Drug Interactions Affecting Antiarrhythmic Drug Use

Circ Arrhythm Electrophysiol. 2022 May;15(5):e007955. doi: 10.1161/CIRCEP.121.007955. Epub 2022 May 2.


Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.

Keywords: ATP Binding Cassettee Transporter; Member 1; Subbfamily B; anti-arrhythmia agents; cytochrome; drug interactions; glycoprotein; pharmacokinetics; torsade de pointes.

Publication types

  • Review

MeSH terms

  • Amiodarone* / therapeutic use
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / drug therapy
  • Drug Interactions
  • Humans
  • Long QT Syndrome* / chemically induced
  • Long QT Syndrome* / drug therapy


  • Anti-Arrhythmia Agents
  • Anti-Bacterial Agents
  • Amiodarone