levocetirizine and Hypersensitivity

Increasing evidence suggests that most of today's allergic rhinitis patients are sensitized to more than one trigger, likely due to constant exposure to increased levels of traditional and new allergens from exotic foods and pets, resulting in manifestation of the more persistent and moderate/severe symptoms. The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative has consequently recommended that allergic rhinitis be classified as "intermittent" or "persistent" allergic rhinitis (IAR and PER, respectively), based on symptom duration and the impact of disease severity on the patient's quality of life. Moreover, ARIA has recommended that the efficacy of H(1)-antihistamines be investigated in patients classified according to ARIA, with the H(1)-antihistamine under investigation being evaluated long-term in terms of clinical efficacy, safety and pharmacological properties in order to fully appreciate its efficacy. Studies of levocetirizine, one of the most recent commercially available H(1)-antihistamines, indicate that this drug is among the most useful H(1)-antihistamines for the management of allergic rhinitis (IAR and PER) and chronic idiopathic urticaria because of its overall more favorable pharmacokinetic and pharmacodynamic profiles compared with other commonly used H(1)-antihistamines, as well as its high efficacy and long-term safety in children and adults. Moreover, continuous treatment with levocetirizine appears to be more effective than on-demand treatment, a property that is likely to benefit today's patients with more persistent and severe symptoms.

Topics: Cetirizine; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity

Levocetirizine, the R-enantiomer of cetirizine dihydrochloride, is a new molecule with a potent and selective antihistamine activity.. To investigate the evidence that levocetirizine is an effective therapy for allergic disease.. Evaluation of published articles in English, or having an English abstract.. Clinical trials indicate that levocetirizine is safe and effective for the treatment of allergic rhinitis and chronic idiopathic urticaria. The compound shows a rapid onset of action, high bioavailability and affinity for the H1 receptor. Moreover, this molecule demonstrates many anti-inflammatory effects that enhance the clinical therapeutic benefit not only in short-term but also in long-term treatments, as reported in recent trials utilizing levocetirizine for several months.. Levocetirizine confirms its safe effective activity for treatment of allergic disease in both adults and children.

Topics: Biological Availability; Cetirizine; Controlled Clinical Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Receptors, Histamine H1; Treatment Outcome

Levocetirizine (Xyzal) is a selective, potent, oral histamine H(1) receptor antagonist of the latest generation that is licensed for the symptomatic treatment of allergic rhinitis (including persistent allergic rhinitis [PER]) and chronic idiopathic urticaria (CIU). Large, well designed trials indicate that levocetirizine is effective and generally well tolerated in the treatment of allergic rhinitis and CIU. Its pharmacological profile offers many positive aspects: a rapid onset and long duration of antihistaminic effect; rapid absorption and high bioavailability; a low potential for drug interactions; a low volume of distribution; and a lack of effect on cognition, psychomotor function and the cardiovascular system. Allergen challenge chamber studies suggest that levocetirizine has better efficacy than desloratadine, loratadine or fexofenadine. Well controlled, long-term studies with other later-generation H(1) receptor antagonists are required to fully define its clinical profile relative to other agents in this class. Overall, levocetirizine is a valuable addition to the oral H(1) receptor antagonists available for the treatment of allergic rhinitis and as first-line therapy in patients with CIU.

Topics: Cetirizine; Clinical Trials as Topic; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Piperazines; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Skin Diseases; Treatment Outcome

To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders.. Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines.. Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals.. On the basis of the evidence on H1 antihistamines, none of them deserve the title "third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

Topics: Anti-Allergic Agents; Blood-Brain Barrier; Central Nervous System Diseases; Cetirizine; Child; Cyproheptadine; Heart Diseases; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Mast Cells; Piperazines; Receptors, Histamine H1; Terfenadine

Histamine is one of the most important steps in the phlogistic allergic reaction. Its activity is due to the link to specific receptors on the cellular surface. H1-receptors of second generation are the most currently prescribed drugs in allergic diseases for their high selectivity, little or no central sedative effect, rapid onset of action and long half lives. Antihistamines can modulate part of immunological mechanisms involved in the pathogenesis of allergic inflammation reducing mediator release and expression of adhesion molecules, regulating the release of cytokines, chemokines and consequently inflammatory cells recruitment. The anti-inflammatory effects of cetirizine, desloratadine and levocetirizine are reviewed. Quality of life is considered too, as a main parameter in a global evaluation of the antihistamine's effects.

Topics: Anti-Allergic Agents; Anti-Inflammatory Agents; Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Quality of Life

Histamine is an important mediator for early phase allergic reactions that are involved in atopic diseases, mediated by specific IgE antibodies. After allergenic contact, its liberation induces unpleasant symptoms like itching, several manifestations as local vasodilatation, bronchoconstriction, mucus hypersecretion. Antagonists of H1 histamine receptors are the most prescribed drugs, due to their symptomatic effects at the levels of nasal or conjunctival mucosa, and the skin. Their major indications cover allergic rhinitis, either seasonal or perennial, and idiopathic chronic urticaria, as a first line medication. The pharmacological evolution allows to distinguish three generations of products differing at the levels of specificity, long acting period, and toxicity. The authors are discussing the respective benefits of two recent molecules presented as 3rd generation molecules: fexofenadine and levocetirizine, while repositioning their use among available treatment strategy.

Topics: Acetates; Anti-Allergic Agents; Cetirizine; Chemistry, Pharmaceutical; Histamine H1 Antagonists; Humans; Hypersensitivity; Piperazines; Rhinitis; Terfenadine; Urticaria

Antihistamines are accepted in the therapy of allergic seasonal and perennial rhinitis. In the paper some anti-inflammatory effects of antihistamines have been presented, and their action mechanisms and clinical applications have been discussed in relation to the new preparates of antihistamines.

Topics: Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Terfenadine

Topics: Acetates; Animals; Area Under Curve; Cetirizine; Half-Life; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Piperazines; Randomized Controlled Trials as Topic

H1 antihistamines increase safety during allergen-specific immunotherapy and might influence the outcome because of immunoregulatory effects.. We sought to analyze the influence of 5 mg of levocetirizine (LC) on the safety, efficacy, and immunologic effects of ultrarush honeybee venom immunotherapy (BVIT).. In a double-blind, placebo-controlled study 54 patients with honeybee venom allergy received LC or placebo from 2 days before BVIT to day 21. Side effects during dose increase and systemic allergic reactions (SARs) to a sting challenge after 120 days were analyzed. Allergen-specific immune response was investigated in skin, serum, and allergen-stimulated T-cell cultures.. Side effects were significantly more frequent in patients receiving placebo. Four patients receiving placebo dropped out because of side effects. SARs to the sting challenge occurred in 8 patients (6 in the LC group and 2 in the placebo group). Seven SARs were only cutaneous, and 1 in the placebo group was also respiratory. Difference of SARs caused by the sting challenge was insignificant. Specific IgG levels increased significantly in both groups. Major allergen phospholipase A(2)-stimulated T cells from both groups showed a slightly decreased proliferation. The decrease in IFN-gamma and IL-13 levels with placebo was not prominent with LC, whereas IL-10 levels showed a significant increase in the LC group only. Decreased histamine receptor (HR)1/HR2 ratio in allergen-specific T cells on day 21 in the placebo group was prevented by LC.. LC reduces side effects during dose increase without influencing the efficacy of BVIT. LC modulates the natural course of allergen-specific immune response and affects the expression of HRs and cytokine production by allergen-specific T cells.

Topics: Adolescent; Adult; Bee Venoms; Cetirizine; Desensitization, Immunologic; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Hypersensitivity; Male; Middle Aged; Prospective Studies; Young Adult

Direct comparisons of antihistamines are rare but very much needed. Newly available antihistamine preparations, levocetirizine, the R-enantiomer of racemate cetirizine, and desloratadine, an active metabolite of loratadine, have been recently released for allergic rhinitis.. We sought to compare levocetirizine and desloratadine in a nasal provocation test (NPT) with grass pollen.. Twenty-four volunteers with grass pollen allergy and a history of rhinitis were enrolled in a double-blind, placebo-controlled, crossover study. Three NPTs were performed in a dose-escalating manner during the out-of-season period 4 hours after a single dose of levocetirizine (5 mg), desloratadine (5 mg), or placebo.. This study demonstrates a better overall protection of a single dose of levocetirizine compared with desloratadine in an NPT with grass pollen allergen. In contrast to late-phase inflammatory markers, which were unaffected, extravascular leakage of the early-phase marker albumin was significantly limited by levocetirizine.

Topics: Adult; Albumins; Allergens; Biomarkers; Cetirizine; Cross-Over Studies; Differential Threshold; Double-Blind Method; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Loratadine; Male; Nasal Lavage Fluid; Nasal Provocation Tests; Piperazines; Poaceae; Pollen; Treatment Outcome

Antihistamines are the most commonly prescribed class of medication for perennial allergic rhinitis (PAR). The primary objective of this study was to determine whether levocetirizine (Xyzal(R)), the active enantiomer of cetirizine, could achieve at least a 50% improvement in PAR symptoms compared to the placebo over the first week of treatment.. A total of 294 patients with PAR due to house dust mites were randomized in this 8-week double-blind, placebo-controlled, multicentre trial to receive either levocetirizine 5 mg/day or placebo. Mean Total Four-Symptom Scores (T4SS) (nasal pruritus, ocular pruritus, rhinorrhoea and sneezing) were compared between treatment groups over weeks 1, 4 and 6. All individual symptom scores, including nasal congestion, were also studied.. Levocetirizine showed an 86% improvement in T4SS over the first week of treatment and a 47% improvement over the entire treatment period compared with placebo. Absolute changes from baseline were 3.64 and 2.47 for levocetirizine and placebo, respectively. Individual symptom scores showed statistically significant (P < or = 0.01) differences in favour of levocetirizine for all study time-points. Nasal congestion was unexpectedly significantly improved (P < 0.001). The incidence of reported adverse events was comparable between treatment and placebo group.. Levocetirizine 5 mg/day is an effective and well-tolerated treatment of PAR. In addition, levocetirizine is effective for the relief of nasal congestion.

Topics: Adolescent; Adult; Animals; Cetirizine; Double-Blind Method; Dust; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Male; Mites; Nasal Obstruction; Piperazines; Treatment Outcome

It has been hypothesised that antiallergic medications (AAMs) like montelukast and levocetirizine both the two bitter chloro compounds could be repurposed either alone or combinedly as an antiviral against SARS-CoV-2, like chloroquine/hydroxychloroquine (CQ/HCQ), another two bitter chloro compounds. Both AAMs and CQ/HCQ are bitter tasted chloro compounds. Depending on their these two similar physical properties and the safety and efficacy of AAMs by controlling over post viral episodes as comparing with viral inhibitory activities including SARS-CoV-2 by CQ/HCQ, a reposition of AAMs either alone/combinedly could be rationalised as an antiviral approach to nCoV.

Topics: Acetates; Anti-Asthmatic Agents; Antiviral Agents; Cetirizine; Clinical Trials as Topic; COVID-19 Drug Treatment; Cyclopropanes; Drug Repositioning; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Models, Theoretical; Patient Safety; Quinolines; Sulfides; Taste

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.

Topics: Cetirizine; Chemical and Drug Induced Liver Injury; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Jaundice; Liver; Male; Middle Aged; Pruritus

Substantial evidence implicates mast cells and their main constituent histamine in the pathogenesis of visceral hypersensitivity. We explored the specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral hypersensitivity in a postinflammatory rat model.. Trinitrobenzenesulfonic acid (TNBS)-colitis was monitored individually by colonoscopy: first on day 3 to confirm the presence of colitis and then every 4 days, starting from day 10, to monitor convalescence and determine the exact timepoint of endoscopic healing in each rat. Experiments were performed 3 days after endoscopic resolution of colitis. Visceral sensitivity was assessed by quantifying visceromotor responses (VMRs) to colorectal distension. Colonic mast cell numbers, histamine release and H4R and H1R mRNA expression were quantified. JNJ7777120 (H4R antagonist) and/or levocetirizine (H1R antagonist) were administered 30 min prior to VMR assessment or histamine release assay.. Postcolitis rats displayed a higher number of colonic mast cells, excessive histamine release and significantly enhanced VMRs. Heightened VMRs were dose-dependently reduced by JNJ7777120 and levocetirizine; combined administration of JNJ7777120 and levocetirizine potentiated the antinociceptive effect. In the colon, both H4R and H1R mRNA were present; in the dorsal root ganglia, only H1R mRNA was found. Only colonic H4R mRNA expression was increased in postcolitis rats. Excessive histamine release in postcolitis rats was attenuated by the highest dose of JNJ7777120.. H4R and H1R antagonists dose-dependently reduce and even normalise postinflammatory visceral hypersensitivity via different underlying mechanisms but with a synergistic effect. Both receptor subtypes represent promising targets for the treatment of postinflammatory visceral hypersensitivity.

Topics: Animals; Cetirizine; Colitis; Colonoscopy; Convalescence; Disease Models, Animal; Histamine; Histamine H1 Antagonists, Non-Sedating; Histamine Release; Hypersensitivity; Indoles; Intestinal Mucosa; Male; Mast Cells; Piperazines; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H4; Regeneration; Trinitrobenzenesulfonic Acid

Osteopontin (OPN), a multifunctional glycoprotein secreted from a wide variety of cells after inflammatory stimulation, is well accepted to contribute to the development of allergic diseases. However, the influence of histamine H1 receptor antagonists (antihistamines) on OPN functions is not well understood. The present study was undertaken to examine the influence of antihistamines on OPN functions in vitro.. Human nasal epithelial cells (5 × 10(5) cells) were stimulated with 250 ng/mL OPN in the presence of either desloratadine (DL), fexofenadine (FEX), or levocetirizine (LCT). The levels of OPN, GM-CSF, Eotaxin, and RANTES in 24 h culture supernatants were examined by ELISA. The influence of LCT on mRNA expression and transcription factor activation in cells were also examined by real-time RT-PCR and ELISA, respectively.. The antihistamines examined significantly suppressed the production of GM-CSF, Eotaxin, and RANTES from cells after OPN stimulation. LCT also exhibited the suppression of mRNA expression for chemokines and transcription factor, NF- κ B and AP-1, activation, which were increased by the stimulation of cells with OPN.. The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases.

Topics: Cetirizine; Histamine H1 Antagonists; Humans; Hypersensitivity; Nasal Mucosa; Osteopontin; RNA, Messenger

Topics: Adult; Allergens; Animals; Antigens, CD; Basophils; Cetirizine; Chironomidae; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Immunoglobulin E; Larva; Platelet Membrane Glycoproteins; Skin Tests; Tetraspanin 30; Treatment Outcome

Levocetirizine was launched onto the UK market in September 2001. It is indicated for symptomatic treatment of allergic rhinitis (AR), including persistent AR and chronic idiopathic urticaria.. The aim of the study was to monitor the safety of levocetirizine prescribed in the primary care setting in England, in the immediate postmarketing period.. Exposure data were derived from dispensed prescriptions written by primary care physicians (general practitioners [GPs]) for levocetirizine (November 2001-November 2002): patient demographic, indication, pattern of use and outcome (event) data from enhanced prescription-event monitoring (PEM) questionnaires (with additional questions to gather further relevant information) returned by GPs. Incidence density observation rates (IDobs) [number of first reports/1000 patient-months] between months 1 and 2 (IDobs(m1/m2)) were compared for the whole cohort and by groups defined by indication and pattern of use.. The cohort comprised 12 367 patients (median age 37 years [interquartile range 22-55]; 58% female). The most frequent indication was AR (67%; n = 8275). After 2 months, 35.7% (n = 2414) of patients were still taking levocetirizine. 'Condition improved' was the most common event and reason for stopping treatment. Headache/migraine was uncommon but associated with starting treatment (IDobs(m1/m2) 2.4 [95% CI 1.1, 6.0]), as was drowsiness/sedation (IDobs(m1/m2) 11.5 [95% CI 4.2, 43.9]). Cardiovascular events occurred rarely or very rarely, as did most central and peripheral nervous system events. No serious adverse drug reactions (ADRs) were reported. Events related to effectiveness were more frequent in month 1 than month 2 for all patient subgroups.. This postmarketing surveillance study shows that levocetirizine is well tolerated when used in general practice in England. No previously unrecognized ADRs were detected. This study highlights how modifications to PEM, such as additional questions, are contributing to the evaluation of drug utilization factors in relation to risks.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Drug Utilization; England; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Male; Middle Aged; Product Surveillance, Postmarketing; Young Adult

The purpose of this study was to assess the effect of levocetirizine on nasal mucociliary clearance in allergic rhinitis patients using rhinoscintigraphy.. Twenty patients with allergic rhinitis (12 males and eight females, mean age 37.7 +/- 10.5 years) were evaluated. All the patients received levocetirizine (5 mg x day(-1)) for 4 weeks, and the speed of nasal mucociliary clearance was assessed before and after treatment. Twenty healthy controls (11 males and nine females, mean age 39.4 +/- 7.8 years) were also evaluated.. The clearance values obtained for the treated group before and after treatment were significantly lower than those of the control group (P = 0.0001), but there was no significant difference in clearance speeds before and after treatment in the patient group (P = 0.444).. The study demonstrated that levocetirizine did not affect the speed of nasal mucociliary clearance in allergic rhinitis patients, and that nasal mucociliary clearance can easily be evaluated by rhinoscintigraphy.

Topics: Adult; Case-Control Studies; Cetirizine; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Hypersensitivity; Male; Middle Aged; Mucociliary Clearance; Nasal Mucosa; Piperazines; Radionuclide Imaging; Radiopharmaceuticals; Rhinitis; Technetium Tc 99m Aggregated Albumin; Time Factors