Moderate
Amitriptyline × tacrolimus
Tricyclic antidepressants (TCA)×Calcineurin inhibitor (immunosuppressant)
Mechanism
Tacrolimus prolongs QT; the TCA does the same independently via a quinidine-like effect on cardiomyocyte Na/K channels. Additive ventricular arrhythmia risk.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Maximum risk in older transplant patients with electrolyte disturbances.
Management
Avoid in prior QT prolongation or electrolyte disturbance. For neuropathic pain, alternatives: gabapentin or pregabalin (minimal QT effect). For depression: sertraline (minimal QT effect). If unavoidable: ECG before starting amitriptyline and at 1 and 4 weeks. Keep potassium and magnesium in the upper half of normal range.