DDInter1008 DDInter1352
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
Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals.[A7926,L43453] Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy. Development of third-generation EGFR-TKIs, such as osimertinib, has been in response to altered tumour resistance patterns following treatment and toxic side effects that impact patient quality of life. Treatment with first-generation EGFR-TKIs (gefitinib and erlotinib) has been associated with the development of resistance through activating mutations in the EGFR gene. Second-generation EGFR-TKIs (afatinib and dacomitinib) were then developed to be more potent inhibitors, although their use is associated with increased toxicity through nonspecific targeting of wild-type EGFR. In contrast, third-generation inhibitors are specific for the gate-keeper T790M mutations which increases ATP binding activity to EGFR and result in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity.[A7926,A7927,A7931]
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
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} Osimertinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Bortezomib
Bortezomib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Osimertinib
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} Osimertinib
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} Osimertinib
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} Osimertinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Ivacaftor
Ivacaftor {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Ketoconazole {u} (Compound) binds {v} (Gene) CYP3A4
CYP3A4 {u} (Gene) is bound by {v} (Compound) Bortezomib
Bortezomib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Osimertinib
Ketoconazole {u} (Compound) resembles {v} (Compound) Posaconazole
Posaconazole {u} may lead to a major life threatening interaction when taken with {v} Vinorelbine
Vinorelbine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Ketoconazole {u} (Compound) binds {v} (Gene) ABCB11
ABCB11 {u} (Gene) is bound by {v} (Compound) Vinblastine
Vinblastine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Osimertinib
Ketoconazole (Compound) resembles Itraconazole (Compound) and Itraconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Osimertinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may cause a moderate interaction that could exacerbate diseases when taken with Bortezomib and Bortezomib may cause a minor interaction that can limit clinical effects when taken with Osimertinib
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 Osimertinib
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 Osimertinib
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 Osimertinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Ivacaftor and Ivacaftor may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Ketoconazole (Compound) binds CYP3A4 (Gene) and CYP3A4 (Gene) is bound by Bortezomib (Compound) and Bortezomib may cause a minor interaction that can limit clinical effects when taken with Osimertinib
Ketoconazole (Compound) resembles Posaconazole (Compound) and Posaconazole may lead to a major life threatening interaction when taken with Vinorelbine and Vinorelbine may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Ketoconazole (Compound) binds ABCB11 (Gene) and ABCB11 (Gene) is bound by Vinblastine (Compound) and Vinblastine may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib