Pill-in-the-pocket warning

BOLOGNA, ITALY. The on-demand or “pill-in-the-pocket” approach is now used by many paroxysmal afibbers to quickly and effectively terminate afib episodes and return to normal sinus rhythm. This approach involves swallowing 450 mg of propafenone (Rythmol) or 200 mg of flecainide (Tambocor) with water as soon as possible after the onset of an episode. The dosages are increased to 600 mg and 300 mg respectively for patients weighing more than 70 kg (154 lbs). It is recommended that patients rest (in a supine or sitting position) until palpitations have stopped or at least 4 hours have passed.

Italian cardiologists now report the case of a 76-year-old woman who fainted 3 hours after taking 600 mg of propafenone to terminate an afib episode. After admission to the emergency department she was found to have left bundle branch block and a first degree atrioventricular block both of which eventually disappeared on their own. The cardiologists noted that the patient was taking the beta-blocker carvedilol (Coreg) on a permanent basis. They surmise that the combination of propafenone and carvedilol produced an abnormally high plasma concentration of propafenone resulting in the transient left bundle branch and atrioventricular blocks. Both propafenone and carvedilol are metabolized in the liver through the CYP2D6 pathway. They also noted that the patient fainted 3 hours following the ingestion of the propafenone which would correspond to the time at which propafenone reaches its peak plasma concentration. They conclude that the “pill-in-the-pocket” approach (with propafenone) should not be used in patients who are taking carvedilol on a permanent basis.

Boriani, G, et al. Atrial fibrillation: Adverse effects of “pill-in-the-pocket” treatment and propafenone-carvedilol interaction. International Journal of Cardiology , Vol. 140, No. 2, April 15, 2010, pp. 242-3

Editor’s comment: The authors make no comment in regard to the safety of using flecainide on demand in patients permanently on carvedilol. However, as CYP2D6 is also involved in the metabolism of flecainide, caution should probably be advised. It is interesting that CYP2D6 (cytochrome P450 2D6) is involved in the metabolism of about one quarter of all pharmaceutical drugs including Paxil, Effexor, metoprolol, bisoprolol and atenolol. This certainly raises an interesting question about the advisability of combining flecainide or propafenone with a beta-blocker in a “new and improved” pill-in-the-pocket approach.