Comparison of H1 versus combined H1/H2 antagonist premedication on incidence of rituximab infusion-related reaction: A retrospective cohort study

IntroductionRituximab, an anti-CD20 monoclonal antibody used in B-cell malignancies, is associated with infusion-related reactions (IRRs) during the initial infusion. Standard premedication includes acetaminophen, corticosteroids, and a histamine-1 (H1) antagonist, typically diphenhydramine. Second-generation H1 antagonists offer similar efficacy with less sedation. Some institutions also incorporate histamine-2 (H2) antagonists despite limited supporting evidence. This study evaluated whether dual H1/H2 antagonist premedication reduces IRRs compared with H1-antagonist monotherapy when given with standard premedication.MethodsThis retrospective study reviewed health records of adults with a hematologic malignancy who received their first rituximab infusion at Brown University Health system between January 1, 2022 and June 30, 2025. Patients received premedication with either an H1-antagonist alone or dual H1/H2 receptor-antagonists with acetaminophen and a corticosteroid. The primary endpoint was IRR incidence during or within 24 h of infusion initiation. Secondary endpoints included IRR severity, incidence of grade 3-4 IRRs across subgroups, and time to IRR onset.ResultsAmong 299 patients (mean age 65; 55% male), 62% had aggressive lymphoma, 28% indolent lymphoma, and 10% leukemia. Baseline features included bone marrow involvement (38%), bone disease (39%), advanced-stage nodal disease (54%), B symptoms (48%), and >2 extranodal sites (28%). IRRs occurred in 38% of patients receiving dual H1/H2 antagonist premedication versus 36.5% with H1-antagonist monotherapy, with no difference in grade 3-4 IRRs. Most IRRs occurred 30 to 60 min after infusion initiation.ConclusionDual H1/H2-antagonist premedication was not associated with differences in the incidence or severity of rituximab IRRs compared with H1-antagonist monotherapy in addition to standard premedication.