Methods of treatment

Abstract

The present disclosure provides for methods of treating a patient with a CYP3A4 substrate drug contraindicated for concomitant administration with a strong CYP3A4 inhibitor, wherein the patient is treated with multiple doses of posaconazole, stops posaconazole treatment, and then is treated with the CYP3A4 substrate drug. In some embodiments, treatment with the CYP3A4 substrate drug is delayed for about 5-21 after stopping posaconazole. In some embodiments, the patient is treated with or prescribed a reduced dose of the CYP3A4 substrate drug for about 5-21 after stopping posaconazole.

1 . A method of treating a patient with a CYP3A4 substrate drug contraindicated for concomitant administration with a strong CYP3A4 inhibitor, comprising:
 (a) treating a patient with multiple doses of posaconazole;   (b) stopping posaconazole treatment;   (c) delaying administration of the CYP3A4 substrate drug after step (b) for up to about 7 days; then   (d) administering a dose of the CYP3A4 substrate drug which is not more than about 50% of the reference dose of the CYP3A4 substrate drug during a time period of 5-21 days after stopping posaconazole treatment.   
     
     
         2 . The method of  claim 1 , wherein the patient is treated with or prescribed the CYP3A4 substrate drug for a disease or condition selected from the group consisting of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy in women in combination with fulvestrant, as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting, cystic fibrosis (CF) in patients age 2 years and older who have one mutation in the CFTR gene that is responsive to ivacaftor based on clinical and/or in vitro assay data, deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer in adult patients who have been treated with three or more prior lines of chemotherapy, intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis, polycythemia vera patients who have had an inadequate response to or are intolerant of hydroxyurea, as an adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD), schizophrenia, cystic fibrosis (CF) patients aged 12 years and older who are homozygous for the F508del mutation or who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to tezacaftor/ivacaftor based on in vitro data and/or clinical evidence, metastatic colorectal cancer (CRC) patients who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an antiVEGF therapy, and, if RAS wild-type, an anti-EGFR therapy, locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) patients who have been previously treated with imatinib mesylate and sunitinib malate, hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, chronic HCV genotype 1 or 3 infection with sofosbuvir and with or without ribavirin, metastatic non-small cell lung cancer (NSCLC) in patients whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test, opioid induced constipation (OIC) in adult patients with chronic non-cancer pain, including patients with chronic pain related to prior cancer or its treatment who do not require frequent (e.g., weekly) opioid dosage escalation, unresectable or metastatic melanoma in patients with BRAF V600E mutation as detected by an FDA-approved test, in combination with trametinib, for unresectable or metastatic melanoma in patients with BRAF V600E or V600K mutations as detected by an FDA-approved test melanoma in patients with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection, metastatic non-small cell lung cancer (NSCLC) in patients with BRAF V600E mutation as detected by an FDA-approved test, locally advanced or metastatic anaplastic thyroid cancer (ATC) in patients with BRAF V600E mutation and with no satisfactory locoregional treatment options, and with or without ribavirin for treatment of chronic HCV genotypes 1 or 4 infection in adults. 
     
     
         3 . The method of  claim 1 , wherein said CYP3A4 substrate drug is selected from the group consisting of lurasidone, ranolazine, lumacaftor/ivacaftor, venetoclax, trabectedin, ribociclib succinate, deflazacort, cinacalcet hydrochloride, pimavanserin tartrate, aripiprazole lauroxil, cariprazine hydrochloride, simeprevir sodium, everolimus, saxagliptin hydrochloride, saxagliptin/metformin hydrochloride, ticagrelor, vilazodone hydrochloride, apixaban, tofacitinib citrate, eletriptan hydrobromide, nilotinib hydrochloride monohydrate, dronedarone hydrochloride, fluticasone propionate/salmeterol xinafoate, rivaroxaban, tadalafil, ibrutinib, cobimetinib, colchicine, cabazitaxel, tolvaptan, fosaprepitant dimeglumine, aprepitant, solifenacin succinate, erlotinib hydrochloride, ado-trastuzumab ematansine, bosutinib monohydrate, sunitinib malate, fesoterodine fumarate, maraviroc, pazopanib hydrochloride, aripiprazole, axitinib, dapagliflozin/saxagliptin, cabozantinib S-malate, ponatinib hydrochloride, isavuconazonium sulfate, lomitapide mesylate, iloperidone, palbociclib, levomilnacipran hydrochloride, pimozide, pomalidomide, abemaciclib, ivacaftor, ruxolitinib phosphate, brexpiprazole, ivacaftor/tezacaftor, regorafenib, daclatasvir, crizotinib, naloxegol oxalate, dabrafenib, olaparib, and elbasvir and grazoprevir. 
     
     
         4 . The method of  claim 1 , wherein said administration of the CYP3A4 substrate drug in step (d) is for about 5-14 days. 
     
     
         5 . The method of  claim 1 , wherein said administration of the CYP3A4 substrate in step (d) is for about 5-10 days. 
     
     
         6 . The method of  claim 1 , wherein said delaying in step (c) is up to one day. 
     
     
         7 . The method of  claim 1 , wherein the patient is not obese and is a normal CYP3A4 metabolizer. 
     
     
         8 . The method of  claim 1 , wherein the patient is a poor or intermediate CYP3A4 metabolizer. 
     
     
         9 . The method of  claim 1 , wherein the patient has a characteristic selected from at least one of the following:
 i) BMI of at least about 35;   ii) % IBW of at least about 150%;   iii) waist size greater than about 42 inches;   iv) % body fat greater than about 40%;   v) total body fat greater than about 40 kg; and   vi) medically diagnosed as obese.