Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs

• US 6,586,458 B1
• Filed: 04/27/2000
• Issued: 07/01/2003
• 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:
  US09/559,753
• Time in Patent Office: 1,160 Days
• Field of Search: 514/449, 514/461, 514/473, 514/415
• 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 31/40 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 31/415 1,2-Diazoles
• 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

Abstract

The invention is directed to methods and compositions that can be used in the treatment of headaches. In particular, methods and compositions are described involving the combination of a long-acting NSAID and a 5-HT agonist. Included among the long-acting NSAIDs are cyclo-oxygenase-2 inhibitors.

Claims

1. A method of treating a patient for migraine headache, comprising:

(a) administering a 5-HT agonist to said patient, wherein said 5-HT agonist is a triptan; and

(b) administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) to said patient, wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

wherein;

(i) said 5-HT agonist and said LA-NSAID are concomitantly administered in unit dosage form; and

(ii) the respective amounts of said 5-HT agonist and said LA-NSAID administered to said patient are sufficient 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.

2. The method of claim 1, wherein said 5-HT agonist and said LA-NSAID are administered after the onset of symptoms associated with migraine headache.

6. The method or composition of any one of claims 1-5, wherein said 5-HT agonist is sumatriptan.

7. The method or composition of any one of claims 1-5, wherein said 5-HT agonist is sumatriptan non-parenterally administered in an amount of from about 25 to 100 mg.

8. The method or composition of any one of claims 1-5, wherein said 5-HT agonist and said said LA-NSAID are administered orally, intranasally, rectally, or sublingually.

9. The method or composition of any one of claims 1-5, wherein said 5-HT agonist is sumatriptan administered parenterally in an amount of about 6 mg.

10. The method or composition of any one of claims 1-5, wherein said LA-NSAID is naproxen or a pharmaceutically acceptable salt thereof.

11. The method or composition of any one of claims 1-5, wherein said LA-NSAID is naproxen or a pharmaceutically acceptable salt in an amount of greater than 200 mg.

12. The method or composition of any one of claims 1-5, wherein said 5-HT agonist is sumatriptan, and said LA-NSAID is naproxen in an oral unit dosage form comprising sumatriptan in an amount of greater than 25 mg and naproxen in an amount of greater than 200 mg.

13. The method or composition of any one of claims 1-5, wherein said concomitant administration comprises the co-timely and coordinated administering of a therapeutically effective amount of at least one additional analgesic.

14. The method or composition of any one of claims 1-5, wherein said 5-HT agonist is selected from the group consisting of sumatriptan, eletriptan, rizatriptan, frovatriptan, almotriptan, zolmitriptan and naratriptan.

15. The method or composition of claim 14, wherein said 5-HT agonist is sumatriptan.

16. The method or composition of claim 14, wherein said 5-HT agonist is eletriptan.

17. The method or composition of claim 14, wherein said 5-HT agonist is rizatriptan.

18. The method or composition of claim 14, wherein said 5-HT agonist is frovatriptan.

19. The method or composition of claim 14, wherein said 5-HT agonist is almotriptan.

20. The method or composition of claim 14, wherein said 5-HT agonist is zolmitriptan.

21. The method or composition of claim 14, wherein said 5 HT agonist is naratriptan.

22. The method or composition of any one of claims 1-5, wherein said LA-NSAID is selected from the group consisting of flurbiprofen, ketoprofen, naproxen, oxaprozin, etodolac, indomethacin, ketorolac, nabumetone, mefanamic acid, and piroxicam.

23. The method or composition of claim 22, wherein said LA-NSAID is naproxen.

24. The method or composition of claim 23, wherein said naproxen is in the form of a sodium salt.

3. A pharmaceutical composition in unit dosage form, useful in treating a migraine headache patient, which comprises:

(a) a 5-HT agonist, wherein said 5-HT agonist is a triptan; and

(b) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID), wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

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 dosage forms of said composition, 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.

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

(a) one or more unit dosage forms, each unit dosage form comprising;

(i) a 5-HT agonist, wherein said 5-HT agonist is a triptan; and

(ii) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID), wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

wherein the respective amounts of said 5-HT agonist and said LA-NSAID in said unit dosage f6 rms are effective, upon concomitant administration to said patient of one or more of said unit dosage forms, 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; and

(b) a finished pharmaceutical container therefore, said container containing said unit dosage form or unit dosage forms, and further comprising labeling directing the use of said package in the treatment of migraine headache.

5. A method for producing longer lasting efficacy in a migraine headache patient which comprises:

(a) administering a 5-HT agonist to said patient, wherein said 5-HT agonist is a triptan; and

(b) administering a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID) to said patient, wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

wherein;

(i) said 5-HT agonist and said LA-NSAID are concomitantly administered in unit dosage form after the onset of symptoms associated with migraine headache; 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.

25. A pharmaceutical composition In unit dosage form, useful in treating a migraine headache patient, wherein the active agents in said pharmaceutical composition consist essentially of:

(a) a 5-HT agonist, wherein said 5-HT agonist is a triptan; and

(b) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID), wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

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 dosage forms of said composition, 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.

26. The pharmaceutical composition of claim 25, wherein said 5-HT agonist is sumatriptan and said LA-NSAID is naproxen.

27. The pharmaceutical composition of claim 26, wherein:

a) said pharmaceutical composition is suitable for oral administration;

b) said sumatriptan is present in an amount of between 25 and 100 mg; and

c) said naproxen is present in an amount of between 200 and 600 mg.

31. A method of treating a patient for migraine headache, comprising administering the pharmaceutical composition of any one of claims 25-30 to said patient after the onset of symptoms associated with migraine headache.

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

(a) the pharmaceutical composition in unit dosage form of any one of claims 25-30; and

(b) a finished pharmaceutical container therefore, said container containing said unit dosage form or unit dosage forms, and further comprising labeling directing the use of said pharmaceutical composition in the treatment of migraine headache.

28. A pharmaceutical composition in unit dosage form, useful in treating a migraine headache patient, wherein the active agents in said pharmaceutical composition consist of:

(a) a 5-HT agonist, wherein said 5-HT agonist is a triptan; and

(b) a long-acting, non-steroidal, anti-inflammatory drug (LA-NSAID), wherein said LA-NSAID has a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours;

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 dosage forms of said composition, 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.

29. The pharmaceutical composition of claim 28, wherein said 5-HT agonist is sumatriptan and said LA-NSAID is naproxen.

30. The pharmaceutical composition of claim 29, wherein:

a) said pharmaceutical composition is suitable for oral administration;

b) said sumatriptan is present in an amount of between 25 and 100 mg; and

c) said naproxen is present in an amount of between 200 and 600 mg.