onomorphic ventricular tachycardia (4.9%), AV block (1.5%), bundle branch block (1.9%), ventricular extrasystoles (5.1%), supraventricular extrasystoles (0.9%), hypotension/postural hypotension (2.0%), bradycardia/sinus bradycardia (1.2%), nodal arrhythmia (0.7%), congestive heart failure (0.5%), tachycardia/sinus tachycardia/supraventricular tachycardia (2.7%), idioventricular rhythm (0.2%), syncope (0.3%), and renal failure (0.3%). The incidence of these events, except for syncope, was greater in the group treated with ibutilide fumarate injection than in the placebo group.
Another adverse reaction that may be associated with the administration of ibutilide fumarate injection 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
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 ibutilide fumarate 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
