DDInter1008 DDInter1480
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
Pitolisant is a selective antagonist or inverse agonist of the histamine H3 receptor used to treat type 1 or 2 narcolepsy. Narcolepsy is a chronic neurological disorder that affects 1 in 2,000 individuals and is characterized by excessive daytime sleepiness, abnormal REM sleep manifestations, sleep paralysis and hypnagogic hallucinations. About 60-70% of patients with narcolepsy experience cataplexy, which is a sudden loss of muscle tone triggered by positive or negative emotions. Histaminergic neuron signalling in the brain plays a role in maintaining wakefulness; by blocking histamine autoreceptors, pitolisant enhances the activity of histaminergic neurons, as well as increasing the signalling of other neurotransmitters in the brain. In a European clinical trial of adult patients with narcolepsy, there was a reduction in the Epworth Sleepiness Scale (ESS) score from pitolisant therapy compared to placebo. The therapeutic effectiveness of pitolisant was comparable to that of [modafinil]. Pitolisant therapy was also effective in treating refractory sleepiness in adolescent patients with narcolepsy, where it decreased ESS score and increased the mean sleep onset latency. Adolescent patients with cataplexy also experienced a slight improvement in the frequency and severity of symptoms ; however, the safety of use in adolescent or paediatric patients have not been established with pitolisant. Commonly marketed under the trade name Wakix, oral pitolisant was approved by the EMA in 2016 for the treatment of narcolepsy with or without cataplexy. FDA approved the use of pitolisant in 2019 for excessive daytime sleepiness (EDS) associated with narcolepsy in adults.
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Metronidazole
Metronidazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Pitolisant
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Repaglinide
Repaglinide {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pitolisant
Ketoconazole {u} (Compound) causes {v} (Side Effect) Skin burning sensation
Skin burning sensation {u} (Side Effect) is caused by {v} (Compound) Metronidazole
Metronidazole {u} may cause a minor interaction that can limit clinical effects when taken with {v} Pitolisant
Ketoconazole {u} (Compound) causes {v} (Side Effect) Skin burning sensation
Skin burning sensation {u} (Side Effect) is caused by {v} (Compound) Isotretinoin
Isotretinoin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pitolisant
Ketoconazole {u} (Compound) causes {v} (Side Effect) Skin burning sensation
Skin burning sensation {u} (Side Effect) is caused by {v} (Compound) Crizotinib
Crizotinib {u} may lead to a major life threatening interaction when taken with {v} Pitolisant
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C8
CYP2C8 {u} (Gene) is bound by {v} (Compound) Halofantrine
Halofantrine {u} may lead to a major life threatening interaction when taken with {v} Pitolisant
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} Pitolisant
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Cobicistat
Cobicistat {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pitolisant
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Fluconazole
Fluconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pitolisant
Ketoconazole {u} (Compound) binds {v} (Gene) CYP1A1
CYP1A1 {u} (Gene) is upregulated by {v} (Compound) Bisacodyl
Bisacodyl {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Pitolisant
Ketoconazole (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Metronidazole (Compound) and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Pitolisant
Ketoconazole (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Repaglinide (Compound) and Repaglinide may cause a moderate interaction that could exacerbate diseases when taken with Pitolisant
Ketoconazole (Compound) causes Skin burning sensation (Side Effect) and Skin burning sensation (Side Effect) is caused by Metronidazole (Compound) and Metronidazole may cause a minor interaction that can limit clinical effects when taken with Pitolisant
Ketoconazole (Compound) causes Skin burning sensation (Side Effect) and Skin burning sensation (Side Effect) is caused by Isotretinoin (Compound) and Isotretinoin may cause a moderate interaction that could exacerbate diseases when taken with Pitolisant
Ketoconazole (Compound) causes Skin burning sensation (Side Effect) and Skin burning sensation (Side Effect) is caused by Crizotinib (Compound) and Crizotinib may lead to a major life threatening interaction when taken with Pitolisant
Ketoconazole (Compound) binds CYP2C8 (Gene) and CYP2C8 (Gene) is bound by Halofantrine (Compound) and Halofantrine may lead to a major life threatening interaction when taken with Pitolisant
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 Pitolisant
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Cobicistat and Cobicistat may cause a moderate interaction that could exacerbate diseases when taken with Pitolisant
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Fluconazole and Fluconazole may cause a moderate interaction that could exacerbate diseases when taken with Pitolisant
Ketoconazole (Compound) binds CYP1A1 (Gene) and CYP1A1 (Gene) is upregulated by Bisacodyl (Compound) and Bisacodyl may cause a moderate interaction that could exacerbate diseases when taken with Pitolisant