Ibutilide (Monograph)

Brand name: Corvert
Drug class: Class III Antiarrhythmics
VA class: CV300
Chemical name: (±)-N-[4-[4-(ethylheptylamino)-1-hydroxybutyl]phenyl]-methanesulfonamide (E)-2-butenedioate (2:1) (salt)
Molecular formula: C₂₀H₃₆N₂O₃S•½C₄H₄ O₄
CAS number: 122647-32-9

Medically reviewed by Drugs.com on Nov 6, 2023. Written by ASHP.

Introduction

Class III antiarrhythmic agent;^{1 2 3 4 7} a methanesulfonanilide derivative.^{1 2 3}

Uses for Ibutilide

Supraventricular Tachyarrhythmias

Used for rapid conversion of recent-onset atrial fibrillation or flutter to sinus rhythm.^{1 7 300 301}

Considered a drug of choice for pharmacologic cardioversion of atrial fibrillation or flutter.^{300 301}

Some experts state that ibutilide also may be used in hemodynamically stable patients with preexcited atrial fibrillation and rapid ventricular response (e.g., Wolff-Parkinson-White syndrome^{† [off-label]}).^{300 301}

Also may be used in selected patients with focal atrial tachycardia^{† [off-label]}.³⁰⁰

Atrial arrhythmias that are not of recent onset are less likely to respond to the drug.¹ Efficacy not determined in atrial arrhythmias of >90 days’ duration.¹

Related/similar drugs

diltiazem, Xarelto, digoxin, rivaroxaban, flecainide, sotalol, propafenone

Ibutilide Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.¹

• Cardiac monitoring equipment, intracardiac pacing facilities, a cardioverter/defibrillator, and therapy for sustained VT (e.g., polymorphic VT) must be available during and after ibutilide administration.¹

• Continuous ECG monitoring recommended for at least 4 hours after completion of ibutilide administration or until the corrected QT interval (QT_c) has returned to baseline.¹ May require longer monitoring if arrhythmic activity is noted.¹

Administration

Administer by IV infusion.¹

IV Administration

May be administered undiluted or diluted.¹

Dilution

Add the contents of a 10-mL vial of ibutilide fumarate to 50 mL of 0.9% sodium chloride or 5% dextrose injection, resulting in a final concentration of about 0.017 mg/mL (17 mcg/mL).¹

Rate of Administration

Administer over 10 minutes.¹

Dosage

Available as ibutilide fumarate; dosage expressed in terms of the hemifumarate salt.¹

Adults

Supraventricular Tachyarrhythmias

Atrial Flutter and/or Fibrillation

IV

Adults weighing ≥60 kg: Initially, 1 mg.^{1 7} Alternatively, 2 mg has been used.¹

Adults weighing <60 kg: Initially, 0.01 mg/kg (10 mcg/kg).^{1 7}

If arrhythmia does not terminate within 10 minutes after completion of initial infusion, repeat initial dose.^{1 7} Value and patient tolerance of additional doses not established.^{1 10}

Atrial Flutter and/or Fibrillation following Coronary Bypass Graft or Valvular Surgery

IV

Adults weighing ≥60 kg: 1 or 2 infusions of 0.5 mg each (given 10 minutes apart) have been used.^{1 7}

Adults weighing <60 kg: 1 or 2 infusions of 0.005 mg/kg (5 mcg/kg) each (given 10 minutes apart) have been used.^{1 7}

Prescribing Limits

Adults

Supraventricular Tachyarrhythmias

IV

Adults weighing ≥60 kg: Maximum 2 mg (e.g., 2 infusions of 1 mg each given 10 minutes apart).¹ Value and patient tolerance of additional doses not established.^{1 10}

Adults weighing <60 kg: Maximum 0.02 mg/kg (2 infusions of 0.01 mg/kg each given 10 minutes apart).¹ Value and patient tolerance of additional doses not established.^{1 10}

Special Populations

Hepatic Impairment

Dosage adjustment unlikely to be required.¹

Renal Impairment

Dosage adjustment unlikely to be required.¹

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosing range because of age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Ibutilide

Contraindications

• History of polymorphic VT (e.g., torsades de pointes).¹ (See Arrhythmogenic Effects under Cautions.)

• Known hypersensitivity to ibutilide or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

Arrhythmogenic Effects

May cause serious or potentially fatal ventricular arrhythmias, particularly sustained polymorphic VT, usually associated with QT prolongation (i.e., torsades de pointes).^{1 7}

Possible increased risk of torsades de pointes in patients with a history of CHF, low left ventricular ejection fraction, bradycardia, varying heart rate, or hypokalemia.¹ Use not recommended in patients with a history of sustained polymorphic VT that required cardioversion.¹

If polymorphic VT occurs, discontinue the drug, correct electrolyte abnormalities (especially potassium and magnesium), and undertake overdrive cardiac pacing, electrical cardioversion, and/or defibrillation as necessary.¹ Generally should avoid treatment with antiarrhythmic drugs, although magnesium sulfate infusions may be beneficial.¹

Metabolic Effects

Hypokalemia or hypomagnesemia may increase the risk of torsades de pointes.¹ Evaluate patient for potassium or magnesium deficiency; if present, correct deficiency prior to initiation of therapy.¹ (See Arrhythmogenic Effects under Cautions.)

General Precautions

Effects on Cardiac Conduction

Possible AV block, bundle branch block, or bradycardia.¹

Risk of torsades de pointes is thought to increase in part with bradycardia or a varying heart rate.¹ (See Arrhythmogenic Effects under Cautions.)

Specific Populations

Pregnancy

Category C.¹

Lactation

Distribution into milk not studied.¹ Use not recommended.¹

Pediatric Use

Safety and efficacy in children <18 years of age not established.¹

Geriatric Use

No differences in efficacy or safety parameters relative to younger adults.¹ However, use with caution due to the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.¹ (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Extend continuous ECG monitoring beyond the usual 4-hour period recommended for other patients.¹

Common Adverse Effects

Generally well tolerated.¹ Adverse events affecting the cardiovascular system (e.g., arrhythmogenic affects, affects on cardiac conduction, palpitation, hypotension, hypertension), nausea, and headache reported in ≤5.1% of patients.¹

Drugs Affecting QT Interval

Potential pharmacodynamic interaction (increased risk of ventricular arrhythmias).¹

Specific Drugs

Ibutilide Pharmacokinetics

Distribution

Extent

Following IV administration, rapidly cleared and widely distributed.¹ Steady-state volume of distribution is 11 L/kg.¹

Distribution appears to be one of the primary mechanisms for termination of pharmacologic effects.¹

Plasma Protein Binding

Approximately 40%.¹

Elimination

Metabolism

Extensively metabolized to numerous metabolites including one active metabolite.¹ Undergoes substantial hepatic clearance.¹

Elimination Route

Excreted in urine (about 82%) and feces (about 19%) principally as metabolites.¹

Half-life

Averages about 6 hours.¹

Special Populations

Clearance is independent of renal function.¹

Pharmacokinetics not affected by patient age or gender.¹

Stability

Storage

Parenteral

Solution for Injection

20–25°C.¹ Diluted solutions are stable for 24 hours at 15–30°C or for 48 hours under refrigeration (2–8°C).¹

Compatibility

Parenteral

Compatible with polyvinyl chloride plastic IV solution bags or polyolefin IV solution bags.¹

Actions

• Exhibits electrophysiologic effects characteristic of class III antiarrhythmic agents (e.g., prolongs repolarization and refractoriness without appreciably affecting conduction).^{1 2 3}

• More selective in its cellular actions than some other class III antiarrhythmic agents (e.g., amiodarone, sotalol).³

• Prolongs the action potential duration and effective refractory period (ERP) in both atrial and ventricular cardiac tissue.^{1 2 3 4 7}

• Delays repolarization by activating a slow, predominantly sodium, inward current.^{1 3 5 6}

• Produces dose-related prolongation of the QT interval, which is thought to be associated with the antiarrhythmic activity.¹ (See Arrhythmogenic Effects under Cautions.)

• Negligible effects on heart rate, cardiac contractility, or BP.³ Lacks β-adrenergic blocking activity.^{2 3}

Advice to Patients

• Importance of patients informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, dietary supplements, and/or herbal products, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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