DDInter1008 DDInter107
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
Apalutamide is a potent androgen receptor (AR) antagonist that selectively binds to the ligand-binding domain of AR and blocks AR nuclear translocation or binding to androgen response elements . It has been used in trials studying the treatment of Prostate Cancer, Hepatic Impairment, Prostatic Neoplasms, Castration-Resistant Prostate Cancer, and Prostatic Neoplasms, Castration-Resistant, among others. Exerting an antitumor action, apalutamide blocking the effect of androgens that promote tumor growth. It targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets in prostate tumors . In mice bearing human CRPC xenograft models, apalutamide treatment produced tumor regressions in a dose-dependent manner that was more effective than that of or . Unlike bicalutamide, apalutamide antagonized AR-mediated signaling in AR overexpressing human CRPC cell lines . Androgen-deprivation therapy, or hormone therapy, can be used as part of maintenance therapy for patients with non-metastatic prostate cancer. Although most patients achieve therapeutic responses at the initial hormone therapy, many patients progress to non-metastatic castration-resistant (resistance to hormone therapy) prostate cancer which is the second-most common cause of cancer-related deaths in American males . Castration-resistant prostate cancer is often incurable, which poses significant clinical challenges for patients. Approximately 10 to 20 % of prostate cancer cases are castration-resistant, and up to 16% of these patients show no evidence of cancer metastasis at the time of castration-resistant diagnosis . Higher prostate-specific antigen (PSA) and shorter PSA doubling time (PSA DT) are associated with a higher risk for metastases and death . In a phase-2 multicenter open-label study, 89% of patients with non-metastatic, castration-resistant prostate cancer had ≥50% PSA decline at week 12 of apalutamide treatment . In a randomized trial, the median metastasis-free survival for patients taking apalutamide was 40.5 months compared to 16.2 months for patients taking a placebo . Apalutamide displayed good tolerability and safety profile in clinical studies. Apalutamide was approved in February 2018 by the FDA as Erleada for the treatment of patients with non-metastatic prostate cancer that is resistant to treatment with hormone therapy (castration-resistant). It is available as oral tablets. Apalutamide is the first FDA-approved treatment for non-metastatic, castration-resistant prostate cancer .
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
Ketoconazole {u} (Compound) resembles {v} (Compound) Itraconazole
Itraconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
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} Apalutamide
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Lidocaine
Lidocaine {u} may cause a minor interaction that can limit clinical effects when taken with {v} Apalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Proguanil
Proguanil {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
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} Apalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {u} (Gene) is bound by {v} (Compound) Nilotinib
Nilotinib {u} may lead to a major life threatening interaction when taken with {v} Apalutamide
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Eplerenone
Eplerenone {u} may cause a minor interaction that can limit clinical effects when taken with {v} Apalutamide
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Bisacodyl
Bisacodyl {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Apalutamide
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} Apalutamide
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
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 Apalutamide
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Lidocaine and Lidocaine may cause a minor interaction that can limit clinical effects when taken with Apalutamide
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Proguanil (Compound) and Proguanil may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
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 Apalutamide
Ketoconazole (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Nilotinib (Compound) and Nilotinib may lead to a major life threatening interaction when taken with Apalutamide
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Eplerenone (Compound) and Eplerenone may cause a minor interaction that can limit clinical effects when taken with Apalutamide
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Bisacodyl and Bisacodyl may cause a moderate interaction that could exacerbate diseases when taken with Apalutamide
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 Apalutamide