Methods of Administering Elagolix

Abstract

The present disclosure relates to the use of GnRH receptor antagonists for the treatment of endometriosis, uterine fibroids, polycystic ovary syndrome (PCOS), or adenomyosis. In particular, the present disclosure describes methods for treating such gynecological disorders, where the methods involve administration of elagolix and may further involve co-administration of a CYP2B6 substrate (e.g., bupropion) or a CYP2C19 substrate (e.g., omeprazole).

1 . A method for treating a gynecological disorder, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein the patient concomitantly receives bupropion, wherein the bupropion is administered without an adjustment to a recommended bupropion dosing schedule. 
     
     
         2 . The method of  claim 1 , wherein the recommended bupropion dosing schedule comprises (i) a 100 mg dose administered twice per day, (ii) a 100 mg dose administered three times per day, and/or (iii) a 150 mg dose administered three times per day for an immediate-release bupropion formulation. 
     
     
         3 . The method of  claim 1 , wherein the recommended bupropion dosing schedule comprises (i) a 150 mg dose administered once per day, and/or (ii) a 200 mg dose administered once per day for an extended-release bupropion formulation. 
     
     
         4 - 14 . (canceled) 
     
     
         15 . A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; wherein the patient receives a dose of 150 mg of bupropion; and wherein: (i) a bupropion C max  ratio, which compares (A) bupropion C max  when co-administered in the presence of elagolix to (B) bupropion C max  when administered alone, is 1.246 with a 90% confidence interval of 1.104-1.407; and/or (ii) a bupropion AUC inf  ratio, which compares (A) bupropion AUC inf  when co-administered in the presence of elagolix to (B) bupropion AUC inf  when administered alone, is 0.965 with a 90% confidence interval of 0.910-1.023. 
     
     
         16 - 24 . (canceled) 
     
     
         25 . The method of  claim 15 , wherein elagolix sodium is administered with an estrogen and progestin combination. 
     
     
         26 . The method of  claim 25 , wherein the estrogen and progestin combination comprises estradiol and norethindrone acetate. 
     
     
         27 . The method of  claim 1 , wherein the method is for the management of moderate to severe pain associated with endometriosis. 
     
     
         28 . The method of  claim 27 , wherein elagolix sodium is administered in an amount equivalent to 150 mg of elagolix free acid once daily or elagolix sodium is administered in an amount equivalent to 200 mg of elagolix free acid twice daily. 
     
     
         29 . The method of  claim 1 , wherein the method is for the management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids). 
     
     
         30 . The method of  claim 29 , wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily. 
     
     
         31 . The method of  claim 30 , wherein elagolix sodium is administered with an estrogen and progestin combination. 
     
     
         32 . The method of  claim 31 , wherein the estrogen and progestin combination comprises estradiol and norethindrone acetate. 
     
     
         33 . A method for management of heavy menstrual bleeding associated with uterine leiomyomas (fibroids), the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 300 mg of elagolix free acid twice daily; further wherein said patient receives bupropion, wherein the bupropion is administered without an adjustment to a recommended bupropion dosing schedule. 
     
     
         34 . A method for management of moderate to severe pain associated with endometriosis, the method comprising: orally administering to a patient in need thereof elagolix sodium, wherein elagolix sodium is administered in an amount equivalent to 150 mg of elagolix free acid once a day or 200 mg of elagolix free acid twice a day; further wherein said patient receives bupropion, wherein the bupropion is administered without an adjustment to a recommended bupropion dosing schedule.