DDInter1008 DDInter997
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
Ivacaftor (also known as Kalydeco or VX-770) is a drug used for the management of Cystic Fibrosis (CF). It is manufactured and distributed by Vertex Pharmaceuticals. It was approved by the Food and Drug Administration on January 31, 2012, and by Health Canada in late 2012. Ivacaftor is administered as a monotherapy and also administered in combination with other drugs for the management of CF.[L6814,L6979,L6847] Cystic Fibrosis is an autosomal recessive disorder caused by one of several different mutations in the gene for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, an ion channel involved in the transport of chloride and sodium ions across cell membranes. CFTR is active in epithelial cells of organs such as of the lungs, pancreas, liver, digestive system, and reproductive tract. Alterations in the CFTR gene result in altered production, misfolding, or function of the protein and consequently abnormal fluid and ion transport across cell membranes.[A20298, A20299] As a result, CF patients produce thick, sticky mucus that clogs the ducts of organs where it is produced making patients more susceptible to complications such as infections, lung damage, pancreatic insufficiency, and malnutrition. Prior to the development of ivacaftor, management of CF primarily involved therapies for the control of infections, nutritional support, clearance of mucus, and management of symptoms rather than improvements in the underlying disease process or lung function (FEV1). Notably, ivacaftor was the first medication approved for the management of the underlying causes of CF (abnormalities in CFTR protein function) rather than control of symptoms.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ivacaftor
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inhibitors
Cytochrome P450 3A4 Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Ivacaftor
Ketoconazole {u} (Compound) causes {v} (Side Effect) Headache
Headache {u} (Side Effect) is caused by {v} (Compound) Ivacaftor
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Modafinil
Modafinil {u} may cause a minor interaction that can limit clinical effects when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Mirabegron
Mirabegron {u} may cause a minor interaction that can limit clinical effects when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inhibitors
Cytochrome P450 3A4 Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Amiodarone
Amiodarone {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) causes {v} (Side Effect) Headache
Headache {u} (Side Effect) is caused by {v} (Compound) Modafinil
Modafinil {u} may cause a minor interaction that can limit clinical effects when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Ivacaftor
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Ivacaftor
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ivacaftor (Compound)
Ketoconazole (Compound) is included by Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) and Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) includes Ivacaftor (Compound)
Ketoconazole (Compound) causes Headache (Side Effect) and Headache (Side Effect) is caused by Ivacaftor (Compound)
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Ivacaftor
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Modafinil (Compound) and Modafinil may cause a minor interaction that can limit clinical effects when taken with Ivacaftor
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Mirabegron (Compound) and Mirabegron may cause a minor interaction that can limit clinical effects when taken with Ivacaftor
Ketoconazole (Compound) is included by Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) and Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) includes Amiodarone (Compound) and Amiodarone may cause a moderate interaction that could exacerbate diseases when taken with Ivacaftor
Ketoconazole (Compound) causes Headache (Side Effect) and Headache (Side Effect) is caused by Modafinil (Compound) and Modafinil may cause a minor interaction that can limit clinical effects when taken with Ivacaftor
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Ivacaftor
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Ivacaftor (Compound)