Major
Clarithromycin × Haloperidol
Macrolide antibiotic×First-generation antipsychotics. Butyrophenone derivatives
Mechanism
Additive QT prolongation. Clarithromycin also blocks CYP3A4 – the main haloperidol clearance route – and haloperidol levels rise.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antibiotics: azithromycin or doxycycline. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.