Inhibitory Effect on Rituximab-induced Infusion Reaction by Premedication with Fexofenadine or Bepotastine

Abstract

Since infusion reaction (IR) frequently occurs in rituximab (RTX) therapy, premedication of antipyretic analgesics and histamine 1 (H₁) receptor antagonists before RTX administration is essential. However, there are no standard drugs for H₁ receptor antagonists. There is a possibility that H₁ receptor antagonists with various pharmacokinetic properties have different preventive/suppressive effects against IR. In this study, we conducted a retrospective study on patients who received RTX first dose with premedication of fexofenadine (n = 31) or bepotastine (n = 33), the second generation H₁ receptor antagonist, to compare the inhibitory effects of both drugs on IR occurrence. The incidence of IR was 58.1％ in the fexofenadine-administered group and 21.2％ in the bepotastine-administered group with a significant difference. The IR occurrence time (median) was 65 min after RTX administration in both groups. Multivariate logistic regression analysis indicated that the fexofenadine-administered group is an independent risk factor to increase the risk of IR occurrence by 8.3 times compared with the bepotastine-administered group. Since fexofenadine takes a longer time to reach maximum blood concentration (T_max) than bepotastine, it is considered that the different effect on IR prevention in both drugs may be caused by the difference in T_max. Based on these results, it was suggested that H1 receptor antagonists to be administered before RTX administration should be selected taking their pharmacokinetic properties into consideration.