DDInter1008 DDInter221
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
Boceprevir is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients . Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as Boceprevir. Boceprevir is an inhibitor of NS3/4A, a serine protease enzyme, encoded by HCV genotypes 1 and 4 [synthesis]. These enzymes are essential for viral replication and serve to cleave the virally encoded polyprotein into mature proteins like NS4A, NS4B, NS5A and NS5B [FDA Label]. The barrier for develoment of resistance to NS3/4A inhibitors is lower than that of NS5B inhibitors, another class of DAAs . Subtitutions at amino acid positions 155, 156, or 168 are known to confer resistance. The substitutions of the enzyme's catalytic triad consisting of H58, D82, and S139 are also likely to alter the affinity of the drug for NS3/4A or the activity of the enzyme itself. Despite this disadvantage Boceprevir is still effective against HCV when paired with , , and . In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) do not reccomend Boceprevir in combination with , , and as first line therapy for Hepatitis C . Boceprevir, , , and are used with the intent to cure, or achieve a sustained virologic response (SVR), after 48 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality . Boceprevir is available as a fixed dose product (tradename Victrelis) used for the treatment of chronic Hepatitis C. Approved in May 2011 by the FDA, Victrelis is indicated for the treatment of HCV genotype 1 in combination with , , and [FDA Label]. Victrelis is no longer widely used as interferon-free therapies have been developed.
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Boceprevir
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inhibitors
Cytochrome P450 3A4 Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Boceprevir
Ketoconazole {u} (Compound) causes {v} (Side Effect) Feeling abnormal
Feeling abnormal {u} (Side Effect) is caused by {v} (Compound) Boceprevir
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB1
ABCB1 {u} (Gene) is bound by {v} (Compound) Telaprevir
Telaprevir {u} (Compound) resembles {v} (Compound) Boceprevir
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) is bound by {v} (Compound) Cabazitaxel
Cabazitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Boceprevir
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A4 Inhibitors
Cytochrome P450 3A4 Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Aprepitant
Aprepitant {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Boceprevir
Ketoconazole {u} (Compound) is included by {v} (Pharmacologic Class) Cytochrome P450 3A5 Inhibitors
Cytochrome P450 3A5 Inhibitors {u} (Pharmacologic Class) includes {v} (Compound) Ticagrelor
Ticagrelor {u} may lead to a major life threatening interaction when taken with {v} Boceprevir
Ketoconazole {u} (Compound) causes {v} (Side Effect) Feeling abnormal
Feeling abnormal {u} (Side Effect) is caused by {v} (Compound) Cabazitaxel
Cabazitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Boceprevir
Ketoconazole {u} (Compound) causes {v} (Side Effect) Body temperature increased
Body temperature increased {u} (Side Effect) is caused by {v} (Compound) Abiraterone
Abiraterone {u} may cause a minor interaction that can limit clinical effects when taken with {v} Boceprevir
Ketoconazole {u} (Compound) causes {v} (Side Effect) Gastrointestinal disorder
Gastrointestinal disorder {u} (Side Effect) is caused by {v} (Compound) Telaprevir
Telaprevir {u} (Compound) resembles {v} (Compound) Boceprevir
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Boceprevir (Compound)
Ketoconazole (Compound) is included by Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) and Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) includes Boceprevir (Compound)
Ketoconazole (Compound) causes Feeling abnormal (Side Effect) and Feeling abnormal (Side Effect) is caused by Boceprevir (Compound)
Ketoconazole (Compound) binds ABCB1 (Gene) and ABCB1 (Gene) is bound by Telaprevir (Compound) and Telaprevir (Compound) resembles Boceprevir (Compound)
Ketoconazole (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) is bound by Cabazitaxel (Compound) and Cabazitaxel may cause a moderate interaction that could exacerbate diseases when taken with Boceprevir
Ketoconazole (Compound) is included by Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) and Cytochrome P450 3A4 Inhibitors (Pharmacologic Class) includes Aprepitant (Compound) and Aprepitant may cause a moderate interaction that could exacerbate diseases when taken with Boceprevir
Ketoconazole (Compound) is included by Cytochrome P450 3A5 Inhibitors (Pharmacologic Class) and Cytochrome P450 3A5 Inhibitors (Pharmacologic Class) includes Ticagrelor (Compound) and Ticagrelor may lead to a major life threatening interaction when taken with Boceprevir
Ketoconazole (Compound) causes Feeling abnormal (Side Effect) and Feeling abnormal (Side Effect) is caused by Cabazitaxel (Compound) and Cabazitaxel may cause a moderate interaction that could exacerbate diseases when taken with Boceprevir
Ketoconazole (Compound) causes Body temperature increased (Side Effect) and Body temperature increased (Side Effect) is caused by Abiraterone (Compound) and Abiraterone may cause a minor interaction that can limit clinical effects when taken with Boceprevir
Ketoconazole (Compound) causes Gastrointestinal disorder (Side Effect) and Gastrointestinal disorder (Side Effect) is caused by Telaprevir (Compound) and Telaprevir (Compound) resembles Boceprevir (Compound)