Non-Sedating Antihistamine Injection Formulations and Methods of Use Thereof

• US 20110003781A1
• Filed: 02/11/2010
• Published: 01/06/2011
• Est. Priority Date: 07/03/2009
• Status: Active Grant

• Current Assignee: JDP Therapeutics, LLC
• Original Assignee: JDP Therapeutics, Inc.
• Inventors: Du, Jie
• Granted Patent: US 8,263,581 B2
• Time in Patent Office: Days
• US Class Current: 514/171
• 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 an acute allergic reaction including anaphylaxis comprising administering to an individual in need thereof an effective amount of an injectable composition comprising a non-sedating antihistamine, wherein the non-sedating antihistamine comprises cetirizine, loratadine, levocetirizine, desloratadine, or fexofenadine.

2. 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 formulation to a logarithmic transformed geometric mean of AUC_0-INF for a reference oral product of the non-sedating antihistamine are 0.80 to 1.25;

and/or wherein the 90% confidence limits of a ratio of a logarithmic transformed geometric mean of AUC_0-t for the injectable formulation to a logarithmic transformed geometric mean of AUC_0-t for the reference oral product of the non-sedating antihistamine are 0.80 to 1.25.

3. The method of claim 2, wherein the non-sedating antihistamine is cetirizine and the reference oral product is a 10 mg cetirizine tablet or capsule having an AUC_0-24=about 2500 to about 5500 ng.hr/mL and an AUC_0-INF=about 3000 to about 6200 ng.hr/mL.

4. The method of claim 2, wherein the non-sedating antihistamine is levocetirizine and the reference oral product is a 5 mg levocetirizine tablet or capsule, having an AUC_0-24=about 1500 to about 5000 ng.hr/mL and an AUC_0-INF=about 2000 to about 5500 ng.hr/mL.

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

6. The method of claim 1, wherein the injectable formulation of the non-sedating antihistamine has a 90% confidence interval around the difference in the reduction of at least one symptom of anaphylaxis or an acute allergic reaction to a reference injectable formulation, for the per protocol evaluable population, within about −

30.00 to about +30.00, wherein the symptom is pruritus severity, pruritus duration, erythema, angioedema, urticaria areas, and erythema areas, and/or wheezing.

7. The method of claim 6, wherein the reference injectable formulation is a 12.5-150 mg dose of a 50 mg/mL diphenydramine injectable formulation.

8. The method of claim 6, wherein the non-sedating antihistamine is cetirizine.

9. The method of claim 6, wherein the non-sedating antihistamine is levocetirizine.

10. The method of claim 1, wherein the injectable formulation of the non-sedating antihistamine is statistically superior (p<

0.05) to a placebo in the reduction of at least one symptom of anaphylaxis or an acute allergic reaction, wherein the symptom is pruritus severity, pruritus duration, erythema, angioedema, urticaria areas, erythema areas, and/or wheezing.

11. An automatic injector designed to allow a user to self-administer a pre-measured dose of a non-sedating antihistamine composition subcutaneously or intramuscularly, comprising

a housing comprising a chamber for the non-sedating antihistamine composition and a dispensing assembly in communication with the chamber,

wherein the non-sedating antihistamine composition comprises a non-sedating antihistamine and a pH adjusting agent and has a pH of 3 to 9, wherein the non-sedating antihistamine comprises cetirizine, loratadine, levocetirizine, desloratadine, or fexofenadine.

12. The automatic injector of claim 11, wherein the non-sedating antihistamine composition further comprises ranitidine, cimetidine, epinephrine, methylprednisolone, prednisolone, or a combination thereof.

13. A kit comprising the automatic injector comprising a non-sedating antihistamine composition of claim 11, and a second autoinjector comprising a second housing comprising a second chamber for an epinephrine composition and a second dispensing assembly in communication with the second chamber.