levocetirizine and fexofenadine

The year 2012 has seen relevant changes in Polish pharmaceutical legislation and drug reimbursement, among others limiting the reimbursement solely to indications stated in the Summaries of Product Characteristics (SPCs). A discrepancy with expert recommendations became apparent. The aim of this study was to analyze discordances between up-to-date expert recommendations, the SPCs in force, and the evidence for the effectiveness of recommended drugs in urticaria. Guidelines for the treatment of urticaria issued by Polish and international expert bodies were analyzed, along with the SPCs. A systematic review of clinical trials of recommended drugs was carried out. Of drugs recommended by the experts, 203 were authorized in Poland for urticaria treatment, including 167 oral preparations of second-generation antihistamines (SGAH, 8 active substances), 29 oral preparations of first-generation antihistamines (6 substances), 4 preparations of systemic glucocorticosteroids (2), 2 topical glucocorticosteroid preparations (2) and one combined preparation of human immunoglobulin with histamine. Among products both recommended by experts and licensed for the treatment of urticaria in Poland, high or moderate-level of evidence of effectiveness was available for 7 active substances (bilastine, cetirizine, desloratadine, fexofenadine, loratadine, levocetirizine, rupatadine). Nevertheless, 39% of SGAH available in Poland (66 preparations of cetirizine, emedastine, levocetirizine, loratadine or fexofenadine) were registered exclusively for "chronic idiopathic urticaria" - a diagnosis inconsistent with the current state of medical knowledge. We conclude that there exist considerable discrepancies between expert recommendations for the pharmacotherapy of urticaria, the licensed use of drugs as defined in Summaries of Product Characteristics and scientific evidence for their effectiveness.

Topics: Administration, Oral; Administration, Topical; Anti-Allergic Agents; Benzimidazoles; Cetirizine; Glucocorticoids; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Piperidines; Poland; Practice Guidelines as Topic; Terfenadine; Treatment Outcome; Urticaria

Urticaria, and especially chronic spontaneous urticaria (CSU), is a difficult condition to treat. Consequently, clinicians need to use the best H(1)-antihistamines currently available and the pharmaceutical industries need to keep developing H(1)-antihistamines that are more effective than the ones we have today. To do this we need to be able to compare the clinical efficacy of both established and new drugs. Obviously, the ideal way to do this is to use head-to-head studies in CSU. However, such studies are extremely expensive and, in the case of novel molecules, have ethical and logistical problems. Consequently, we need to have predictive models. Although determination of Ki, an indicator of the in vitro potency of an H(1)-antihistamine, may help in the initial selection of candidate molecules, the large differences in volume of distribution and tissue accumulation in humans, precludes this from being a good predictor of clinical efficacy in CSU. From the data reviewed in this article, especially the direct comparative data of desloratadine and levocetirizine in weal and flare studies and CSU, weal and flare response would appear to be the best indicator we have of effectiveness of H(1)-antihistamines in clinical practice. However, it must be pointed out that the conclusion is, essentially, based on detailed comparisons of two drugs in studies sponsored by pharmaceutical companies. Consequently, to confirm the conclusions of this review, a multicentre study independent from the influence of pharmaceutical companies should be commissioned to compare the speed of onset and effectiveness of desloratadine, fexofenadine and levocetirizine in chronic spontaneous urticaria and against histamine-induced weal and flare responses in the same patients so that we have a clear understanding of the predictive value of our models.

Topics: Anti-Allergic Agents; Cetirizine; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Predictive Value of Tests; Skin Tests; Terfenadine; Urticaria

Nasal congestion is the most troublesome symptom of allergic rhinitis (AR). First-generation and older second-generation antihistamines, while effective against nasal itching, sneezing, and rhinorrhea, have limited efficacy in relieving nasal congestion.. This review included nasal challenge studies and clinical trials that reported the effects on nasal congestion of the newer second-generation antihistamines desloratadine, fexofenadine, and levocetirizine.. MEDLINE and EMBASE were searched for nasal challenge studies and clinical trials published in English between January 1, 1991, and January 31, 2009, using the following terms, alone or in combination: antihistamines, second-generation antihistamines, allergic rhinitis, intermittent allergic rhinitis, perennial allergic rhinitis, persistent allergic rhinitis, seasonal allergic rhinitis, nasal challenge, nasal blockage, and nasal congestion. Studies that were not active or placebo controlled, that did not evaluate change in nasal congestion scores, or that focused on treatments other than desloratadine, fexofenadine, and levocetirizine for nasal congestion associated with AR were excluded.. Twenty-six clinical trials met the criteria for inclusion in the review. In 11 placebo-controlled trials that included objective assessment of nasal congestion, desloratadine, fexofenadine, and levocetirizine were associated with reductions in the severity of nasal congestion through maintenance of nasal airflow. The mean AUC for nasal airflow over 6 hours was significantly greater with desloratadine compared with placebo in 3 studies (P < 0.05); placebo-controlled trials of fexofenadine and levocetirizine had similar results. In 25 placebo- and active-controlled trials that reported subject-rated symptom scores, the 3 newer antihistamines were efficacious in the treatment of nasal congestion associated with AR. In 10 trials that reported objective and/or subjective measures, desloratadine was associated with significant improvements in nasal congestion compared with placebo (P < or = 0.05), beginning as early as the first 2 hours after allergen challenge. Fexofenadine was associated with significantly lower nasal congestion scores compared with placebo in 4 studies (P <- 0.05); nasal congestion scores were significantly reduced with levocetirizine in 3 placebo-controlled trials (P < or = 0.005).. In the studies reviewed, desloratadine, fexofenadine, and levocetirizine were effective in relieving the nasal congestion associated with AR compared with placebo. This effect began as early as day 2 and was consistent and progressive throughout treatment. Desloratadine, fexofenadine, and levocetirizine are appropriate options for the treatment of nasal congestion in patients with AR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Clinical Trials as Topic; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Male; Middle Aged; Nasal Obstruction; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome; Young Adult

Second-generation histamine H(1) receptor antagonists were developed to provide efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) while decreasing adverse effects associated with first-generation agents. When comparing the efficacy and safety profiles of the newest second-generation antihistamines - desloratadine, fexofenadine and levocetirizine - many pharmacological and clinical criteria must be considered. Most importantly, these elements should not be evaluated separately but, rather, as parts of a puzzle that create a whole picture. As a class, second-generation antihistamines are highly selective for the H(1) receptor. Some bind to it with high affinity, although there is marked heterogeneity among the various compounds. They have a limited effect on the CNS, and clinical studies have noted almost no significant drug-drug interactions in the agents studied. No major cytochrome P450 inhibition has been reported with desloratadine, fexofenadine and levocetirizine, and the bioavailability of desloratadine is minimally affected by drugs interfering with transporter molecules. Of the second-generation antihistamines, desloratadine has the greatest binding affinity for the H(1) receptor. The use of desloratadine, fexofenadine and levocetirizine is not associated with clinically relevant antimuscarinic effects. Desloratadine and fexofenadine do not impair cognitive or psychomotor functioning and are comparable with placebo in terms of somnolence. Based on these pharmacological characteristics, as well as clinical endpoints such as symptom scores, quality-of-life surveys, inflammatory cell counts and investigators' global evaluations, we conclude that desloratadine, fexofenadine and levocetirizine are all efficacious treatments for AR and CIU. However, differences among the antihistamines in relation to a lack of significant interaction with drug transporter molecules and somnolence in excess of placebo may provide some advantages for the overall profile of desloratadine compared with fexofenadine and levocetirizine.

Topics: Cetirizine; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Terfenadine; Urticaria

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

Allergic rhinitis (AR) is now recognised as a global health problem that affects 10-30% of adults and up to 40% of children. Each year, millions of patients seek treatment from their healthcare provider. However, the prevalence of AR maybe significantly underestimated because of misdiagnosis, under diagnosis and failure of patients to seek medical attention. In addition to the classical symptoms such as sneezing, nasal pruritus, congestion and rhinorrhoea, it is now recognised that AR has a significant impact on quality of life (QOL). This condition can lead to sleep disturbance as a result of nasal congestion, which leads to significant impairment in daily activities such as work and school. Traditionally, AR has been subdivided into seasonal AR (SAR) or perennial AR (PAR). SAR symptoms usually appear during a specific season in which aeroallergens are present in the outdoor air such as tree and grass pollen in the spring and summer and weed pollens in the autumn (fall); and PAR symptoms are present year-round and are triggered by dust mite, animal dander, indoor molds and cockroaches. Oral histamine H(1)-receptor antagonists (H(1) antihistamines) are one of the most commonly prescribed medications for the treatment of AR. There are several oral H(1) antihistamines available and it is important to know the pharmacology, such as administration interval, onset of action, metabolism and conditions that require administration adjustments. When prescribing oral H(1) antihistamines, the healthcare provider must take into account the clinical efficacy and weigh this against the risk of adverse effects from the agent. In addition to the clinical efficacy, potential for improvement in QOL with a particular treatment should also be considered.

Topics: Administration, Oral; Cardiovascular System; Central Nervous System; Cetirizine; Drug Interactions; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Long QT Syndrome; Loratadine; Piperazines; Practice Guidelines as Topic; Quality of Life; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome

Abstract Absorption, distribution, metabolism and excretion of desloratadine, fexofenadine, levocetirizine, and mizolastine in humans have been compared. The time required to reach peak plasma levels (tmax) is shortest for levocetirizine (0.9 h) and longest for desloratadine (> or =3 h). Steady-state plasma levels are attained after about 6 days for desloratadine, 3 days for fexofenadine, 2-3 days for mizolastine and by the second day for levocetirizine. The apparent volume of distribution is limited for levocetirizine (0.4 L/kg) and mizolastine (1-1.2 L/kg), larger for fexofenadine (5.4-5.8 L/kg) and particularly large for desloratadine (approximately 49 l/kg). Fexofenadine and levocetirizine appear to be very poorly metabolized (approximately 5 and 14% of the total oral dose, respectively). Desloratadine and mizolastine are extensively metabolized. After administration of 14C-levocetirizine to healthy volunteers, 85 and 13% of the radioactivity are recovered in urine and faeces, respectively. In contrast, faeces are the preferential route of excretion for 14C-fexofenadine (80% vs. 11% of the radioactive dose in urine). The corresponding values are 41% (urine) and 47% (faeces) for 14C-desloratadine, 84-95% (faeces) and 8-15% (urine) for 14C-mizolastine. The absolute bioavailability is 50-65% for mizolastine; it is high for levocetirizine as the percentage of the drug eliminated unchanged in the 48 h urine is 77% of the oral dose; the estimation for fexofenadine is at least 33%; no estimation was found for desloratadine. Fexofenadine is a P-glycoprotein (P-gp) substrate and P-gp is certainly involved both in the poor brain penetration by the compound and, at least partially, in a number of observed drug interactions. An interaction of desloratadine with P-gp has been suggested in mice, whereas the information on mizolastine is very poor. The fact that levocetirizine is a substrate of P-gp, although weak in an in vitro model, could contribute to prevent drug penetration into the brain, whereas it is unlikely to be of any clinical relevance for P-gp-mediated drug interactions.

Topics: Absorption; Animals; Area Under Curve; Benzimidazoles; Biological Availability; Cetirizine; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Loratadine; Metabolic Clearance Rate; Piperazines; Terfenadine; Tissue Distribution

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

Antihistamines are often used for treating allergic rhinitis. However, many older antihistamines cause sedative side effects. The sedative effects of antihistamines on car-driving have been investigated. This has not been investigated for levocetirizine, a new-generation antihistamine, in Asian populations, and so we evaluated its sedative effects in healthy Japanese subjects.. In this double-blind, placebo-controlled, four-way crossover study, healthy volunteers received single doses of levocetirizine 5 mg, fexofenadine 60 mg, diphenhydramine 50 mg, and placebo at intervals of at least 6 days. Simple brake reaction time and choice brake reaction time task (CBRT), a lateral tracking (LT) task, and a multiple task, a mixture of CBRT and LT task, were used to compare driving performance between the four drugs. Subjective sedation was also assessed.. The simple brake reaction time and CBRT, and the CBRT component of the multiple task, did not show any significant differences between the drugs. In contrast, the LT, both as a single parameter and as a component of the multiple task, showed significant differences between diphenhydramine and the newer-generation antihistamines in a manner that corresponds with subjective sedation.. Levocetirizine and fexofenadine did not impair psychomotor performance in subjects performing simulated car-driving tasks, while diphenhydramine did impair psychomotor performance in the subjects. Copyright © 2016 John Wiley & Sons, Ltd.

Topics: Adult; Asian People; Automobile Driving; Cetirizine; Cross-Over Studies; Diphenhydramine; Double-Blind Method; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Psychomotor Performance; Reaction Time; Terfenadine; Young Adult

Histamine H1 receptor (H1R) antagonists often have sedative side effects, which are caused by the blockade of the neural transmission of the histaminergic neurons. We examined the brain H1R occupancy (H1RO) and the subjective sleepiness of levocetirizine, a new second-generation antihistamine, comparing fexofenadine, another non-sedating antihistamine, as a negative active control.. Eight healthy volunteers underwent positron emission tomography (PET) imaging with [(11)C]doxepin, a PET tracer that specifically binds to H1Rs, after a single oral administration of levocetirizine (5 mg), fexofenadine (60 mg) or placebo in a double-blind crossover study. Binding potential ratios and H1ROs in the cerebral cortices regions were calculated using placebo. Subjective sleepiness was assessed with the Line Analogue Rating Scale and the Stanford Sleepiness Scale.. There was no significant difference between the mean brain H1RO after levocetirizine administration (8.1%; 95% CI: -9.8 to 26.0%) and fexofenadine administration (-8.0%; 95% CI: -26.7 to 10.6%). Similarly, subjective sleepiness was not significantly different between the two antihistamines and placebo. Neither subjective sleepiness nor plasma concentrations was significantly correlated with the brain H1RO of the two antihistamines.. At therapeutic dose, levocetirizine does not bind significantly to the brain H1Rs and does not induce significant sedation.

Topics: Administration, Oral; Brain; Carbon Radioisotopes; Cetirizine; Cross-Over Studies; Double-Blind Method; Doxepin; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Neuroimaging; Positron-Emission Tomography; Radioligand Assay; Receptors, Histamine H1; Sleep; Terfenadine; Young Adult

This randomized, double-blind, placebo-controlled crossover study compared inhibition by one 5 mg dose of levocetirizine with two 60 mg doses of fexofenadine separated by 12 h of histamine-induced wheal and flare responses in 9 Caucasian and 9 Japanese healthy male volunteers. Levocetirizine was more inhibitory than fexofenadine on wheal, flare and pruritus (p < 0.005). Variability, evaluated from the standard deviation of inhibition, ranged from 14% to 23.2% for levocetirizine and 65.4% to 112.4% for fexofenadine. Levocetirizine had a faster onset of action (30-90 min versus 2 h), shorter time to maximum effect (3-4 versus 3-6 h) and longer duration of action (at least 24 h versus ~12 h) than fexofenadine. The plasma levels of levocetirizine rose more quickly, reached higher levels, were more consistent and decreased slower than those of fexofenadine. There were no clinically significant ethnic differences in responsiveness to the drugs.

Topics: Adult; Asian People; Cetirizine; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Germany; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Japan; Male; Pruritus; Skin; Terfenadine; Time Factors; Treatment Outcome; Urticaria; White People; Young Adult

To assess the antihistaminic activity of levocetirizine and fexofenadine 2 h and 24 h after drug administration using facial thermography and to compare the results with those using well-established parameters of antihistaminic activity in the nose and skin.. This was a randomized, double-blind, three-treatment, three-period, single-dose, cross-over study in healthy males taking levocetirizine 5 mg, fexofenadine 120 mg or placebo. The primary endpoint was nasal skin temperature after nasal histamine challenge recorded for 20 min at 2 and 24 h after drug intake. The secondary endpoints were nasal symptoms and a histamine skin prick test.. Thirty subjects were randomized. At 2 h after drug intake the inhibition of the nasal temperature increase from baseline was not significantly different between levocetirizine and fexofenadine. At 24 h it was significantly more pronounced after levocetirizine than fexofenadine (difference: least-squares mean: -0.13 degrees C; P < or = 0.024, 95% CI -0.24, -0.02). Both drugs significantly reduced (P < or = 0.001) the mean temperature increase from baseline compared with placebo at 2 and 24 h (least-squares mean increase and (95% CI): levocetirizine, -0.28 degrees C (-0.42, -0.14) and -0.32 degrees C (-0.43, -0.21); fexofenadine -0.35 degrees C (-0.49, -0.21) and -0.19 degrees C (-0.30, -0.08), respectively). Results of nasal symptom score and wheal and flare were consistent with the thermography results.. Facial thermography is an objective, non-invasive and sensitive method to study antihistaminic activity at the nose level. Levocetirizine and fexofenadine demonstrate the same activity at 2 h after drug intake, but levocetirizine has a more sustained activity at 24 h.

Topics: Adolescent; Adult; Cetirizine; Cross-Over Studies; Double-Blind Method; Face; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Nasal Provocation Tests; Nose; Piperazines; Skin Temperature; Terfenadine; Thermography

of this study was to compare the effect of the following antihistamines: cetirizine 10mg, desloratadine 5mg, fexofenadine 120 and 180mg, levocetirizine 5mg, loratadine 10mg, and placebo, administered in the recommended doses over the period of 5 days, on the visually assessed histamine-induced skin reaction, using the Laser Doppler flowmetry (LDF).. Forty two volunteers (aged 18-22) who gave a written consent before entering the study, were randomized in seven groups of six subjects each. The skin prick test with histamine solution of 10mg/ml was performed on the ventral forearm, 10 cm from the elbow, before and at 2, 4, 6, 8, 10, 12, 18, and 24 hours after drug administration, as well as once daily for the next 4 days of antihistamine drug or placebo intake, and 9 days following the treatment. Diameters of wheal and flare as well as the LDF index measured with Periflux PF3 flowmeter and skin probe, 5mm from the histamine-provoked area, were assessed 10 minutes after performing the above-mentioned skin prick test.. The current study revealed that during the 5-day treatment with recommended doses of cetirizine, desloratadine, fexofenadine, levocetirizine, and loratadine, a significant reduction of histamine-induced wheal, flare and the LDF index was observed as compared to the initial values and placebo intake, reaching the maximum value within the first 24 hours, weakening on the next day, and then gradually increasing during the following days. After the 5-day treatment drugs used for the study were lined up according to the volume of reduction in histamine-induced skin reaction (largest>smallest): levocetirizine > cetirizine > fexofenadine 180mg = fexofenadine 120mg > loratadine = desloratadine.. Following the end of the treatment, the effect of the antihistamines on skin reaction was subsiding in such an order: after 24 hours in case of loratadine and desloratadine, after two days for both doses of fexofenadine, and 3-4 days for cetirizine and levocetirizine.

Topics: Administration, Oral; Adult; Cetirizine; Double-Blind Method; Drug Administration Schedule; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Laser-Doppler Flowmetry; Loratadine; Male; Piperazines; Regional Blood Flow; Skin; Skin Tests; Terfenadine; Treatment Outcome; Urticaria

The aim of the study was to compare the effect of inhibition skin reactivity after administration of single dose administration of various second generation antihistamines in the healthy people group.. Forty two healthy subjects (aged 22+/-18 years) were randomized into seven groups which received orally: cetirizine 10 mg, loratadine 10 mg, desloratadine 5 mg, levocetirizine 5 mg, fexofenadne 120 mg and 180 mg, or placebo respectively. The skin microcirculation reaction after 10 mg/ml histamine administration was estimated visually on the forearm (diameter of wheal and flare) and by Laser Doppler flowmetry before and after study drug or placebo administration prior and, 2, 4, 6, 8, 10, 12, 18, 24 h and one time daily every next 9 days.. There were significant differences of histamine-induced wheal, flare and skin blood flow inhibition vs baseline and placebo after drug administration. There were different dyr'mmics in suppression effect after histamine-induced skin reactivity in various drug groups. The overall inhibitory potency was statistically higher for cetirizine, levocetirizine and fexofenadine (even 95% ve basline) as compared to loratadine and desloratadine (even 65% vs basline). Different times of retreated inhibition effect after administered drugs were observed.. The study drugs shown significant different dynamics of skin reaction inhibition vs baseline and placebo. There were observed strongest effect after levocetirizine and cetirizine and next order after fexofenadine, desloratadine and loratadine.

Topics: Administration, Oral; Adult; Cetirizine; Double-Blind Method; Histamine; Histamine H1 Antagonists, Non-Sedating; Humans; Laser-Doppler Flowmetry; Loratadine; Male; Piperazines; Placebos; Skin; Skin Tests; Terfenadine; Treatment Outcome; Urticaria

To compare the onset and duration of action of the new antihistamine levocetirizine with that of the second-generation antihistamine fexofenadine using the Vienna Challenge Chamber (VCC). The latter is an environment where subjects can be exposed to specific aeroallergens in controlled and reproducible conditions allowing for precise comparisons of anti-allergic drugs.. Ninety-four subjects received a single dose of levocetirizine 5 mg, fexofenadine 120 mg or placebo in a random order using a three-way cross-over design. On day 1, subjects were exposed to grass pollens (1500 grains/m(3)) in the VCC over a period of 4 h. Treatment was given 2 h after the start of challenge. On day 2, 22 h after drug intake, subjects were again exposed to pollens for 6 h. Specified symptoms were assessed by the subjects every 15 min using 5-point scales. The main efficacy parameter was the change from baseline in the Major Symptom Complex Score (MSCS = sum of rhinorrhea, sneezing, itchy nose and eyes).. Baseline characteristics, including symptoms scores, were similar in the three study groups. During the first 2 h after drug intake both antihistamines achieved clinically relevant and significant (P < 0.001) improvements in symptom scores. Twenty-two to 24 h after drug intake, mean (SEM) MSCS reductions were: 1.9 (0.3) after placebo (baseline of 9.7), 3.8 (0.3) after fexofenadine (baseline of 9.9), and 5.1 (0.3) after levocetirizine (baseline of 9.8). Levocetirizine was significantly (P < 0.001) more effective than fexofenadine with a score difference of 1.3 (95% CI 0.7, 1.9). This was maintained until the end of the study (up to 28 h).. A rapid onset of action in alleviating seasonal allergic rhinitis (SAR) symptoms of subjects exposed to grass pollens in the VCC was observed after levocetirizine and fexofenadine. Levocetirizine was more effective than fexofenadine at and later than 22 h after drug intake, an indication of the longer-duration of action of levocetirizine.

Topics: Adult; Cetirizine; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Nose Diseases; Patient Satisfaction; Piperazines; Terfenadine

Summary Background There are no data directly comparing the relative efficacy of modern H(1)-antihistamines in allergic rhinitis using nasal provocation challenge. Objective We elected to study the comparative effectiveness of usual clinically recommended doses of desloratadine (DES), fexofenadine (FEX), and levocetirizine (LEV), on nasal adenosine monophosphate (AMP) challenge in patients with perennial allergic rhinitis (PAR). Methods 16 patients with PAR were randomized in double-blind cross-over fashion to receive single doses of DES 5 mg, FEX 180 mg, LEV 5 mg, or placebo (PL), with nasal AMP challenge performed 12 h after dosing. Measurements of peak nasal inspiratory flow (PNIF) were made over 60 min after nasal AMP challenge. Results Pre-challenge values (mean+/-SEM) for PNIF (L/min) were not significantly different comparing all groups; DES (129+/-9), FEX (128+/-11), LEV (128+/-13), and PL (128+/-12). The maximum % PNIF fall from baseline over 60 min after nasal AMP challenge was significantly attenuated (P<0.05) compared to PL (50+/-4), with DES (32+/-5), FEX (36+/-4), and LEV (36+/-4). The area under the 60-min time-response curve (%.min) was also significantly attenuated (P<0.05) compared to PL (2110+/-268), with DES (1126+/-285), FEX (1225+/-255), and LEV (1261+/-194). There were no significant differences between the three H(1)-antihistamines for any outcomes. Conclusion DES, FEX, and LEV were equally effective in attenuating the response to nasal AMP challenge. However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells.

Topics: Adenosine Monophosphate; Adult; Aged; Aged, 80 and over; Anti-Allergic Agents; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Nasal Provocation Tests; Piperazines; Rhinitis, Allergic, Perennial; Terfenadine; Treatment Outcome

Modern H(1)-antihistamines differ in their in vitro binding affinity, but their comparative in vivo bioactivity in asthmatic airways is unknown.. We compared clinically recommended doses of 3 H(1)-antihistamines on airway hyperresponsiveness to AMP challenge (the primary outcome variable).. Sixteen atopic patients with mild-to-moderate asthma of whom 10 were receiving inhaled corticosteroid therapy (all had positive results to house dust mite on skin prick testing) were randomized in a double-blind, placebo-controlled, cross-over fashion to receive single doses of 5 mg of desloratadine, 180 mg of fexofenadine hydrochloride (FEX), 5 mg of levocetirizine dihydrochloride (LEV), or placebo, with AMP challenge performed 12 hours after dosing.. All H(1)-antihistamines demonstrated significantly greater (P <.05) geometric mean +/- SEM AMP PC(20) values compared with that of placebo (86 +/- 29 mg/mL): desloratadine, 189 +/- 54 mg/mL; FEX, 176 +/- 57 mg/mL; and LEV, 163 +/- 48 mg/mL. Prechallenge forced expiratory flow at 25% to 75% of maximal lung volume (percent predicted) but not FEV(1) was significantly higher (P <.05) for all H(1)-antihistamines compared with that of placebo (53% +/- 4%): desloratadine, 62% +/- 4%; FEX, 62% +/- 4%; and LEV, 59% +/- 3%. There were no significant differences in either AMP PC(20) or lung function values among the H(1)-antihistamines.. Single doses of H(1)-antihistamines improved airway hyperresponsiveness and small-airways caliber to a similar degree. Data for in vitro binding affinity do not therefore translate into commensurate differences in in vivo bioactivity at clinically recommended doses.

Topics: Acetates; Adenosine Monophosphate; Adult; Aged; Asthma; Bronchial Provocation Tests; Cetirizine; Cross-Over Studies; Double-Blind Method; Female; Forced Expiratory Volume; Histamine H1 Antagonists; Humans; Loratadine; Male; Middle Aged; Piperazines; Respiratory Hypersensitivity; Terfenadine

Topics: Adult; Angioedema; Cetirizine; Diarrhea; Famotidine; Female; Food Hypersensitivity; Histamine Antagonists; Humans; Male; Middle Aged; Postprandial Period; Ranitidine; Terfenadine; Urticaria

Allergic rhinitis (AR) affects a large percentage of paediatric patients. With the wide array of available agents, it has become a challenge to choose the most appropriate treatment for patients. Second-generation antihistamines have become increasingly popular because of their comparable efficacy and lower incidence of adverse effects relative to their first-generation counterparts, and the safety and efficacy of this drug class are established in the adult population. Data on the use of the second-generation antihistamines oral cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, and the leukotriene receptor antagonist montelukast as well as azelastine nasal spray in infants and children are evaluated in this review. These agents have been found to be relatively safe and effective in reducing symptoms associated with AR in children. Alternative dosage forms such as liquids or oral disintegrating tablets are available for most agents, allowing ease of administration to most young children and infants; however, limited data are available regarding use in infants for most agents, except desloratadine, cetirizine and montelukast. Unlike their predecessors, such as astemizole and terfenadine, the newer second-generation antihistamines and montelukast appear to be well tolerated, with absence of cardiotoxicities. Comparative studies are limited to cetirizine versus ketotifen, oxatomide and/or montelukast. Although second-generation antihistamines and montelukast are deemed relatively safe for use in paediatric patients, there are some noteworthy drug interactions to consider when selecting an agent. Given the wide variety of available agents for treatment of AR in paediatric patients, the safety and efficacy data available for specific age groups, type of AR, dosage form availability and cost should be considered when selecting treatment for AR in infants and children.

Topics: Acetates; Administration, Oral; Adult; Anti-Allergic Agents; Anti-Asthmatic Agents; Astemizole; Cetirizine; Child; Cyclopropanes; Drug Administration Schedule; Drug Interactions; Histamine H1 Antagonists, Non-Sedating; Humans; Ketotifen; Leukotriene Antagonists; Loratadine; Piperazines; Quinolines; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Safety; Sulfides; Tablets; Terfenadine; Treatment Outcome

Allergic rhinitis and urticaria are common allergic disorders that may affect approximately 15% of people at some time in their lives. Antihistamines are the most widely used therapeutic interventions for these disorders but the newer generation agents have differing pharmacokinetic characteristics that may result in different patient satisfaction and preferences. The objective of this study was to investigate patients' and physicians' satisfaction with their current antihistamine treatment for allergic disease.. In an observational study, physicians in nine European countries completed questionnaires evaluating 7,274 patients treated with an oral antihistamine. The satisfaction of patients and physicians with the efficacy and tolerability of treatment was rated on a visual analogue scale. In addition, the proportion of patients satisfied with treatment (overall satisfaction) and willing to continue treatment with the same antihistamine were assessed. Safety and tolerability data were also gathered.. The results of this study indicate that modern antihistamines are generally considered effective and well tolerated by patients. In general, levocetirizine scored significantly higher in terms of perception of efficacy, tolerability and overall satisfaction. In terms of tolerability, three-quarters of patients were 'very satisfied' and a further fifth were moderately satisfied with levocetirizine and almost all (95%) were happy to continue treatment. Overall, the most commonly reported adverse event in this study was somnolence, a well known effect of antihistamines. The rate of somnolence in the levocetirizine group (3.8%) was similar to that for fexofenadine (both doses) and desloratadine, two products which are considered to be nonsedating antihistamines, and significantly less than half the rate for cetirizine.. Levocetirizine is considered an effective and well tolerated option for treating allergic disease by patients and physicians alike, particularly when the best available effectiveness and tolerability are required.

Topics: Activities of Daily Living; Administration, Oral; Adult; Aged; Aged, 80 and over; Cetirizine; Child; Child, Preschool; Data Collection; Disorders of Excessive Somnolence; Dose-Response Relationship, Drug; Europe; Female; Histamine H1 Antagonists; Humans; Infant; Male; Middle Aged; Patient Satisfaction; Piperazines; Prevalence; Rhinitis, Allergic, Seasonal; Terfenadine; Treatment Outcome; Urticaria

The long QT syndrome is a rare disease. The prevalence is estimated at 1/5 000 to 1/20,000. Numerous drugs are contra-indicated because they can lengthen the QT interval. A case of pollen allergy in an adolescent with LQTS is described. The possibility to prescribe anti-H1 drugs is reviewed since cases of torsades de pointe and even deaths have been reported for terfenadine and astemizole. Diphenhydramine, orphenadrine and hydroxyzine are contra-indicated. No accidents and no effects on the QT interval have been published for ebastine, fexofenadine, desloratadine and levocetirizine. These anti-H1 drugs could be used with great care, without any association with drugs resulting in low serum potassium level. Azelastine eye drops have been authorized and a routine protection by inhaled corticosteroids during the pollinic period has been advised in this adolescent treated by betablockers.

Topics: Adolescent; Adrenergic beta-Antagonists; Anti-Asthmatic Agents; Butyrophenones; Cetirizine; Conjunctivitis, Allergic; Cromolyn Sodium; Diabetes Mellitus, Type 1; Heart; Histamine H1 Antagonists; Humans; Long QT Syndrome; Male; Piperazines; Piperidines; Rhinitis, Allergic, Seasonal; Terfenadine

The predictive efficacy of drugs in humans is frequently estimated from both a high affinity for their receptor as measured in vitro and a long plasmatic half-life. This is grossly misleading since one key parameter is missing: drug concentration at the receptor site in vivo. As a case study we compared the efficacies of three H(1) antihistamines in inhibiting histamine-induced wheal and flare in humans at two different time points with the above mentioned parameters. It is concluded that estimating in vivo receptor occupancy, which takes into account both the affinity of the drug for the receptor and its free plasma concentration, is a far better predictor for human pharmacodynamics and hence antihistamine potency, than considering in vitro affinity and plasmatic half-life only.

Topics: Animals; Cetirizine; CHO Cells; Cricetinae; Cricetulus; Histamine H1 Antagonists; Humans; Loratadine; Piperazines; Predictive Value of Tests; Receptors, Histamine H1; Recombination, Genetic; Terfenadine; Urticaria