DDInter1008 DDInter822
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
Glasdegib, also known as PF-04449913, is a small-molecule hedgehog signaling inhibitor selected under the group of benzimidazoles. In early research, benzimidazoles attracted large interest as they represented a class of inhibitors with low molecular weight, potent inhibitory activity, and lacking unstable functionality. The great lipophilicity of this group of compounds brought interest to further modification. This analysis concluded that the presence of p-cyano ureas presented good physicochemical and pharmacokinetic properties from which glasdegib was developed. Glasdegib was developed by Pfizer Inc and approved on November 21, 2018 by the FDA for the treatment of Acute Myeloid Leukemia (AML). Glasdegib targets cancerous cells by inhibiting the sonic hedgehog receptor smoothened (SMO), a transmembrane protein involved in the Hedgehog (Hh) signaling cascade. Aberrant of Hh signaling is one of the main pathophysiologies of AML, with observed overexpression or constitutive activation of SMO.[A258498,A258503] Although the efficacy of glasdegib monotherapy is limited, the landmark Phase 2 Bright AML 1003 trial showed a superior overall survival and complete response when glasdegib is combined with low dose cytarabine. Currently, the current gold standard of AML in older patients is still venetoclax with hypomethylation agents, new clinical combinations of glasdegib are being tested in hope of replacing venetoclax due to glasdegib's more favorable side effects profile.
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Glasdegib
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} Glasdegib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Naloxegol
Naloxegol {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Ketoconazole {u} (Compound) resembles {v} (Compound) Econazole
Econazole {u} (Compound) resembles {v} (Compound) Miconazole
Miconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Metronidazole
Metronidazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Darolutamide
Darolutamide {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Nefazodone
Nefazodone {u} may lead to a major life threatening interaction when taken with {v} Glasdegib
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} Glasdegib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sulfamethoxazole
Sulfamethoxazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Glasdegib
Ketoconazole {u} (Compound) binds {v} (Gene) SLCO1A2
SLCO1A2 {u} (Gene) is bound by {v} (Compound) Fexofenadine
Fexofenadine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Glasdegib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Glasdegib
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Glasdegib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Naloxegol and Naloxegol may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Ketoconazole (Compound) resembles Econazole (Compound) and Econazole (Compound) resembles Miconazole (Compound) and Miconazole may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a minor interaction that can limit clinical effects when taken with Metronidazole and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Darolutamide and Darolutamide may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Nefazodone (Compound) and Nefazodone may lead to a major life threatening interaction when taken with Glasdegib
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 Glasdegib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sulfamethoxazole (Compound) and Sulfamethoxazole may cause a minor interaction that can limit clinical effects when taken with Glasdegib
Ketoconazole (Compound) binds SLCO1A2 (Gene) and SLCO1A2 (Gene) is bound by Fexofenadine (Compound) and Fexofenadine may cause a moderate interaction that could exacerbate diseases when taken with Glasdegib