INTRAVENEOUS DOFETILIDE TO TERMINATE ARRHYTHMIC STORM FOLLOWING IMPLANTATION OF A CARDIAC DEFIBRILATOR
The invention involves a novel method of terminating arrhythmic storm in patients following implementation of an implantable defibrillator by administrating loading and maintenance infusions of dofetilide intravenously followed by oral dosing.
1 . A method of terminating arrhythmic storm in a patient after implementation of an implantable defibrillator, comprising:
a intravenously administering a loading dose of dofetilide to the patient who presents with arrhythmic storm after implementation of an implantable defibrillator, wherein:
(A) the loading dose is about 450-500 μg of dofetilide; and,
(B) the loading dose is administered over about 30-60 minutes;
b about 0-4 h after completion of the IV loading dose, intravenously administering a maintenance infusion of dofetilide over about 12 h, the maintenance infusion given being based on the creatinine clearance (CrCl) of the patient as given in the following table;
IV Maintenance Infusion
Oral Dose
CrCl
(over 12 h)
(every 12 h)
≥60
mL/min
450-500 μg
500 μg
40-<60
mL/min
225-250 μg
250 μg
20-<40
mL/min
100-125 μg
125 μg
<20
mL/min
Dofetilide not indicated
Dofetilide not indicated
c once the patient has recovered from the termination of the arrhythmic storm to take dofetilide orally, stopping the IV maintenance infusion; and,
d about 2-6 h after stopping the IV maintenance infusion, orally administering dofetilide every 12 h, the oral dose given being based on the CrCl of the patient as given in the above table;
provided that if the patient's QT c increases by 15% over the baseline QT c or if the QT c is measured at >500 msec or >550 msec if the patient has a ventricular conduction abnormality, the oral dose is reduced to 250 μg from 500 μg, 125 μg from 250 μg, or discontinued if originally 125 μg.
2 . The method of claim 1 , further comprising:
measuring the QT c of the patient prior to the IV loading dose of dofetilide to establish a baseline QT c and then measuring the QT c about every 15-30 minutes thereafter for 60 min and prior to the IV maintenance infusion and before each oral dose.
3 . The method of claim 1 , wherein the loading dose is about 450 μg.
4 . The method of claim 1 , wherein the loading dose is about 460 μg.
5 . The method of claim 1 , wherein the loading dose is about 470 μg.
6 . The method of claim 1 , wherein the loading dose is about 480 μg.
7 . The method of claim 1 , wherein the loading dose is about 490 μg.
8 . The method of claim 1 , wherein the loading dose is about 500 μg.
9 . The method of claim 1 , wherein the loading dose is administered over about 30 minutes.
10 . The method of claim 1 , wherein the loading dose is administered over about 40 minutes.
11 . The method of claim 1 , wherein the loading dose is administered over about 50 minutes.
12 . The method of claim 1 , wherein the loading dose is administered over about 60 minutes.
13 . The method of claim 1 , wherein the maintenance infusion is started about 0 h after completion of the loading dose.
14 . The method of claim 1 , wherein the maintenance infusion is started about 1 h after completion of the loading dose.
15 . The method of claim 1 , wherein the maintenance infusion is started about 2 h after completion of the loading dose.
16 . The method of claim 1 , wherein the maintenance infusion is started about 3 h after completion of the loading dose.
17 . The method of claim 1 , wherein the maintenance infusion is started about 4 h after completion of the loading dose.
18 . The method of claim 1 , wherein the patient has a CrCl of ≥60 m/min, the IV maintenance infusion is about 450-500 μg given over about 12 h and the oral doses are 500 μg.
19 . The method of claim 18 , wherein the oral doses are reduced to 250 μg due to a QT c that increased by 15% over baseline QT c or if the QT c is measured at >500 msec or >550 msec if the patient has a ventricular conduction abnormality.
20 . The method of claim 1 , wherein the patient has a CrCl of 40-<60 m/min, the IV maintenance infusion is about 225-250 μg given over about 12 h and the oral doses are 250 μg.
21 . The method of claim 20 , wherein the oral doses are reduced to 125 μg due to a QT, that increased by 15% over baseline QT c or if the QT c is measured at >500 msec or >550 msec if the patient has a ventricular conduction abnormality.
22 . The method of claim 1 , wherein the patient has a CrCl of 20-<40 m/min, the IV maintenance infusion is about 100-125 μg given over about 12 h and the oral doses are 125 μg.
23 . The method of claim 22 , wherein the oral doses are discontinued due to a QT c that increased by 15% over baseline QT c or if the QT c is measured at >500 msec is observed or >550 msec if the patient has a ventricular conduction abnormality.