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Ibutilide


General


Pronunciation

(i BYOO ti lide)


Brand Names: U.S.

  • Corvert

Indications


Use: Labeled Indications

Acute termination of atrial fibrillation or flutter of recent onset; the effectiveness of ibutilide has not been determined in patients with arrhythmias >90 days in duration

Note: According to the American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines for the management of atrial fibrillation, in patients with pre-excited atrial fibrillation and rapid ventricular response who are not hemodynamically compromised, the use of ibutilide to restore sinus rhythm or slow the ventricular rate is recommended (AHA/ACC/HRS [January, 2014]).


Contraindications


Hypersensitivity to ibutilide or any component of the formulation; QTc >440 msec


ALERT: U.S. Boxed Warning

Life-threatening arrhythmias:

Ibutilide fumarate can cause potentially fatal arrhythmias, particularly sustained polymorphic ventricular tachycardia usually in association with QT prolongation (torsades de pointes), but sometimes without documented QT prolongation. In registration studies, these arrhythmias, which require cardioversion, occurred in 1.7% of treated patients during or within a number of hours of using ibutilide fumarate.

These arrhythmias can be reversed if treated promptly. It is essential that ibutilide be administered in a setting of continuous ECG monitoring and by personnel trained in identification and treatment of acute ventricular arrhythmias, particularly polymorphic ventricular tachycardia. Patients with atrial fibrillation of more than 2 to 3 days duration must be adequately anticoagulated, generally for at least 2 weeks.

Appropriate treatment environment:

Choice of patients: Patients with chronic atrial fibrillation have a strong tendency to revert after conversion to sinus rhythm and treatments to maintain sinus rhythm carry risks. Patients to be treated with ibutilide fumarate, therefore, should be carefully selected such that the expected benefits of maintaining sinus rhythm outweigh the immediate risks of ibutilide, and the risks of maintenance therapy, and are likely to offer an advantage compared with alternative management.


Dosing and Administration


Dosing: Adult

Atrial fibrillation/flutter: IV:

<60 kg: 0.01 mg/kg over 10 minutes

≥60 kg: 1 mg over 10 minutes

Note: Discontinue infusion if arrhythmia terminates, if sustained or nonsustained ventricular tachycardia occurs, or if marked prolongation of QT/QTc occurs. If the arrhythmia does not terminate within 10 minutes after the end of the initial infusion, a second infusion of equal strength may be infused over a 10-minute period.


Dosing: Geriatric

Refer to adult dosing. Dose selection should be cautious, usually starting at the lower end of the dosing range.


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

No dosage adjustment necessary.


Reconstitution

No dilution required. May dilute in 50 mL diluent (0.9% NS or D5W).


Administration

Infuse undiluted or diluted over 10 minutes. Observe patient with continuous ECG monitoring for at least 4 hours (>4 hours in patients with abnormal hepatic function) following infusion or until QTc has returned to baseline. Skilled personnel and proper equipment should be available during administration of ibutilide and subsequent monitoring of the patient.


Storage

Admixtures are chemically and physically stable for 24 hours at room temperature and for 48 hours at refrigerated temperatures.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as fumarate:

Corvert: 1 mg/10 mL (10 mL)

Generic: 1 mg/10 mL (10 mL)


Drug Interactions

Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Avoid combination

Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination

Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Lidocaine (Topical): May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Antiarrhythmic Agents (Class III) may increase the serum concentration of Lidocaine (Topical). This mechanism specifically applies to amiodarone and dronedarone. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination

Propafenone: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Management: Concurrent use of propafenone with quinidine, amiodarone, or other class IA or class III antiarrhythmics should be avoided. Treatment with such agents should be withheld for at least 5 half-lives prior to initiation of propafenone. Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination


Monitoring Parameters

Electrolytes; observe patient with continuous ECG monitoring for at least 4 hours following infusion or until QTc has returned to baseline; skilled personnel and proper equipment should be available during administration of ibutilide and subsequent monitoring of the patient

Consult individual institutional policies and procedures.


Adverse Reactions


1% to 10%:

Cardiovascular: Ventricular extrasystoles (5.1%), nonsustained monomorphic ventricular tachycardia (4.9%), nonsustained polymorphic ventricular tachycardia (2.7%), tachycardia/supraventricular tachycardia (2.7%), hypotension (2%), bundle branch block (1.9%), sustained polymorphic ventricular tachycardia (eg, torsade de pointes) (1.7%, often requiring cardioversion), AV block (1.5%), bradycardia (1.2%), QT segment prolongation, hypertension (1.2%), palpitation (1%)

Central nervous system: Headache (4%)

Gastrointestinal: Nausea (>1%)

<1% (Limited to important or life-threatening): CHF, erythematous bullous lesions, idioventricular rhythm, nodal arrhythmia, renal failure, supraventricular extrasystoles, sustained monomorphic ventricular tachycardia, syncope (0.3%, not > placebo)


Warnings/Precautions


Concerns related to adverse effects:

- Conduction disturbances: Monitor for heart block.

- Proarrhythmic effects: [U.S. Boxed Warning]: Potentially fatal arrhythmias (eg, polymorphic ventricular tachycardia) can occur with ibutilide, usually in association with torsade de pointes (QT prolongation). Studies indicate a 1.7% incidence of arrhythmias in treated patients. The use of intravenous magnesium (2 g) immediately prior to and after ibutilide administration has been shown to be helpful in reducing QT interval prolongation due to ibutilide (Caron, 2003) and may enhance the efficacy of ibutilide (Kalus, 2003). Whether or not prophylactic magnesium reduces the incidence of TdP has yet to be determined; however, it is thought that this measure will reduce the incidence of TdP (Coleman, 2004).

Disease-related concerns:

- Arrhythmias: Appropriate use: The drug should be given in a setting of continuous ECG monitoring and by personnel trained in treating arrhythmias particularly polymorphic ventricular tachycardia.

- Chronic atrial fibrillation: [U.S. Boxed Warning]: Patients with chronic atrial fibrillation may not be the best candidates for ibutilide since they often revert after conversion and the risks of treatment may not be justified when compared to alternative management.

- Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

- Hepatic impairment: Dosing adjustments are not required in patients with hepatic impairment.

- Renal impairment: Dosing adjustments are not required in patients with renal impairment.

Concurrent drug therapy issues:

- Drugs with QT prolongation potential: Avoid concurrent use with any drug that can prolong QT interval.

Special populations:

- Pediatric: Safety and efficacy have not been established in children.

Other warnings/precautions:

- CAST trial: In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, non-life-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Use in pregnancy may be considered (ESG [Regitz-Zagrosek 2011]); however, information related to the use of ibutilide in pregnancy is limited (Burkart 2007; Kockova 2007).


Actions


Pharmacology

Exact mechanism of action is unknown; prolongs the action potential in cardiac tissue


Metabolism

Extensively hepatic; oxidation


Excretion

Urine (82%; 7% as unchanged drug and metabolites); feces (19%)


Onset of Action

~90 minutes after start of infusion (1/2 of conversions to sinus rhythm occur during infusion)


Half-Life Elimination

2-12 hours (average: 6 hours)


Protein Binding

40%


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Have patient report immediately to prescriber angina, bradycardia, tachycardia, arrhythmia, severe dizziness, or passing out (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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