Intravenous Cetirizine Versus Intravenous Diphenhydramine for the Treatment of Acute Urticaria: A Phase III Randomized Controlled Noninferiority Trial.

STUDY OBJECTIVE: Acute urticaria is a frequent presentation in emergency departments (EDs), urgent care centers, and other clinical arenas. Treatment options are limited if diphenhydramine is the only intravenous antihistamine offered because of its short duration of action and well-known adverse effects. We evaluate cetirizine injection, the first second-generation injectable antihistamine, for acute urticaria in this multicenter, randomized, noninferiority, phase 3 clinical trial. METHODS: Adult patients presenting to EDs and urgent care centers with acute urticaria requiring an intravenous antihistamine were randomized to either intravenous cetirizine 10 mg or intravenous diphenhydramine 50 mg. The primary endpoint was the 2-hour pruritus score change from baseline, with time spent in treatment center and rate of return to treatment centers as key secondary endpoints. Frequency of sedation and anticholinergic adverse effects were also recorded. RESULTS: Among 262 enrolled patients, the 2-hour pruritus score change from baseline for intravenous cetirizine was statistically noninferior to that for intravenous diphenhydramine (-1.6 versus -1.5; 95% confidence interval -0.1 to 0.3), and in favor of cetirizine. Treatment differences also favored cetirizine for mean time spent in treatment center (1.7 versus 2.1 hours; P=.005), return to treatment center (5.5% versus 14.1%; P=.02), lower change from baseline sedation score at 2 hours (0.1 versus 0.5; P=.03), and adverse event rate (3.9% versus 13.3%). CONCLUSION: Intravenous cetirizine is an effective alternative to intravenous diphenhydramine for treating acute urticaria, with benefits of less sedation, fewer adverse events, shorter time spent in treatment center, and lower rates of revisit to treatment center.

Non-target impurity profiling of marketplace Cetirizine using high-resolution mass spectrometry and multivariate data analysis.

RATIONALE: As always, drug impurity is the first concern of medication safety. The quality of pre- and post-marketed drugs is estimated through systematic analysis of potential hazardous substances by impurity profiling. Impurity profile is the general name of all unwanted materials which may affect the purity of an active pharmaceutical ingredient (API). The safety of original drugs is guaranteed by an enormous amount of animal experiments and clinical research while the safety of generic drugs should also be ensured by comparative analysis for consistency evaluation. The significantly differential impurities between them should be focused on and the toxicity should be further estimated if necessary. Herein, we take a marketplace drug named Cetirizine as an example to investigate if there was a method which could effectively discover the potential markers among Cetirizine tablets with different brands and describe specific impurity profiling which makes the unknown brand of Cetirizine tablets predictable. METHODS: Liquid chromatography coupled with high-resolution mass spectrometry (LC/HRMS) was applied to capture the characteristic features of the impurity profile for three brands of marketplace Cetirizine tablets using full scan data-dependent MS/MS scan mode (FS-ddMS(2) ). RESULTS: Unsupervised learning: principal component analysis (PCA) and supervised learning: consensus orthogonal partial least squares discriminant analysis (OPLS-DA) were utilized to reveal the essential character of Cetirizine impurity profile; 16 differential impurities were finally found, their structures were speculated by HRMS(2) data. CONCLUSIONS: The cause of formation was further elucidated which gave a suggestion for production process optimization. Copyright © 2016 John Wiley & Sons, Ltd.