US 12,343,320 B2
Intraveneous dofetilide to reduce the risk of developing AF/AFL post coronary bypass surgery
John Somberg, Lake Forest, IL (US)
Assigned to Hyloris Developments SA, Liege (BE)
Filed by Hyloris Developments SA, Liège (BE)
Filed on Jan. 31, 2023, as Appl. No. 18/162,092.
Prior Publication US 2024/0252455 A1, Aug. 1, 2024
Int. Cl. A61K 31/18 (2006.01); A61K 9/00 (2006.01); A61P 9/06 (2006.01)
CPC A61K 31/18 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0053 (2013.01); A61P 9/06 (2018.01)] 23 Claims
 
1. A method of reducing the risk of developing atrial fibrillation (AF) and/or atrial flutter (AFL) in a patient who has undergone coronary bypass surgery (CABS), and who has a creatinine clearance (CrCl) of 60 mL/min or higher, 40-<60 mL/min or 20-<40 mL/min, comprising:
a measuring the QTc of the patient who has undergone CABS to establish a baseline QTc and then measuring the QTc about every 15-30 minutes thereafter;
b intravenously administering a loading dose of dofetilide to the patient who has undergone CABS, wherein:
(A) the loading dose is about 450-500 μg of dofetilide; and,
(B) the loading dose is administered over about 30-60 minutes;
c about 0-4 h after completion of the IV loading dose, intravenously administering a maintenance dose of dofetilide over about 12 h, the maintenance dose given being based on the creatinine clearance (CrCl) of the CABS patient as given in the following table;
 
CrCl IV Maintenance Dose Oral Dose
 
60 mL/min or higher 450-500 μg 500 μg
40-<60 mL/min 225-250 μg 250 μg
20-<40 mL/min 100-125 μg 125 μg
 
d when the patient's medical staff determines the patient can take dofetilide orally, stopping the IV maintenance dose and QTc measuring; and,
e about 2-6 h after stopping the IV maintenance dose, orally administering dofetilide every 12 h, the oral dose given being based on the CrCl of the patient who has undergone CABS as given in the above table;
provided that if the patient's QTc increases by 15% over the baseline QTc or if the QTc 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;
thereby reducing the risk of developing AF and/or AFL in the CABS patient 3-5 days post-operative.