Propafenone and carvedilol share a common hepatic metabolism involving the oxidative pathway (CYP2D6). Therefore, oral loading with propafenone (as "pill-in-the-pocket" treatment of recent-onset atrial fibrillation) in a patient on concurrent carvedilol treatment may lead to a pharmacokinetic interaction, with high plasma levels of propafenone and potential drug-related adverse effects. In clinical practice, in order to improve the safety of "pill-in-the-pocket" treatment, use of propafenone loading should, in our view, be discouraged in patients on concurrent treatment with carvedilol.