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

• US 20030232876A1
• Filed: 04/16/2003
• Published: 12/18/2003
• Est. Priority Date: 08/16/1996
• Status: Active Grant

• Current Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.)
• Original Assignee: Pozen Incorporated (Aralez Pharmaceuticals Inc.)
• Inventors: Plachetka, John R.
• Granted Patent: US 8,022,095 B2
• Time in Patent Office: Days
• US Class Current: 514/419
• 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 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• 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 31/403 condensed with carbocyclic rings, e.g. carbazole
• 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
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

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-HT1_B/1_D agonist.

Claims

1. A method of treating a patient for a migraine headache, comprising simultaneously administering to said patient:

(a) a 5-HT1_B/1_D agonist; and

(b) a nonsteroidal anti-inflammatory drug having a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours (“

LA-NSAID”

);

wherein;

said 5-HT1_B/1_D agonist and said LA-NSAID are administered to said patient orally after the onset of migraine symptoms; and

the amount of said 5-HT1_B/1_D agonist and said LA-NSAID administered to said patient are sufficient to produce longer lasting efficacy compared to the administration of said 5-HT1_B/1_D agonist in the absence LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT1_B/1_D agonist.

2. The method of claim 1, wherein said 5-HT1_B/1_D agonist and said LA-NSAID are administered together in a single dosage form.

3. The method of claim 2, wherein said single dosage form is a tablet, capsule, dragee or trochee.

4. The method of claim 1, wherein said 5-HT1_B/1_D agonist is selected from the group consisting of:

sumatriptan;

eletriptan;

rizatriptan;

frovatriptan;

almotriptan;

zolmitriptan; and

naratriptan.

5. The method of any one of claims 1-4, wherein said LA-NSAID is selected from the group consisting of:

flurbiprofen;

naproxen;

oxaprozin;

indomethacin;

ketorolac;

mefenamic acid;

nabumetone, etodolac; and

piroxicam.

6. The method of any one of claims 1-4, wherein said LA-NSAID inhibits COX-2 to a greater extent than it inhibits COX-1.

7. The method of claim 6, wherein said LA-NSAID is either etodolac or mefenamic acid.

8. The method of claim 6, wherein said 5-HT1_B/1_D agonist is sumatriptan.

9. The method of any one of claims 1-3 or 5, wherein said 5-HT1_B/1_D agonist is sumatriptan.

10. The method of claim 1, wherein said 5-HT1_B/1_D agonist and said LA-NSAID are administered in a single dosage form and wherein said 5-HT1_B/1_D agonist is sumatriptan present at between 5 mg and 100 mg and said LA-NSAID is naproxen present at between 200 mg and 600 mg.

11. A pharmaceutical composition useful in treating migraine headache which comprises in a single oral dosage form:

(a) a 5-HT1_B/1_D agonist; and

(b) a nonsteroidal anti-inflammatory drug having a pharmacokinetic half-life of at least 4 hours and a duration of action of at least 6 hours (“

LA-NSAID”

);

wherein the respective amounts of said 5-HT1_B/1_D agonist and said LA-NSAID in said pharmaceutical composition are effective upon co-timely or simultaneous administration of one or more single oral dosage forms to produce longer lasting efficacy compared to the administration of said 5-HT1_B/1_D agonist in the absence of said LA-NSAID or the administration of said LA-NSAID in the absence of said 5-HT1_B/1_D agonist.

12. The pharmaceutical composition of claim 11, wherein said oral dosage form is a tablet, capsule, dragee or trochee.

13. The pharmaceutical composition of claim 11, wherein said 5-HT1_B/1_D agonist is selected from the group consisting of:

sumatriptan;

eletriptan;

rizatriptan;

frovatriptan;

almotriptan;

zolmitriptan; and

naratriptan.

14. The method of any one of claims 11-13, wherein said LA-NSAID is selected from the group consisting of:

flurbiprofen;

naproxen;

oxaprozin;

indomethacin;

ketorolac;

mefenamic acid;

nabumetone;

etodolac; and

piroxicam.

15. The pharmaceutical composition of any one of claims 11-13, wherein said LA-NSAID inhibits COX-2 to a greater extent than COX-1.

16. The pharmaceutical composition of claim 15, wherein said LA-NSAID is either etodolac or mefenamic acid.

17. The pharmaceutical composition of claim 15, wherein said 5-HT1_B/1_D agonist is sumatriptan.

18. The pharmaceutical composition of claim 11, wherein said 5-HT1_B/1_D agonist is sumatriptan present at between 5 mg and 100 mg and said LA-NSAID is naproxen present at between 200 mg and 600 mg.

19. A therapeutic package comprising:

(a) the pharmaceutical composition of claim 11;

and

(b) a finished pharmaceutical container containing said pharmaceutical composition and further comprising labeling directing the use of said pharmaceutical composition in the treatment of migraine headache.

20. The therapeutic package of claim 19, wherein said pharmaceutical composition is in the form of a tablet, capsule, dragee or trochee.