Major
Amitriptyline × Clarithromycin
Tricyclic antidepressants (TCA)×Macrolide antibiotic
Mechanism
Clarithromycin blocks CYP3A4 and prolongs QT itself. Amitriptyline plasma levels rise; additive QT risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antibiotics: azithromycin or doxycycline (minimal CYP3A4 and QT effect). Alternative for neuropathic pain instead of TCA: gabapentin or pregabalin.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.