han 1% and Higher Than That of Placebo
Event Placebo
N=127 All Ibutilide
N=586
Patients Patients
n % n %
CARDIOVASCULAR
Ventricular extrasystoles 1 0.8 30 5.1
Nonsustained monomorphic VT 1 0.8 29 4.9
Nonsustained polymorphic VT — — 16 2.7
Hypotension 2 1.6 12 2.0
Bundle branch block — — 11 1.9
Sustained polymorphic VT — — 10 1.7
AV block 1 0.8 9 1.5
Hypertension — — 7 1.2
QT segment prolonged — — 7 1.2
Bradycardia 1 0.8 7 1.2
Palpitation 1 0.8 6 1.0
Tachycardia 1 0.8 16 2.7
GASTROINTESTINAL
Nausea 1 0.8 11 1.9
CENTRAL NERVOUS SYSTEM
Headache 4 3.1 21 3.6
In the post-cardiac surgery study (see CLINICAL STUDIES), similar types of medical events were reported. In the 1 mg ibutilide fumarate treatment group (N=70), 2 patients (2.9%) developed sustained polymorphic ventricular tachycardia and 2 other patients (2.9%) developed nonsustained polymorphic ventricular tachycardia. Polymorphic ventricular tachycardia was not reported in the 73 patients in the 0.5 mg dose group or in the 75 patients in the 0.25 mg dose group.
OVERDOSAGE
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/m2 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.
DOSAGE AND ADMINISTRATION
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
Patient Weight Initial Infusion (over 10 minutes) Second Infusion
60 kg (132 lb)
or more One vial
(1 mg ibutilide fumarate) If the arrhythmia does not terminate within 10 minutes after the end of the initial infusion, a second 10-minute infusion of equal strength may be administ |
