Methods for reducing the risk of an adverse dronedarone/beta-blockers interaction in a patient suffering from atrial fibrillation

• US 8,602,215 B2
• Filed: 06/30/2011
• Issued: 12/10/2013
• Est. Priority Date: 06/30/2010
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Radzik, Davide
• Primary Examiner(s): RAO, SAVITHA M
• Application Number:
  US13/172,984
• Publication Number:
  US 20120000806A1
• Time in Patent Office: 894 Days
• Field of Search: 206/459.5, 514/469
• US Class Current: 206/459.5
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system

Abstract

The disclosure relates to a method for managing the risk of dronedarone/beta-blockers interaction by using dronedarone or pharmaceutically acceptable salts thereof in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted to reduce the risk of cardiovascular hospitalization, said patients also expecting to receive a beta-blockers treatment, by performing the following steps:

• • a—initiate beta-blockers treatment at a low dose;
  • b—performing a electrocardiogram (ECG) verification of good tolerability;
  • c—increase of beta-blockers dose only if results in step b) are satisfying.

Claims

1. A method for managing the risk of dronedarone/beta-blocker interaction in a patient with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who is in sinus rhythm or who will be cardioverted to reduce the risk of cardiovascular hospitalization, said patient also expecting to receive a beta-blocker treatment, comprising administering dronedarone or a pharmaceutically acceptable salt thereof to said patient, and then performing the following steps:

a—

initiating beta-blocker treatment in said patient at a low dose;

b—

and then performing a electrocardiogram (ECG) assessment in said patient; and

c—

then increasing beta-blocker dose to said patient only if results in step b) verify good tolerability.

2. The method according to claim 1, wherein dronedarone is administered 400 mg twice daily with meals.

3. The method according to claim 1, wherein the pharmaceutically acceptable salt of dronedarone is hydrochloride.

4. The method according to claim 1, wherein in step b), the beta-blocker dose may be increased up to a fraction of the recommended dose higher than the low dose.

5. The method according to claim 1, wherein the beta-blocker is metoprolol.

6. The method according to claim 5, wherein the low dose of metoprolol is less than 200 mg.

7. The method according to claim 5, wherein the low dose of metoprolol is 100 mg.

8. The method according to claim 1, wherein the beta-blocker is propranolol.

9. The method according to claim 8, wherein the low dose of propranolol is less than 160 mg.

10. The method according to claim 8, wherein the low dose of propranolol is 40 mg.

11. The method according to claim 1, wherein good tolerability is indicated by a heart rate higher than 50 bpm.

12. The method according to claim 1, wherein good tolerability is indicated by a PR-interval shorter than 200 ms.

13. The method according to claim 1, wherein the patient has at least one associated cardiovascular risk factor selected from the group consisting of:

i. an age greater than 70;

ii. hypertension;

iii. diabetes;

iv. a prior cerebrovascular accident,

v. a left atrial diameter greater than or equal to 50 mm; and

vi. a left ventricular ejection fraction less than 40%.

14. The method according to claim 13, wherein the patient has hypertension.

15. The method according to claim 13, wherein the patient has diabetes.

16. The method according to claim 1, wherein the patient had an episode of atrial fibrillation or atrial flutter with the last 6 months.