KADCYLA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/VIAL FOR INTRAVENOUS USE

Product Information

Registration Status: Active

KADCYLA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/VIAL is approved to be sold in Singapore with effective from 2014-01-24. It is marketed by ROCHE SINGAPORE PTE LTD, with the registration number of SIN14497P.

This product contains Trastuzumab Emtansine 100mg/vial in the form of INJECTION, POWDER, FOR SOLUTION. It is approved for INTRAVENOUS use.

This product is manufactured by Patheon Manufacturing Services LLC in UNITED STATES, andF. Hoffmann-La Roche Ltd (Bulk Production in SWITZERLAND.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Description

Trastuzumab emtansine, formerly called Trastuzumab-DM1 (T-DM1) is a first-in-class HER2 antibody drug conjugate (ADC) comprised of Genentech's trastuzumab antibody linked to ImmunoGen's cell-killing agent, DM1. T-DM1 combines two strategies-- anti-HER2 activity and targeted intracellular delivery of the potent anti-microtubule agent, DM1 (a maytansine derivative)--to produce cell cycle arrest and apoptosis. Trastuzumab emtansine is marketed under the brand name Kadcyla and is indicated for use in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment. The FDA label has two precautions. First that trastuzumab emtansine and trastuzumab cannot be interchanged. Second that there is a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity.

Indication

Used in HER2-positive, metastatic breast cancer patients who have already used taxane and/or trastuzumab for metastatic disease or had their cancer recur within 6 months of adjuvant treatment.

Mechanism of Action

Trastuzumab emtansine is a HER2 antibody drug conjugate. The antibody portion is trastuzumab, which is humanized anti-HER2 IgG1, and produced in the mammalian Chinese Hamster Ovary cells. The drug portion is DM1, which is a maytansine derivative that inhibits microtubules. These two portions are covalently connected by 4-[N-maleimidomethyl] cyclohexane-1-carboxylate (MCC), which is a stable thioether linker. Together MCC and DM1 are called emtansine and are produced by chemical synthesis. Trastuzumab emtansine binds to the HER2 receptor’s sub-domain IV and goes into the cell by receptor-mediated endocytosis. Lysosomes degrade trastuzumab emtansine and release DM1. DM1 binds to tubulin in microtubules and inhibits microtubule function producing cell arrest and apoptosis. As well, similar to trastuzumab, in vitro studies have shown that both HER2 receptor signalling inhibition and antibody-dependent cytotoxicity are mediated by trastuzumab emtansine.

Pharmacokinetics

Absorption: The absorption/ bioavailability should be close to 100% since trastuzumab emtansine is administered IV.
Distribution: The volume of distribution of trastuzumab emtansine is about 3.13 L.
Metabolism: Trastuzumab emtansine undergoes lysosomal degradation to MCC-DM1, Lys-MCC-DM1, and DM1. All of these products are detected at low levels in the plasma. DM1 undergoes further degradation by CYP3A4 and CYP3A5, but DM1 does not induce or inhibit any of the CYP450 enzymes.
Elimination

Clearance

After IV infusion, trastuzumab emtansine has a clearance of 0.68 L/day.

Toxicity

The FDA label includes a black box warning of serious side effects such as hepatotoxicity, embryo-fetal toxicity, and cardiac toxicity.

Active Ingredient/Synonyms

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.