Premedication in the Outpatient Setting: IV Cetirizine or IV Diphenhydramine? A Literature Review

Background: Premedication regimens to prevent infusion-related reactions typically include steroids and first-generation antihistamines, primarily diphenhydramine. With the recent approval of intravenous cetirizine, a second-generation antihistamine, for acute urticaria and angioedema, reevaluating premedication standard regimens is warranted. This review explores whether cetirizine can improve efficiency and reduce side effects in outpatient infusion settings. Methods: A literature review was conducted using the PICO question: “In adult and pediatric outpatient infusion patients receiving premedication, how does intravenous (IV) cetirizine compare to IV diphenhydramine in preventing infusion-related and adverse drug reactions?” The authors searched in CINAHL, EBSCOhost, and PubMed for English-language articles from 2019 to 2025, reflecting the time since intravenous cetirizine’s FDA approval. Keywords included diphenhydramine, cetirizine, infusion-related reactions, and premedication. Thirty-five articles were identified; after removing duplicates and excluding those using only oral cetirizine or focused solely on acute urticaria, 8 studies were selected for full review. Results: Intravenous cetirizine was found to be a safe, effective alternative to IV diphenhydramine, with similar efficacy in preventing reactions. It was associated with fewer adverse effects, less sedation, and reduced patient chair time, potentially improving both workflow efficiency and patient satisfaction.