Department of Pediatrics, Medical College of Georgia at Augusta University, Augusta, Georgia.
Medical College of Georgia at Augusta University, 1090 Windfaire Place, 30076, Roswell, Georgia.
Adv Ther. 2022 Jan;39(1):178-192. doi: 10.1007/s12325-021-01999-x. Epub 2021 Dec 4.
Since 1955, the only available H antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.
自 1955 年以来，唯一可用于静脉给药的 H 抗组胺药为第一代制剂，其中只有静脉注射（IV）苯海拉明仍在美国获得批准。口服第二代 H 抗组胺药盐酸西替利嗪多年来一直安全地在柜台上使用。2019 年，IV 西替利嗪被批准用于治疗急性荨麻疹。鉴于这一批准，本叙述性综述讨论了用于治疗组氨酸介导病症的 IV 抗组胺药不断变化的格局。具体而言，IV 抗组胺药将被讨论为急性荨麻疹和血管性水肿的治疗选择、作为预防与抗癌药物和其他生物制剂相关输注反应的预防用药，以及作为过敏反应和其他过敏反应的辅助治疗。在 IV 西替利嗪开发之前，这些适应症的 IV 抗组胺药的随机对照试验缺乏。在门诊环境中，已经进行了三项 IV 西替利嗪与 IV 苯海拉明的随机对照试验。一项 III 期试验比较了 IV 西替利嗪 10mg 与 IV 苯海拉明 50mg 治疗 262 例因急性荨麻疹需要抗组胺治疗而就诊于急症/急诊室的成人。主要疗效终点定义为 2 小时时患者自评瘙痒评分与基线相比的变化，结果显示 IV 西替利嗪非劣效于 IV 苯海拉明（评分分别为-1.6 与-1.5，95%CI-0.1，0.3）。与 IV 苯海拉明相比，IV 西替利嗪不良反应更少，包括镇静作用更小、治疗中心停留时间明显缩短，以及在 24 和 48 小时时返回治疗中心的次数更少。另一项 II 期急性荨麻疹试验和一项评估 IV 西替利嗪在肿瘤/免疫学领域用于预防输注反应的 II 期试验也得出了类似的发现。IV 西替利嗪与 IV 苯海拉明相比，具有相似的患者结局、更少的不良反应和更高的治疗中心效率。
