory rate, signs of sedation, liver function tests (LFTs), signs of misuse or addiction, and pain control.

• Special Considerations: Patients with respiratory conditions, elderly patients, and those with CNS depressants should be closely monitored.

9. Adverse Effects

• Common Adverse Effects (≥10%): Nausea, vomiting, constipation, dizziness, sedation, and drowsiness.

• Less Common but Clinically Significant: Urinary retention, orthostatic hypotension, pruritus, and dry mouth.

• Serious Adverse Reactions: Severe respiratory depression, hypotension, anaphylaxis, serotonin syndrome (when combined with serotonergic drugs), and rare liver toxicity (especially with acetaminophen combination products).

10. Drug Interactions

• Major Drug Interactions:

  • CNS Depressants (e.g., benzodiazepines, alcohol): Increased risk of sedation, respiratory depression, coma, and death.

  • CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Can increase hydrocodone plasma concentrations, leading to enhanced effects and toxicity.

  • CYP3A4 Inducers (e.g., rifampin): May reduce hydrocodone levels, compromising efficacy.

  • CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): Can reduce conversion to hydromorphone, potentially decreasing analgesic effect.

• Food-Drug Interactions: High-fat meals can affect absorption rates of extended-release formulations.

• Lab Test Interference: Hydrocodone can yield false positives for opiates in some drug screens.

11. Clinical Pharmacology

• Pharmacodynamic Profile: Hydrocodone’s μ-receptor agonist activity provides effective pain relief with risks of dependence, tolerance, and respiratory depression. Its conversion to hydromorphone, a more potent metabolite, can also contribute to analgesic effects in patients with CYP2D6 activity.

• Additional Effects: At higher doses or in misuse, hydrocodone may cause euphoria, leading to abuse potential, especially in combination with other CNS depressants.

12. Special Populations

• Pregnancy: Category C; use only if the potential benefits outweigh risks, as prolonged use may result in neonatal opioid withdrawal syndrome.

• Lactation: Excreted in breast milk; may cause drowsiness or respiratory depression in breastfed infants.

• Geriatric Use: Increased sensitivity to effects; close monitoring and dose adjustments may be needed.

• Renal/Hepatic Impairment: Adjustments recommended for patients with moderate-to-severe hepatic or renal dysfunction; monitor closely for prolonged effects and toxicity.

13. Therapeutic Uses

• First-Line Use: Often prescribed as a short-term analgesic for moderate to severe pain, particularly for acute injuries or post-operative pain.

• Combination Therapy: Frequently combined with acetaminophen or NSAIDs for added analgesic effect and reduced opioid dose requirements.

• Clinical Trials and Efficacy: Clinical trials have demonstrated efficacy in pain reduction, though concerns over dependence and respiratory depression limit its use to controlled, short-term scenarios.

14. Monitoring and Follow-Up

• Recommended Lab Tests: Baseline liver and renal function tests, respiratory rate, and monitoring of sedation levels.

• Patient Symptom Checklists: Regular assessment for signs of misuse, dependency, respiratory status, and pain control.

• Therapeutic and Toxic Levels: Monitor for therapeutic efficacy while observing for early signs of toxicity, especially in long-term use.

15. Overdose Management

• Symptoms of Overdose: Respiratory depression, miosis (pinpoint pupils), extreme somnolence progressing to stupor or coma, cyanosis, and hypotension.

• Treatment Protocols:

  • Naloxone: Opioid antagonist used to reverse the effects; may require repeated dosing due to hydrocodone’s duration.

  • Supportive Measures: Maintain airway patency, administer oxygen, and provide mechanical ventilation if necessary.

• Monitoring in Overdose: Continuous observation of respiratory function, cardiovascular status, and mental status.

16. Patient Counseling Information

• Key Counseling Points:

  • Instruct on the proper use of hydrocodone, especially with extended-release formulations, to avoid accidental overdose.

  • Warn against combining with alcohol, benzodiazepines, or other CNS depressants.

  • Educate about the risk of dependence and potential withdrawal symptoms with abrupt discontinuation.

  • Highlight the importance of adherence to prescribed dosages and timing to avoid side effects and enhance pain control.

• Signs Requiring Immediate Attention: Difficulty breathing, extreme drowsiness, confusion, severe allergic reactions, and symptoms of overdose.