Mitapivat therapy and modulators of cytochrome p450

Abstract

Described herein are methods of treating pyruvate kinase deficiency (PKD), sickle cell disease or thalassemia with mitapivat or a pharmaceutically acceptable salt thereof, or use of the drug for the treatment of these conditions, in combination with or in the absence of with a secondary drug, such as an inducer or an inhibitor of cytochrome P450. Various doses and dosing regimens of mitapivat in monotherapy and in concomitant medications are described.

1 - 45 . (canceled) 
     
     
         46 . A method of treating hemolytic anemia in a subject, comprising administering to the subject about 10 mg/day, about 40 mg/day, about 100 mg/day, or about 200 mg/day of mitapivat sulfate and a moderate inducer of cytochrome P450 3A4/5 (CYP3A4/5). 
     
     
         47 . The method of  claim 46 , wherein the subject is administered about 10 mg/day of mitapivat sulfate. 
     
     
         48 . The method of  claim 47 , wherein the subject is administered about 5 mg of mitapivat sulfate twice per day. 
     
     
         49 . The method of  claim 46 , wherein the subject is administered about 40 mg/day of mitapivat sulfate. 
     
     
         50 . The method of  claim 49 , wherein the subject is administered about 20 mg of mitapivat sulfate twice per day. 
     
     
         51 . The method of  claim 46 , wherein the subject is administered about 100 mg/day of mitapivat sulfate. 
     
     
         52 . The method of  claim 51 , wherein the subject is administered about 50 mg of mitapivat sulfate twice per day. 
     
     
         53 . The method of  claim 46 , wherein the subject is administered about 200 mg/day of mitapivat sulfate. 
     
     
         54 . The method of  claim 53 , wherein the subject is administered about 100 mg of mitapivat sulfate twice per day. 
     
     
         55 . The method of  claim 46 , wherein the mitapivat sulfate is orally administered as part of a tablet composition. 
     
     
         56 . The method of  claim 48 , wherein the mitapivat sulfate is orally administered as part of a tablet composition. 
     
     
         57 . The method of  claim 50 , wherein the mitapivat sulfate is orally administered as part of a tablet composition. 
     
     
         58 . The method of  claim 52 , wherein the mitapivat sulfate is orally administered as part of a tablet composition. 
     
     
         59 . The method of  claim 54 , wherein the mitapivat sulfate is orally administered as part of a tablet composition. 
     
     
         60 . The method of  claim 55 , wherein the tablet composition further comprises microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate. 
     
     
         61 . The method of  claim 56 , wherein the tablet composition further comprises microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate. 
     
     
         62 . The method of  claim 57 , wherein the tablet composition further comprises microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate. 
     
     
         63 . The method of  claim 58 , wherein the tablet composition further comprises microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate. 
     
     
         64 . The method of  claim 59 , wherein the tablet composition further comprises microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate.