METHODS AND FORMULATIONS OF TREATING THROMBOSIS WITH BETRIXABAN AND A P-GLYCOPROTEIN INHIBITOR
This invention is directed to methods of inhibiting coagulation or treating thrombosis using a factor Xa inhibitor and a P-glycoprotein (Pgp) inhibitor. The invention is also directed to formulations used in the methods.
1 . A method for treating thrombosis or inhibiting blood coagulation in a patient receiving administration of a P-glycoprotein inhibitor, the method comprising administering to the patient a subtherapeutic dose of betrixaban.
2 . The method of claim 1 , wherein the amount of betrixaban administered is about 20% less than the therapeutically effective amount.
3 . The method of claim 1 , wherein the amount of betrixaban administered is about 50% less than the therapeutically effective amount.
4 . The method of claim 1 , wherein the patient is a human patient and the patient is administered an aggregate daily dose of about 25 to about 35 mg of betrixaban.
5 . The method of claim 1 , wherein the patient is a human patient and the patient is administered an aggregate daily dose of about 10 to about 20 mg of betrixaban.
6 . (canceled)
7 . The method of claim 1 , wherein the patient receives the administration of the P-glycoprotein inhibitor at least half an hour before or after administration of betrixaban.
8 . The method of claim 1 , wherein the patient is concurrently administered with the P-glycoprotein inhibitor and betrixaban.
9 . The method of claim 1 , wherein the patient receives administration of an therapeutically effective amount of the P-glycoprotein inhibitor.
10 . The method of claim 1 , wherein the P-glycoprotein inhibitor is in a controlled release form.
11 . The method of claim 1 , wherein the P-glycoprotein inhibitor is selected from the group consisting of verapamil, amiodarone and ketoconazole.
12 . The method of claim 11 , wherein the P-glycoprotein inhibitor is verapamil.
13 . The method of claim 12 , wherein verapamil is administered in an amount of about 100 mg to about 300 mg.
14 . The method of claim 11 , wherein the P-glycoprotein inhibitor is amiodarone.
15 . The method of claim 14 , wherein amiodarone is administered in an amount of about 200 mg to about 400 mg.
16 . The method of claim 11 , wherein the P-glycoprotein inhibitor is ketoconazole.
17 . The method of claim 16 , wherein ketoconazole is administered in an amount of about 100 mg to about 300 mg.
18 . (canceled)
19 . The method of claim 1 , wherein the betrixaban is a maleate salt.
20 . The method of claim 19 , wherein the maleate salt is in a crystalline form selected from the group consisting of Form I, Form II, Form III and combinations thereof.
21 - 24 . (canceled)
25 . The method of claim 1 , wherein the patient is a patient with atrial fibrillation or atrial flutter.
26 . An unit dose comprising from about 25 to about 35 mg of betrixaban and an effective amount of a P-glycoprotein inhibitor.
27 - 28 . (canceled)