What are the potential interactions between quetiapine (Seroquel) and amiodarone (Cordarone)?

Potential Interactions Between Quetiapine and Amiodarone

The concomitant use of quetiapine and amiodarone creates a significant risk for QT interval prolongation and potentially life-threatening torsades de pointes, requiring careful monitoring and consideration of alternative therapies when possible.

Major Interaction Mechanisms

• Both quetiapine and amiodarone can independently cause QT interval prolongation, creating an additive effect when used together 1, 2
• Amiodarone inhibits multiple cytochrome P450 enzymes (CYP3A4, CYP1A2, CYP2C9, CYP2D6) which may increase quetiapine levels and toxicity 3, 4
• Amiodarone's extremely long half-life (averaging 58 days) means this interaction can persist for months even after discontinuation 3

Clinical Risks and Consequences

• Over 13% of patients receiving quetiapine develop severe QT prolongation (QTc >500ms or increase >60ms) 2
• Amiodarone use is an independent risk factor for developing severe QT prolongation in patients taking quetiapine 2
• Severe QT prolongation in quetiapine users is significantly associated with:
  • Increased risk of ventricular arrhythmias (OR 2.84) 2
  • Higher rates of sudden cardiac death (OR 2.29) 2

Risk Factors That Amplify the Interaction

• Advanced age 2, 5
• Female sex 5
• Heart failure with reduced ejection fraction 2, 5
• Electrolyte abnormalities (particularly hypokalemia, hypomagnesemia, hypocalcemia) 1, 5
• Bradycardia 5
• Concomitant use of other QT-prolonging medications 4, 5
• Renal dysfunction without appropriate dose adjustment 5

Monitoring Recommendations

• Obtain baseline ECG before initiating either medication 3
• Monitor QTc interval regularly, with particular attention if:
  • QTc exceeds 500ms 5
  • QTc increases ≥60ms from baseline 5
• Check electrolytes (potassium, magnesium, calcium) before and periodically during treatment 3, 5
• Maintain continuous ECG monitoring during initiation of therapy in high-risk patients 4
• Have defibrillator immediately available when administering these medications in combination 4

Management Strategies

• Consider alternative antipsychotic with lower QT prolongation risk if clinically appropriate 5
• If combination cannot be avoided:
  • Use lowest effective doses of both medications 3
  • Correct any electrolyte abnormalities promptly 5
  • Avoid additional QT-prolonging medications 4
• For patients developing torsades de pointes:
  • Discontinue the offending drugs 5
  • Correct electrolyte abnormalities 5
  • Administer intravenous magnesium sulfate 1-2g 5

Contraindications for Combined Use

• Pre-existing severe QT prolongation 4
• History of torsades de pointes 1
• Severe sinus node dysfunction 4
• Second or third-degree AV block without pacemaker 3, 4
• Severe bradycardia 3

Documentation and Consultation

• Document baseline QTc interval and ongoing monitoring results 3
• Consider cardiology consultation before combining these medications, especially in high-risk patients 4
• When prescribing this combination, document the clinical necessity and risk-benefit assessment 5