USE OF DRONEDARONE FOR THE TREATMENT OF PATIENTS WITH ARRHYTHMIA AND HAVING AN INCREASE OF CREATININE LEVEL DUE TO DRONEDARONE ADMINISTRATION

• US 20100016423A1
• Filed: 04/29/2009
• Published: 01/21/2010
• Est. Priority Date: 04/28/2008
• Status: Abandoned Application

• Current Assignee: Sanofi
• Original Assignee: Sanofi-Aventis (Sanofi-Synthélabo SA)
• Inventors: CLAUDEL, Sophie, HAMDANI, Nacera, GAUDIN, Christophe
• Application Number:
  US12/431,830
• Publication Number:
  US 20100016423A1
• Time in Patent Office: Days
• US Class Current: 514/469
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/06 Antiarrhythmics

Abstract

Methods of using dronedarone or a pharmaceutically acceptable salt thereof for the treatment of patients with arrhythmia, said patients having an increase of creatinine level due to dronedarone administration, said creatinine level increasing following dronedarone treatment initiation, said creatinine level increase reaching a plateau and being used as a new baseline, said creatinine level increase being reversible after dronedarone discontinuation.

Claims

1. A method of treating arrhythmia in a patient comprising administering to said patient dronedarone or a pharmaceutically acceptable salt thereof, wherein said patient has an increase of creatinine level due to dronedarone administration, said creatinine level increasing following dronedarone treatment initiation, said creatinine level increase reaching a plateau and being used as a new baseline, said creatinine level increase being reversible after dronedarone discontinuation.

10. The method according to any one of claims 1 to 9, wherein said patient is being treated for atrial fibrillation or atrial flutter.

2. A method of treating arrhythmia in a patient comprising:

i) initiating treatment of dronedarone, or a pharmaceutically acceptable salt thereof, to said patient,

ii) measuring serum creatinine level increases following dronedarone treatment initiation, which provides a reference level, said serum creatinine level reaching a plateau,

iii) discontinuing temporarily dronedarone, or the pharmaceutically acceptable salt thereof, and

iv) measuring that the increase is reversible after discontinuation of dronedarone or the pharmaceutically acceptable salt thereof.

3. A method of treating arrhythmia in a patient comprising administering to said patient dronedarone or a pharmaceutically acceptable salt thereof, wherein, after said administration, said patient has an increase of creatinine level not due to administration of a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics administration, which method comprises steps i) to iv) as defined in claim 2.

4. A method of managing the risk of an increase in the mortality rate in a patient treated by an association of dronedarone or a pharmaceutically acceptable salt thereof, and of at least a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics which method comprises the steps i) to iv) as defined in claim 2.

5. A method of treating arrhythmia comprising administering dronedarone or a pharmaceutically acceptable salt thereof in combination with at least a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics, and further comprising the following steps:

a) initially measuring serum creatinine levels, which provides a reference level,

b) monitoring serum creatinine levels at regular intervals during treatment of the patient by dronedarone or the pharmaceutically acceptable salt thereof, and by the compound B,

c) if the serum creatinine levels increases above the reference level, determining if the increase is due to dronedarone or the pharmaceutically acceptable salt thereof, to compound B or to another cause,

d) if the increase in the serum creatinine level above the reference level is due to dronedarone or the pharmaceutically acceptable salt thereof, then the treatment with dronedarone or the pharmaceutically acceptable salt thereof and compound B can be pursued;

if the increase in the serum creatinine level above the reference level is due to compound B, then the treatment with compound B may be interrupted;

if the increase in the serum creatinine level above the reference level is due to another cause than administration of dronedarone or the pharmaceutically acceptable salt thereof or of compound B, then appropriate treatment of such another cause shall be undertaken,

e) repeating steps b), c) and d) for the duration of the treatment with dronedarone or the pharmaceutically acceptable salt thereof and compound B.

6. The method according to claim 5 wherein said patient has an increase of creatinine level due to administration of dronedarone or the pharmaceutically acceptable salt thereof, said patient being defined with the following steps:

a) initially measuring serum creatinine levels, which provides a reference level,

b) monitoring serum creatinine levels at regular intervals during treatment of the patient by dronedarone or the pharmaceutically acceptable salt thereof and by the compound B,

c₁) if the serum creatinine levels increases above the reference level, temporarily interrupting treatment with dronedarone or the pharmaceutically acceptable salt thereof, while maintaining treatment with compound B,

d₁) when the increase is reversible, treatment with said combination is pursued,

e₁) repeating steps b), c₁) and d₁) for the duration of the treatment with said combination.

7. The method according to claim 5 wherein said patient has an increase of creatinine level due to compound B administration, said patient being defined with the following steps:

a) initially measuring serum creatinine levels, which provides a reference level,

b) monitoring serum creatinine levels at regular intervals during treatment of the patient by dronedarone or the pharmaceutically acceptable salt thereof and by the compound B,

c₁) if the serum creatinine levels increases above the reference level, temporarily interrupting treatment with dronedarone or the pharmaceutically acceptable salt thereof, while maintaining treatment with compound B,

d₂) when the increase is not reversible, treatment with compound B may be interrupted,

e₂) repeating steps b), c₁) and d₂) for the duration of the treatment with said combination.

11. The method according to any one of claims 5 to 9, wherein the serum creatinine level in step a) is measured within 3 to 15 days after initiation of treatment with dronedarone or a pharmaceutically acceptable salt thereof.

12. The method according to any one of claims 5 to 9, wherein the serum creatinine level in step a) is measured within one week after initiation of treatment with dronedarone.

13. The method according to any one of claims 5 to 9, wherein the monitoring of the serum creatinine level is effected according to the prescription labelling for the compound B.

14. The method according to claim 5, wherein step c) is achieved by temporarily interrupting treatment with dronedarone, or the pharmaceutically acceptable salt thereof, while maintaining treatment with compound B.

15. The method according to claim 14, wherein the treatment interruption of dronedarone or the pharmaceutically acceptable salt thereof ranges from 1 to 2 weeks.

16. A method of managing the risk of an increase in the mortality rate in a patient treated by an association of dronedarone, or a pharmaceutically acceptable salt thereof, and of at least a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics which method comprises the steps a) to e) as defined in claim 5.

17. A method of treating patients with cardiac arrhythmia comprising the administration of dronedarone to patients treated, in addition, by at least a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics, which method comprising the steps a) to e) as defined in claim 5.

18. The method according to claim 16, for the treatment of patients with atrial fibrillation or atrial flutter.

20. The method according to claim 18 further comprising:

iv) discontinuing administration of dronedarone, or the pharmaceutically acceptable salt thereof, temporarily, and

v) obtaining a blood sample from the patient following discontinuance of administration of dronedarone or the pharmaceutically acceptable salt thereof to the patient, and

vi) measuring the serum creatinine level in the blood sample from the patient following discontinuance.

8. A method for preventing death in a patient being treated with dronedarone, or a pharmaceutically acceptable salt thereof, and a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics, wherein said patient has an increase of creatinine level due to administration of dronedarone or the pharmaceutically acceptable salt thereof, said method comprising:

a) initially measuring serum creatinine levels, which provides a reference level,

b) monitoring serum creatinine levels at regular intervals during treatment of the patient by dronedarone or the pharmaceutically acceptable salt thereof and by the compound B,

c₁) if the serum creatinine levels increases above the reference level, temporarily interrupting treatment with dronedarone or the pharmaceutically acceptable salt thereof, while maintaining treatment with compound B

d₁) when the increase is reversible, treatment with said combination is pursued,

e₁) repeating steps b), c₁) and d₁) for the duration of the treatment with said combination.

9. A method for preventing death in a patient being treated with dronedarone or a pharmaceutically acceptable salt thereof and a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics, wherein said patient has an increase of creatinine level due to compound B administration, said method comprising:

a) initially measuring serum creatinine levels, which provides a reference level,

b) monitoring serum creatinine levels at regular intervals during treatment of the patient by dronedarone or the pharmaceutically acceptable salt thereof and by the compound B,

c₁) if the serum creatinine levels increases above the reference level, temporarily interrupting treatment with dronedarone or the pharmaceutically acceptable salt thereof, while maintaining treatment with compound B,

d₂) when the increase is not reversible, treatment with compound B may be interrupted,

e₂) repeating steps b), c₁) and d₂) for the duration of the treatment with said combination.

19. A method of treating patients with arrhythmia comprising:

i) initiating administration of dronedarone or a pharmaceutically acceptable salt thereof in said patient;

ii) obtaining a blood sample from the patient following initiation of administration of dronedarone, or the pharmaceutically acceptable salt thereof, to the patient, and

iii) measuring the serum creatinine level from the blood sample to provide a reference level.

21. The method according to claim 19 or claim 20, wherein the patient is also being treated with a compound selected from the group consisting of ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics.

22. A method of treating patients with arrhythmia, wherein dronedarone or a pharmaceutically acceptable salt thereof is administered in combination with at least a compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics, said method comprising

i) initiating administration of dronedarone, or the pharmaceutically acceptable salt thereof, in said patient,

ii) obtaining a blood sample from the patient following initiation of administration of dronedarone, or the pharmaceutically acceptable salt thereof, to the patient,

iii) measuring the serum creatinine levels in the blood sample to provide a reference level,

iv) obtaining a blood sample from the patient and measuring serum creatinine levels during treatment of the patient by dronedarone, or the pharmaceutically acceptable salt thereof, and by the compound B,

v) determining the cause of an increase serum creatinine levels above the reference level,

vi) continuing treatment of dronedarone or the pharmaceutically acceptable salt thereof and compound B when the increase is due to treatment with dronedarone or the pharmaceutically acceptable salt thereof;

or interrupting treatment with compound B when the increase is caused by treatment with compound B;

or undertaking appropriate treatment when the increase is due to a cause other than administration of dronedarone or the pharmaceutically acceptable salt thereof or of compound B, and

vii) repeating steps iv) to vii) at regular intervals for the duration of the treatment with dronedarone, or the pharmaceutically acceptable salt thereof, and compound B.

23. The method according to claim 22 for the treatment of patients with atrial fibrillation or atrial flutter.

24. The method according to claim 22, wherein the serum creatinine level in step iii) is measured within 3 to 15 days after initiation of treatment with dronedarone or the pharmaceutically acceptable salt thereof.

25. The method according to claim 22 or claim 23, wherein the serum creatinine level in step iii) is measured within one week after initiation of treatment with dronedarone or the pharmaceutically acceptable salt thereof.

26. A method of providing dronedarone, or a pharmaceutically acceptable salt thereof, comprising providing dronedarone or the pharmaceutically acceptable salt thereof along with information indicating that serum creatinine levels increase following treatment initiation of dronedarone or the pharmaceutically acceptable salt thereof.

27. The method according to claim 26 wherein the information comprises printed matter that indicates that serum creatinine level increases following treatment initiation of dronedarone or the pharmaceutically acceptable salt thereof.

28. The method according to claim 26 or claim 27 wherein the information comprises written material recommending that if an increase in creatininemia is observed, this value should be used as the new baseline.

29. The method according to claim 27 wherein the printed matter is a label.

30. The method according to claim 28 wherein the printed matter is a label.

31. A method of promoting the use of dronedarone or a pharmaceutically acceptable salt thereof, the method comprising the step of conveying to a recipient at least one message selected from the group consisting of:

(1) measure plasma creatinine values 7 days after treatment initiation of dronedarone or a pharmaceutically acceptable salt thereof;

(2) if an increase in creatininemia is observed, this value should be used as the new baseline;

(3) serum creatinine levels increase following treatment initiation of dronedarone or a pharmaceutically acceptable salt thereof;

(4) dronedarone, or a pharmaceutically acceptable salt thereof, causes an increase in serum creatinine;

(5) the elevation of serum creatinine level reaches a plateau; and

(6) an increase in serum creatinine levels is reversible after discontinuation of dronedarone or a pharmaceutically acceptable salt thereof.

32. An article of manufacture comprising

a) a packaging material;

b) dronedarone or a pharmaceutically acceptable salt thereof; and

c) a label or package insert contained within the packaging material indicating that serum creatinine levels may change following treatment initiation of dronedarone, or a pharmaceutically acceptable salt thereof.

33. A package comprising dronedarone or a pharmaceutically acceptable salt thereof and a label, said label comprising a printed statement which informs a prospective user that an increase in serum creatinine has been observed following initiation of treatment with dronedarone or a pharmaceutically acceptable salt thereof.

34. A package comprising dronedarone or a pharmaceutically acceptable salt thereof and a label, said label comprising a printed statement which recommends that if an increase in creatininemia is observed following treatment initiation of dronedarone, or a pharmaceutically acceptable salt thereof, the increased value should be used as a baseline.

35. A method of transforming a patient treated by an association of dronedarone and at least one compound B selected from ACE inhibitors, angiotensin II receptor antagonists and potassium sparing diuretics by managing the risk of an increase in the mortality rate in said patient which method comprises:

i) initiating treatment of dronedarone, or a pharmaceutically acceptable salt thereof, to said patient,

ii) measuring serum creatinine levels increase following treatment initiation of dronedarone or a pharmaceutically acceptable salt thereof, which provides a reference level, said serum creatinine level reaching a plateau,

iii) temporarily discontinuing treatment with dronedarone or a pharmaceutically acceptable salt thereof, and

iv) measuring that the increase is reversible after discontinuation of dronedarone or a pharmaceutically acceptable salt thereof.