|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(i BYOO ti lide)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Pharmacologic Category
Pharmacologic Category Synonyms
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
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic and embryocidal in rats; avoid use in pregnancy
Lactation
Enters breast milk/contraindicated
Contraindications
Hypersensitivity to ibutilide or any component of the formulation; QTc >440 msec
Warnings/Precautions
Boxed warnings:
• Chronic atrial fibrillation: See “Disease-related concerns” below.
• Proarrhythmic effects: See “Concerns related to adverse effects” below.
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.
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:
• Elderly: Use with caution in the elderly.
• Pediatrics: 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.
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 (3.6%)
Gastrointestinal: Nausea (>1%)
<1% (Limited to important or life-threatening): Supraventricular extrasystoles (0.9%), nodal arrhythmia (0.7%), CHF (0.5%), syncope (0.3%, not > placebo), idioventricular rhythm (0.2%), sustained monomorphic ventricular tachycardia (0.2%), renal failure (0.3%)
Postmarketing and/or case reports: Erythematous bullous lesions
Metabolism/Transport Effects
None known.
Drug Interactions
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Eribulin: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class III). Risk C: Monitor therapy
Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class III). Management: Obtain baseline ECG (if not recently available) if initiating fingolimod during treatment with class III antiarrhythmic agents. Monitor for bradycardia and AV block. The Canadian labeling recommends avoiding concomitant use of these agents. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Storage
Admixtures are chemically and physically stable for 24 hours at room temperature and for 48 hours at refrigerated temperatures.
Reconstitution
May be administered undiluted or diluted in 50 mL diluent (0.9% NS or D5W).
Mechanism of Action
Exact mechanism of action is unknown; prolongs the action potential in cardiac tissue
Pharmacodynamics/Kinetics
Onset of action: ~90 minutes after start of infusion (1/2 of conversions to sinus rhythm occur during infusion)
Distribution: Vd: 11 L/kg
Protein binding: 40%
Metabolism: Extensively hepatic; oxidation
Half-life elimination: 2-12 hours (average: 6 hours)
Excretion: Urine (82%; 7% as unchanged drug and metabolites); feces (19%)
Dosage
I.V.: Initial:
Adults:
<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.
Elderly: Refer to adult dosing. Dose selection should be cautious, usually starting at the lower end of the dosing range.
Administration: I.V.
May be administered undiluted or diluted in 50 mL diluent (0.9% NS or D5W). Infuse over 10 minutes.
Administration: I.V. Detail
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.
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
Patient Education
This drug is only given I.V. and you will be on continuous cardiac monitoring during and for several hours following administration. You may experience headache or irregular heartbeat during infusion. Report chest pain or respiratory difficulty immediately.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Ibutilide may lower the energy requirement for direct current cardioversion in atrial fibrillation; effective for termination of postsurgical atrial fibrillation or atrial flutter, but at the risk of precipitating ventricular arrhythmias (eg, torsade de pointes). Patients who receive ibutilide should be evaluated for risk of development of QT prolongation and subsequent torsade de pointes (TdP). A major risk factor for development of TdP is reduced left ventricular function, and therefore ibutilide should be avoided in these patients (Blomström-Lundqvist, 2003). Patients should be observed with continuous ECG monitoring during infusion and for at least 4 hours following infusion or until QTc has returned to baseline.
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).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Ibutilide is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Ibutilide is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Ibutilide is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Concurrent use with phenothiazine and antidepressants may produce prolongation of the QT interval; use combination with caution; consider a nonphenothiazine antipsychotic
Nursing: Physical Assessment/Monitoring
Requires infusion pump and continuous cardiac and hemodynamic monitoring during and for 4 hours following infusion.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as fumarate: 0.1 mg/mL (10 mL)
Corvert®: 0.1 mg/mL (10 mL)
References
Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al, “ACC/AHA/ESC Guidelines for the Management of Patients With Supraventricular Arrhythmias--Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias),” Circulation, 2003, 108(15):1871-909.
Caron MF, Kluger J, Tsikouris JP, et al, “Effects of Intravenous Magnesium Sulfate on the QT Interval in Patients Receiving Ibutilide,” Pharmacotherapy, 2003, 23(3):296-300.
Coleman CI, Kalus JS, Caron MF, et al, “Model of Effect of Magnesium Prophylaxis on Frequency of Torsades de Pointes in Ibutilide-Treated Patients,” Am J Health Syst Pharm, 2004, 61(7):685-8.
Fuster V, Ryden LE, Cannom DS, et al, “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation-Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society,” J Am Coll Cardiol, 2006, 48(4):854-906.
Kalus JS, Spencer AP, Tsikouris JP, et al, “Impact of Prophylactic I.V. Magnesium on the Efficacy of Ibutilide for Conversion of Atrial Fibrillation or Flutter,” Am J Health Syst Pharm, 2003, 60(22):2308-12.
Wann SL, Curtis AB, January CT, et al, “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 123 (1):104-23.
International Brand Names
Lexi-Comp.com
Last full review/revision January 2012
Content last modified January 2012
| 
