Gonadotropin-releasing hormone antagonist dosing regimens for treating uterine fibroids and reducing menstrual blood loss

Abstract

The invention provides compositions and methods for reducing the volume of menstrual blood loss in a patient, such as a human patient, for instance, that has uterine fibroids, by administration of a gonadotropin-releasing hormone (GnRH) antagonist. Suitable GnRH antagonists useful in conjunction with the compositions and methods described herein include thieno[3,4d]pyrimidine derivatives, such as 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4d]pyrimidine-5-carboxylic acid and the choline salt thereof.

1 . A method of reducing the volume of menstrual blood loss in a female human patient, the method comprising administering to the patient a compound, 3-[2-fluoro-5-(2,3-difluoro-6-methoxpenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, in an amount of about 100 mg per day or about 200 mg per day. 
     
     
         2 . The method of  claim 1 , wherein the patient has uterine fibroids. 
     
     
         3 . The method of  claim 1 , wherein the compound is administered to the patient in an amount of about 100 mg per day. 
     
     
         4 . The method of  claim 1 , wherein the compound is administered to the patient in an amount of about 200 mg per day. 
     
     
         5 . The method of  claim 1 , wherein the compound is administered to the patient in the form of a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 5 , wherein the pharmaceutically acceptable salt is a choline salt. 
     
     
         7 . The method of  claim 1 , wherein the compound is administered to the patient orally. 
     
     
         8 . The method of  claim 1 , wherein the compound is administered to the patient once daily. 
     
     
         9 . A method of treating uterine fibroids in a female human patient in need thereof, the method comprising administering to the patient a compound, 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, in an amount of about 100 mg per day or about 200 mg per day. 
     
     
         10 . The method of  claim 9 , wherein the compound is administered to the patient in an amount of about 100 mg per day. 
     
     
         11 . The method of  claim 9 , wherein the compound is administered to the patient in an amount of about 200 mg per day. 
     
     
         12 . The method of  claim 9 , wherein the compound is administered to the patient in the form of a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 12 , wherein the pharmaceutically acceptable salt is a choline salt. 
     
     
         14 . The method of  claim 9 , wherein the compound is administered to the patient orally. 
     
     
         15 . The method of  claim 9 , wherein the compound is administered to the patient once daily. 
     
     
         16 . A kit comprising a compound, 3-[2-fluoro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyphenyl]-2,4-dioxo-1,2,3,4-tetrahydrothieno [3,4d]pyrimidine-5-carboxylic acid, or a pharmaceutically acceptable salt thereof, wherein the compound is present in the kit in a unit dosage form comprising about 100 mg or about 200 mg of the compound, and wherein the kit further comprises a package insert that instructs a user of the kit to perform the method of  claim 1 . 
     
     
         17 . The kit of  claim 16 , wherein the compound is present in the kit in the form of a pharmaceutically acceptable salt thereof. 
     
     
         18 . The kit of  claim 17 , wherein the pharmaceutically acceptable salt is a choline salt. 
     
     
         19 . The kit of  claim 16 , wherein the compound is present in the kit in a unit dosage form comprising about 100 mg of the compound. 
     
     
         20 . The kit of  claim 16 , wherein the compound is present in the kit in a unit dosage form comprising about 200 mg of the compound.