Can hydroxychloroquine be added to amitriptyline (tricyclic antidepressant)?

Hydroxychloroquine and Amitriptyline Combination: Cardiac Risk Assessment

Hydroxychloroquine should not be added to amitriptyline due to the significant risk of QT prolongation and potential for life-threatening cardiac arrhythmias when these medications are combined.

Cardiac Safety Concerns

• Both hydroxychloroquine and amitriptyline (a tricyclic antidepressant) are classified as sodium channel blockers that can cause QT interval prolongation, increasing the risk of torsades de pointes and sudden cardiac death 1
• The American Heart Association specifically identifies both hydroxychloroquine and tricyclic antidepressants (including amitriptyline) as medications that can cause sodium channel blockade, QRS prolongation, and life-threatening cardiotoxicity 1
• This combination creates an additive risk for QT prolongation, as both drugs independently affect cardiac conduction 1

Specific Risks and Monitoring Requirements

• The combination of hydroxychloroquine with tricyclic antidepressants like amitriptyline requires:

  • Baseline ECG monitoring 1, 2
  • Regular follow-up ECGs 2
  • Close monitoring for signs of cardiotoxicity 1
  • Electrolyte monitoring, particularly potassium levels, as hypokalemia further increases arrhythmia risk 3

• Even in studies examining hydroxychloroquine with antidepressants in lupus patients, some patients developed QTc intervals exceeding 500 milliseconds, which significantly increases arrhythmia risk 4

Risk Factors That Increase Danger

• Pre-existing cardiac conditions significantly increase the risk of QTc prolongation beyond 500ms when using this combination 4
• Electrolyte disturbances, particularly hypokalemia, further increase the risk of arrhythmias when using hydroxychloroquine with QT-prolonging medications like amitriptyline 3
• The French Society for Oncology Pharmacy guidelines specifically warn against combining hydroxychloroquine with medications that have the same cardiac toxicity profile 1

Alternative Approaches

• If treatment with both medication classes is absolutely necessary:
  • Consider alternative antidepressants with lower QT prolongation risk 5
  • Implement rigorous cardiac monitoring including baseline and follow-up ECGs 2
  • Maintain strict electrolyte monitoring, particularly potassium levels 3
  • Be prepared to use sodium bicarbonate for treatment of life-threatening cardiotoxicity if it develops 1

Conclusion

The combination of hydroxychloroquine and amitriptyline presents a significant cardiac safety concern due to their additive effects on QT prolongation and sodium channel blockade. The American Heart Association and other guidelines strongly caution against combining medications with these cardiac effects due to the increased risk of life-threatening arrhythmias 1.