Article Author:
Michael Szymanski
Article Editor:
Mark Pellegrini
10/27/2018 12:31:39 PM
PubMed Link:


Ibutilide is indicated for the conversion of acute atrial flutter and atrial fibrillation to normal sinus rhythm (NSR).[1]

Off-Label Uses

Ibutilide may be used as a pretreatment for electrocardioversion. Pretreatment with ibutilide, sotalol, or dofetilide may help conversion to NSR in cases of refractory atrial fibrillation. Ibutilide may also be given post cardioversion to prevent recurrent atrial fibrillation.[2]

Ibutilide may be administered following surgery.[3]

Mechanism of Action

Ibutilide is a potassium channel blocker that prolongs phase 3 of the cardiac action potential, resulting in increased refractoriness of atrial and ventricular myocytes, the atrioventricular node, and His-Purkinje system.[1]

The cardiac action potential is divided into the following five stages:

Phase 0: Rapid Depolarization

During phase 0, fast sodium channels open when the cell reaches the threshold. This results in a rapid depolarization of the myocyte continuing until inactivation gates close, thus abolishing sodium conductance. The closure of inactivation gates is mediated by a time-dependent mechanism. Reopening of inactivation gates occurs during cell repolarization, specifically upon re-approaching threshold.

Phase 1: Early repolarization

Potassium channels open causing an efflux of potassium called the transient outward current (ito). The end of phase 1 is characterized by a balance between calcium influx and potassium efflux, thus leading to the plateau phase.

Phase 2: Plateau

The plateau phase consists of a balance between calcium influx and potassium efflux. The calcium channels are L-type dihydropyridine-receptor channels that inactivate slowly. Drugs that alter the conductance of calcium modulate this phase and belong to Class 4 of the Vaughn-Williams classification system.

During the latter stages of the plateau phase, delayed rectifying potassium channels (iKr) open and allow the myocyte to begin repolarization as the calcium current declines.

Phase 3: Repolarization

In phase 3 of the cardiac action potential, potassium efflux exceeds inward calcium current causing repolarization. When positively charged potassium ions move out of the cell it restores the negative potential of the cardiac myocyte. Three potassium channels are involved in the repolarization phase. While the cell membrane is still depolarized, iKr and ito are the major contributors to potassium efflux. As the myocyte approaches threshold, the inwardly rectifying current (iK1) channels open and contribute to repolarization. Although iK1 channels are termed “inwardly rectifying,” potassium efflux occurs due to the electrochemical potential of potassium derived from the cord conductance equation.

Ibutilide is a potassium-blocking agent that primarily exerts its effect on the delayed rectifying potassium channels (iKr). By blocking potassium channels, phase 3 is lengthened, prolonging the QTc interval and increasing the refractoriness of the atrial and ventricular myocytes. When a myocyte is in the absolute refractory period, a subsequent action potential cannot be propagated thus causing a decrease in the heart rate of patients presenting with tachydysrhythmias. [4]

Ibutilide has also been shown to activate a slow, delayed, inward sodium current during the early stages of repolarization. However, blockade of iKr channels is the major contributor to its antiarrhythmic properties.[5]

Phase 4: Resting

Phase 4 is dominated by the Na+/K+ ATPase. For every three Na+ ions pumped out of the cell, two K+ ions are pumped in, resulting in a negative resting membrane potential. 

A primary active transporter called the calcium ATPase re-sequesters the majority of the intracellular calcium into the sarcoplasmic reticulum. The sarcoplasmic calcium ATPase is regulated by an intracellular protein called phospholamban. When phospholamban is phosphorylated by protein kinase A (PKA), the calcium ATPase is active and incorporates cytosolic calcium ions into the sarcoplasmic reticulum. During the next action potential, more calcium is released into the cytosol thus causing increased contractility. When phospholamban is de-phosphorylated, it inhibits the sarcoplasmic calcium ATPase.

Remaining calcium ions are pumped out of the myocytes by secondary active transport through the Na+/Ca++ exchanger. 

It is important to note that the cardiac myocyte Na+/K+ ATPase is inhibited pharmacologically by the cardiac glycosides (digoxin). Inhibition of the Na+/K+ ATPase causes an increase in intracellular Na+ ions and leads to a series of biochemical changes, beginning with the reverse action of membrane-bound Na+/Ca++ exchangers. The change in polarity of Na+/Ca++ exchangers causes an efflux of Na+ and influx of Ca++ in order to restore the resting membrane potential in the absence of Na+/K+ ATPase activity. The increased concentration of intracellular calcium is responsible for the positive ionotropic properties of digoxin therapy. [6]

Notable ECG Changes

Slowing of heart rate

Prolongation of QT interval (risk of developing torsades de pointes)


Ibutilide is available as a solution administered intravenously (1 mg/10 mL)

For patients weighing less than 60 kg, the dose is 0.01 mg/kg over 10 minutes.

For patients weighing more than 60 kg, the dose is 1 mg over 10 minutes. 

It may be administered diluted or undiluted. Discontinue infusion upon resolution of presenting arrhythmia or new-onset ventricular tachycardia. If the arrhythmia does not terminate within 10 minutes post infusion, another dose may be given over 10 minutes.

Renal or Hepatic Impairment: Dosing for renal or hepatic impairment does not need to be adjusted.

Geriatrics: Start at the lower end of the dosing range

Addition of Magnesium Sulfate: Magnesium has been shown to enhance the ability of Ibutilide to convert atrial flutter or fibrillation to normal sinus rhythm. Magnesium can also help prevent prolongation of the QT interval and is commonly used in the treatment of torsades de pointes in hemodynamically stable patients.[7],[8],[7]

Class 1C Antiarrhythmics: Ibutilide can be given safely with Class 1C antiarrhythmics since class 1C antiarrhythmics do not affect the QT interval.[9]

Amiodarone: The risk of arrhythmia is not increased when ibutilide is given with amiodarone.[10]

Pharmacokinetics:  Conversion to sinus rhythm occurs in less than 90 minutes after the start of infusion. Ibutilide has a half-life of 2 to 12 hours with an average half-life of 6 hours. It is metabolized extensively by the liver into eight metabolites (1 active). The volume of distribution is approximately 11 L/kg. The majority of the drug is excreted via the urine in the form of inactive metabolites.

Adverse Effects

According to the Institute for Safe Medication Practices (ISMP), this drug has a heightened risk of causing significant patient harm.

Cardiac Adverse Effects

  • Nonsustained monomorphic ventricular tachycardia
  • Premature ventricular contractions
  • Nonsustained polymorphic ventricular tachycardia
  • Atrioventricular Block
  • Bundle branch block
  • Hypotension
  • Torsades de pointes
  • Prolonged QT interval
  • Hypertension
  • Palpitations
  • Bradycardia 

Extracardiac Adverse Effects

  • Nausea
  • Headache
  • Renal failure
  • Erythematous rash

Drug Interactions

Category X (avoid)

  • Amifampridine
  • Fingolimod
  • Hydroxychloroquine
  • Macimorelin
  • Mifepristone
  • Mizolastine
  • Probucol
  • Promazine
  • Vinflunine

Category D (modify regimen)

  • Indapamide

Category C (monitor)

  • Bilastine
  • Fluoxetine
  • Pefloxacin
  • Teneligliptin
  • Xipamide

Pregnancy Implications: Use of Ibutilide may be considered in pregnancy; however, data regarding its effects are limited. Breastfeeding is not recommended. [11]


  • Hypersensitivity to Ibutilide
  • Prolonged QT interval (prior to Ibutilide infusion)
  • Sinus node disease
  • Structural cardiac disease


Patients need to be continuously monitored via ECG for 4 hours post discontinuation of ibutilide infusion or until the QTc returns to normal (less than 440 msec). If arrhythmia presents, continue monitoring patients for more than 4 hours. Equipment for the management of potentially fatal arrhythmias should be rapidly available.