Granted Patent B2

US 12,343,320 · App. 18/162,092 · Granted Jul 1, 2025

Inventor: John Somberg (Lake Forest, IL)

Assignee: Hyloris Developments SA

A61K31/18A61K9/0019A61K9/0053A61P9/06

Abstract

Claims (53)

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 QT c of the patient who has undergone CABS to establish a baseline QT c and then measuring the QT c 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.

2. The method of claim 1 , wherein the loading dose is about 450 μg.

3. The method of claim 1 , wherein the loading dose is about 460 μg.

4. The method of claim 1 , wherein the loading dose is about 470 μg.

5. The method of claim 1 , wherein the loading dose is about 480 μg.

6. The method of claim 1 , wherein the loading dose is about 490 μg.

7. The method of claim 1 , wherein the loading dose is about 500 μg.

8. The method of claim 1 , wherein the loading dose is administered over about 30 minutes.

9. The method of claim 1 , wherein the loading dose is administered over about 40 minutes.

10. The method of claim 1 , wherein the loading dose is administered over about 50 minutes.

11. The method of claim 1 , wherein the loading dose is administered over about 60 minutes.

12. The method of claim 1 , wherein the maintenance dose is started about 0 h after completion of the loading dose.

13. The method of claim 1 , wherein the maintenance dose is started about 1 h after completion of the loading dose.

14. The method of claim 1 , wherein the maintenance dose is started about 2 h after completion of the loading dose.

15. The method of claim 1 , wherein the maintenance dose is started about 3 h after completion of the loading dose.

16. The method of claim 1 , wherein the maintenance dose is started about 4 h after completion of the loading dose.

17. The method of claim 1 , wherein the patient has a CrCl of ≥60 mL/min, the IV maintenance dose is about 450-500 μg given over about 12 h and the oral doses are 500 μg.

18. The method of claim 17 , 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 QTc is measured at >500 msec or >550 msec if the patient has a ventricular conduction abnormality.

19. The method of claim 1 , wherein the patient has a CrCl of 40-<60 mL/min, the IV maintenance dose is about 225-250 μg given over about 12 h and the oral doses are 250 μg.

20. The method of claim 19 , wherein the oral doses are reduced to 125 μg due to a QT c that increased by 15% over baseline QT c or if the QTc is measured at >500 msec or >550 msec if the patient has a ventricular conduction abnormality.

21. The method of claim 1 , wherein the patient has a CrCl of 20-<40 mL/min, the IV maintenance dose is about 100-125 μg given over about 12 h and the oral doses are 125 μg.

22. The method of claim 21 , wherein the oral doses are discontinued due to a QT c that increased by 15% over baseline QT c or if the QTc is measured at >500 msec is observed or >550 msec if the patient has a ventricular conduction abnormality.

23. 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 20-<40 mL/min, comprising:

a measuring the QT c of the patient who has undergone CABS to establish a baseline QT c and then measuring the QT c 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 100-125 μg maintenance dose of dofetilide over about 12 h, this maintenance dose being based on the CrCl of the CABS patient;

f stopping the IV maintenance dose and QTc measuring when the patient's medical staff determines the patient can take dofetilide orally; and,

d about 2-6 h after stopping the IV maintenance dose, orally administering 125 μg of dofetilide every 24 h;

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 discontinued;

thereby reducing the risk of developing AF and/or AFL in the CABS patient 3-5 days post-operative.

Assignments (1)

Continuity (1)

References Cited (10)