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Anti-arrhythmics, Class III

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Ibutilide doses are administered by IV infusion.
Continuous ECG monitoring is recommended during administration and for at least 4 hours following infusion or until the QT interval corrected for heart rate (QTc) has returned to baseline. If any arrhythmic activity is noted, longer monitoring is required. Patients with abnormal hepatic function should be monitored for more than the 4 hour period.
Dilution
If desired, one 10 mL vial (0.1 mg/mL) of ibutilide may be diluted in 50 mL of 0.9% Sodium Chloride for injection or 5% Dextrose for injection to give approximately 0.017 mg/mL of ibutilide.
Intravenous Infusion
Infuse each IV dose over 10 minutes. Infusion of ibutilide should be stopped as soon as the arrhythmia is terminated or if sustained or nonsustained ventricular tachycardia occur, or if marked prolongation of QT or QTc develops.

Severe

ventricular tachycardia / Early / 2.7-2.7
torsade de pointes / Rapid / 1.7-1.7
AV block / Early / 1.5-1.5
bradycardia / Rapid / 1.2-1.2
heart failure / Delayed / 0.5-0.5
renal failure (unspecified) / Delayed / 0.3-0.3
arrhythmia exacerbation / Early / Incidence not known

Moderate

sinus tachycardia / Rapid / 2.7-2.7
hypotension / Rapid / 2.0-2.0
orthostatic hypotension / Delayed / 2.0-2.0
bundle-branch block / Early / 1.9-1.9
QT prolongation / Rapid / 1.2-1.2
palpitations / Early / 1.0-1.0

Mild

headache / Early / 3.6-3.6
nausea / Early / 1.9-1.9
syncope / Early / 0.3-0.3

Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, geriatric, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, requires a specialized care setting, requires an experienced clinician, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE), ventricular arrhythmias, ventricular dysfunction, ventricular tachycardia

Similar to other Class III antiarrhythmic agents, ibutilide can aggravate or induce serious cardiac arrhythmias and its use requires both a proper environment for administration and care in optimal patient selection. Ibutilide administration requires a specialized care setting with continuous ECG monitoring by trained personnel, capable of identifying and treating acute ventricular arrhythmias (particularly polymorphic ventricular tachycardia). Use also requires an experienced clinician who is familiar with carefully selecting patients for therapy, where the expected benefits of maintaining sinus rhythm with the agents outweigh the immediate risks. This clinician should guide ibutilide administration. Patients with atrial fibrillation lasting more than 2 to 3 days should be adequately anticoagulated (generally for at least 2 weeks duration). Patients with chronic atrial fibrillation have a strong tendency to revert after conversion to sinus rhythm and treatments to maintain sinus rhythm are associated with substantial risks. The drug is given to patients where the benefits of maintaining sinus rhythm using ibutilide are likely to offer an advantage compared with alternative management. Potentially fatal ventricular arrhythmias following administration usually occur in association with QT prolongation and can lead to torsade de pointes, though serious arrhythmias may occur without documented QT prolongation. In clinical trials, serious ventricular arrhythmias occurred in about 1.7% of patients during or within hours of ibutilide administration; these arrhythmias can be reversed if promptly treated with cardioversion. The risk for developing ventricular arrhythmias or torsade de pointes is increased in patients with bradycardia, hypokalemia, or hypomagnesemia. Ibutilide therapy is not recommended for patients with a history of polymorphic ventricular tachycardia such as torsade de pointes. The manufacturer reports that there is a higher incidence of sustained polymorphic ventricular tachycardia in patients with a history of congestive heart failure or left ventricular dysfunction. Use ibutilide with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric adults 65 years of age and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

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Rx

Class III antiarrhythmic agent; used IV for rapid conversion of atrial fibrillation or atrial flutter to normal sinus rhythm.

For the rapid cardioversion of recent onset atrial fibrillation or atrial flutter to sinus rhythm. Intravenous dosage Adults weighing 60 kg or more

1 mg IV as a single dose. May repeat the dose once if the arrhythmia is not terminated within 10 minutes after the end of the initial infusion. In a study comparing ibutilide and sotatol, 2 mg IV as a single dose was also effective. Guidelines recommend ibutilide for pharmacological cardioversion of atrial fibrillation or atrial flutter, if no contraindications exist. Ibutilide is also recommended in persons with Wolff-Parkinson-White syndrome or pre-excitation syndromes to restore sinus rhythm or slow the ventricular rate in persons with pre-excited atrial fibrillation and rapid ventricular response who are not hemodynamically compromised.

Adults weighing less than 60 kg

0.01 mg/kg/dose IV as a single dose. May repeat the dose once if the arrhythmia is not terminated within 10 minutes after the end of the initial infusion. In a post-cardiac surgery study, 0.005 mg/kg/dose for 1 or 2 doses was also effective. Guidelines recommend ibutilide for pharmacological cardioversion of atrial fibrillation or atrial flutter, if no contraindications exist. Ibutilide is also recommended in persons with Wolff-Parkinson-White syndrome or pre-excitation syndromes to restore sinus rhythm or slow the ventricular rate in persons with pre-excited atrial fibrillation and rapid ventricular response who are not hemodynamically compromised.

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. In patients with abnormal hepatic function, the ECG should be monitored for more than the recommended 4 hour period.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Adagrasib: (Major) Concomitant use of adagrasib and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alfuzosin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Based on electrophysiology studies performed by the manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
Amiodarone: (Contraindicated) Amiodarone should not be administered concomitantly during the first four hours post-infusion of ibutilide, due to the potential for additive Class III antiarrhythmic effects. In addition, both ibutilide and amiodarone are associated with a risk of QT prolongation and torsades de pointes (TdP).
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with ibutilide. Amisulpride causes dose- and concentration- dependent QT prolongation. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include ibutilide.
Apomorphine: (Major) Use apomorphine and ibutilide together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Aripiprazole: (Major) Concomitant use of ibutilide and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Artemether; Lumefantrine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation and should be avoided. Consider ECG monitoring if ibutilide must be used with or after artemether; lumefantrine treatment.
Articaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Atomoxetine: (Major) Concomitant use of ibutilide and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azithromycin: (Major) Avoid coadministration of azithromycin with ibutilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with ibutilide. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bretylium: (Major) Do not use bretylium concurrently with ibutilide or within 4 hours of ibutilide infusion due to the potential to prolong refractoriness. During ibutilide clinical trials, class III antiarrhythmics, such as bretylium, were withheld for at least 5 half-lives before ibutilide infusion and for 4 hours after dosing.
Bupivacaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Buprenorphine: (Major) Buprenorphine should be avoided in combination with ibutilide. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Ibutilide, a class III antiarrhythmic, has an established risk for QT prolongation and TdP and caution is recommended if concurrent use with buprenorphine is required. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
Buprenorphine; Naloxone: (Major) Buprenorphine should be avoided in combination with ibutilide. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Ibutilide, a class III antiarrhythmic, has an established risk for QT prolongation and TdP and caution is recommended if concurrent use with buprenorphine is required. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
Cabotegravir; Rilpivirine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Ceritinib: (Major) Avoid coadministration of ceritinib with ibutilide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Chloroquine: (Major) Avoid coadministration of chloroquine with ibutilide due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the use of other drugs that prolong the QT interval.
Chlorpromazine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Because of the potential for TdP, concurrent use is contraindicated.
Citalopram: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Citalopram causes dose-dependent QT interval prolongation. According to the manufacturer, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. If concurrent therapy is considered essential, ECG monitoring is recommended.
Clarithromycin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Class IA Antiarrhythmics: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Clofazimine: (Major) Concomitant use of clofazimine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Crizotinib: (Major) Avoid coadministration of crizotinib with ibutilide due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Ibutilide administration can also cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Dasatinib: (Major) Use caution during concurrent use of dasatinib and ibutilide. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). Cautious dasatinib administration is recommended to patients who have or may develop QT prolongation such as patients taking drugs that lead to QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Degarelix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents like ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
Desflurane: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Halogenated anesthetics can prolong the QT interval and should be used cautiously with ibutilide.
Deutetrabenazine: (Major) Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Quinidine: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Disopyramide: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Dofetilide: (Major) Coadministration of dofetilide and ibutilide is not recommended as concurrent use may increase the risk of QT prolongation. Class III antiarrhythmic agents, such as ibutilide, should be withheld for at least 3 half-lives prior to initiating dofetilide therapy. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Dolasetron: (Major) Use caution during concurrent use of dolasetron and ibutilide. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Dolutegravir; Rilpivirine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include ibutilide.
Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include ibutilide.
Dronedarone: (Contraindicated) Concurrent use of ibutilide and dronedarone is contraindicated. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. The concomitant use of dronedarone with other drugs that prolong the QTc may induce Torsade de Pointes (TdP) and is contraindicated.
Droperidol: (Major) Use caution during concurrent use of droperidol and ibutilide. Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). In December 2001, the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data. According to the revised 2001 labeling for droperidol, any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Efavirenz: (Major) Coadministration of efavirenz and ibutilide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and ibutilide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of efavirenz and ibutilide may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Eliglustat: (Major) Coadministration of ibutilide and eliglustat is not recommended. If coadministration is necessary, use extreme caution and close monitoring. Ibutilide administration is associated with QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration may result in additive effects on the QT interval, further increasing the risk of serious adverse events (e.g., cardiac arrhythmias).
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Encorafenib: (Major) Avoid coadministration of encorafenib and ibutilide due to QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Entrectinib: (Major) Avoid coadministration of entrectinib with ibutilide due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Eribulin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ibutilide include eribulin. If eribulin and and ibutilide are coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Concurrent use of erythromycin with Class III antiarrhythmic agents should be avoided. Erythromycin administration is associated with QT prolongation and torsades de pointes (TdP). In addition to potential pharmacokinetic interactions, erythromycin may cause QT prolongation and exhibit additive electrophysiologic effects with Class III antiarrhythmics. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Escitalopram: (Major) Concomitant use of ibutilide and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Etrasimod: (Major) Concomitant use of etrasimod and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexinidazole: (Major) Concomitant use of fexinidazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Contraindicated) Fingolimod is contraindicated in patients requiring treatment with ibutilide, a Class III antiarrhythmic. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Ibutilide can cause QT prolongation and torsade de pointes (TdP).
Flecainide: (Major) Combined use of antiarrhythmics can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. In general, combination therapy with Class III and Class IC antiarrhythmics has been reported to increase the risk of proarrhythmias. However, combination antiarrhythmic therapy may be beneficial in some patients with refractory arrhythmias; close monitoring is prudent to reduce the risk of adverse effects. A recent study evaluated the use of ibutilide therapy in 71 patients receiving long-term treatment with Class IC agents (n=46 propafenone; n=25 flecainide) for atrial fibrillation or atrial flutter. The majority of patients had normal left ventricular systolic function (91.5%). Conversion of atrial fibrillation was achieved in 23 of 48 patients (47.9%) receiving ibutilide, while conversion of atrial flutter occurred in 17 of 23 patients (73.9%) studied. Ibutilide resulted in a small increase in the QTc interval (from 442 +/- 61 ms to 462 +/- 59 ms). Two patients developed proarrhythmias, non-sustained polymorphous ventricular tachycardia and sustained torsade de pointes (TdP), which were successfully treated. Administration of ibutilide to patients who have received flecainide should be done with cautious monitoring.
Fluconazole: (Major) Use caution during concurrent use of ibutilide and fluconazole. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Fluconazole has also been associated with QT prolongation and rare cases of TdP.
Fluoxetine: (Major) Concomitant use of ibutilide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with ibutilide. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and ibutilide. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Ibutilide can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as ibutilide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostemsavir: (Major) Coadminister ibutilide with fostemsavir with caution due to the potential for additive QT prolongation. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Concurrent use of ibutilide and gemifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Ibutilide can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Gemifloxacin may prolong the QT interval in some patients with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Use gemtuzumab ozogamicin and ibutilide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Gilteritinib: (Major) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and ibutilide is necessary. Gilteritinib has been associated with QT prolongation. Ibutilide can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Glasdegib: (Major) Avoid coadministration of glasdegib with ibutilide due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Goserelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Granisetron: (Major) Drugs with a possible risk for QT prolongation and torsade de pointes (TdP), such as ibutilide, should be used cautiously with granisetron. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Halogenated Anesthetics: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Halogenated anesthetics can prolong the QT interval and should be used cautiously with ibutilide.
Haloperidol: (Major) QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. According to the manufacturer of haloperidol, caution is advisable when prescribing the drug concurrently with medications known to prolong the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Histrelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of ibutilide and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Caution is recommended if hydroxyzine is administered with ibutilide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Iloperidone has been associated with QT prolongation; however, TdP has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with ibutilide due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Isoflurane: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Halogenated anesthetics can prolong the QT interval and should be used cautiously with ibutilide.
Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include ibutilide.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with ibutilide due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and ibutilide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction, such as Class III antiarrhythmics, because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of lapatinib with ibutilide is necessary; correct electrolyte abnormalities prior to treatment. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Ibutilide administration can also cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Lefamulin: (Major) Avoid coadministration of lefamulin with ibutilide as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with ibutilide due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Ibutilide administration can also cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Leuprolide: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of levofloxacin and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and ibutilide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lidocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Lithium: (Major) Ibutilide should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with ibutilide due to the potential for additive QT prolongation and torsade de pointes (TdP). Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of TdP. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Loperamide: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like ibutilide, should be used cautiously and with close monitoring with loperamide.
Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like ibutilide, should be used cautiously and with close monitoring with loperamide.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with ibutilide due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as ibutilide. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated.
Maprotiline: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with ibutilide. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Mefloquine: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with mefloquine. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Methadone: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as methadone. The need to coadminister methadone with ibutilide should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Metronidazole: (Major) Concomitant use of metronidazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) The concomitant use of midostaurin and ibutilide may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin and in patients who received ibutilide.
Mirtazapine: (Major) Concomitant use of ibutilide and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mobocertinib: (Major) Concomitant use of mobocertinib and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Moxifloxacin: (Major) Prolongation of the QT interval has been reported with administration of moxifloxacin. Post-marketing surveillance has identified very rare cases of ventricular arrhythmias including torsade de pointes (TdP), usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. According to the manufacturer, moxifloxacin should be avoided in patients taking drugs that can result in prolongation of the QT interval. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and ibutilide; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Ibutilide administration can cause QT prolongation and torsades de pointes; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Ofloxacin: (Major) Concomitant use of ofloxacin and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Fluoxetine: (Major) Concomitant use of ibutilide and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Samidorphan: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The pote

ntial for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Ondansetron: (Major) Concomitant use of ondansetron and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Monitor ECGs in patients receiving osilodrostat with ibutilide. Osilodrostat is associated with dose-dependent QT prolongation. Ibutilide administration can cause QT prolongation and torsade de pointes; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Osimertinib: (Major) Avoid coadministration of ibutilide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of ibutilide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking ibutilide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Pacritinib: (Major) Concomitant use of pacritinib and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Antiarrhythmic medicines with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include ibutilide.
Pasireotide: (Major) Cautious use of pasireotide and ibutilide is needed, as coadministration may have additive effects on the prolongation of the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as ibutilide, is not advised; pazopanib has been reported to prolong the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. If pazopanib and ibutilide must be continued, closely monitor the patient for QT interval prolongation.
Pentamidine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as pentamidine. Pentamidine has been associated with QT prolongation.
Perphenazine: (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with ibutilide. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Perphenazine; Amitriptyline: (Minor) Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with ibutilide. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as ibutilide. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of ibutilide with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with ibutilide as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking ibutilide due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Posaconazole: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as posaconazole. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP.
Prilocaine; Epinephrine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias.
Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include ibutilide.
Procainamide: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Prochlorperazine: (Minor) Phenothiazines have been reported to prolong the QT interval. Concurrent use of drugs that are associated with a possible risk for QT prolongation and torsade de pointes (TdP), such as ibutilide, with prochlorperazine should be approached with caution. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Promethazine: (Major) Concomitant use of promethazine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of quetiapine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, Class IA antiarrhythmics (e.g., disopyramide, quinidine, and procainamide) and other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, Class IA or other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. Before switching from ibutilide to dofetilide therapy, ibutilide should generally be withheld for at least three half-lives prior to initiating dofetilide.
Quinine: (Major) Concurrent use of quinine and ibutilide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Quizartinib: (Major) Concomitant use of quizartinib and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, such as ibutilide, coadministration may result in additive QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Relugolix: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents such as ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Ribociclib: (Major) Avoid coadministration of ribociclib with ibutilide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with ibutilide due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Rilpivirine: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation; caution is advised when administering rilpivirine with other drugs that may prolong the QT or PR interval.
Risperidone: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval, such as risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with TdP. Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically.
Romidepsin: (Major) Romidepsin has been reported to prolong the QT interval. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. If romidepsin and ibutilide must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
Saquinavir: (Major) The concurrent use of saquinavir boosted with ritonavir and ibutilide should be avoided if possible due to the risk of life threatening cardiac arrhythmias such as torsades de pointes (TdP). If no alternative therapy is acceptable, perform a baseline ECG prior to initiation of concomitant therapy and follow recommended ECG monitoring.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with ibutilide is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Sertraline: (Major) Concomitant use of sertraline and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Halogenated anesthetics can prolong the QT interval and should be used cautiously with ibutilide.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving ibutilide due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Ibutilide administration can cause QT prolongation and torsade de pointes; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Ibutilide should be used cautiously and with close monitoring with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation.
Sorafenib: (Major) Avoid coadministration of sorafenib with ibutilide due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Sorafenib is also associated with QTc prolongation.
Sotalol: (Contraindicated) Combined use of antiarrhythmic drugs can have additive, antagonistic, or synergistic electrophysiologic, pharmacodynamic, or toxic effects. Because of their potential to prolong refractoriness, other Class III antiarrhythmics (e.g., amiodarone, dofetilide and sotalol) are not recommended for use concurrently or within 4 hours after an infusion of ibutilide. In general, combination therapy with Class III antiarrhythmics has been reported to increase the risk of proarrhythmias. The manufacturer reported that during clinical trials, other Class III antiarrhythmics were not given for at least 5 half-lives prior to ibutilide infusion or 4 hours after ibutilide dosing. If sotalol is to be initiated in a patient previously receiving ibutilide, ibutilide should be withdrawn under careful monitoring for a minimum of (2-3) plasma half-lives.
Sunitinib: (Major) Monitor patients for QT prolongation if coadministration of ibutilide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Tacrolimus: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Tacrolimus causes QT prolongation and should be used cautiously with ibutilide.
Tamoxifen: (Major) Concomitant use of tamoxifen and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Telavancin has been associated with QT prolongation. Use caution and close monitoring during concurrent administration.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc, such as ibutilide. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Thioridazine: (Contraindicated) Coadministration of thioridazine and ibutilide is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with ibutilide. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Toremifene: (Major) Avoid coadministration of ibutilide with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Toremifene has also been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trazodone: (Major) Concomitant use of trazodone and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation and should be used cautiously with ibutilide. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Triptorelin: (Major) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving ibutilide. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Androgen deprivation therapy may also prolong the QT/QTc interval.
Vandetanib: (Major) Avoid coadministration of vandetanib with ibutilide due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Ibutilide administration can also cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Vardenafil: (Major) Concomitant use of vardenafil and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of vemurafenib. If vemurafenib and ibutilide must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Venlafaxine: (Major) Concomitant use of venlafaxine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Voclosporin: (Major) Use caution if ibutilide is coadministered with voclosporin due to the risk of additive QT prolongation. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Ibutilide administration can cause QT prolongation and torsade de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with ibutilide. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated.
Vorinostat: (Major) Vorinostat therapy is associated with a risk of QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Use caution and close monitoring during concurrent administration.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and class III antiarrhythmics, such as ibutilide, is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Class III antiarrhythmics are associated with a well-established risk of QT prolongation and TdP.

Corvert/Ibutilide Fumarate Intravenous Inj Sol: 0.1mg, 1mL

Adults

2 mg IV (infused over at least 20 minutes).

Elderly

2 mg IV (infused over at least 20 minutes).

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Unlike other commercially available class III antiarrhythmic agents that block outward potassium currents, ibutilide exerts its actions by promoting the influx of sodium through slow inward sodium channels. As a result of its actions, ibutilide prolongs the action potential duration, thereby causing a mild slowing of the sinus rate and AV conduction. These effects are in contrast to class I antiarrhythmic agents, which inhibit the influx of sodium. Clinically, ibutilide converts atrial fibrillation or flutter to normal sinus rhythm without altering blood pressure, heart rate, QRS duration, or PR interval.

Ibutilide is administered by intravenous infusion.  The pharmacokinetics of ibutilide show considerable intersubject variability. Systemic clearance is approximately equal to liver blood flow (29 mL/minute/kg), and protein binding is about 40%. Metabolism occurs in the liver by omega-oxidation with sequential beta-oxidation to eight metabolites. According to animal models, only one metabolite possesses class III antiarrhythmic effects that are similar to those of ibutilide, however, the plasma concentration of this metabolite is less than 10% of that of ibutilide. Excretion of ibutilide and its metabolites occurs via the urine and feces. Approximately 82% of a 0.01 mg/kg dose may be excreted in the urine, with 7% as unchanged drug. About 19% may be excreted in the feces. The elimination half-life of ibutilide is about 6 hours, with a range of 2—12 hours.

Intravenous Route

Following intravenous infusion, ibutilide is rapidly cleared from the plasma.

Pregnancy

Ibutilide is classified as FDA pregnancy risk category C. Animal studies using oral ibutilide revealed evidence of embryocidal and teratogenic effects, but these effects have not been studied in humans. Ibutilide should not be administered during pregnancy unless the benefits to the mother outweigh the risks to the fetus.

According to the manufacturer, the extent of excretion of ibutilide into breast milk is unknown, and breast-feeding should be discouraged during ibutilide therapy. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.