Corvert Drug Information

CORVERT Injection is indicated for the rapid conversion of atrial fibrillation or atrial flutter of recent onset to sinus rhythm. Patients with atrial arrhythmias of longer duration are less likely to respond to CORVERT. The effectiveness of ibutilide has not been determined in patients with arrhythmias of more than 90 days in duration.

The recommended dose based on controlled trials (see CLINICAL STUDIES ) is outlined in the Table below. Ibutilide infusion should be stopped as soon as the presenting arrhythmia is terminated or in the event of sustained or nonsustained ventricular tachycardia, or marked prolongation of QT or QTc. Recommended Dose of CORVERT Injection In a trial comparing ibutilide and sotalol (see CLINICAL STUDIES ), 2 mg ibutilide fumarate administered as a single infusion to patients weighing more than 60 kg was also effective in terminating atrial fibrillation or atrial flutter.

In the post-cardiac surgery study (see CLINICAL STUDIES ), one or two intravenous infusions of 0.5 mg (0.005 mg/kg per dose for patients weighing less than 60 kg) was effective in terminating atrial fibrillation or atrial flutter. Patients should be observed with continuous ECG monitoring for at least 4 hours following infusion or until QTc has returned to baseline. Longer monitoring is required if any arrhythmic activity is noted.

Skilled personnel and proper equipment (see WARNINGS, Proarrhythmia ), such as a cardioverter/defibrillator, and medication for treatment of sustained ventricular tachycardia, including polymorphic ventricular tachycardia, must be available during administration of CORVERT and subsequent monitoring of the patient. Dilution: CORVERT Injection may be administered undiluted or diluted in 50 mL of diluent. CORVERT may be added to 0.9% Sodium Chloride Injection or 5% Dextrose Injection before infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Strict adherence to the use of aseptic technique during the preparation of the admixture is recommended in order to maintain sterility.

CORVERT Injection was generally well tolerated in clinical trials. The incidence of these events, except for syncope, was greater in the group treated with CORVERT than in the placebo group. Another adverse reaction that may be associated with the administration of CORVERT was nausea, which occurred with a frequency greater than 1% more in ibutilide-treated patients than those treated with placebo.

The medical events reported for more than 1% of the placebo- and ibutilide-treated patients are shown in the following Table. Treatment-Emergent Medical Events With Frequency of More Than 1% and Higher Than That of Placebo In the post-cardiac surgery study (see CLINICAL STUDIES ), similar types of medical events were reported.

• Drug Interactions: No specific pharmacokinetic or other formal drug interaction studies were conducted.
• Digoxin: Supraventricular arrhythmias may mask the cardiotoxicity associated with excessive digoxin levels. Therefore, it is advisable to be particularly cautious in patients whose plasma digoxin levels are above or suspected to be above the usual therapeutic range. Coadministration of digoxin did not have effects on either the safety or efficacy of ibutilide in the clinical trials.
• Calcium channel blocking agents: Coadministration of calcium channel blockers did not have any effect on either the safety or efficacy of ibutilide in the clinical trials.

Pregnancy: Ibutilide administered orally was teratogenic (abnormalities included adactyly, interventricular septal defects, and scoliosis) and embryocidal in reproduction studies in rats. On a mg/m 2 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/m 2 basis, or 16 times the MRHD on a mg/kg basis. CORVERT should not be administered to a pregnant woman unless clinical benefit outweighs potential risk to the fetus.

Pediatric Use: Clinical trials with CORVERT 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.

CORVERT Injection is contraindicated in patients who have previously demonstrated hypersensitivity to ibutilide fumarate or any of the other product components.

• Acute Experience in Animals: Acute overdose in animals results in CNS toxicity; notably, CNS depression, rapid gasping breathing, and convulsions. The intravenous median lethal dose in the rat was more than 50 mg/kg which is, on a mg/m 2 basis, at least 250 times the maximum recommended human dose.
• Human Experience: In the registration trials with CORVERT Injection, four patients were unintentionally overdosed. The largest dose was 3.4 mg administered over 15 minutes. One patient (0.025 mg/kg) developed increased ventricular ectopy and monomorphic ventricular tachycardia, another patient (0.032 mg/kg) developed AV block—3rd degree and nonsustained polymorphic VT, and two patients (0.038 and 0.020 mg/kg) had no medical event reports. Based on known pharmacology, the clinical effects of an overdosage with ibutilide could exaggerate the expected prolongation of repolarization seen at usual clinical doses. Medical events (eg, proarrhythmia, AV block) that occur after the overdosage should be treated with measures appropriate for that condition.