Major
Clarithromycin × ritonavir
Macrolide antibiotic×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Dual CYP3A4 inhibition (clarithromycin + ritonavir). Plasma levels of both drugs rise, plus additive QT prolongation.
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 without CYP3A4 inhibition: azithromycin or doxycycline. If clarithromycin is needed: ECG before start and every 3 days during therapy; do not increase clarithromycin dose.