DDInter1042 DDInter1352
Leuprolide is a synthetic 9-residue peptide analogue of gonadotropin-releasing hormone (GnRH). Unlike the endogenous decapeptide GnRH, leuprolide contains a single D-amino acid (D-leucyl) residue, which helps to increase its circulating half-life from three to four minutes to approximately three hours. As a GnRH mimic, leuprolide is capable of binding to the GnRH receptor (GnRHR) and inducing downstream modulation of both gonadotropin hormone and sex steroid levels. Prolonged activation of GnRHR results in significant downregulation of sex steroid levels, which is primarily responsible for the clinical efficacy of leuprolide in diverse conditions, including advanced prostate cancer, endometriosis, and central precocious puberty.[A203126, A203132] Leuprolide was first approved in 1985 as a daily subcutaneous injection under the tradename
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