DDInter1008 DDInter1087
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
Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant disorder estimated to affect approximately one in 20 million individuals resulting in adverse symptoms associated with premature ageing: skeletal dysplasia, joint contractures, atherosclerosis, myocardial fibrosis/dysfunction, scleroderma-like cutaneous effects, lipoatrophy, alopecia, and a severe failure to thrive; HGPS is uniformly fatal.[A224379, A224384, A224389, A224394, A224399] Mechanistically, HGPS is underpinned by a single heterozygous C-to-T mutation at position 1824 of the _LMNA_ gene, which results in the accumulation of an aberrant farnesylated form of lamin A called progerin in the inner nuclear membrane.[A224379, A224394] Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin; as progerin farnesylation is important for localization to the nuclear membrane, lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients.[A224379, A224414, A224419, L23414] Merck originally developed Lonafarnib and subsequently licensed it to Eiger Biopharmaceuticals Inc., which currently markets it under the trademark ZOKINVY™.[L23414, L23544] Lonafarnib was granted FDA approval on November 20, 2020, and is the first FDA-approved treatment for HGPS and other related progeroid laminopathies.[L23414, L23549]
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Leukopenia
Leukopenia {u} (Side Effect) is caused by {v} (Compound) Sibutramine
Sibutramine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Loratadine
Loratadine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Leukopenia
Leukopenia {u} (Side Effect) is caused by {v} (Compound) Nitisinone
Nitisinone {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Angiopathy
Angiopathy {u} (Side Effect) is caused by {v} (Compound) Cabazitaxel
Cabazitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Cabazitaxel
Cabazitaxel {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Menstrual disorder
Menstrual disorder {u} (Side Effect) is caused by {v} (Compound) Budesonide
Budesonide {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
Ketoconazole {u} (Compound) causes {v} (Side Effect) Hepatic function abnormal
Hepatic function abnormal {u} (Side Effect) is caused by {v} (Compound) Pazopanib
Pazopanib {u} may lead to a major life threatening interaction when taken with {v} Lonafarnib
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} Lonafarnib
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 moderate interaction that could exacerbate diseases when taken with {v} Lonafarnib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib
Ketoconazole (Compound) causes Leukopenia (Side Effect) and Leukopenia (Side Effect) is caused by Sibutramine (Compound) and Sibutramine may cause a minor interaction that can limit clinical effects when taken with Lonafarnib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Loratadine (Compound) and Loratadine may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Ketoconazole (Compound) causes Leukopenia (Side Effect) and Leukopenia (Side Effect) is caused by Nitisinone (Compound) and Nitisinone may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Ketoconazole (Compound) causes Angiopathy (Side Effect) and Angiopathy (Side Effect) is caused by Cabazitaxel (Compound) and Cabazitaxel may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Cabazitaxel (Compound) and Cabazitaxel may cause a moderate interaction that could exacerbate diseases when taken with Lonafarnib
Ketoconazole (Compound) causes Menstrual disorder (Side Effect) and Menstrual disorder (Side Effect) is caused by Budesonide (Compound) and Budesonide may lead to a major life threatening interaction when taken with Lonafarnib
Ketoconazole (Compound) causes Hepatic function abnormal (Side Effect) and Hepatic function abnormal (Side Effect) is caused by Pazopanib (Compound) and Pazopanib may lead to a major life threatening interaction when taken with Lonafarnib
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 Lonafarnib
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 moderate interaction that could exacerbate diseases when taken with Lonafarnib