A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study

Abstract

Purpose Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. Methods This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). Results Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. Conclusion The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. Trial registration ClinicalTrials.gov, NCT04237090 (22.01.2020). Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06734-4.

Repurposing of H1-receptor antagonists (levo)cetirizine, (des)loratadine, and fexofenadine as a case study for systematic analysis of trials on clinicaltrials.gov using semi-automated processes with custom-coded software

“…J Infus Nurs 44:315–322. https://doi.org/10.1097/NAN.0000000000000444 Cetirizine (10 mg IV) Prevention of Infusion associated reactions Randomized, double-blind with parallel arms “IV cetirizine (10 mg) is an effective and safe alternative to IV diphenhydramine (50 mg) in the prevention of hypersensitivity infusion reactions” Small sample size 10 Beaucage-Charron J, Gaudet L, Lamothe S, et al ( 2022 ) A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study. Support Care Cancer 30:3389–3399.…”

“…In NCT04237090, the feasibility of a clinical trial was tested and deemed acceptable. Here, cetirizine produced less drowsiness and seemed to be a replacement worth looking into further (Beaucage-Charron et al 2022 ).…”

“…In the case of infusion-associated reactions, the literature suggests cetirizine to be a viable substitute for diphenhydramine with the advantages of less adverse reactions and less drowsiness (Durham et al 2019 ; Holmes et al 2021 ; Beaucage-Charron et al 2022 ). Although this is not surprising, as both diphenhydramine and cetirizine are H 1 R antagonists, the use of the newer generation antagonist cetirizine seems to be a good alternative and replacement for the future.…”

Premedication of Ranitidine and the Action of Hypersensitivity Reactions to Paclitaxel

“…This revelation highlights the noteworthy inf luence of diphenhydramine on psychomotor function, underscoring the importance of considering potential cognitive effects when utilizing this medication for hypersensitivity reactions. [8][9][10][11][12] Cetirizine and its second-generation H1 antihistamine counterparts minimize side effects by precisely targeting H1 receptors and exhibiting limited blood-brain barrier penetration. Renowned for their excellent safety and efficacy, these modern H1 antihistamines have ascended to the forefront, establishing themselves as the preferred firstline treatment for allergic rhinitis and urticaria.…”

Overview of premedication prescription and intake in an oncology day hospital: What do we need to change to improve patient management?

“…Medications proposed for the oral substitution are: cetirizine as an anti-H1 instead of dexchlorpheniramine, which has shown its iso-efficacy while being less sedative [35][36][37] ; ondansetron as an anti-5HT3 because it is the best balance between efficacy and cost, 38 prednisolone or dexamethasone depending on the protocol.…”