DDInter927 DDInter1352
Inotuzumab ozogamicin is an antibody-drug conjugate using linker and cytotoxic drug technology similar to that developed for the ground-breaking treatment Mylotarg (), which was approved by the US FDA in 2000 for the treatment of acute myeloid leukaemia. Inotuzumab ozogamicin consists of a recombinant humanised IgG4 kappa CD22-targeting monoclonal antibody covalently attached to calicheamicin derivative, N-acetyl-gamma-calicheamicin dimethylhydrazide, which is a potent DNA-binding cytotoxic agent. Developed by Pfizer and UCB, inotuzumab ozogamicin was granted approval by EU in June 2017 followed by FDA on August 17th, 2017 for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). ALL is a rapidly progressing cancer of the bone marrow that is associated with
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]
Osimertinib {u} may cause a minor interaction that can limit clinical effects when taken with {v} Bortezomib
Osimertinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Ivacaftor
Osimertinib {u} may cause a moderate interaction that could exacerbate diseases when taken with {v} Tazemetostat
Osimertinib {u} may lead to a major life threatening interaction when taken with {v} Tetrabenazine
Osimertinib {u} may lead to a major life threatening interaction when taken with {v} Entrectinib
Osimertinib may cause a minor interaction that can limit clinical effects when taken with Bortezomib
Osimertinib may cause a moderate interaction that could exacerbate diseases when taken with Ivacaftor
Osimertinib may cause a moderate interaction that could exacerbate diseases when taken with Tazemetostat
Osimertinib may lead to a major life threatening interaction when taken with Tetrabenazine
Osimertinib may lead to a major life threatening interaction when taken with Entrectinib