DDInter458 DDInter1352
Cyclosporine is a calcineurin inhibitor known for its immunomodulatory properties that prevent organ transplant rejection and treat various inflammatory and autoimmune conditions. It is isolated from the fungus _Beauveria nivea_. Initially manufactured by Sandoz and approved for use by the FDA in 1983, cyclosporine is now available in various products by Novartis (previously known as Sandoz).[L11097,L3734,L11118]
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]
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C9
CYP2C9 {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
Cyclosporine {u} (Compound) binds {v} (Gene) CYP2C19
CYP2C19 {u} (Gene) is bound by {v} (Compound) Melatonin
Melatonin {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Cyclosporine {u} (Compound) upregulates {v} (Gene) EPRS
EPRS {u} (Gene) is upregulated by {v} (Compound) Bortezomib
Bortezomib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Osimertinib
Cyclosporine {u} (Compound) downregulates {v} (Gene) HSPA8
HSPA8 {u} (Gene) is upregulated by {v} (Compound) Bortezomib
Bortezomib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Osimertinib
Cyclosporine {u} (Compound) upregulates {v} (Gene) EPRS
EPRS {u} (Gene) is downregulated by {v} (Compound) Bisacodyl
Bisacodyl {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Cyclosporine {u} (Compound) downregulates {v} (Gene) HSPA8
HSPA8 {u} (Gene) is downregulated by {v} (Compound) Dabrafenib
Dabrafenib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Cyclosporine {u} (Compound) upregulates {v} (Gene) HSPA5
HSPA5 {u} (Gene) is downregulated by {v} (Compound) Pentamidine
Pentamidine {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Cyclosporine {u} (Compound) upregulates {v} (Gene) EPRS
EPRS {u} (Gene) is upregulated by {v} (Compound) Vemurafenib
Vemurafenib {u} may lead to a major life threatening interaction when taken with {v} Osimertinib
Cyclosporine {u} (Compound) downregulates {v} (Gene) HSPB1
HSPB1 {u} (Gene) is upregulated by {v} (Compound) Vinblastine
Vinblastine {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Cyclosporine {u} (Compound) upregulates {v} (Gene) HMOX1
HMOX1 {u} (Gene) is upregulated by {v} (Compound) Formoterol
Formoterol {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Osimertinib
Cyclosporine (Compound) binds CYP2C9 (Gene) and CYP2C9 (Gene) is bound by Bortezomib (Compound) and Bortezomib may cause a minor interaction that can limit clinical effects when taken with Osimertinib
Cyclosporine (Compound) binds CYP2C19 (Gene) and CYP2C19 (Gene) is bound by Melatonin (Compound) and Melatonin may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Cyclosporine (Compound) upregulates EPRS (Gene) and EPRS (Gene) is upregulated by Bortezomib (Compound) and Bortezomib may cause a minor interaction that can limit clinical effects when taken with Osimertinib
Cyclosporine (Compound) downregulates HSPA8 (Gene) and HSPA8 (Gene) is upregulated by Bortezomib (Compound) and Bortezomib may cause a minor interaction that can limit clinical effects when taken with Osimertinib
Cyclosporine (Compound) upregulates EPRS (Gene) and EPRS (Gene) is downregulated by Bisacodyl (Compound) and Bisacodyl may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Cyclosporine (Compound) downregulates HSPA8 (Gene) and HSPA8 (Gene) is downregulated by Dabrafenib (Compound) and Dabrafenib may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Cyclosporine (Compound) upregulates HSPA5 (Gene) and HSPA5 (Gene) is downregulated by Pentamidine (Compound) and Pentamidine may lead to a major life threatening interaction when taken with Osimertinib
Cyclosporine (Compound) upregulates EPRS (Gene) and EPRS (Gene) is upregulated by Vemurafenib (Compound) and Vemurafenib may lead to a major life threatening interaction when taken with Osimertinib
Cyclosporine (Compound) downregulates HSPB1 (Gene) and HSPB1 (Gene) is upregulated by Vinblastine (Compound) and Vinblastine may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib
Cyclosporine (Compound) upregulates HMOX1 (Gene) and HMOX1 (Gene) is upregulated by Formoterol (Compound) and Formoterol may cause a moderate interaction that could exacerbate diseases when taken with Osimertinib