NEW ORLEANS — An extra dose of oral propafenone or flecainide achieves pharmacologic conversion of breakthrough atrial fibrillation in two-thirds of affected patients who are already taking the same class 1C antiarrhythmic agent for daily maintenance therapy, James A. Reiffel, M.D., reported at the annual meeting of the Heart Rhythm Society.
The key to making this strategy work safely is to use as a guide the maximum daily dose as defined in the product label. That would be 900 mg for propafenone immediate release (IR), available generically; 850 mg for the sustained-release formulation (Rythmol SR); and 400 mg for flecainide (Tambocor).
The combined total of an individual's daily maintenance dose plus the supplemental dose should not exceed these ceilings, said Dr. Reiffel, professor of clinical medicine at Columbia University, New York.
For example, a patient who experiences an episode of atrial fibrillation (AF)while on propafenone IR at 600 mg/day for maintenance therapy would take a single 300-mg bolus of the drug at least 3 hours after the prior maintenance dose. A patient on 450 mg/day would take a 300-mg extra dose, then another 150 mg 4 hours later if conversion hasn't occurred.
The pharmacokinetic curve of propafenone IR at 450 mg/day approximates that of propafenone SR at 650 mg/day, whereas 675 mg/day of propafenone IR is similar pharmacokinetically to 850 mg/day of propafenone SR. So a patient who experiences an episode of AF on 325 mg b.i.d. of propafenone SR as maintenance would take a single 300-mg supplemental dose of propafenone IR. An individual on 425 mg b.i.d. of propafenone SR would take no more than 150 mg of propafenone IR, he said.
He reported on 24 patients who had experienced a total of 42 episodes of recurrent AF despite taking daily maintenance doses of propafenone IR or SR or flecainide. The rate of conversion to sinus rhythm in response to the extra dose was 67% in all three patient groups. Adverse effects were limited to mild nausea and vague dizziness.
The appeal of this strategy is that it is safe, effective, and falls within the scope of the approved Food and Drug Administration (FDA)indications for these drugs. The FDA has deemed both propafenone and flecainide to be appropriate drugs for initiation of management of AF in outpatient settings in individuals without structural heart disease. The additional dose appears to be as well tolerated in patients on maintenance doses as in patients not on daily antiarrhythmic therapy.
Dr. Reiffel noted that this treatment approach is based on the “pill-in-a-pocket” strategy recently described by Italian investigators. They showed in 210 patients with recurrent AF who were not on daily antiarrhythmic therapy that out-of-hospital, self-administered oral loading doses of propafenone or flecainide converted 94% of recent-onset episodes of AF to sinus rhythm in a mean of 113 minutes.
This suggests that supplemental doses in patients already on daily antiarrhythmic therapy may not be quite as effective as in patients not yet on daily maintenance therapy.
During the 15-month study of Italian patients, both emergency department visits and hospital admissions were reduced roughly 10-fold in this population, compared with the time period immediately before the institution of the pill-in-a-pocket approach (N. Engl. J. Med. 2004;351:2384–91).