Third-generation Antihistamines Research Articles

Features of diagnostic search and experience inthetreatment of chronic urticaria in obese patients withpulmonary pathology

Background. In recent decades, along with the growth of allergic diseases, there has been a progressive increase in the number of people with overweight of varying severity, as evidenced by numerous epidemiological studies. Therefore, both allergies and obesity are among the global problems of modern healthcare due to their high prevalence and medical and social significance. The purpose of the study was analysis of the etiological factors of chronic urticaria (CU) in obese patients with pulmonary pathology, optimization of diagnosis and treatment of CU for further planning of preventive measures. Materials and methods. We examined 250 patients who applied for medical care to the regional clinical hospital in Chernivtsi and had CU associated with pulmonary pathology and obesity. Based on the analysis of the obtained data, a group of 140 patients was formed for further clinical and anamnestic examination: analysis of the anamnesis, determination of the severity of urticaria, assessment of quality of life, control of urticaria symptoms, general clinical laboratory studies, tests for verification of urticaria. Allergy testing was carried out when the patient’s anamnestic data indicated its expediency. The survey was carried out for one month and included a diagnostic period and 3 consultations every 7–10 days. Results. Among the causes of CU in patients with pulmonary disease, drug intolerance and parasitic infection dominate. Polyetiology is observed in 60% of cases. Differences in CU in obese patients are the long-term persistence of urticaria or other elements of the rash, the lack of effectiveness of therapy with the second- and third-generation antihistamines and glucocorticosteroids. Conclusions. The results obtained indicate a positive effect of the quinuclidine derivative quifenadine for the treatment of CU in patients with pulmonary pathology and obesity. Complete and significant effects were obtained in 91.43% of patients. The worst results (8.57%) were demonstrated by patients with the etiological significance of chemical factors (including occupational ones), which is associated with more problematic compliance with the elimination regimen in this category of patients.

Levo Cetirizine - the Drug with Numerous Plus to Cure Allergic Syndrome Compared to other Treatment Systems

Many drugs are available to treat allergic condition. This review focused on why antihistaminics are best choice for treatment of allergic disorder especially allergic rhinitis (AR). AR is a chronic inflammatory disease. AR can be detected by its characteristics of nasal congestion, nasal itching, sneezing, rhinorrhoea, pruritis, redness, tearing and itching of eyes. This is very common and increases day after day. Allergic rhinitis is not lethal but interferes with daily schedule in a sustained manner. It is also observed that after COVID-19, stimuli reactions such as allergic condition, breathing difficulties and nasal irritation are quite common. It is very necessary to treat AR with an effective and powerful medicine because nowadays, many factors trigger these responses such as the environment, food products, pollution, etc. Before treatment of any symptoms it is very necessary to know it pathogenesis. Hence, in this review, we discuss the introduction of AR, its pathogenesis, diagnostics, classification and treatment. We also understand why levocetirizine, a third-generation antihistamine, is superior to all other antihistamines and the most favourable in paediatric patients in many ways. Keywords: Allergic rhinitis, Antihistaminic, Levocetirizine, COVID­19, Asthma, Nasal congestion

Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f

Mast cells (MCs) are main effector cells in chronic spontaneous urticaria (CSU). Both Fc epsilon RI (FcεRΙ)- and MAS-related G coupled receptor-X2 (MRGPRX2)-mediated MC activations affect CSU course. Leukocyte mono-immunoglobulin-like receptor 3 (CD300f) has been shown to regulate FcεRΙ activation. However, no study has verified CD300f is a target to cure CSU. Therefore this study aimed to verify whether clarithromycin (CLA) regulates FcεRΙ- and MRGPRX2-mediated MC activations via CD300f and shows therapeutic effect on CSU. The target of CLA was verification. CLA inhibited FcεRΙ- and MRGPRX2-mediated MC activations were shown in vivo and in vitro. A single-center, self-comparison study was performed, and CLA-treated CSU was investigated in 28 patients who were not sensitive to the third-generation antihistamines. Serum inflammatory mediators in patients before and after CLA administration were analyzed. CLA effectively inhibited type Ι anaphylactic reactions and pseudo-allergic reactions in mice. Moreover, CLA inhibited FcεRΙ- and MRGPRX2-mediated MC signaling pathway activation. Regulatory effects of CLA were decreased significantly after CD300f knockdown. CLA effectively alleviated the symptoms of wheal and itch and reduced serum cytokine levels in patients. CLA negatively regulated FcεRΙ- and MRGPRX2-mediated MC activation via CD300f and showed significant therapeutic effect on CSU.

Green potentiometric determination of some of the third-generation antihistamines: Fexofenadine, Desloratadine, and Levocetirizine by using new carbon paste electrodes

BackgroundThe Current study describes the construction of three carbon paste electrodes for the quantitative measurement of the third-generation antihistamines fexofenadine (FEX), Desloratadine (DES), and Levocetirizine (LEV). The different assembly steps of the sensor are described. The proposed potentiometric method Presents a green, fast, simple, and sensitive procedure for the determination of these drugs in their pure and pharmaceutical forms. ResultsThe quantitative determination of the antihistamines drugs was achieved using the constructed carbon paste electrodes. The presented analytical method obeyed linearity in the concentration range (5 × 10−6–1 × 10−2) M for FEX and DES, (1 × 10−5 – 1 × 10−2) M for LEV. The values of the Nernstian slopes (-57.40, -29.01, -56.01) mV/ decade indicate the closeness of these values from the ideal Nernstian slope value. The limits of quantification (LOQ) were (2.17 × 10−8- 6.31 × 10−8- 3.3 × 10−8) M, respectively. In addition, the electrodes exhibited good selectivity, repeatability (RSD<2%), stability, and fast response time. The method was validated and employed for the determination of the studied drugs in pharmaceutical dosage forms, the average recovery values were (99.13–99.53–99.90)% for FEX, DES, and LEV, respectively. ConclusionOur study included the construction of the first carbon paste electrodes for potentiometric determination of some of the third-generation antihistamines. The findings have shown that carbon paste electrodes excel over the traditional ion -selective electrodes and present an accurate, precise, green, robust, and cost-effective analytical method.

Levocetirizine, a Third-generation Antihistamine, Inhibits Proliferation and Induces Apoptosis of Melanoma Cancer

Levocetirizine, a Third-generation Antihistamine, Inhibits Proliferation and Induces Apoptosis of Melanoma Cancer

Levocetirizine and montelukast in the COVID-19 treatment paradigm

Levocetirizine, a third-generation antihistamine, and montelukast, a leukotriene receptor antagonist, exhibit remarkable synergistic anti-inflammatory activity across a spectrum of signaling proteins, cell adhesion molecules, and leukocytes. By targeting cellular protein activity, they are uniquely positioned to treat the symptoms of COVID-19. Clinical data to date with an associated six-month follow-up, suggests the combination therapy may prevent the progression of the disease from mild to moderate to severe, as well as prevent/treat many of the aspects of ‘Long COVID,’ thereby cost effectively reducing both morbidity and mortality. To investigate patient outcomes, 53 consecutive COVID-19 test (+) cases (ages 3–90) from a well-established, single-center practice in Boston, Massachusetts, between March – November 2020, were treated with levocetirizine and montelukast in addition to then existing protocols [2]. The data set was retrospectively reviewed. Thirty-four cases were considered mild (64%), 17 moderate (32%), and 2 (4%) severe. Several patients presented with significant comorbidities (obesity: n = 22, 41%; diabetes: n = 10, 19%; hypertension: n = 24, 45%). Among the cohort there were no exclusions, no intubations, and no deaths. The pilot study in Massachusetts encompassed the first COVID-19 wave which peaked on April 23, 2020 as well as the ascending portion of the second wave in the fall. During this period the average weekly COVID-19 case mortality rate (confirmed deaths/confirmed cases) varied considerably between 1 and 7.5% [37]. FDA has approved a multicenter, randomized, placebo-controlled, Phase 2 clinical trial design, replete with electronic diaries and laboratory metrics to explore scientific questions not addressed herein.

Trends in the use of antihistamines with reference to drivers between 2015 and 2019: A population-based registry analysis.

First-generation antihistamines are considered driving-impairing medicines (DIM), while second- and third-generation antihistamines are relatively safe for driving. The aim of this study was to know the trend of consumption of antihistamines and other DIMs in Spain between 2015 and 2019. This is a population-based registry study. The population distribution by age and gender has been taken into account, as well the treatment duration with these medicines and the concomitant use of other DIMs. Adjusted consumption for licensed drivers is also presented. Between 2015 and 2019, antihistamines were dispensed to 12.1% of the population and 9.25% of drivers. Oral antihistamines are the most consumed with 85.83%, and generally more used by women than men. Regardless of systemic antihistamines, the second-generation were the most consumed (8.9%) followed by the third-generation (2.07%) and the first-generation (0.61%). Subacute use was predominant in second -generation antihistamines (4.96%) and third-generation (1.26%), while acute use was predominant in third-generation antihistamines. On the other hand, only 0.36% of the population consumed antihistamines daily. The concomitant use of antihistamines with other DIMS was considerable, especially anxiolytics, opioids, other analgesics and antipyretics and antidepressants. The results in drivers were similar than in the general population. The use of antihistamines has increased in recent years, however, in Spain, the use of less sedatives predominates, which is safe for driving. Finally, it is important to consider that concomitant use with other DIMs was frequent, which may affect the fitness to drive.

Antihistamines Modulate Functional Activity of Macrophages

We compared the effects of the first-, second- and third-generation antihistamines in different doses on enzyme activity and cytokine production by macrophages and their death using an in vitro model. It was found that decreasing the dose led to an increase in the number of viable cells; after contact with second-generation antihistamines (loratadine, desloratadine), apoptosis of macrophages predominated. A dose-dependent increase in activity of ATPase and 5'-AMP with less pronounced effect of second-generation drugs was revealed. It was shown that under the influence of drugs, macrophages do not produce IL-1β, but actively synthesize TNFα and IL-10, which indicates the immunomodulatory properties of these drugs.

Effect of the Fexofenadine on the expression of HRH-1 and HRH-4 receptor in Peripheral Blood Mononuclear Cell isolated from children with diagnosed allergy - in vitro study Short communication.

Fexofenadine (FXF) is the active metabolite of terfenadine with selective peripheral H1receptor antagonist activity. FXF is a third-generation antihistamine, non-sedating, rapid and very long acting used in symptoms associated with allergic diseases such as allergic rhinitis, asthma and dermatitis. The pleiotropic effects of histamine are mediated by four types of receptors that belong to the G-protein-coupled receptor family: histamine H1 receptor (HRH-1), histamine H2 receptor, histamine H3 receptor, and histamine H4 receptor. Our hypothesis is that HRH-4 opens new possibility in treatment in allergy diseases and FXF could be the antagonist of both HRH-1 and HRH-4. We isolated a peripheral blood mononuclear cell (PBMC) from children with diagnosed allergies and healthy - control group and measured the HRH-1 and HRH-4 mRNA gene expression using Quantitive Real-Time PCR. We obtained the results from basal gene expression and after FXF and histamine stimulation. HRH-1 mRNA basal gene expression shows significantly higher, and HRH-4 shows significantly lower expression in allergy group compared to control. In both groups HRH-1 mRNA gene expression was observed as statistically significant increased after histamine stimulation compared to cells not treated, while in HRH-4 only in allergy group we observed statistical increase. FXF successively blocked histamine affinity in HRH-1 mRNA gene expression but not in HRH-4, where we not observed any reaction. Results clearly overturned our hypothesis about the possibility of using FXF to block over-expression HRH-4 and open new way of treatment in allergy diseases.

Synergistic enantioseparation systems with either cyclodextrins or cyclofructans and L-alanine Tert butyl ester lactate.

The combined use of chiral ionic liquids (CILs) and conventional chiral selectors (CSs) in CE, to establish a synergistic system, has proven to be an effective approach for the separation of enantiomeric pairs. In this study, a new CE method was developed, employing a binary system of a CS, either a cyclodextrin (CD) or a cyclofructan (CF), and a chiral amino acid ester-based ionic liquid (AAIL), for the chiral separation of four basic, acidic and zwitterionic drug compounds. In particular, the enantioseparation of two anticoagulants, warfarin (WAR) and coumachlor (COU), a non-opioid analgesic, nefopam (NEF) and a third-generation antihistamine, fexofenadine (FXD), was examined, by supporting the BGE with a CS and the chiral AAIL L-alanine tert butyl ester lactate (L-AlaC4 Lac). Parameters, such as the type of the CS, the concentration of both the CS and L-AlaC4 Lac, and the BGE pH, were methodically examined in order to optimize the chiral separation of each analyte. It was observed that, in some cases, the addition of the AAIL into the BGE improved both resolution (Rs ) and efficiency (N) significantly. In other cases, the synergistic effect enabled baseline separation of analyte enantiomers, at a much lower concentration of the CS. Finally, after optimization of separation conditions, baseline separations (Rs >1.5) of all four analytes were achieved in less than 5min.

Desloratadine and depression, a drug safety signal based on worldwide spontaneous reporting of side effects

Objective: Desloratadine, a third-generation antihistamine, is claimed to cause fewer central nervous system (CNS) adverse drug reactions (ADRs) than antihistamines of the first- and second-generation. While literature is inconclusive regarding the possible CNS effects, symptoms like somnolence and hallucinations are acknowledged ADRs of desloratadine, indeed suggesting some passage of this drug across the blood–brain barrier. Depression is currently not described as an ADR in the approved desloratadine product labelling.Materials and methods: In a joint signal detection workshop with the Uppsala Monitoring Centre and the Netherlands Pharmacovigilance Centre Lareb, case reports of suspected drug–ADR associations were analysed.Results: Forty-nine unique case reports of desloratadine associated with depression or depressed mood were detected in the WHO global ADR database. In these reports, the median time to onset of depression was three days. Most patients recovered after withdrawal of desloratadine, and in five patients the symptoms of depression recurred after re-administration of desloratadine.Conclusion: We hypothesize that desloratadine may enter the CNS and that it hence in rare cases may cause a clinically relevant state of depression, a relation that patients and their treating physicians should be made aware of.

The Use of a Poisson Regression to Evaluate Antihistamines and Fatal Aircraft Mishaps in Instrument Meteorological Conditions.

Research indicates that first-generation antihistamine usage may impair pilot performance by increasing the likelihood of vestibular illusions, spatial disorientation, and/or cognitive impairment. Second- and third-generation antihistamines generally have fewer impairing side effects and are approved for pilot use. We hypothesized that toxicological findings positive for second- and third-generation antihistamines are less likely to be associated with pilots involved in fatal mishaps than first-generation antihistamines. The evaluated population consisted of 1475 U.S. civil pilots fatally injured between September 30, 2008, and October 1, 2014. Mishap factors evaluated included year, weather conditions, airman rating, recent airman flight time, quarter of year, and time of day. Due to the low prevalence of positive antihistamine findings, a count-based model was selected, which can account for rare outcomes. The means and variances were close for both regression models supporting the assumption that the data follow a Poisson distribution; first-generation antihistamine mishap airmen (N = 582, M = 0.17, S2 = 0.17) with second- and third-generation antihistamine mishap airmen (N = 116, M = 0.20, S2 = 0.18). The data indicate fewer airmen with second- and third-generation antihistamines than first-generation antihistamines in their system are fatally injured while flying in IMC conditions. Whether the lower incidence is a factor of greater usage of first-generation antihistamines versus second- and third-generation antihistamines by the pilot population or fewer deleterious side effects with second- and third-generation antihistamines is unclear. These results engender cautious optimism, but additional research is necessary to determine why these differences exist.Gildea KM, Hileman CR, Rogers P, Salazar GJ, Paskoff LN. The use of a Poisson regression to evaluate antihistamines and fatal aircraft mishaps in instrument meteorological conditions. Aerosp Med Hum Perform. 2018; 89(4):389-395.

CLINICAL EFFICACY OF PELARGONIUM SIDOIDES EPS® 7630 IN COMPLEX THERAPY OF CHILDREN WITH CHRONIC ADENOIDITIS, WHO HAS UNDERGONE ADENOIDECTOMY

200 children aged 4 to 12 years diagnosed with grade 3 adenoids, chronic adenoiditis, admitted for routine surgical intervention – adenoidectomy, have been examined and treated in the Pediatric ENT-pathology Department of the Moscow Department of Health L.I. Sverzhevskiy Otorhinolaryngology Healthcare Research Institute. 2 groups of patients were formed depending on the treatment performed in the postoperative period. Group I (active treatment): 100 children who underwent conservative treatment after adenoidectomy, including: tested/investigational drug – Umckalor solution (per os), dosing regimen: children aged from 4 to 6 years – 5–10 drops 3 times a day, aged from 6 to 12 years – 10 to 20 drops 3 times a day; topical decongestants (in the age-related dosage); silver proteinate (nasal drops in age-specific doses); secondand third-generation antihistamines (in the age-specific doses). Group II (control): 100 children, who received conservative therapy after adenoidectomy, including: antibacterial therapy (in the age-specific doses) (third-generation cephalosporins); topical decongestants (in the age-specific doses); silver proteinate (nasal drops in age-specific doses); secondand third-generation antihistamines (in the age-specific doses). In both groups, the course of postoperative therapy amounted to 7 days. The clinical studies have shown that in the early postoperative period the clinical efficacy of Umckalor as part of combined therapy in children, who underwent adenoidectomy, involves reducing the duration of reactive events, accelerating the healing of the postoperative nasopharynx wound. The combined antiviral, antibacterial, immunomodulatory, anti-inflammatory, mucolytic and secretory-motor effect of the drug allows Umckalor to be used as an alternative to antibacterial drugs as part of combined therapy in children who underwent adenoidectomy.

Changes in gene expression induced by histamine, fexofenadine and osthole: Expression of histamine H1 receptor, COX-2, NF-κB, CCR1, chemokine CCL5/RANTES and interleukin-1β in PBMC allergic and non-allergic patients

IntroductionFexofenadine (FXF) is a third-generation antihistamine drug and osthole is assumed as a natural antihistamine alternative. This paper compares results of histamine, FXF and osthole impact on HRH-1, COX-2, NF-κB-p50, CCR1 mRNA expression. We also measured mRNA expression of IL-1β and CCL5/RANTES in incubated peripheral blood mononuclear cells (PBMC) to compared how histamine, FXF and osthole had influence on expression level and interacts on product secretion. ObjectiveThe purpose was to investigate expression pattern in asthma PBMC. MethodsThe cultures were treated 72h with FXF and osthole. We measured mRNA expression of histamine HRH-1, COX-2, NF-κB-p50, CCR1, IL-1β and CCL5/RANTES with Real-Time PCR (RT-PCR). ResultsThe present study suggest that osthole may be a potential inhibitor of histamine H1 receptor activity. We also demonstrated that cells cultured with histamine increase COX-2 mRNA expression and osthole reduce it. ConclusionAllergy remains one of the most common chronic diseases in Europe and it is rapidly approaching epidemic proportions; with current predictions estimating that the number of allergy-afflicted will equal the healthy population by 2020. It is therefore paramount to find new pharmaceuticals which successfully combat allergic disease.

Cytokine production by PBMC and serum from allergic and non-allergic subjects following in vitro histamine stimulation to test fexofenadine and osthole anti-allergic properties

FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. This paper compares peripheral blood mononuclear cell (PBMC) incubation with FXF and osthole, by studying FXF, osthole and histamine cytokine secretion in PBMC in vitro cultures. Mabtech kits determined the interleukins IL-1β, IL-4, IL-10, IL-13 and TNF-α. The influence of the above active substances on cytokine secretion in PBMC's and serum was assessed: cytokines were IL-1β, IL-4, IL-10, IL-13 and TNF-α; and cytokine levels secreted by untreated PBMCs in pure culture medium formed the absolute control (ctrl).We determined that osthole affects PBMC cytokine secretion to almost precisely the same extent as FXF (IL-1β, IL-4, IL-10 and TNF). In addition osthole had greater IL-13 blocking ability than FXF. Moreover, we observed significantly decreased IL-4 level in histamine/osthole theatment compared to histamine alone. Meanwhile, FXF not significantly decrease the level of IL-4 increased by histamine. This data indicates osthole's strong role in allergic inflamation.All results confirm our hypothesis that osthole is a natural histamine antagonist and therefore can be beneficially used in antihistamine treatment of conditions such as allergies.

Impact of fexofenadine, osthole and histamine on peripheral blood mononuclear cell proliferation and cytokine secretion

This paper compares results of peripheral blood mononuclear cell (PBMC) incubation with fexofenadine (FXF) and osthole. FXF is a third-generation antihistamine drug and osthole is assumed a natural antihistamine alternative. To our best knowledge, this is the first comparative study on FXF, osthole and histamine cytokine secretion and cytotoxicity in PBMC in vitro cultures using cell proliferation ELISA BrdU. The cultures were treated 12, 42, 48 and 72h with FXF and osthole at 150, 300 and 450ng/ml concentrations and histamine at 50, 100 and 200ng/ml. Our study results confirm that FXF, osthole and histamine exert no cytotoxic effect on PBMCs and that IL-6, IL-10 and TNF-α cytokine secretion following osthole cell stimulation was similar to that by FXF stimulation.This confirms our hypothesis that osthole is a natural histamine antagonist, and can therefore be beneficially applied in antihistamine treatment.

The determination of crystal structures of active pharmaceutical ingredients from X-ray powder diffraction data: a brief, practical introduction, with fexofenadine hydrochloride as example.

This study describes the general method for the determination of the crystal structures of active pharmaceutical ingredients (API) from powder diffraction data and demonstrates its use to determine the hitherto unknown crystal structure of fexofenadine hydrochloride, a third-generation antihistamine drug. Fexofenadine hydrochloride was subjected to a series of crystallisation experiments using re-crystallisation from solvents, gas diffusion, layering with an antisolvent and gel crystallisation. Powder diffraction patterns of all samples were recorded and inspected for polymorphism and for crystallinity. All samples corresponded to the same polymorph. The crystal structure was determined from an X-ray powder diffraction pattern using a real-space method with subsequent Rietveld refinement. The structure exhibits a two-dimensional hydrogen bond network. Crystal structures of API can be determined from X-ray powder diffraction data with good reliability. Fexofenadine exhibits only one polymorphic form, which is stabilised in the crystal by strong hydrogen bonds of the type (+)N-H···Cl(-), O-H···Cl(-), and between COOH groups.

Indications, Protocols, and Outcomes of Drug Desensitizations for Chemotherapy and Monoclonal Antibodies in Adults and Children

Advances in the understanding of various malignancies and chronic inflammatory diseases has led to the development of better treatment options for prolonging patient survival and minimizing morbidity. The recognition of "first-line" chemotherapy and monoclonal agents for these conditions has given more urgency to the need to re-administer these drugs in cases of drug hypersensitivity reactions. Therefore, in these cases, not only is desensitization considered when there is no alternative therapy available but also when alternative treatments are considered therapeutically inferior and/or more toxic. In this article, we describe the steps involved in the evaluation of these patients, factors to consider before making a decision to desensitize, the implementation of desensitization protocols, and the outcomes of such procedures.

Результаты терапии атопического дерматита у детей с использованием препарата левоцетиризина гидрохлорид

В статье дана характеристика препарата L-цет — представителя ІІІ поколения антигистаминных препаратов, содержащего левовращающий изомер цетиризина. Приведены результаты лечения детей с атопическим дерматитом с использованием препарата L-цет, свидетельствующие о его высокой эффективности и безопасности.

Efficacy and tolerability of second- and third-generation antihistamines in the treatment of acquired cold urticaria: a meta-analysis

Acquired cold urticaria (ACU) is a form of physical urticaria that has been treated with first-generation antihistamines; there is a paucity of data regarding second- and third-generation antihistamines for the treatment of ACU. To perform a systematic review of the literature to determine the efficacy of second- and third-generation antihistamines in the treatment of ACU. Data were extracted via a MEDLINE search of the literature between 1950 and May 2009. We included double-blind, randomized, placebo-controlled studies comparing the treatment of patients with ACU with second- and third-generation antihistamine medications vs placebo. Overall, 98 patients were identified from 4 included studies. Two trials indicated that second- and third-generation antihistamines significantly eliminated the presence of wheals after treatment vs placebo (odds ratio [OR], 8.88; 95% confidence interval [CI], 4.35 to 18.13). Two trials demonstrated a reduction in wheal area after treatment with a second- or third-generation antihistamine compared with placebo (mean difference, -347.99 mm2; 95% CI, -489.43 to -206.54 mm2). Two trials demonstrated significant elimination of pruritus with second- or third-generation antihistamine treatment vs placebo (OR, 10.44; 95% CI, 4.39 to 24.84). All 4 studies assessed the tolerability of a second- or third-generation antihistamine vs placebo and found an increased rate of adverse events (OR, 3.04; 95% CI, 1.53 to 6.06), although the complaints were mild. The newer, less-sedating antihistamines seem to be effective in the treatment of ACU in terms of their ability to significantly reduce the presence of wheals and pruritus after cold exposure. These medications are usually well tolerated, with only mild adverse effects.