General Antiarrhythmics: Class Ia antiarrhythmic drugs (Vaughan Williams Classification), such as disopyramide, quinidine, and procainamide, and other class III drugs, such as amiodarone and sotalol, should not be given concomitantly with CORVERT (ibutilide fumarate injection) Injection or within 4 hours postinfusion because of their potential to prolong refractoriness. In the clinical trials, class I or other class III antiarrhythmic agents were withheld for at least 5 half-lives prior to ibutilide infusion and for 4 hours after dosing, but thereafter were allowed at the physician's discretion. Other drugs that prolong the QT interval: The potential for proarrhythmia may increase with the administration of CORVERT (ibutilide fumarate injection) Injection to patients who are being treated with drugs that prolong the QT interval, such as phenothiazines, tricyclic antidepressants, tetracyclic antidepressants, and certain antihistamine drugs (H1 receptor antagonists). Heart block: Of the nine (1.5%) ibutilide-treated patients with reports of reversible heart block, five had first degree, three had second degree, and one had complete heart block. Laboratory Test Interactions None known. Carcinogenesis, Mutagenesis, Impairment of Fertility No animal studies have been conducted to determine the carcinogenic potential of CORVERT (ibutilide fumarate injection) ; however, it was not genotoxic in a battery of assays, (Ames assay, mammalian cell forward gene mutation assay, unscheduled DNA synthesis assay, and mouse micronucleus assay). Similarly, no drug-related effects on fertility or mating were noted in a reproductive study in rats in which ibutilide was administered orally to both sexes up to doses of 20 mg/kg/day. On a mg/m2 basis, corrected for 3% bioavailability, the highest dose tested was approximately four times the maximum recommended human dose (MRHD). Pregnancy Pregnancy Category C. Ibutilide administered orally was teratogenic (abnormalities included adactyly, interventricular septal defects, and scoliosis) and embryocidal in reproduction studies in rats. On a mg/m2 basis, corrected for the 3% oral bioavailability, the "no adverse effect dose" (5 mg/kg/day given orally) was approximately the same as the maximum recommended human dose (MRHD); the teratogenic dose (20 mg/kg/day given orally) was about four times the MRHD on a mg/m2 basis, or 16 times the MRHD on a mg/kg basis. CORVERT (ibutilide fumarate injection) should not be administered to a pregnant woman unless clinical benefit outweighs potential risk to the fetus. Nursing Mothers The excretion of ibutilide into breast milk has not been studied; accordingly, breastfeeding should be discouraged during therapy with CORVERT (ibutilide fumarate injection) . Pediatric Use Clinical trials with CORVERT (ibutilide fumarate injection) in patients with atrial fibrillation and atrial flutter did not include anyone under the age of 18. Safety and effectiveness of ibutilide in pediatric patients has not been established. Geriatric Use Clinical studies of ibutilide fumarate (involving 586 patients) did not include sufficient numbers of subjects less than age 65 (45%) to determine whether they respond differently from older subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Use in Patients With Hepatic or Renal Dysfunction The safety, effectiveness, and pharmacokinetics of CORVERT (ibutilide fumarate injection) have not been established in patients with hepatic or renal dysfunction. However, it is unlikely that dosing adjustments would be necessary in patients with compromised renal or hepatic function based on the following considerations: (1) CORVERT (ibutilide fumarate injection) is indicated for rapid intravenous therapy (duration ≤ 30 minutes) and is dosed to a known, well-defined pharmacologic action (termination of arrhythmia) or to a maximum of two 10-minute infusions; (2) less than 10% of the dose of CORVERT (ibutilide fumarate injection) is excreted unchanged in the urine; and (3) drug distribution appears to be one of the primary mechanisms responsible for termination of the pharmacologic effect. Nonetheless, patients with abnormal liver function should be monitored by telemetry for more than the 4-hour period generally recommended. In 285 patients with atrial fibrillation or atrial flutter who were treated with CORVERT (ibutilide fumarate injection) , the clearance of ibutilide was independent of renal function, as assessed by creatinine clearance (range 21 to 140 mL/min). Last reviewed on RxList: 6/25/2008
This monograph has been modified to include the generic and brand name in many instances.