Critical
Dronedarone × ritonavir
Class III antiarrhythmic×HIV protease inhibitor / pharmacokinetic booster
Mechanism
Ritonavir is the most potent CYP3A4 inhibitor available. Dronedarone plasma levels may rise 25-fold or more, plus both drugs prolong QT. FDA Multaq Section 4.3 specifically lists ritonavir.
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 rises with hypokalaemia and hypomagnesaemia.
Management
The combination is not prescribed. For HIV-positive patients with atrial fibrillation, use a beta-blocker (rate control) or catheter ablation (rhythm control). Ritonavir-free antiretroviral regimens are discussed with the infectious diseases team.