Drug intelligence / Profile preview

Ado-trastuzumab emtansine + Imatinib

Development stage
Unknown
Lead developer
Genentech
Modality
Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral
01

Overview

The combination of ado-trastuzumab emtansine (T-DM1) and imatinib represents a case where two medications are used concomitantly, with potential drug interactions. According to the search results, imatinib can interact with ado-trastuzumab emtansine by increasing T-DM1 concentrations, potentially leading to T-DM1-related toxicity[1][3]. ## Drug Information **Ado-trastuzumab emtansine (T-DM1)** is an antibody-drug conjugate that combines the HER2-targeted monoclonal antibody trastuzumab with the cytotoxic agent DM1 (a maytansine derivative)[2][7]. It's marketed under the brand name Kadcyla and is primarily used for treating HER2-positive metastatic breast cancer in patients who previously received trastuzumab and a taxane[5][6]. **Imatinib** is a tyrosine kinase inhibitor that acts as a CYP3A4 inhibitor. It's commonly used in treating chronic myeloid leukemia (CML) and other cancers[1]. ## Interaction Mechanism The interaction between these drugs occurs because: - Imatinib is a CYP3A4 inhibitor - Ado-trastuzumab emtansine (T-DM1) is a CYP3A4 substrate - This interaction can increase T-DM1 concentrations, potentially leading to increased toxicity[1][3] ## Clinical Evidence There is limited published evidence on the concomitant use of these medications. The search results mention a case report of a 37-year-old female with both chronic myeloid leukemia (treated with imatinib) and metastatic HER2-positive breast cancer who received T-DM1 while continuing imatinib therapy[1]. In this case: - The patient had developed lung metastasis after previous treatment with trastuzumab and vinorelbine - T-DM1 and imatinib were administered concomitantly - No significant side effects were observed except for grade 1 fatigue - This case report was noted as the first to document the concomitant use of these medications[1] ## Safety Considerations When considering this combination, healthcare providers should be aware of: - The potential for increased T-DM1 concentrations due to the metabolic interaction - Possible increased risk of T-DM1-related toxicities - The need for careful monitoring when these medications are used together While the single case report suggested tolerability, more research would be needed to establish the safety profile of this combination across a broader patient population.

02

Targets

ABL1 myristoyl pocketERBB2 (Erb-b2 receptor tyrosine kinase 2)KIT (c-KIT proto-oncogene receptor tyrosine kinase)PDGFR (PDGFR family)ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase)Tyrosine kinase

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