IV diphenhydramine has been considered the standard of care for hypersensitivity infusion reactions. However, IV diphenhydramine has an adverse-event (AE) profile that includes potent anticholinergic effects, and it is a Beer's list drug, making its use undesirable in older adults. IV cetirizine, approved in 2019 for the treatment of acute urticaria in adults, may offer a more favorable AE profile.

A randomized, double-blind, parallel-group, pilot, exploratory, phase II trial was conducted to assess the incidence of hypersensitivity infusion reactions (HIRs) associated with administration of the anti-CD20 agent rituximab or paclitaxel following premedication with a single dose of either IV cetirizine 10 mg or IV diphenhydramine 50 mg via IV push over 1 to 2 minutes. Labeling for both rituximab and paclitaxel carries a black-box warning about fatal HIRs.

Between March 2020 and November 2020, the study enrolled 34 adults with hematologic and solid tumors. The IV diphenhydramine group and the IV cetirizine group each contained 17 patients. The median age of the overall population was 66 years, and most patients (64.7%) were male.

Of the total group, 73.5% had received rituximab for hematologic malignancies: 70.6% of the IV cetirizine patients and 76.5% of the IV diphenhydramine patients. Because of study-recruitment issues related to COVID-19, the trial started enrolling patients on paclitaxel (26.5%) in August 2020. Paclitaxel patients had solid tumors.

Steroids or H2-receptor antagonists could be used as rescue medications. Patients were observed for at least 1 hour post administration of anti-inflammatory drugs to assess for signs or symptoms of an HIR. Patients also rated how drowsy they felt on a scale of 0 to 4 post pretreatment administration; health professionals completed a similar patient assessment.

The primary object of this study was to compare the incidence of HIR after premedication with either IV cetirizine or IV diphenhydramine. Secondary objectives were assessment of sedation, time spent at the treatment center (time from injection to discharge), and safety. A subgroup analysis was conducted of patients aged 65 years or older.

This descriptive report found that the overall incidence of HIR was 11.8% (2 patients) in the IV cetirizine group and 17.6% (3 patients) in the IV diphenhydramine group. In the elderly subgroup analysis (n = 9), 11.1% (1 patient) of older adults who received IV cetirizine and 16.7% (2 patients) of seniors who received IV diphenhydramine experienced an HIR.

Mean sedation scores were higher for the total IV diphenhydramine group compared with the IV cetirizine group at all time points measured, which included 1 and 2 hours post pretreatment and at discharge. A similar trend was found in the elderly subgroup. Median time for readiness to discharge was 25 minutes longer for the total IV diphenhydramine group and increased to 30 minutes for the first-generation antihistamine in the older-adult population.

Overall, one-half of all study patients experienced at least one AE, including 47.1% of the IV cetirizine group and 52.9% of the IV diphenhydramine group. In the elderly subgroup, 61.9% had experienced at least one AE, including 55.6% in the IV cetirizine group and 66.7% in the IV diphenhydramine group. When causality was assessed for the total population, there were fewer patients with possible or probable treatment-related AEs with IV cetirizine (n = 2) versus IV diphenhydramine (n = 4).

Although this pilot study lacked statistical power, it supported work by Durham et al, which also found that IV cetirizine could be a viable substitute for IV diphenhydramine in preventing chemotherapy-related HIRs.

Pharmacists should be aware of emerging drug-therapy trends in order to both understand and participate in patient treatment decisions.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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