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; a methanesulfonanilide derivative.

Uses for Ibutilide

Supraventricular Tachyarrhythmias

Used for rapid conversion of recent-onset atrial fibrillation or flutter to sinus rhythm.

Considered a drug of choice for pharmacologic cardioversion of atrial fibrillation or flutter.

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]}).

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

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

Ibutilide Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.

• 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.

• 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. May require longer monitoring if arrhythmic activity is noted.

Administration

Administer by IV infusion.

IV Administration

May be administered undiluted or diluted.

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).

Rate of Administration

Administer over 10 minutes.

Dosage

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

Adults

Supraventricular Tachyarrhythmias

Atrial Flutter and/or Fibrillation

IV

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

Adults weighing <60 kg: Initially, 0.01 mg/kg (10 mcg/kg).

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

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.

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

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). Value and patient tolerance of additional doses not established.

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

Special Populations

Hepatic Impairment

Dosage adjustment unlikely to be required.

Renal Impairment

Dosage adjustment unlikely to be required.

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.

Cautions for Ibutilide

Contraindications

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

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

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).

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. Use not recommended in patients with a history of sustained polymorphic VT that required cardioversion.

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. Generally should avoid treatment with antiarrhythmic drugs, although magnesium sulfate infusions may be beneficial.

Metabolic Effects

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

General Precautions

Effects on Cardiac Conduction

Possible AV block, bundle branch block, or bradycardia.

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

Specific Populations

Pregnancy

Category C.

Lactation

Distribution into milk not studied. Use not recommended.

Pediatric Use

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

Geriatric Use

No differences in efficacy or safety parameters relative to younger adults. 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. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

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

Common Adverse Effects

Generally well tolerated. 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.

Drugs Affecting QT Interval

Potential pharmacodynamic interaction (increased risk of ventricular arrhythmias).

Specific Drugs

Ibutilide Pharmacokinetics

Distribution

Extent

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

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

Plasma Protein Binding

Approximately 40%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

Averages about 6 hours.

Special Populations

Clearance is independent of renal function.

Pharmacokinetics not affected by patient age or gender.

Stability

Storage

Parenteral

Solution for Injection

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

Compatibility

Parenteral

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

Actions

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

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

• Prolongs the action potential duration and effective refractory period (ERP) in both atrial and ventricular cardiac tissue.

• Delays repolarization by activating a slow, predominantly sodium, inward current.

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

• Negligible effects on heart rate, cardiac contractility, or BP. Lacks β-adrenergic blocking activity.

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.

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

• Importance of advising patients of other important precautionary information. (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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