Safety of Pill-in-the-Pocket Class 1C Antiarrhythmic Drugs for Atrial Fibrillation

JACC Clin Electrophysiol. 2022 Dec;8(12):1515-1520. doi: 10.1016/j.jacep.2022.07.010. Epub 2022 Aug 31.


Background: Guidelines recommend that initial trial of a "pill-in-the-pocket" (PIP) Class 1C antiarrhythmic drug (AAD) for cardioversion of atrial fibrillation (AF) be performed in a monitored setting because of the potential for adverse reactions.

Objectives: This study sought to characterize real-world, contemporary use of the PIP approach, including the setting of initiation and incidence of adverse events.

Methods: This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania treated with a PIP approach for AF between 2007 and 2020.

Results: A total of 273 patients (age 56 ± 13 years; 182 [67%] male; CHA2DS2VASc score 1.1 ± 1.2) took a first dose of PIP AAD. Flecainide was used in 151 (55%) and propafenone in 122 (45%). The first dose of PIP AAD was taken in a monitored setting in 167 (62%). Significant adverse events occurred in 7 patients (3%), 2 of whom had taken the dose in a monitored setting. Significant adverse events included unexplained syncope (1 of 7), symptomatic bradycardia/hypotension (4 of 7), and 1:1 atrial flutter (2 of 7). All occurred in patients taking 300 mg of flecainide (n = 4) or 600 mg of propafenone (n = 3). Electrical cardioversion was performed in 29 (11%) patients because of failure of the AAD to terminate AF. One patient required intravenous fluids and vasopressors for 2 hours because of persistent hypotension and bradycardia. Two patients required permanent pacemakers for bradycardia. The remaining patients required no intervention.

Conclusions: Our data support the current recommendation to initiate PIP AAD in a monitored setting because of rare significant adverse reactions that can require urgent intervention.

Keywords: antiarrhythmic drug; atrial fibrillation; flecainide; pill-in-the-pocket; propafenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Arrhythmia Agents / adverse effects
  • Atrial Fibrillation*
  • Bradycardia
  • Female
  • Flecainide / adverse effects
  • Humans
  • Hypotension*
  • Male
  • Middle Aged
  • Propafenone / adverse effects
  • Retrospective Studies


  • Anti-Arrhythmia Agents
  • Propafenone
  • Flecainide