|API type||One vial contains 150 mg of trastuzumab, a humanised IgG1 monoclonal antibody produced by mammalian (Chinese hamster ovary) cell suspension culture and purified by affinity and ion exchange chromatography including specific viral inactivation and removal procedures
|Antineoplastic agents, monoclonal antibodies
|Target of antibody|
|HER2; Synonyms: CD340, HER-2, HER-2/neu, MLN 19, NEU, NGL, TKR1, Erbb-2, Neu, c-erbB2, c-neu, mKIAA3023, wu:fv70f10, zgc:63601, erb2
(Mechanism of action; Source EMA document)
|The pharmacokinetics of trastuzumab were evaluated in a population pharmacokinetic model analysis using pooled data from 1,582 subjects, including patients with HER2 positive MBC, EBC, AGC or other tumor types, and healthy volunteers, in 18 Phase I, II and III trials receiving Herceptin IV. A two-compartment model with parallel linear and non-linear elimination from the central compartment described the trastuzumab concentration-time profile. Due to non-linear elimination, total clearance increased with decreasing concentration. Therefore, no constant value for half-life of trastuzumab can be deduced. The t1/2 decreases with decreasing concentrations within a dosing interval (see Table 16).
MBC and EBC patients had similar PK parameters (e.g. clearance (CL), the central compartment volume (Vc)) and population-predicted steady-state exposures (Cmin, Cmax and AUC). Linear clearance was 0.136 L/day for MBC, 0.112 L/day for EBC and 0.176 L/day for AGC. The non-linear elimination parameter values were 8.81 mg/day for the maximum elimination rate (Vmax) and 8.92 μg/mL for the Michaelis-Menten constant (Km) for the MBC, EBC, and AGC patients. The central compartment volume was 2.62 L for patients with MBC and EBC and 3.63 L for patients with AGC.
In the final population PK model, in addition to primary tumor type, body-weight, serum aspartate aminotransferase and albumin were identified as a statistically significant covariates affecting the exposure of trastuzumab. However, the magnitude of effect of these covariates on trastuzumab exposure suggests that these covariates.
|Pharmacodynamic properties (Pharmacodynamic effects; Source EMA document)||n/a
|Original license holder|
|Marketing authorisation numbers|
|EU/1/00/145/001 - 003
|Marketing authorisation holder|
|Roche Registration Limited
6 Falcon Way
Welwyn Garden City
|Name of the manufacturer of the biological active substance|
|Roche Diagnostics GmbH
Pharma Biotech Penzberg
1000 New Horizons Way
Vacaville, CA 95688
Roche Singapore Technical Operations Pte. Ltd.
10 Tuas Bay Link
Lonza Biologics Tuas Pte Ltd
35 Tuas South Ave. 6
|Name and address of the manufacturer(s) responsible for batch release||Roche Pharma AG
|Max shelf life|
|2°C – 8°C
|List of excipients|