Method for treating headache with loxapine

• US 8,288,372 B2
• Filed: 11/20/2003
• Issued: 10/16/2012
• Est. Priority Date: 11/26/2002
• Status: Active Grant

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Munzar, Patrik, Rabinowitz, Joshua D.
• Primary Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US10/719,540
• Publication Number:
  US 20040102434A1
• Time in Patent Office: 3,253 Days
• Field of Search: 514/211.01, 514/211.11, 514/211.13, 514/211.15, 514/217
• US Class Current: 514/211.13
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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

Loxapine, amoxapine, or salts or prodrugs of either, is effective in alleviating pain, particularly headache pain such as migraine, cluster headaches and tension headaches. Preferably the loxapine or amoxapine is administered systemically, most preferably by inhalation.

Claims

1. A method for treating headache comprising administering to a subject in need of headache relief, an effective amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts of loxapine, and prodrugs of loxapine wherein 0.3 to 6.0 mg of loxapine is administered, or an amount of a salt or prodrug of loxapine is administered that produces in the subject a blood concentration of loxapine equivalent to the administration of 0.3 to about 6.0 mg of loxapine.

2. A method in accordance with claim 1, wherein said headache is a migraine headache.

3. A method in accordance with claim 1, wherein said headache is a cluster headache.

4. A method in accordance with claim 1, wherein said headache is a tension-type headache.

5. A method in accordance with claim 1, wherein said compound is administered by inhalation.

6. A method in accordance with claim 1, wherein said subject is human, said headache is a migraine headache, and said compound is administered by inhalation.

7. A method in accordance with claim 1, wherein the compound is formulated so as to result in a maximum blood level of loxapine within about 30 minutes from administration.

8. A method in accordance with claim 1, wherein the compound is formulated so as to result in a maximum blood level of loxapine within about 15 minutes from administration.

9. A method in accordance with claim 1, wherein the compound is formulated so as to result in a peak rate of increase in the blood level of loxapine of at least about 1 ng/ml/minute.

10. A method in accordance with claim 1, wherein the compound is formulated so as to result in a blood level of loxapine of at least about 5 ng/ml within about 15 minutes from administration.

11. A method in accordance with claim 1, wherein said compound is administered via inhalation using a rapid-heating drug delivery article or a thin-film drug delivery article.

12. A method in accordance with claim 1, wherein said compound is administered via an inhalation delivery device, wherein said compound is vaporized and condensed to provide at least 50% recovery of said compound in an aerosol, and wherein said aerosol contains less than about 5% by weight of compound degradation products.

13. A method in accordance with claim 12, wherein said compound is coated on a substrate in the delivery device as a film having a thickness between about 0.5 and 20 μ

m.

14. A method in accordance with claim 1, wherein said compound is administered in the form of an aerosol having a mass median aerodynamic diameter of between about 0.01 and about 3 μ

m.

15. A method in accordance with claim 1, wherein said compound is administered via a rapid heating drug delivery article, and wherein said compound is volatized from a compound composition film under conditions sufficient to provide an aerosol having at least 50% recovery of said compound and containing less than about 10% by weight of compound degradation products.

16. A method for treating headache pain in a subject comprising administering to said subject an effective amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts of loxapine and prodrugs of loxapine wherein 0.3 to 6.0 mg of loxapine is administered, or an amount of a salt or prodrug of loxapine is administered that produces in the subject a blood concentration of loxapine equivalent to the administration of 0.3 to about 6.0 mg of loxapine.