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The article presents the current pharmacology, chemical properties, pharmacokinetics and metabolism of levocetirizine. The article also reviews the clinical efficacy of levocetirizine for seasonal allergic and perennial rhinitis, as well as chronic urticaria. The article is formed through the review of all the published literature in English retrieved from the PubMed/MEDLINE database between 1966 and March 2011 using the search terms: levocetirizine, allergic rhinitis, chronic urticaria and antihistamine. Furthermore, the article also reviews data provided by the manufacturer in addition to reports from governmental agencies.
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A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent.
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A review of the preclinical pharmacology of non-sedating H1 antihistamines includes comparative data on potency, duration of action, side effect liability, especially CNS depressant and anticholinergic activity and new approaches that may further enhance the efficacy of these newer compounds. Data discussed mainly involve studies in which multiple comparative agents were used and usually include astemizole, cetirizine, loratadine and terfenadine. New research approaches include the combination of PAF inhibition with antihistamine activity and the inhibitory effects these compounds may have on cellular influx in allergic diseases.
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The study was conducted according to a three-way, double-blind, cross-over design. Treatments were single oral doses of cetirizine 10 and 20 mg and placebo. Effects on cognition were assessed using tests of word learning, memory scanning, vigilance, divided attention, tracking and visual information processing speed.
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Cetirizine, a highly specific H1 receptor antagonist with modest sedation and anticholinergic effects at the higher doses required for bronchodilation, may be useful for treating concomitant allergy and symptoms of asthma.
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Levocetirizine is absorbed rapidly and reaches a steady-state plasma concentration more quickly than does desloratadine. It is also metabolized to a lesser extent than desloratadine, has a lower V(d), and has higher specificity for histamine(1) receptors. Eight well-controlled trials were identified that directly compared the effects of levocetirizine and desloratadine in the skin and nose of healthy individuals and patients with allergic rhinitis. Drug activity was measured in terms of wheal, flare, and itch reactions; nasal symptoms or symptom scores; increases in concentrations of inflammatory markers; or facial thermography. In most of these trials, levocetirizine had a faster onset and greater consistency of effect than desloratadine. The differences in the pharmacokinetic and pharmacodynamic profiles of the 2 drugs may partially explain these clinical findings.
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This study was intended to confirm a previous study comparing cetirizine, loratadine, and placebo in the EEU using an identical protocol design (randomized, double-blind, parallel-group comparison having the same symptom scoring system, endpoints, and statistical analyses), thus demonstrating reproducibility of studies conducted in the EEU.
Over the 6-month treatment period, levocetirizine showed statistically significant improvements over placebo in HRQOL (P < 0.001 for all RQLQ domains and overall scores) and health status (P < or = 0.004 for SF-36 physical and mental summary scores; P < 0.05 for all SF-36 scales). The relative improvement of levocetirizine over placebo exceeded the predefined clinically meaningful threshold of 30% for all RQLQ scores and the improvement from baseline was 3 times the established MID for RQLQ.
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Both mizolastine and cetirizine were effective in relieving the symptoms of SAR. After 7 days of treatment, the improvement in TS and responder's rate were significantly (P < .05) greater in patients treated with mizolastine (TS change versus baseline, mean +/- SD: -6.40 +/- 5.71; R: 55%) and cetirizine (TS change versus baseline: -6.24 +/- 5.24; R: 53%) than with placebo (TS change versus baseline: -4.11 +/- 5.91; R: 40%). Both drugs acted rapidly, within 2 hours of the first intake. During the first 3 days, mizolastine relieved symptoms more effectively than cetirizine, the difference being significant on the second (P = .027) and third (P = .050) day. Both mizolastine and cetirizine were well tolerated.
An electronic literature search was performed using Medline and EMBASE from January 01, 2001 through August 6, 2015. Randomized controlled trials (RCTs) comparing levocetirizine with other antihistamines or placebo for patients with allergy and healthy subjects were selected. Primary outcome was risk ratio between levocetirizine and comparators. Secondary outcome was change in psychomotor speed. Data were pooled for meta-analysis using a fixed-effect model.
Multilamellar vesicles (MLV) were prepared by thin-lipid film hydration using L-alpha-phosphatidylcholine (PC) and buffer containing 80 mg hydroxyzine at pH 7. For MLV containing hydroxyzine, the liposomes were subjected to 1) hydration for 1 h, 24 h, or 48 h for the control batch, batch B, or batch D respectively; and 2) hydration for 1 h, 24 h, or 48 h with freeze-thawing for 5-cycles for batch A, batch C, or batch E, respectively. These formulations were stored at 10 +/- 2 degrees C and 37 +/- 0.1 degrees C. Small unilamellar vesicles (SUV) and MLV were prepared using L-alpha-phosphatidylcholine (PC), and buffer at pH 5.0, 5.5, 6.0, 6.5, and 7.0, containing 80 mg hydroxyzine or 82 mg cetirizine by the ethanol injection and thin-lipid film hydration methods, respectively. These formulations were stored at 10 +/- 2 degrees C. Liposomes were evaluated immediately after preparation and after storage by determining percent entrapment of hydroxyzine (PETH) or of cetirizine (PEC) and by observing changes in the physical appearance (PA). Particle size (PSA) of the liposomes freshly prepared at pH=6.5 was measured from transmission electron micrographs (TEM).
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Treatment of severe recalcitrant chronic idiopathic urticaria (CIU) is difficult.
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Fifty AR patients at the age of 26.2 ± 9.1 years (64% females), were recruited to the trial according to the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria. Participants randomly received either intranasal injection of BTX-A (75IU Dysport®) or cetirizine (10mg/day). Symptoms (based on the ARIA) and side effects were assessed every two weeks for two months. Quality of life was evaluated before and after the study using the Rhinasthma questionnaire.
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Eighteen individuals completed a randomized, double-masked study. Participants were evaluated in a CAE (a chamber that regulates humidity, temperature, airflow, and visual tasking) at baseline and after taking 10 mg of either loratadine or cetirizine hydrochloride daily for 4 days. Keratitis, conjunctival staining, and tear film break-up time (TFBUT) were examined before and after a 45-minute CAE exposure. Participant-reported ocular discomfort was recorded every 5 minutes during CAE challenge.
To review the cutaneous adverse events related to EGFR inhibitors.
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A total of 116 patients, aged 17 to 65 years, with CIU (urticarial wheals for at least two days per week for six consecutive weeks before entry) were enrolled in this randomised double-blind study. Study period was 28 days with patient visits on days 14 and 28 for investigator evaluation of the clinical response. Patient evaluation was on the basis of an analogue scale. Final response to treatment was judged as symptom free, partial improvement, and no improvement.
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The optimal properties of oral H(1)-antihistamines and current ARIA recommendations for their use in allergic rhinitis are presented, as well as relevant pharmacological and clinical data for bilastine obtained from the published literature that specifically address the defined criteria.
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Our objective was to study the effect of long-term treatment with the H(1)-receptor antagonist cetirizine in the prevention of urticaria in young children with atopic dermatitis.
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The patient is a 22-year-old male with the evaluation of osteosarcoma, T1Gr2NxM0. He received neoadjuvant chemotherapy and later underwent a right above the knee amputation without complication. He was then scheduled to receive adjuvant chemotherapy with high-dose MTX, 12 g/m2 body surface area, followed by leucovorin rescue and ifosfamide. He had an immediate hypersensitivity reaction during the initiation of the MTX infusion with diffuse urticaria, facial swelling, cough, and chest tightness. The infusion was terminated and his symptoms abated. He was later skin tested to confirm allergy to MTX. In order for him to receive the needed chemotherapy, we developed a desensitization protocol that was administered in the intensive care unit. Before the infusion he was pretreated with ranitidine, cetirizine, hydroxyzine, montelukast, and prednisone. He underwent the desensitization without incident on repeated infusions. Serum tryptase levels drawn during the infusions were low, signifying controlled mast cell degranulation.
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Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.
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This long-standing IDDM patient presented two types of reactions to human insulin: the immediate type (systemic urticaria), treated with antihistamines and desensitization, and the Arthus' type III reaction (nodules and hematomas occurring 6-8 h after the insulin injection) that required glucocorticoid therapy for more than 4 months.
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We previously reported that streptozotocin-induced diabetic mice showed depressive-like behavior in the tail suspension test. It is well known that the central histaminergic system regulates many physiological functions including emotional behaviors. In this study, we examined the role of the central histaminergic system in the diabetes-induced depressive-like behavior in the mouse tail suspension test. The histamine contents in the hypothalamus were significantly higher in diabetic mice than in non-diabetic mice. The histamine H(1) receptor antagonist chlorpheniramine (1-10 mg/kg, s.c.) dose-dependently and significantly reduced the duration of immobility in both non-diabetic and diabetic mice. In contrast, the selective histamine H(1) receptor antagonists epinastine (0.03-0.3 microg/mouse, i.c.v.) and cetirizine (0.01-0.1 microg/mouse, i.c.v.) dose-dependently and significantly suppressed the duration of immobility in diabetic mice, but not in non-diabetic mice. Spontaneous locomotor activity was not affected by histamine H(1) receptor antagonists in either non-diabetic or diabetic mice. In addition, the number and affinity of histamine H(1) receptors in the frontal cortex were not affected by diabetes. In conclusion, we suggest that the altered neuronal system mediated by the activation of histamine H(1) receptors is involved, at least in part, in the depressive-like behavior seen in diabetic mice.
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All randomised controlled trials comparing anti-histamines with a placebo or placebo-like medication with cough as an outcome, where cough is not primarily related to an underlying respiratory disorder such as cystic fibrosis, asthma, or suppurative lung disease.
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Eosinophilic pustular folliculitis is a rare condition which is being increasingly reported in HIV-positive patients. Many therapies have been used to treat this condition. We report the first successful use of the H1 antihistamine cetirizine to treat the condition and postulate that the specific antieosinophilic action of this drug may explain the beneficial clinical effect seen in our patient.
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Cetirizine at high concentrations (10(2)-10(3) microM) markedly inhibited IFNgamma-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (10(2) microM) enhanced IFNgamma-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFNgamma-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNgamma-stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release.
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To assess the efficacy and safety of oral cyclosporin A (CsA) in CIU.
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Nonsedating anti-H1 antihistamines taken regularly were the most common drugs prescribed, followed by nonsedating anti-H1 antihistamines taken as needed, corticosteroids, sedating antihistamines taken regularly, sedating antihistamines taken as needed, anti-H2 antihistamines, leukotriene antagonists, ciclosporin and doxepin. Nonsedating antihistamines plus corticosteroids was the most frequent drug combination prescribed. When comparing between allergists and dermatologists we found a positive and significant correlation only between prescription of cetirizine, dexchlorfeniramine, leukotriene antagonists and anti-H2 antihistamines and being treated by an allergist. A positive correlation was found with desloratadine and being seen by a dermatologist. We did not find any difference in CU management in the rest of the treatments studied.
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The model control group had typical symptoms of allergic rhinitis and the eosinophilic granulocytes could be found more frequently. The contents of cAMP and cAMP/cGMP rose in the blood plasma and nasal mucosa (P < 0.01). However, the changes of jieminqufeng decoction group were small.
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We report a rare case of exercise-induced anaphylaxis (EIA), occurring exclusively with exercise, without any other associated trigger, detected in the prodromal phase, and prevented from additional anaphylaxis episodes by treatment with cetirizine and 10 mg daily of antileukotriene montelukast to date. EIA is a syndrome in which patients experience a spectrum of the symptoms of anaphylaxis ranging from mild cutaneous signs to severe systemic manifestations such as hypotension, syncope, and even death after increased physical activity. Many people have triggers, such as, a variety of foods, various medications, alcohol, cold weather, humidity, and seasonal and hormonal changes along with exercise that cause the symptoms. Typically, either exercise or the specific trigger alone will rarely cause symptoms. It is differentiated from cholinergic urticaria by the absence of response to passive body warming and emotional stress.
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Patients will be randomised in a 2:1:1 ratio to one of three groups: (a) semi-standardised acupuncture plus rescue medication (cetirizine); (b) penetrating sham acupuncture at non-acupuncture points plus rescue medication; or (c) rescue medication alone for 8 weeks (standard treatment group). Acupuncture and sham acupuncture will consist of 12 treatments per patient over 8 weeks.
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Acute urticaria occurred in 16.2% of the placebo-treated children and in 5.8% of the children treated with cetirizine (P <.001). The protective effect of cetirizine disappeared when treatment was stopped. In the study population as a whole, urticaria episodes were most commonly associated with intercurrent infection or with food ingestion or direct skin contact.
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Antihistamines were investigated for use in asthma shortly after discovery over fifty years ago. Earlier compounds proved ineffective because of side effects: this class of drugs was not thought useful for asthma, and were actually considered contraindicated. More recent drugs have greater potency, fewer side-effects, and no evidence of adverse effects in asthma. There are some studies showing second generation antihistamines, especially cetirizine, improve certain parameters of asthma.
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fexofenadine is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria for which it is a suitable option for first-line therapy. Comparative data suggest that fexofenadine is as effective as loratadine or cetirizine in the treatment of seasonal allergic rhinitis. In those with excessive nasal congestion the combination of fexofenadine plus pseudoephedrine may be useful. In clinical trials fexofenadine is not associated with adverse cardiac or cognitive/psychomotor effects.
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Patients were told to avoid the allergen. Because accidental ingestion is frequent in peanut allergy, they were equipped with a document stating the severity of the allergy and emergency medication (antihistamines, oral steroids, adrenaline injector).
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Azelastine nasal spray and oral cetirizine are selective histamine H(1)-receptor antagonists that are approved in the United States for the treatment of seasonal allergic rhinitis (SAR).
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The potent histamine H(1)-receptor antagonist cetirizine (Zyrtec) is a racemic mixture of levocetirizine (now available under the trademark Xyzal and dextrocetirizine. In this Commentary, we examine some biological properties of cetirizine and levocetirizine, namely enantioselectivity in pharmacological activity and pharmacokinetic properties, with emphasis on the possibility of racemization, the compared behavior of the two enantiomers, and the potential for interactions with other drugs. Recent data demonstrate that the antihistaminergic activity of the racemate is primarily due to levocetirizine. Levocetirizine is rapidly and extensively absorbed, poorly metabolized, and not subject to racemization. Its pharmacokinetic characteristics are comparable after administration alone or in the racemate. Its apparent volume of distribution is smaller than that of dextrocetirizine (0.41 L kg(-1) vs. 0.60 L kg(-1)). Moreover, the non-renal (mostly hepatic) clearance of levocetirizine is also significantly lower than that of dextrocetirizine (11.8 mL min(-1) vs. 29.2 mL min(-1)). Our conclusion is that levocetirizine is indeed the eutomer of cetirizine. The evidence reviewed here confirms preclinical findings and offers a rationale for the chiral switch from the racemate to levocetirizine.