DDInter1008 DDInter1760
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
Telotristat ethyl is a prodrug of telotristat that was approved by the FDA in March 2017 as Xermelo. It was previously referred to as telotristat etiprate, the hippurate salt form; however, the FDA recommends the use of the name of the neutral form rather than that of the salt.[A252937, A252942] Currently, telotristat ethyl is used to treat carcinoid syndrome diarrhea from neuroendocrine tumors that are inadequately controlled by short-acting somatostatin analog (SSA) treatment. Neuroendocrine cells are cells that secrete regulatory peptides and biogenic amines in response to chemical, neural, or other types of stimuli. Neuroendocrine tumors (NET) arising from these cells can therefore secrete chemical mediators into the bloodstream to cause side effects in distant sites, a phenomenon called carcinoid syndrome. The most common peptides and amines secreted by NET are histamines, tachykinins, kallikrein, and serotonin. Overexposure to serotonin can cause severe diarrhea, one of the main clinical symptoms of carcinoid syndrome. Serotonin is metabolized in the urinary metabolite 5-hydroxy indole acetic acid (u5-HIAA), and high levels of u5-HIAA is associated with poor survival outcome in patients with NET. The first line treatment of carcinoid syndrome diarrhea is SSA, but symptoms still reoccur over the course of the disease.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) upregulates {v} (Gene) DDIT4
DDIT4 {u} (Gene) is upregulated by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) upregulates {v} (Gene) IDI1
IDI1 {u} (Gene) is downregulated by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatobiliary disease
Hepatobiliary disease {u} (Side Effect) is caused by {v} (Compound) Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) upregulates {v} (Gene) HMGCR
HMGCR {u} (Gene) is bound by {v} (Compound) and {u} (Gene) is upregulated by {v} (Compound) Simvastatin
Simvastatin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatobiliary disease
Hepatobiliary disease {u} (Side Effect) is caused by {v} (Compound) Octreotide
Octreotide {u} may lead to a major life threatening interaction when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Bexarotene
Bexarotene {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Sorafenib
Sorafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Cabazitaxel
Cabazitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Halofantrine
Halofantrine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Telotristat ethyl
Ketoconazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) upregulates DDIT4 (Gene) and DDIT4 (Gene) is upregulated by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) upregulates IDI1 (Gene) and IDI1 (Gene) is downregulated by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) causes Hepatobiliary disease (Side Effect) and Hepatobiliary disease (Side Effect) is caused by Sorafenib (Compound) and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) upregulates HMGCR (Gene) and HMGCR (Gene) is bound by Simvastatin (Compound) and HMGCR (Gene) is upregulated by Simvastatin (Compound) and Simvastatin may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) causes Hepatobiliary disease (Side Effect) and Hepatobiliary disease (Side Effect) is caused by Octreotide (Compound) and Octreotide may lead to a major life threatening interaction when taken with Telotristat ethyl
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a minor interaction that can limit clinical effects when taken with Bexarotene and Bexarotene may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Sorafenib and Sorafenib may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Cabazitaxel and Cabazitaxel may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Halofantrine and Halofantrine may cause a moderate interaction that could exacerbate diseases when taken with Telotristat ethyl