Intravenous dofetilide to convert atrial fibrillation/flutter
The invention involves a novel method of converting atrial fibrillation (AF) or atrial flutter (AFL) in a patient presenting with highly symptomatic AF or AFL by administering at least a loading dose of dofetilide intravenously, or if that fails cardioversion and a maintenance infusion followed by a switch to chronic oral dosing.
1 . A method of converting atrial fibrillation (AF) or atrial flutter (AFL) in a patient who presents with highly symptomatic AF or AFL, comprising:
a subjecting a patient to electrical cardioversion, wherein the patient has a Creatinine Clearance (CrCl) of ≥20 mL/min and has not converted to sinus rhythm following a chemical cardioversion, wherein the chemical cardioversion, comprised:
intravenously administering a loading dose of dofetilide to the patient who presents with highly symptomatic AF or AFL, wherein:
(A) the loading dose is about 450-500 ug of dofetilide; and,
(B) the loading dose is administered over about 30-60 minutes;
b from 0 to about 1 h after conversion with electrical cardioversion, intravenously administering a maintenance dose of dofetilide for about 12 h, the maintenance dose is given being on the CrCl of the patient using the table below:
CrCl
IV Maintenance Dose
Oral Dose
≥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
c once the patient has recovered from the electrical cardioversion and able to take dofetilide orally, stopping the IV maintenance dose; and,
d about 2-6 h after stopping the IV maintenance dose, orally administering dofetilide every 12 h at the oral dose based on the CrCl of the patient in the above table;
provided that when:
(i) the patient's QTc increases by 15% over the baseline QTc; or,
(ii) the QTc is measured at >500 msec and the patient does not have a ventricular conduction abnormality; or,
(iii) the QTc is measured at >550 msec and the patient has a ventricular conduction abnormality:
the oral dose is reduced to 250 μg from 500 ug, 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 dose is started 0 h after conversion with electrical cardioversion.
14 . The method of claim 1 , wherein the maintenance dose is started about 1 h after conversion with electrical cardioversion.
15 . The method of claim 1 , wherein the patient has a CrCl of ≥60 mL/min.
16 . The method of claim 15 , wherein the oral doses are reduced to 250 μg because:
(i) the patient's QTc increases by 15% over the baseline QTc; or,
(ii) the QTc is measured at >500 msec and the patient does not have a ventricular conduction abnormality; or,
(iii) the QTc is measured at >550 msec and the patient has a ventricular conduction abnormality.
17 . The method of claim 1 , wherein the patient has a CrCl of 40-<60 mL/min.
18 . The method of claim 17 , wherein the oral doses are reduced to 125 μg because:
(i) the patient's QTc increases by 15% over the baseline QTc; or,
(ii) the QTc is measured at >500 msec and the patient does not have a ventricular conduction abnormality; or,
(iii) the QTc is measured at >550 msec and the patient has a ventricular conduction abnormality.
19 . The method of claim 1 , wherein the patient has a CrCl of 20-<40 mL/min.
20 . The method of claim 19 , wherein the oral doses are discontinued because:
(i) the patient's QTc increases by 15% over the baseline QTc; or,
(ii) the QTc is measured at >500 msec and the patient does not have a ventricular conduction abnormality; or,
(iii) the QTc is measured at >550 msec and the patient has a ventricular conduction abnormality.