Anti-migraine methods and compositions using 5-HT agonists with long-acting NSAIDs

• US 6,060,499 A
• Filed: 09/11/1998
• Issued: 05/09/2000
• Est. Priority Date: 08/16/1996
• Status: Expired due to Term

• Current Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.)
• Original Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.)
• Inventors: Plachetka, John R.
• Primary Examiner(s): Jones, Dwayne C.
• Assistant Examiner(s): DELACROIX MUIRHEI, CYBILLE
• Application Number:
  US09/151,912
• Time in Patent Office: 606 Days
• Field of Search: 514/415, 514/569, 514/570, 514/629
• US Class Current: 514/415
• 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 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention comprises a method of treating migraine in a human comprising co-timely administering of a therapeutically effective amount of a 5-HT agonist coordinated with a therapeutically effective amount of an analgesic, particularly a long-acting NSAID, and in some instances, doses below those ordinarily considered as minimum effective doses as to one or both 5-HT agonist and long-acting NSAID. Dosage forms are also included herein.

Claims

1. In a method for treating a migraine patient by administering a 5-HT agonist, the improvement which comprises:

concomitantly administering to said patient a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) in an amount that, together with said 5-HT agonist, is effective to reduce migraine relapse or produce longer lasting efficacy compared to the administration of said 5-HT agonist in the absence of said LA-NSAID.

9. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said 5-HT agonist is sumatriptan.

10. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said 5-HT agonist is sumatriptan non-parenterally administered in an amount of from about 1 to about 15 mg.

11. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein both of said agents are administered either orally, intranasally, rectally or sublingually.

12. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said 5-HT agonist is sumatriptan administered parenterally from about 1 to about 4 mg.

13. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said LA-NSAID is naproxen, or a pharmaceutically acceptable salt thereof.

14. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said LA-NSAID is naproxen or a pharmaceutically acceptable salt thereof and is administered to a human in an amount greater than 200 mg.

15. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said 5-HT agonist is sumatriptan, said LA-NSAID is naproxen and the unit dosage form is an oral unit dosage form comprising sumatriptan in an amount greater than 15 mg, and naproxen in an amount greater than 200 mg.

16. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said concomitant administration comprises co-timely and coordinated administering of a therapeutically effective amount of at least one additional analgesic.

17. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said 5-HT agonist is selected from the group consisting of sumatriptan, eletriptan, rizatriptan, frovatriptan, almotriptan, zolmitriptan, and naratriptan.

18. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is sumatriptan.

19. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is eletriptan.

20. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is rizatriptan.

21. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is frovatriptan.

22. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is almotriptan.

23. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is zolmitriptan.

24. The improvement, method, or composition of claim 17, wherein said 5-HT agonist is naratriptan.

25. The improvement, method, or composition of claims 1, 2, 3, 4, 5, 6, 7, or 8, wherein said LA-NSAID is selected from the group consisting of flurbiprofen, ketoprofen, naproxen, oxaprozin, etodolac, indomethacin, ketorolac, nabumetone, mefanamic acid, and piroxicam.

26. The improvement, method, or composition of claim 25 wherein said LA-NSAID is naproxen.

27. The improvement, method, or composition of claim 26 wherein said naproxen is in the form of a sodium salt.

2. In a method for treating a migraine patient by administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID), the improvement which comprises:

concomitantly administering to said patient a 5-HT agonist in an amount that, together with said LA-NSAID, is effective to reduce migraine relapse or produce longer lasting efficacy compared to the administration of said LA-NSAID in the absence of said 5-HT agonist.

3. A method for treating a migraine patient which comprises:

(a) administering a 5-HT agonist to said patient and

(b) administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) to said patient;

wherein

(i) the 5-HT agonist and LA-NSAID are concomitantly administered and

(ii) the respective amounts of said 5-HT agonist and said LA-NSAID administered to said patient are effective to reduce migraine relapse or produce longer lasting efficacy compared to the administration of said 5-HT agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT agonist.

4. A pharmaceutical composition in unit dose form, useful in treating a migraine patient, which comprises:

(a) a 5-HT agonist and

(b) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID);

wherein the respective amounts of said 5-HT agonist and said LA-NSAID in said composition are effective, upon concomitant administration to said patient of one or more of said unit doses of said composition, to reduce migraine relapse or produce longer lasting efficacy compared to the administration of said 5-HT agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT agonist.

5. A therapeutic package for dispensing to, or for use in dispensing to, a migraine patient, which comprises:

(a) one or more unit doses, each such unit dose comprising;

(i) a 5-HT agonist and

(ii) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID);

wherein the respective amounts of said 5-HT agonist and said LA-NSAID in said unit dose are effective, upon concomitant administration to said patient of one or more of said unit doses, to reduce migraine relapse or produce longer lasting efficacy compared to the administration of said 5-HT agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT agonist, and

(b) a finished pharmaceutical container therefor,

said container containing said unit dose or unit doses,

said container further containing or comprising labeling directing the use of said package in the treatment of migraine.

6. A method for reducing relapse in a migraine patient which comprises:

(a) administering a 5-HT agonist to said patient and

(b) administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) to said patient;

wherein

(i) the 5-HT agonist and LA-NSAID are concomitantly administered and

(ii) the respective amounts of said 5-HT agonist and said LA-NSAID administered to said patient are effective to reduce migraine relapse compared to the administration of said 5-HT agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT agonist.

7. A method for produce longer lasting efficacy in a migraine patient which comprises:

(a) administering a 5-HT agonist to said patient and

(b) administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) to said patient;

wherein

(i) the 5-HT agonist and LA-NSAID are concomitantly administered and

(ii) the respective amounts of said 5-HT agonist and said LA-NSAID administered to said patient are effective to produce longer lasting efficacy compared to the administration of said 5-HT agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT agonist.

8. In a method for treating a migraine patient receiving 5-HT agonist monotherapy or long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) monotherapy, the improvement which comprises:

concomitantly administering to said patient said LA-NSAID and said 5-HT agonist in respective amounts that working together reduce migraine relapse or produce longer lasting efficacy compared to the administration of said monotherapy.