What are the potential interactions between amiodarone and hydroxyzine?

Amiodarone and Hydroxyzine Interaction: Risk of QT Prolongation

The concomitant use of amiodarone and hydroxyzine poses a significant risk of QT prolongation and potentially torsades de pointes due to their additive effects on cardiac repolarization, and this combination should be avoided whenever possible. 1, 2

Mechanism of Interaction

• Amiodarone is a potent inhibitor of multiple cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C9, CYP2D6) which may increase hydroxyzine levels and enhance its QT-prolonging effects 3
• Amiodarone has an extremely long half-life (averaging 58 days), meaning this interaction can persist for months even after discontinuation 3, 4
• Both medications independently cause QT prolongation:
  • Hydroxyzine has been shown to inhibit hERG potassium ion channels, which are critical for cardiac repolarization 1
  • Amiodarone causes QT prolongation as part of its mechanism of action as a class III antiarrhythmic 5, 6

Risk Factors for Adverse Outcomes

• The combination of cardiovascular disorders plus concomitant QT-prolonging medications represents the greatest risk factor for developing torsades de pointes 1
• Electrolyte abnormalities, particularly hypokalemia and hypocalcemia, significantly increase the risk of QT prolongation with either medication 3, 2
• Chronic kidney disease patients may be at higher risk, as both medications were associated with significant QT prolongation in this population 2

Monitoring Recommendations

• Obtain baseline ECG before initiating either medication 3
• Check electrolytes (potassium, magnesium, calcium) before and periodically during treatment 3
• Maintain continuous ECG monitoring during initiation of therapy in high-risk patients 3
• Have defibrillator immediately available when administering these medications in combination in inpatient settings 3

Management Strategies

• If combination cannot be avoided:
  • Use lowest effective doses of both medications 3
  • Avoid additional QT-prolonging medications 3
  • Monitor QTc interval closely 3
  • Maintain normal electrolyte levels 3, 2
• Consider alternative antihistamines with less QT-prolonging potential when a patient is on amiodarone 1
• Document baseline QTc interval and ongoing monitoring results 3

Contraindications for Combined Use

• Second or third-degree AV block without pacemaker 3, 7
• Severe bradycardia 3
• Pre-existing QT prolongation 1
• History of torsades de pointes 1
• Severe electrolyte abnormalities 3, 2

Special Considerations

• Hydroxyzine is listed as a drug with "conditional risk of TdP," meaning the risk is significantly higher in patients with underlying risk factors 1
• Amiodarone's QT prolongation may actually be a marker of its therapeutic efficacy, but the additive effect with hydroxyzine could push this into dangerous territory 5
• The interaction risk persists for months after amiodarone discontinuation due to its extremely long half-life 3, 4, 8