Non-sedating antihistamine injection formulations and methods of use thereof

• US 8,314,083 B2
• Filed: 07/02/2010
• Issued: 11/20/2012
• 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:
  US12/829,857
• Publication Number:
  US 20110004164A1
• Time in Patent Office: 872 Days
• Field of Search: None
• 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

Disclosed are injectable formulations of cetirizine for treating acute allergic reactions and methods for treating acute allergic reactions. In particular, an intravenous injectable is disclosed as are methods of treating acute allergic reactions therewith.

Claims

1. A method for treating angioedema associated with an acute allergic reaction comprising:

administering to a patient in an emergency situation in need of such treatment an injection composition comprising racemic cetirizine or a pharmaceutically acceptable salt thereof, in an amount of effective to treat said angioedema associated with an acute allergic reaction,

wherein the injection composition is an aqueous solution having a pH of 3 to 9, and wherein administering comprises administration of 1 to 20 mg of racemic cetirizine.

2. The method of claim 1, wherein said injection comprises:

about 0.1% to about 2% w/v of cetirizine or a pharmaceutically acceptable salt thereof;

about 0.1 to about 0.9% w/v NaCl;

with pH adjusted to about 3 to about 9; and

Q.S. water.

3. The method of claim 1, wherein said injection is an intravenous injection comprising:

about 1% w/v cetirizine or a pharmaceutically acceptable salt thereof;

about 0.65% w/v NaCl; and

adjusted to about pH 5.4;

in a 1 mL single dosage form.

4. The method of claim 1, wherein administering the cetirizine injection while minimizes sedation, is free of hemolytic potential, and does not demonstrate an effect on the QTc interval.

5. The method of claim 1, wherein administering is intravenous.

6. The method of claim 1, wherein administering is intramuscular.

7. 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 cetirizine are 0.80 to 1.25.

8. The method of claim 1, wherein the injectable composition of cetirizine has a 90% confidence interval around the difference in the reduction of at least one symptom of angioedema associated with an acute allergic reaction to a reference injectable formulation, for the per protocol evaluable population, within about −

30.00 to about +30.00.

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

10. 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.

11. The method of claim 1, wherein the patient is a human or animal patient.

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