Post‐marketing assessment of generic tamoxifen in Brazilian breast cancer patients

Abstract

Generic formulations of tamoxifen are commonly prescribed to oestrogen receptor‐positive breast cancer patients at the Brazilian National Cancer Institute (INCA). We carried out a post‐marketing surveillance of the generic tamoxifen formulation in current use at INCA, by comparing plasma concentrations of the parent drug and metabolites obtained with the generic vs the reference formulation. Thirty patients participated in an open‐label, bracketed protocol, comprising 3 successive phases of 30‐32 days each: the generic formulation was used in phases 1 and 3 and the reference formulation in phase 2. Two blood samples were collected in the last 4 days of each phase, for LC‐MS/MS quantification of tamoxifen and metabolites in plasma. The median plasma concentrations (ng/mL) for the reference formulation were as follows: tamoxifen, 135.0 (CI 95% 114.2‐155.8); endoxifen, 35.3 (30.0‐40.8); and 4‐hydroxytamoxifen, 4.8 (4.2‐5.4). The endoxifen/tamoxifen plasma concentration ratio was 0.27 (0.21‐0.25). ANOVA detected no statistically significant difference in plasma concentrations of tamoxifen, metabolites or the endoxifen/tamoxifen ratio among the three phases. The genetic component (rGC) of the CYP2D6‐mediated conversion of tamoxifen into endoxifen, estimated using the repeated drug administration procedure across the three phases, was 0.87, pointing to an important component of genetic variability. In conclusion, this first post‐marketing surveillance trial of oncologic generic drugs carried out in Brazilian patients verified the switchability between the reference and the generic tamoxifen formulation currently used at our institution. The adopted bracketed protocol adds confidence to this conclusion and may serve as a frame for future trials of post‐marketing assessment of other generic drug products.

Postmarketing assessment of a switchable similar anastrozole product in Brazilian breast cancer patients

“…6 We have recently verified the switchability between the reference and a generic tamoxifen formulation prescribed to breast cancer patients at the Brazilian National Cancer Institute (INCA). 7 INCA is the organization of the Brazilian Ministry of Health responsible for development and coordination of integrated actions in prevention and control of cancer in Brazil. 8 The present study explores the switchability between the reference product and a similar anastrozole formulation in current use at INCA for treatment of postmenopausal breast cancer patients.…”