Non-sedating antihistamine injection formulations and methods of use thereof

• US 9,119,771 B2
• Filed: 07/27/2012
• Issued: 09/01/2015
• Est. Priority Date: 07/03/2009
• Status: Active Grant

• Current Assignee: JDP Therapeutics, LLC
• Original Assignee: JDP Therapeutics, Inc.
• Inventors: Du, Jie
• Primary Examiner(s): RICCI, CRAIG D
• Application Number:
  US13/559,954
• Publication Number:
  US 20120289489A1
• Time in Patent Office: 1,131 Days
• Field of Search: None
• US Class Current: 1/1
• 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 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• 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 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

Described herein are injectable compositions containing non-sedating or second and third generation antihistamines such as cetirizine/levocetirizine and methods of use thereof. Specifically, methods of treating acute allergic reactions including anaphylaxis with the compositions are disclosed. In certain embodiments, the injectable compositions are bioequivalent to currently marketed oral dosage forms. In other embodiments, the non-sedating or second and third generation antihistamine injectable formulations are therapeutically equivalent to diphenhydramine injectable formulations and/or are more effective than placebo. In other embodiments, a non-sedating antihistamine injectable composition is delivered by an autoinjector.

Claims

1. A method of treating acute urticaria or angioedema associated with an acute allergic reaction comprising administering to an individual in an emergency situation an effective amount of an injectable composition comprising racemic cetirizine or a salt thereof,

wherein the injectable composition is a sterile parenteral solution comprising 1 to 100 mg of cetirizine per milliliter of solution.

2. The method of claim 1, wherein treating comprises treating acute urticaria.

3. The method of claim 1, wherein treating comprises treating angioedema.

4. The method of claim 1, wherein the acute allergic reaction is anaphylaxis.

5. The method of claim 1, wherein the 90% confidence limits of a ratio of a logarithmic transformed geometric mean of AUC_0-INF for the injectable composition to a logarithmic transformed geometric mean of AUC_0-INF for a reference oral product of racemic cetirizine are 0.80 to 1.25.

6. The method of claim 1, wherein the injectable composition further comprises a second active agent comprising ranitidine, cimetidine, epinephrine, methylprednisolone, prednisolone, or a combination thereof.

7. The method of claim 2, wherein the injectable composition of cetirizine has a 90% confidence interval around the difference in the reduction of at least one symptom of acute urticaria to a reference injectable formulation, for the per protocol evaluable population, within about −

30.00 to about +30.00, wherein the symptom is pruritus, number of urticaria areas, or urticaria areas.

8. The method of claim 7, wherein the reference injectable formulation is a 12.5-150 mg dose of a 50 mg/mL diphenydramine injectable formulation.

9. The method of claim 3, wherein the injectable composition of cetirizine has a 90% confidence interval around the difference in the reduction of at least one symptom of angioedema to a reference injectable formulation, for the per protocol evaluable population, within about −

30.00 to about +30.00.

10. The method of claim 9, wherein the reference injectable formulation is a 12.5-150 mg dose of a 50 mg/mL diphenydramine injectable formulation.

11. The method of claim 2, wherein the injectable composition of the non-sedating antihistamine is statistically superior (p<

0.05) to a placebo in the reduction of at least one symptom of acute urticaria, wherein the symptom is pruritus, number of urticaria areas, or urticaria areas.

12. The method of claim 3, wherein the injectable composition of the non-sedating antihistamine is statistically superior (p<

0.05) to a placebo in the reduction of at least one symptom of angioedema.

13. The method of claim 1, wherein administering is intravenous injection.

14. The method of claim 1, wherein administering is intramuscular injection.

15. The method of claim 1, wherein the injectable composition is an aqueous solution.

16. The method of claim 1, wherein the injectable composition comprises 1.5 to 50 mg of cetirizine per milliliter of solution.

17. The method of claim 1, wherein the injectable composition comprises 2 to 25 mg of cetirizine per milliliter of solution.

18. The method of claim 1, wherein 2 to 10 mg of cetirizine are administered.