DDInter1008 DDInter1659
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
Activation of the Raf-MEK-ERK signalling pathway is known to be implemented in several types of malignancies; thus, mitogen-activated protein kinase kinase (MEK) inhibitors such as selumetinib are important tools that can target the problematic overactivity of this pathway. Results from clinical trials investigating earlier developed MEK inhibitors were underwhelming. However, selumetinib demonstrated impressive efficacy and tolerability in Phase I trials, leading to its continued investigation for the treatment of various types of tumours in Phase II trials. Currently, the novel MEK 1 / 2 inhibitor, selumetinib, is approved solely for the treatment of Neurofibromatosis type 1 (NF-1) in a limited age group. NF-1 is considered rare, with an estimated incidence of 1/3000 individuals. It is a genetic, autosomal dominant condition resulting from mutations of the NF1 gene, which can lead to various complications, including the development of multiple tumours in the nervous system.[A193533,A193608] Some patients with this disorder develop plexiform neurofibromas (PN); however, this is considered relatively uncommon compared to other variants of NF-1. Luckily, the use of selumetinib in patients with NF-1 have shown efficacy in shrinking associated tumours and is linked to other positive clinical outcomes. Selumetinib was approved by the FDA on April 10, 2020. It was later approved by Health Canada on August 23, 2022.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Argatroban
Argatroban {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Dyspepsia
Dyspepsia {u} (Side Effect) is caused by {v} (Compound) Argatroban
Argatroban {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A5
CYP3A5 {u} (Gene) is bound by {v} (Compound) Fluconazole
Fluconazole {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Ivosidenib
Ivosidenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Lapatinib
Lapatinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Cimetidine
Cimetidine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Constipation
Constipation {u} (Side Effect) is caused by {v} (Compound) Fluconazole
Fluconazole {u} may lead to a major life threatening interaction when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Betrixaban
Betrixaban {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Apixaban
Apixaban {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pazopanib
Pazopanib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Selumetinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Argatroban (Compound) and Argatroban may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) causes Dyspepsia (Side Effect) and Dyspepsia (Side Effect) is caused by Argatroban (Compound) and Argatroban may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) binds CYP3A5 (Gene) and CYP3A5 (Gene) is bound by Fluconazole (Compound) and Fluconazole may lead to a major life threatening interaction when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Ivosidenib and Ivosidenib may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Lapatinib and Lapatinib may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Cimetidine and Cimetidine may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) causes Constipation (Side Effect) and Constipation (Side Effect) is caused by Fluconazole (Compound) and Fluconazole may lead to a major life threatening interaction when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Betrixaban and Betrixaban may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Apixaban and Apixaban may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Pazopanib and Pazopanib may cause a moderate interaction that could exacerbate diseases when taken with Selumetinib