DDInter1008 DDInter287
Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[A181802,T116] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981. At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[A188054,A188057] These effects combined with waning efficacy led to its eventual replacement by triazole agents, [fluconazole], [itraconazole], [voriconazole], and [posaconazole]. Ketoconazole and its predecessor [clotrimazole] continue
Capmatinib is a small molecule kinase inhibitor targeted against c-Met (a.k.a. hepatocyte growth factor receptor [HGFR]), a receptor tyrosine kinase that, in healthy humans, activates signaling cascades involved in organ regeneration and tissue repair. Aberrant c-Met activation - via mutations, amplification, and/or overexpression - is known to occur in many types of cancer, and leads to overactivation of multiple downstream signaling pathways such as STAT3, PI3K/ATK, and RAS/MAPK. Mutations in _MET_ have been detected in non-small cell lung cancer (NSCLC), and the prevalence of _MET_ amplification in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-naive patients with NSCLC has been reported to be 1.4% - 21%. This co-occurrence has made c-Met a desirable target in the treatment of NSCLC. Manufactured by Novartis and marketed under the brand name Tabrecta, capmatinib was granted accelerated approval by the FDA on May 6, 2020, for the treatment of NSCLC in patients whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping. The presence of the mutation must be confirmed by an FDA-approved test, such as the FoundationOne CDx assay (manufactured by Foundation Medicine, Inc.), which was approved by the FDA on the same day. As this indication was granted under an accelerated approval, its continued approval is contingent upon verification of capmatinib's benefit in confirmatory trials. Capmatinib was approved by Health Canada on June 8, 2022.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Fluconazole
Fluconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) ACAT2
ACAT2 {u} (Gene) is downregulated by {v} (Compound) Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatitis cholestatic
Hepatitis cholestatic {u} (Side Effect) is caused by {v} (Compound) Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) ACAT2
ACAT2 {u} (Gene) is downregulated by {v} (Compound) Vemurafenib
Vemurafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatitis cholestatic
Hepatitis cholestatic {u} (Side Effect) is caused by {v} (Compound) Imatinib
Imatinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatitis cholestatic
Hepatitis cholestatic {u} (Side Effect) is caused by {v} (Compound) Clarithromycin
Clarithromycin {u} may lead to a major life threatening interaction when taken with {v} Capmatinib
Ketoconazole {u} (Compound) upregulates {v} (Gene) ACAT2
ACAT2 {u} (Gene) is upregulated by {v} (Compound) Afatinib
Afatinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Capmatinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is bound by {v} (Compound) Dexamethasone
Dexamethasone {u} may lead to a major life threatening interaction when taken with {v} Capmatinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pantoprazole
Pantoprazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Capmatinib
Ketoconazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Pantoprazole (Compound) and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib
Ketoconazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Fluconazole (Compound) and Fluconazole may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Ketoconazole (Compound) upregulates ACAT2 (Gene) and ACAT2 (Gene) is downregulated by Pantoprazole (Compound) and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib
Ketoconazole (Compound) causes Hepatitis cholestatic (Side Effect) and Hepatitis cholestatic (Side Effect) is caused by Pantoprazole (Compound) and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib
Ketoconazole (Compound) upregulates ACAT2 (Gene) and ACAT2 (Gene) is downregulated by Vemurafenib (Compound) and Vemurafenib may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Ketoconazole (Compound) causes Hepatitis cholestatic (Side Effect) and Hepatitis cholestatic (Side Effect) is caused by Imatinib (Compound) and Imatinib may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Ketoconazole (Compound) causes Hepatitis cholestatic (Side Effect) and Hepatitis cholestatic (Side Effect) is caused by Clarithromycin (Compound) and Clarithromycin may lead to a major life threatening interaction when taken with Capmatinib
Ketoconazole (Compound) upregulates ACAT2 (Gene) and ACAT2 (Gene) is upregulated by Afatinib (Compound) and Afatinib may cause a moderate interaction that could exacerbate diseases when taken with Capmatinib
Ketoconazole (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is bound by Dexamethasone (Compound) and Dexamethasone may lead to a major life threatening interaction when taken with Capmatinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Pantoprazole and Pantoprazole may cause a minor interaction that can limit clinical effects when taken with Capmatinib