Methods of treatment with cyp3a4 substrate drugs

Abstract

The present disclosure provides for methods of treating a patient with a CYP3A4 substrate drug, wherein the patient is treated with posaconazole. In some embodiments, the patient stops posaconazole treatment, waits for at least 2 days, and then is treated with the CYP3A4 substrate drug as soon as it is safe to do so. In some embodiments, treatment with the CYP3A4 substrate drug is delayed for about 2-42 days after stopping posaconazole. In some embodiments, the patient is treated with a reduced dose of the CYP3A4 substrate drug for about 2-42 days.

1 . A method of treating a patient for a condition selected from chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML), with venetoclax, wherein the patient is treated with posaconazole, comprising:
 (a) stopping posaconazole treatment;   (b) delaying administering 400 mg of venetoclax until at least 9 days after stopping posaconazole in step (a); and then   (c) administering 400 mg of venetoclax.   
     
     
         2 . The method of  claim 1 , wherein the patient is not obese. 
     
     
         3 . The method of  claim 1 , wherein the patient has at least one characteristic selected from the group consisting of the following:
 i) BMI of at least about 35;   ii) waist size greater than about 42 inches;   iii) % body fat greater than about 40%;   iv) total body fat greater than about 40 kg, and;   v) medically diagnosed as obese.   
     
     
         4 . The method of  claim 1 , wherein the patient is administered 10 mg to 300 mg of venetoclax concurrently with posaconazole prior to stopping posaconazole in step (a). 
     
     
         5 . The method of  claim 4 , wherein the patient is administered 10 mg. 
     
     
         6 . The method of  claim 4 , wherein the patient is administered 20 mg. 
     
     
         7 . The method of  claim 4 , wherein the patient is administered 50 mg. 
     
     
         8 . The method of  claim 4 , wherein the patient is administered 70 mg. 
     
     
         9 . The method of  claim 4 , wherein the patient is administered 100 mg. 
     
     
         10 . The method of  claim 4 , wherein the patient is administered 200 mg. 
     
     
         11 . The method of  claim 4 , wherein the patient is administered 10 mg to 300 mg of venetoclax after stopping posaconazole in step (a) and until administering 400 mg of venetoclax in step (c). 
     
     
         12 . The method of  claim 4 , wherein the patient is administered 70 mg. 
     
     
         13 . The method of  claim 4 , wherein the patient is administered 100 mg. 
     
     
         14 . The method of  claim 4 , wherein the patient is administered 200 mg. 
     
     
         15 . The method of  claim 1 , wherein said administering in step (c) is 9-21 days after stopping posaconazole in step (a). 
     
     
         16 . The method of  claim 1 , wherein said administering in step (c) is 9 days after stopping posaconazole in step (a). 
     
     
         17 . The method of  claim 1 , wherein said administering in step (c) is 10 days after stopping posaconazole in step (a). 
     
     
         18 . The method of  claim 1 , wherein said administering in step (c) is 11 days after stopping posaconazole in step (a). 
     
     
         19 . The method of  claim 1 , wherein said administering in step (c) is 12 days after stopping posaconazole in step (a). 
     
     
         20 . The method of  claim 1 , wherein said administering in step (c) is 13 days after stopping posaconazole in step (a). 
     
     
         21 . The method of  claim 1 , wherein said administering in step (c) is 14 days after stopping posaconazole in step (a). 
     
     
         22 . The method of  claim 1 , wherein said administering of step (c) is at least 21 days after stopping posaconazole in step (a). 
     
     
         23 . The method of  claim 1 , wherein the condition is CLL, with or without 17p deletion. 
     
     
         24 . The method of  claim 1 , wherein the condition is SLL, with or without 17p deletion. 
     
     
         25 . The method of  claim 1 , wherein the condition is AML.