A role for oral antiarrhythmic drugs (AADs) remains in clinical practice for patients with atrial and ventricular arrhythmias in spite of advances in nonpharmacologic therapy. Pharmacists play a vital role in the appropriate use of AAD dosing, administration, adverse effects, interactions, and monitoring. Pharmacists who are involved in providing care to patients with cardiac arrhythmias must remain updated regarding the efficacy and safety of the most commonly used AADs. This review will address key issues for appropriate initiation and maintenance of commonly selected Vaughan-Williams Class Ic and III agents in the outpatient setting.
HohnloserSHKuckKHLilienthalJ. Rhythm or rate control in atrial fibrillation: Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial. Lancet2000;356(9244):1789–1794.
2.
Van GelderICHagensVEBoskerHA. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347(23):1834–1840.
3.
CarlssonJMiketicSWindelerJ. Randomized trial of rate-control vs. rhythm-control in persistent atrial fibrillation: the Strategies of Treatment of Atrial Fibrillation (STAF) study. J Am Coll Cardiol. 2003;41(10):1690–1696.
4.
OpolskiGTorbickiAKosiorDA. Rate control vs. rhythm control in patients with nonvalvular persistent atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT CAFE) Study. Chest. 2004;126(2):476–486.
5.
RoyDTalajicMNattelS. Rhythm control vs. rate control for atrial fibrillation and heart failure. N Engl J Med. 2008;358(25):2667–2677.
6.
WyseDGWaldoALDiMarcoJP. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM). A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347(23):1825–1833.
7.
Vaughan-SerrazinMSMazurAChrischillesE. Trends in the pharmacologic management of atrial fibrillation: data from the Veterans Affairs health system. Am Heart J. 2014;168(1):53–59.
8.
HerreJMTitusCOeffM. Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation. Ann Intern Med. 1990;113(9):671–676.
9.
Van der WerfCKannankerilPJSacherF. Flecainide therapy reduces exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia. J Am Coll Cardiol. 2011;57(22):2244–2254.
10.
Cardiac Suppression Trial Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med. 1989;321(6):406–412.
11.
JanuaryCTWannLSAlpertJS. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):e199–e267.
12.
SlavikRSTisdaleJEBorzakS. Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence. Prog Cardiovasc Dis. 2001;44(2):121–152.
13.
CammAJCammCFSavelievaI. Medical treatment of atrial fibrillation. J Cardiovasc Med. 2012;13(2):97–107.
14.
AlboniPBottoGLBaldiN. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med. 2004;351(23):2384–2391.
15.
WilliamsAJMcQuinnRLWallsJ. Pharmacokinetics of flecainide acetate in patients with severe renal impairment. Clin Pharmacol Ther. 1988;43(4):449–455.
16.
PaulTBertramHBökenkampR. Supraventricular tachycardia in infants, children, and adolescents: diagnosis and pharmacological and interventional therapy. Paediatr Drugs. 2000;2(3):171–181.
17.
LimKSChoJYJangIJ. Pharmacokinetic interaction of flecainide and paroxetine in relation to the CYP2D6*10 allele in healthy Korean subjects. Br J Clin Pharmacol. 2008;66(5):660–666.
18.
Tjandra-MagaTBvan HeckenAvan MelleP. Altered pharmacokinetics of oral flecainide by cimetidine. Br J Clin Pharmacol. 1986;22(1):108–110.
19.
Funck-BrentanoCBecquemontLKroemerHK. Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clin Pharmacol Ther. 1994;55(3):256–269.
20.
GrossASMikusGFischerC. Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH. Eur J Clin Pharmacol. 1991;40(2):155–162.
21.
WeeksCEConardGJKvamDC. The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels. J Clin Pharmacol. 1986;26(1):27–31.
22.
KroemerHKFunck-BrentanoCSilbersteinDJ. Stereoselective disposition and pharmacologic activity of propafenone enantiomers. Circulation. 1989;79(5):1068–1076.
23.
BotschSGautierJCBeauneP. Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol. 1992;43(1):120–126.
24.
MalfattoGZazaAForsterM. Electrophysiologic, inotropic, and antiarrhythmic effects of propafenone, 5-hydsroxypropafenone, and N-depropylpropafenone. J Pharmacol Exp Ther. 1988;246(2):419–426.
25.
LeeJTKroemerHKSilbersteinDJ. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med. 1990;322(25):1764–1768.
26.
HemeryckADe VriendtCBelpaireFM. Effect of selective serotonin reuptake inhibitors on the oxidative metabolism of propafenone: in vitro studies using human liver microsomes. J Clin Psychopharmacol. 2000;20(4):428–434.
27.
TrujilloTCNolanPE. Antiarrhythmic drugs: drug interactions of clinical significance. Drug Saf. 2000;23(6):509–532.
28.
PritchettELSmithWMKirstenEB. Pharmacokinetic and pharmacodynamics interactions of propafenone and cimetidine. J Clin Pharmacol. 1988;28(7):619–624.
29.
DilgerKGreinerBFrommMF. Consequences of rifampicin treatment on propafenone disposition in extensive and poor metabolizers of CYP2D6. Pharmacogenetics. 1999;9(5):551–559.
30.
CalvoMVMartin-SuarezAMartin LuengoC. Interaction between digoxin and propafenone. Ther Drug Monit. 1989;11(1):10–15.
31.
WoodlandCVerjeeZGiesbrechtE. The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther. 1997;283(1):39–45.
32.
IMF Health. National prescription auditTM: 2006-2010. (Extracted January 2011).
33.
FreemantleNLafuente-LafuenteCMitchellS. Mixed treatment comparison of dronedarone, amiodarone, sotalol, flecainide, and propafenone for the management of atrial fibrillation. Europace. 2011;13(3):329–345.
34.
RoyDTalajicMDorianP. Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med. 2000;342(13):913–920.
35.
SinghSNSinghBNRedaDJ. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005;352(18):1861–1872.
36.
DeedwaniaPCSinghBNEllenbogenK. Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients with heart failure and atrial fibrillation: observations from the Veterans Affairs Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT). Circulation. 1998;98(23):2574–2579.
37.
RangeFTHilkerEBreithardtG. Amiodarone-induced pulmonary toxicity: a fatal case report and review of the literature. Cardiovasc Drugs Ther. 2013;27(3):247–254.
38.
BogazziFTomisitiLBartalenaL. Amiodarone and the thyroid: a 2012 update. J Endocrinol Invest. 2012;35(3):340–348.
39.
PassmanRSBennettCLPurpuraJM. Amiodarone-associated optic neuropathy: a critical review. Am J Med. 2012;125(5):447–453.
40.
SinghBN. Amiodarone: a multifaceted drug. Curr Cardiol Rep. 2006;8(5):349–355.
JaworskiKWaleckaIRudnickaL. Cutaneous adverse reactions of amiodarone. Med Sci Monit. 2014;20:2369–2372.
43.
GoldschlagerNEpsteinAENaccarelliGV. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm. 2007;4(9):1250–1259.
44.
SanoskiCASchoenMDGonzalezRC. Rationale, development, and clinical outcomes of a multidisciplinary amiodarone clinic. Pharmacotherapy. 1998;18(6 pt 2):146s–151s.
45.
SpenceMMPolzinJKWeisbergerCL. Evaluation of a pharmacist-managed amiodarone monitoring program. J Manag Care Pharm. 2011;17(7):5135–22.
46.
SanoskiCABaumanJL. Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy. Chest. 2002;121(1):19–23.
47.
NademaneeKKannanRHendricksonJ. Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms, and therapeutic implications. J Am Coll Cardiol. 1984;4(1):111–116.
48.
SinghBNConnollySJCrijnsHJ. Dronedarone for the maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987–999.
49.
KoberLTorp-PedersenCMcMurrayJJ. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med. 2008;358(25):2678–2687.
50.
HohnloserSHCrijnsHJvan EickelsM. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668–678.
51.
Le HeuzeyJYDe FerrariGMRadzikD. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol. 2010;21(6):597–605.
52.
ConnollySJCammAJHalperinJL. Dronedarone in high-risk atrial fibrillation. N Engl J Med. 2011;365(24):2268–2276.
Hernández VothARCatalánJSBenavides MañasPD. A 73-year-old man with interstitial lung disease due to dronedarone. Am J Respir Crit Care Med. 2012;186(2):201–202.
55.
YoungCMaruthappuMWayneRP. Reversible acute kidney injury requiring haemodialysis five days after starting dronedarone in a stable 71-year-old man at risk of cardiovascular polypharmacy. J R Coll Physicians Edinb. 2013;43(2):122–125.
56.
SmithHBattjesEYanS. Chronic digoxin toxicity precipitated by dronedarone. Ann Pharmacother. 2014;48(7):923–927.
57.
ShantsilaEWatsonTLipGY. Drug-induced QT-interval prolongation and proarrhythmic risk in the treatment of atrial arrhythmias. Europace. 2007;9(suppl 4):iv37–iv44.
58.
SinghSZobleRGYellenL. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study. Circulation. 2000;102(19):2385–2390.
59.
Torp-PedersenCMollerMBloch-ThomsonPE. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med. 1999;341(12):857–865.
60.
PedersenHSElmingHSeibaekM. Risk factors and predictors of torsades de pointes ventricular tachycardia in patients with left ventricular dysfunction receiving dofetilide. Am J Cardiol. 2007;100(5):876–880.
