Optimizing paclitaxel pretreatment: cetirizine as a safe and patient-centered alternative to clemastine

Paclitaxel is widely used in breast cancer treatment but is associated with hypersensitivity reactions (HSRs), historically prompting routine premedication with corticosteroids, histamine 2 (H2)- and histamine 1 (H1)-antagonists. First-generation H1-antagonists such as clemastine or diphenhydramine frequently cause sedation and anticholinergic adverse effects, whereas second-generation agents such as cetirizine or loratidine have a more favorable safety profile. Optimizing premedication regimens may reduce treatment burden and improve patient safety. To evaluate the comparative safety and effectiveness of cetirizine versus clemastine in preventing paclitaxel induced HSRs in patients with breast cancer. A multicenter prospective observational cohort study was conducted across three Dutch hospitals. Female patients receiving weekly paclitaxel following dose dense doxorubicin/cyclophosphamide were included. Premedication consisted of either oral cetirizine or intravenous clemastine according to institutional protocols. HSRs during the first two paclitaxel doses were graded using CTCAE v5.0. Premedication-related adverse events were assessed using a structured nurse-administered questionnaire. Among 100 patients (50 per cohort), HSR incidence was identical: 8% in both groups, predominantly grade 1, with no severe reactions and no treatment discontinuations. By contrast, adverse events were markedly more frequent with clemastine (80%) than with cetirizine (10%), driven predominantly by higher rates of sedation and drowsiness in the clemastine group. Cetirizine appeared to provide efficacy comparable to clemastine in preventing paclitaxel induced HSRs, while markedly reducing sedative adverse effects. Its oral administration also streamlines clinical workflows. These findings may support cetirizine as a safer, more patient centered H1-antagonist option for paclitaxel premedication and warrant consideration in efforts to optimize supportive care protocols.