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To gain a comprehensive overview of the landscape of clinical trials for the H 1 -receptor antagonists (H 1 R antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, H 1 R antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of H 1 R antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of H 1 R antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future., (© 2023. The Author(s).)

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., (© 2012 Blackwell Publishing Ltd.)

Background: 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., Objective: 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., Methods: 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., Results: 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)., Conclusions: 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.

Allergic rhinitis (AR) affects approximately 500 million people worldwide, and prevalence is increasing. Second-generation nonsedating antihistamines are first-line treatments for seasonal AR (SAR). This study was performed to evaluate early SAR symptom relief with second-generation antihistamines through a retrospective analysis of previously published data. In this study, 835 subjects aged 12-60 years with a > or = 2-year history of SAR were randomized to receive loratadine, 10 mg, once daily; fexofenadine, 60 mg, twice daily; or placebo for 7 days. Each subject recorded the severity of five symptoms of SAR on a scale of 0-3. This primary post hoc efficacy analysis was the mean change from baseline in daily average A.M./P.M. reflective and instantaneous total symptom score (TSS) on days 2 and 3. Significantly greater mean reductions from baseline were shown with loratadine compared with fexofenadine in average A.M./P.M. reflective TSS on days 2 (-3.51 versus -2.84, respectively; p < 0.002) and 3 (-3.80 versus -3.19, respectively; p = 0.007) and in average A.M./P.M. instantaneous TSS on day 3 (-3.68 versus -3.15, respectively; p = 0.022). Similar results were noted in average A.M./P.M. reflective and instantaneous total nasal symptom scores and for 10 of 20 individual symptom time points (p < 0.05). Loratadine was significantly more effective than placebo for all time points (p < 0.001). Early, sustained symptom relief was seen with loratadine, suggesting that it may be more effective for treating SAR symptoms.

To date, no published articles exist comparing the H1-receptor antagonist activities of fexofenadine and desloratadine using the histamine-induced skin wheal-and-flare model. The aim of this study was to compare the efficacy of fexofenadine versus desloratadine in suppressing histamine-induced skin flares and wheals in adults and adolescents. This was a two-center, randomized, placebo-controlled, complete-crossover study. Subjects were administered either single-dose fexofenadine HCl, 180 mg; desloratadine, 5 mg; or placebo and their response to skin-prick testing with histamine and diluent was recorded at predetermined time intervals. The primary end point was change in size of histamine-induced summation skin flares. Secondary end points included change in skin wheal summation measurements, onset, duration, maximum percent suppression, and time to maximum suppression of flares and wheals. Fexofenadine suppressed skin flares significantly more than desloratadine from 2 to 6 hours, and wheals from 2 to 4 hours, 6 to 9 hours, and 12 hours posttreatment. In addition, fexofenadine suppressed flares more than placebo at all time points from 2 to 24 hours and wheals more than placebo at all time points from 2 to 12 hours posttreatment. Desloratadine suppressed flares significantly more than placebo from 6 to 10 hours and at 12 and 24 hours but suppressed wheals significantly versus placebo only at 10 hours. Fexofenadine had a faster onset of flare suppression than desloratadine (1 hour versus 5 hours) and an equally rapid onset of wheal suppression. Fexofenadine HCl, 180 mg, was superior to desloratadine, 5 mg, in histamine-induced wheal-and-flare suppression, suggesting increased in vivo H1-receptor antagonist potency of fexofenadine versus desloratadine.

This is the first U.S.-based study to compare efficacy and safety of desloratadine with fexofenadine in subjects with symptomatic seasonal allergic rhinitis (SAR). In this double-blind study, subjects were randomized to desloratadine, 5 mg (n = 290),fexofenadine, 180 mg (n = 288), or placebo (n = 144) once daily for 15 days. Primary end point was mean change from baseline to study end in morning instantaneous total symptom score (AM NOW TSS) excluding congestion. Secondary measures included change from baseline in the morning/evening reflective TSS (AM/PM PRIOR TSS) excluding congestion, AM NOW individual symptom score (AM NOW ISS) including congestion, and the AM/PM PRIOR ISS including congestion. Subjects self-evaluated their symptoms on a five-point scale. Mean AM NOW TSSs were significantly reduced from baseline at day 15 with desloratadine (p = 0.006) and fexofenadine (p = 0.024) versus placebo. Desloratadine and fexofenadine were not statistically different (p = 0.491); the upper limit of the 95% CI for desloratadine to fexofenadine (0.259) was within the prespecified noninferiority margin of 0.7 U. Decrease in mean AM/PM PRIOR TSS excluding congestion was comparable between desloratadine and fexofenadine (p = 0.405; CI = 0.221) but was significantly greater with both active treatments versus placebo (desloratadine, p < 0.001;fexofenadine, p = 0.003). Desloratadine and fexofenadine provided greater reduction in the AM NOW ISS and AM/PM PRIOR ISS (both including congestion) versus placebo; reductions were comparable between active treatments. All treatments were well tolerated. Desloratadine, 5 mg, and fexofenadine, 180 mg, provide comparable efficacy and tolerability in the treatment of SAR. Both treatments are significantly more effective than placebo.

Background: Allergic rhinitis is manifested by watery discharge; however its clinical effect on the watery volume in the oral cavity is unknown. In addition, the low incidence of dry mouth due to treatment with the new generation antihistamines is based on subjective patients' reports only. This study aimed to examine the effect of loratadine and fexofenadine on the salivary gland function in patients diagnosed with allergic rhinitis compared to untreated allergic patients and healthy individuals., Methods: A comparative observational study assessed parameters related to the patients' perception of dry mouth as well as clinically observed parameters in fexofenadine-treated patients (group A) and in loratadine-treated patients (group B). Allergic patients without pharmacological treatment (group C) and healthy individuals (group D) served as a double control in order to evaluate the effect of allergy itself on dry mouth. A total of 36 patients were enrolled., Results: Patients in groups A and C reported the highest intensity of xerostomia. Sialometry values were significantly lower in these 2 groups compared to the healthy controls (p = 0.02 and 0.03, respectively). Average sialometry was over 0.2 ml/min in all groups and subjective dry mouth sensation ranged in the lower quarter of the visual analogue scale., Conclusions: In this pilot study, patients diagnosed with allergy presented a significant difference in salivary flow rate compared to healthy controls. Unlike the effect of loratadine, fexofenadine-treated patients showed significantly lower salivary flow rates compared to healthy individuals. In all cases the intensity of dry mouth was low.

Background: The effects of the selective H1-receptor antagonist fexofenadine have been widely demonstrated in Western populations; however, to date, limited data comparing the effects of fexofenadine with other antihistamines have been reported in Japanese subjects., Objective: To investigate the effect of fexofenadine and loratadine on the histamine-induced cutaneous wheal and flare response in healthy Japanese volunteers., Methods: Eighteen healthy male and female Japanese volunteers aged 20-53 years were randomized to receive fexofenadine HCl 60 mg twice daily, loratadine 10 mg once daily or placebo in a 1-day, three-period, double-blind, crossover study. For each treatment, the wheal and flare response to 100 mg/mL histamine was assessed at baseline and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 8, 12 and 24 hours post-dose. Blood samples were taken for pharmacokinetic analysis., Results: Fexofenadine produced significantly greater percentage suppression of the overall wheal response compared with placebo and loratadine (43.1% versus 10.0% and 15.2%, respectively; p < 0.001). Similarly, fexofenadine significantly suppressed the overall flare response compared with placebo and loratadine (43.0% versus 3.5% and -8.9%, respectively; p < 0.01). Loratadine was statistically no different from placebo in terms of both overall wheal and flare suppression. Area under the curve analysis for wheal and flare reduction (0-12 hours post-dose) confirmed these findings. For wheal inhibition, fexofenadine had a significantly faster onset of action (defined as time to > or = 35% inhibition) compared with placebo (p < 0.001) and loratadine (p < 0.01); for flare, fexofenadine had a significantly faster onset of action than loratadine (p < 0.01). Mean maximum inhibition (the mean of the greatest inhibition achieved from baseline for each treatment) for wheal was achieved significantly faster with fexofenadine than loratadine (p < 0.01), and fexofenadine had a significantly longer duration of effect on suppressing wheal and flare compared with placebo and loratadine (p < 0.05 for all). The antihistamine effects of fexofenadine correlated significantly with its Cmax, while loratadine activity did not correlate significantly with its plasma levels., Conclusions: Fexofenadine is a potent suppressor of the histamine-induced wheal and flare response in healthy Japanese volunteers. These results support findings in Caucasian subjects, and confirm that fexofenadine has greater antihistaminergic activity than loratadine in this human model.

Background and Objective: Non-sedating antihistamines (loratadine, fexofenadine, and cetirizine) have been widely used in Thailand. This study examined the time-of-onset and compared the 95% inhibitory effect of these agents on histamine-induced cutaneous reaction so as to understand the diversity of their efficacy., Patients and Method: Thirty-one atopic patients were randomized into 4 treatment groups, placebo (n = 7), loratadine (n = 8), fexofenadine (n = 8), and cetirizine (n = 8). They were pricked with histamine every 30 min for 4 hrs. The percentage change of the wheal/flare area was calculated., Results: All active treatments showed wheal suppression superior to placebo after 210 min for loratadine (P = 0.04); 90 min for fexofenadine (P = 0.009); and 60 min for cetirizine (P = 0.02), while flare suppression was significantly marked after 150 min (P = 0.0008) for loratadine; 90 min for fexofenadine (P = 0.0001), and 60 min for cetirizine (P = 0.006). All drugs except loratadine demonstrated a 95% suppression of wheal superior to the placebo (P = 0.001 for fexofenadine; P = 0.0001 for cetirizine). Only fexofenadine exhibited a 95% suppression of flare statistically superior to placebo (P = 0.02). Discrepancies among the effects of these 3 antihistamines were also detected., Discussion and Conclusion: All antihistamines tested repressed the wheal-and-flare area superbly over the placebo within 4 hours. Cetirizine exerted the fastest onset, and it also appeared to be the most efficacious inhibitor. The heterogeneity of their efficacy probably stems from their diverse physicochemical properties, which have also been discussed.

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.

Onset of action for relief of allergic rhinitis symptoms is of clinical significance to both the physician and the patient. Using either subjective or objective methods, the onset of action after a single, oral dose of an antihistamine can be measured. Multicenter studies, outdoor studies, and pollen challenge systems have been used to measure the onset of action. A literature search from 1985 to May 2002 was performed. All published, randomized, placebo-controlled clinical studies pertaining to the onset of action for relief of allergic rhinitis symptoms after a single, oral dose of a second-generation antihistamine (not combined with a decongestant) including cetirizine, desloratadine, fexofenadine, and loratadine, were reviewed. The onset of action for cetirizine ranged from 59 minutes to 2 hours and 6 minutes and for loratadine onset of action ranged from 1 hour and 42 minutes to none identified during the duration of the study. Cetirizine had a shorter onset of action than loratadine for all comparisons. Fexofenadine had an onset of action within 60 minutes. The literature search did not reveal any published onset of action studies for desloratadine. The onset of action for a given second-generation antihistamine depends on how it is defined and subsequently measured.

A number of prescription and nonprescription nonsedating antihistamines are available for the treatment of allergic rhinitis. From a managed care perspective, determining the extent to which a medication conversion to desloratadine from loratadine, fexofenadine, or cetirizine results in maintained or increased patient satisfaction with allergy care would be informative for formulary decision makers and other budget holders. To that end, a survey was undertaken of patient medication assessments after a switch in antihistamines. On average, patients who converted to desloratadine from loratadine, fexofenadine, or cetirizine reported increased satisfaction with desloratadine treatment.

Background: Antihistamine-decongestant combinations are used routinely for the treatment of seasonal allergic rhinitis. Recently, the combination of an antihistamine and a leukotriene receptor antagonist has been shown to be efficacious., Objective: To compare the 2 combinations in the treatment of seasonal allergic rhinitis., Methods: This was a randomized, double-blind, double-dummy, parallel study in which patients with seasonal allergic rhinitis received either fexofenadine, 60 mg, and pseudoephedrine, 120 mg, twice daily, or loratadine, 10 mg, and montelukast, 10 mg, once daily, for 2 weeks. The Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed at the beginning and end of the study. Patients recorded nasal symptoms and measured nasal peak inspiratory flow (NPIF) twice daily. Baseline measurements were obtained before initiation of treatment., Results: Compared with baseline, both treatments resulted in statistically and clinically meaningful reductions of overall and individual RQLQ domain scores (P < .01) except for the sleep domain, for which only loratadine-montelukast led to significant improvement. There was a significant reduction in total symptoms (P < or = .05) compared with baseline on most treatment days in patients receiving both combinations. When the change from baseline was analyzed, there were no statistically significant differences in total symptoms between fexofenadine-pseudoephedrine and loratadine-montelukast (median, -28.5 vs -22.5; P = .33). There was a significant improvement in NPIF from baseline on all treatment days in both groups (P < .05), with no significant difference between treatments., Conclusions: Fexofenadine-pseudoephedrine and loratadine-montelukast have comparable efficacy in improving symptoms, RQLQ scores, and nasal obstruction in seasonal allergic rhinitis. The lack of improvement in sleep in the fexofenadine-pseudoephedrine group is probably related to insomnia, a known adverse effect of pseudoephedrine.

Background: The FDA recently moved loratadine (Claritin) from prescription only status to over-the-counter (OTC). In response to the availability of an OTC non-sedating antihistamine, many managed care organizations are reevaluating which if any prescription antihistamines should remain on formulary. From a managed care perspective, determining which of the remaining prescription antihistamines results in the greatest patient satisfaction with allergy treatment would be informative., Methods: We report on a weighted cross sectional survey (n = 10,023) delivered online to a sample of allergy sufferers in the U.S. during the month of December 2002. Two segments were identified for analysis: patient who were dissatisfied with loratadine and converted to desloratadine (Clarinex; n = 61), and patients who were dissatisfied with loratadine and converted to fexofenadine (Allegra; n = 211). The two segments were compared along a series of measures that the literature suggests are related to treatment satisfaction., Results: The survey found that two of the satisfaction measures differentiated desloratadine converters from fexofenadine converters (p <.05): mean sum of self-reported adverse events and nighttime awakening due to allergy symptoms. For the remainder of satisfaction measures though, patients who were dissatisfied with loratadine reported equal duration of coverage and satisfaction with desloratadine as fexofenadine. When severity of disease was controlled for in the analysis, a pattern emerged suggesting greater levels of satisfaction amongst loratadine dissatisfied patients who converted to desloratadine. Point estimates suggest a consistent pattern favoring desloratadine patient satisfaction, with statistically significant results reported for sum of adverse effects, nighttime awakening due to symptoms, symptom severity just prior to the next dose, and overall satisfaction (p < 0.05)., Conclusions: On average, patients who were dissatisfied with loratadine reported equal or better satisfaction with desloratadine as fexofenadine. Patients with severe allergic rhinitis reported greater satisfaction when converted from loratadine to desloratadine than fexofenadine for select satisfaction measures. These results suggest that if managed care intends to position prescription antihistamines as second line for OTC loratadine treatment dissatisfaction, desloratadine is a useful treatment alternative. These findings, while informative to formulary decision-makers, must be interpreted with caution. Only through head-to-head controlled clinical trials can differences in efficacy and safety be established.

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.

Background: Modern H(1)-antihistamines differ in their in vitro binding affinity, but their comparative in vivo bioactivity in asthmatic airways is unknown., Objectives: We compared clinically recommended doses of 3 H(1)-antihistamines on airway hyperresponsiveness to AMP challenge (the primary outcome variable)., Methods: 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., Results: 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., Conclusion: 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.

Background: In vitro studies have shown much higher H1-receptor antagonist potency with desloratadine (DL) compared to fexofenadine (FEX), although it is unclear whether this has any clinical relevance on disease control parameters in seasonal allergic rhinitis (SAR), especially for nasal congestion., Objective: To compare the relative efficacy between presently recommended doses of DL and FEX on daily measurements of peak nasal inspiratory flow (PNIF) and nasal symptoms in SAR., Methods: Forty-nine patients with SAR were randomized into a double-blind, placebo-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 180 mg FEX or (b) 5 mg DL, taken in the morning. There was a 7-10 day placebo run-in and washout prior to each randomized treatment. Measurements were made in the morning (AM) and in the evening (PM) for PNIF (the primary outcome variable), nasal and eye symptoms. The average of AM/PM values were used for analysis., Results: There were significant (P < 0.05) improvements, compared to placebo, with FEX and DL, for PNIF, nasal blockage, nasal irritation, and total nasal symptoms, but not nasal discharge or eye symptoms. There were no significant differences between active treatments. Values for PNIF (L/min) for mean placebo baseline, mean difference from baseline (95% CI for difference) were 126, 10 (4-16) for FEX; and 122, 11 (4-17) for DL. The mean difference (95% CI) between FEX vs. DL was 1 L/min (-7-8). Values for total nasal symptoms (out of 12) were: 3.2, 0.7 (0.2-1.2) for FEX; and 3.4, 0.9 (0.3-1.5) for DL, and for nasal blockage (out of 3) were: 1.1, 0.2 (0.1-0.4) for FEX; and 1.2, 0.3 (0.1-0.5) for DL. The mean difference (95% CI) in total nasal symptoms and nasal blockage between FEX vs. DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively., Conclusions: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR.

Background: The combination of montelukast (ML) and loratadine (LT) has previously been shown to be superior to either drug alone in managing seasonal allergic rhinitis (SAR), whilst fexofenadine (FEX) has been shown to be better than LT as monotherapy., Objectives: We wished to compare ML + LT vs. FEX alone for effects on daily measurements (am/pm) of peak inspiratory flow (PIF) and symptoms., Methods: Thirty-seven patients with SAR (skin prick positive to grass pollen) were randomised into a single-blind, double-dummy placebo (PL)-controlled cross-over study during the grass pollen season, comparing 2 weeks of once daily treatment with (a) 120mg FEX or (b) 10mg ML + 10mg LT. There was a 7-10 day placebo run-in and washout prior to each randomised treatment. The average of am/pm PIF (the primary outcome variable) was analysed. Patients recorded their symptom scores (from 0 to 3) twice daily, for nasal blockage, discharge, itching and sneezing with; total eye symptoms, ocular cromoglycate use, and daily activity. The total nasal symptom score was calculated as a composite (out of 24)., Results: There were no significant differences between baselines after the run-in and washout placebos for any variables. There were significant (P < 0.05, Bonferroni) improvements in all symptoms and PIF compared to pooled placebo with both treatments for all end-points, but no differences between the two treatment regimes (as means and within-treatment 95% confidence intervals): PIF: PL 102 (98-107), FEX 111 (107-116), ML+LT 113 (109-118); total nasal symptoms: PL 7.4 (6.7-2.0), FEX 5.0 (4.3-5.7), ML + LT 4.0 (3.3-4.7)., Conclusions: Once daily FEX as monotherapy was equally effective as the combination of once daily ML + LT in improving nasal peak flow and controlling symptoms in SAR. Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR.

Background: As there have been no previously published studies, this multinational, double-blind, randomized, placebo-controlled, parallel group study compared the efficacy, safety and impact on quality of life (QoL) in seasonal allergic rhinitis patients (SAR) of fexofenadine and loratadine (with placebo), when administered once daily., Methods: Six hundred and eighty-eight SAR patients were randomized to receive fexofenadine HCl 120 mg, loratadine 10 mg or placebo, once daily for 2 weeks. The key parameters were the change from baseline in: mean 24-h reflective total symptom scores (TSS); sum of four individual symptom scores, excluding nasal congestion; instantaneous TSS; individual symptom scores including nasal congestion; and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Adverse events were recorded., Results: Mean 24-h reflective and instantaneous TSS were significantly reduced by both fexofenadine HCl (both P

Background: Nonsedating antihistamines are well-established treatment for seasonal allergic rhinitis (SAR), but patients do not always respond to the first antihistamine prescribed., Objective: This double-blind, double-dummy, randomized, 2-phase, multicenter study was designed primarily to compare the therapeutic responses to loratadine and fexofenadine in patients who failed initial therapy with the other drug., Methods: Male and female patients aged 12 to 60 years received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale) subsequently received the alternate medication for 14 days (phase 2). The investigator's rating of relief (complete, marked, moderate, or slight relief of symptoms or treatment failure) at the end of phase 2 was the primary efficacy measure; changes in total symptom severity (TSS) assessed by the investigator (4-point scale) and the patient (11-point visual analog scale) were secondary measures., Results: Mean decreases in TSS were significantly greater with loratadine than with fexofenadine for the 659 patients who completed phase 1 (-12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389 patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037; investigator assessment). Of the 389 patients who responded to initial therapy, 61.0% had received loratadine and 57.0% had received fexofenadine. More nonresponders to initial therapy had moderate, marked, or complete relief of symptoms after switching to loratadine than after switching to fexofenadine (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs 21.7%, respectively (P = 0.011)., Conclusion: Overall, ioratadine provided significantly better therapeutic response than fexofenadine in patients who failed to respond to initial therapy with the other drug.

The sedation related to first-generation antihistamine use has been shown to compromise performance at school and at work, impair driving, and decrease the ability to handle tasks that require a high degree of alertness or concentration. Second-generation antihistamines are less likely to produce sedation. Loratadine, cetirizine, and fexofenadine are the most commonly prescribed second-generation antihistamines. Many tests have been conducted to assess the central effects of these three drugs. Compared with placebo, at recommended doses loratadine is not associated with performance impairment. Cetirizine, at recommended doses, has been shown to impair performance and cognition in several studies, although to a much lesser degree than older antihistamines. Clinical trials show fexofenadine is nonsedating, even at very high doses; psychomotor and driving tests reinforce these findings. Loratadine, cetrizine, and fexofenadine all have excellent safety records. Their cardiovascular safety has been demonstrated in drug-interaction studies, elevated-dose studies, and clinical trials. These three antihistamines have also been shown safe in special populations, including pediatric and elderly patients.

In a multicenter, parallel-group, double-masked, randomized study, two questionnaires were administered to a clinical study population to identify which specific symptoms of seasonal allergic rhinitis patients perceived as most important to relieve (personal preferences) and to learn whether any relationship existed between patient preferences and the severity of their symptoms during treatment with antihistamines. The group was composed of 256 males and 313 females. Their mean age was 32.4 years, and mean duration of seasonal allergic rhinitis was 14.5 years, with mean age of onset of 17.7 years. After receiving placebo for 1 week, patients were randomly allocated to receive an antihistamine (fexofenadine or loratadine) for 2 weeks. Patient preferences for relief of individual allergy symptoms (rhinitis; sneezing; itchy, watery, red eyes; itchy nose, palate, or throat) and related conditions (fatigue, physical limitations) were scored using 2 different questionnaires before treatment (0-to-10 category rating scale for assessing the 4 symptoms of allergic rhinitis) and after receiving placebo for 1 week (Feeling Thermometer). Symptom severity was reported in patient diaries after 1 and 2 weeks of antihistamine treatment and was measured by patient self-assessment. All symptoms were considered by the patients to be important to relieve, the most important being itchy, watery, red eyes and rhinorrhea. The severity of allergy symptoms was consistently related to the importance of symptoms identified before treatment. Therefore, including patient preferences in medical evaluations might be a useful tool in evaluating the success of their treatment.

Nonsedating H1 antihistamines such as terfenadine, loratadine, and astemizole are widely prescribed for the treatment of allergic rhinitis. The comparative efficacy of these agents has not been thoroughly studied. We studied 14 subjects in an open-label four-way crossover trial. Patients were recruited from an outpatient allergy clinic. Inclusion criteria were documented rhinitis symptoms for at least 2 years before the study and skin-test positivity in response to perennial allergens. Each subject underwent sequential 2-week trials of each of four H1 antihistamines: terfenadine, loratadine, astemizole, and chlorpheniramine. No placebo was included. Outcome measures were subjective rhinitis symptom scores, overall efficacy scores, and concomitant pseudoephedrine use. In addition, nasal-examination scores were obtained by way of physician assessment at the end of each 2-week trial, and side effects were tabulated. Nasal-examination scores for each of the four H1 antihistamines were significantly better than the baseline scores (p < 0.05). No statistically significant differences in rhinitis symptom scores, overall efficacy scores, or concomitant pseudoephedrine use were noted. We detected no clinically significant differences in efficacy among terfenadine, loratadine, astemizole, and chlorpheniramine in the treatment of perennial allergic rhinitis.

Background: Terfenadine, astemizole, cetirizine, and loratadine are compared in their abilities to produce relief of symptoms of allergic rhinitis., Objective: The aim of this study was to compare the onset of action and efficacy of the study medications., Methods: 111 ragweed-sensitive subjects were primed with pollen in the Environmental Exposure Unit. Study entry required adequate symptoms over a 3 hour exposure to 5000 +/- 300 grains/m3 of ragweed pollen. On the test day, subjects were given a single dose of either terfenadine 60 mg (22), astemizole 10 mg (22), cetirizine 10 mg (23), loratadine 10 mg (22), or placebo (22) when sufficiently symptomatic after a 60-minute exposure. Allergen levels were maintained and symptoms recorded every 30 minutes., Results: Proportions of subjects with clinically important relief were cetirizine, 69.6%; terfenadine, 54.5%; loratadine, 50.0%; astemizole, 40.9%; and placebo, 31.8% but differences weren't significant between treatment groups (P = .119). Survival curves for times to onset of clinically important relief for the four treatment groups were not different (P = .119). Subjects realizing definitive relief were cetirizine, 65.2%; terfenadine, 45.5%; loratadine, 31.8%; placebo, 27.3%; and astemizole, 22.7% (P = .023). Survival analysis of onset time for definitive relief found significant differences (P = .010). The ranking was cetirizine --> terfenadine --> loratadine --> astemizole (quickest to slowest). Global evaluation based on subject willingness to take the medication again yielded percentages: cetirizine, 82.6%; terfenadine, 66.7%; astemizole, 63.6%; loratadine, 40.9%; and placebo, 36.4% (P = .036)., Conclusion: Cetirizine and terfenadine continuously ranked higher in terms of onset of action and efficacy, while loratadine and astemizole ranked lower. Significance was detected in definitive relief and relative efficacy.

Objective: To evaluate the effect of terfenadine and loratadine on the early nasal allergic response to challenge and the subsequent cellular influx and hyperresponsiveness., Design: Double-blind, placebo-controlled, triple-crossover study., Subjects: Fourteen, asymptomatic, allergic volunteers., Interventions: After an initial challenge with methacholine chloride, subjects received treatment with placebo, loratadine (10 mg by mouth daily), or terfenadine (60 mg by mouth twice daily) for 1 week, followed by a nasal allergen challenge with lavages; 24 hours later, while the subjects were still receiving medication, the quantity of cells in the nasal lavage was determined, and another challenge with methacholine was done. Mediator levels were quantified in the nasal lavages after the allergen c hallenge, and the weight of the methacholine-induced nasal secretions was measured., Results: Both loratadine and terfenadine treatment resulted in significant reductions in allergen-induced sneezing and the levels of histamine, kinins, albumin, and N-alpha-tosyl-L-arginine methyl ester-esterase activity in recovered nasal lavages compared with the reductions that resulted from placebo treatment, with no significant difference among the treatments. Treatment had no effect on the levels of tryptase, prostaglandin D2 or leukotriene C4. A significant eosinophil influx into nasal secretions 24 hours after the allergen challenge in patients who were receiving placebo (P=.006) was not affected by loratidine or terfenadine treatment. Comparing methacholine-induced secretions between screening challenges and challenges with the patients who were being treated with either loratadine or terfenadine, there was a significant decrease in secretions after the use of these antihistamines (P<.05)., Conclusion: Both loratadine and terfenadine partially inhibit the early nasal response to allergen challenge and the subsequent reactivity to a challenge with methacholine without affecting the influx of eosinophils into nasal secretions.

We studied 104 medical student from the UANL with symptoms of Perennial Allergic Rhinitis, including only 30 patients for this study; seven patients with Loratadine 10 mg, eight with Loratadine 20 mg, and 15 with Terfenadine 120 mg/day/21 days, 20 mg of Loratadine and 120 mg of Terfenadine demonstrated significant decrease of the symptoms (P > 0.005). Two patients had collateral effects with Terfenadine, but Terfenadine were more effective than the Loratadine in the reduction of the skin reactivity.

We studied 104 medical student from the UANL, with symptoms of perenneal allergic rhinitis, including only 30 patients for this study; seven patients with loratadin 10 mg, eight with loratadine 20 mg and 15 with terfenadine 120 mg/day/21 days, 20 mg of loratadine and 120 mg of terfenadine demonstrated significant decrease of the symptoms (P). Two patients had collateral effects with terfenadine, but terfenadine were more effective than the loratadine in the reduction of the skin reactivity.

The safety and efficacy of loratadine (Sch 29851, CAS 79794-75-5) syrup (5 or 10 mg QD) was compared to terfenadine (CAS 50679-08-8) suspension (30 mg b.i.d.) in a randomized, third party blind, parallel-group, multicenter trial. Two hundred thirty-six children ages 6-12 years, with chronic allergic skin disorders were treated for 14 days. The predominant skin condition was atrophic dermatitis (88% of the efficacy population). Evaluation of efficacy was based on investigator and patient assessment of symptoms, overall condition of the disease, and therapeutic response to treatment. After 7 and 14 days of treatment, and in the endpoint analysis (last valid study visit for all patients) the decreases from baseline in mean total sign/symptom scores, and all individual symptoms, did not differ significantly (p > 0.05) between treatments. Itching improved 54% in the loratadine group and 58% in the terfenadine group in the endpoint analysis. Forty-five percent of patients treated with loratadine and 46% of terfenadine-treated patients treated had complete or marked relief of their symptoms at endpoint. The efficacy of loratadine increased during the study, suggesting that patients did not develop tolerance to the medication over the 14-day course of therapy. Mild to moderate treatment-related adverse experiences were reported in 7/113 patients (6%) treated with loratadine and 11/119 patients (9%) treated with terfenadine. Single daily doses of 5 mg or 10 mg loratadine syrup were comparable to terfenadine suspension 30 mg twice daily for improving the symptoms of chronic allergic skin disorders in children. Loratadine was safe and well tolerated.

The efficacy and safety of loratadine and terfenadine in the treatment of 3- to 6-year-old children with seasonal allergic rhinitis were compared in a third-party-blind, randomized, parallel-group study. A total of 96 children were included in the efficacy analysis: 49 children received 5 or 10 mg of loratadine once daily, and 47 received 15 mg of terfenadine twice daily, for 14 days. The mean total score for both nasal and non-nasal symptoms was decreased significantly from baseline at days 3, 7, and 14 in both treatment groups. At endpoint, these scores had improved 73% in each group. There were no statistically significant differences between the two groups in the total symptom scores at any point during the study. Both treatments were effective in relieving individual nasal and nonnasal symptoms. Therapeutic response to treatment was good or excellent in 82% of loratadine-treated children and in 60% of terfenadine-treated children. Few adverse events were reported during the study; all were mild or moderate and were not significantly different between the two treatment groups. There were no reports of sedation or dry mouth in either group. Once-daily treatment with 5 or 10 mg of loratadine was as effective as twice-daily treatment with 15 mg of terfenadine in improving the symptoms of seasonal allergic rhinitis in children 3 to 6 years old. Both treatments were well tolerated.

The efficacy of loratadine and terfenadine in perennial allergic rhinitis was evaluated in a double-blind, selected cross-over study consisting of two phases. During the first phase, 76 patients with perennial allergic rhinitis, 8-67 years old, were included in the study. Of these, 41 patients received loratadine 10 mg daily, and 35 patients received terfenadine 60 mg twice daily, for 2 weeks. According to symptoms and side-effects, 32 patients were classified as responders to loratadine, and 28 patients as responders to terfenadine. All observed symptoms were significantly reduced in both treatment groups, but with no significant differences between the two groups. Side-effects were few and mild. In patients with normal IgE, loratadine was significantly superior to terfenadine in relieving nasal secretion, whereas terfenadine was significantly superior to loratadine in relieving nasal congestion. In patients with increased IgE, patients treated with loratadine showed significantly greater reduction in sneezing than patients treated with terfenadine. A positive correlation between total IgE and reduction in overall symptoms was found for patients treated with loratadine, whereas a negative correlation was found for patients treated with terfenadine. During the second study phase, the nonresponders received the other drug for 2 weeks. All seven nonresponders to terfenadine responded to loratadine after crossing over, whereas four of nine nonresponders to loratadine responded to terfenadine. Nonresponders to one drug may respond to the other drug. Thus, more than one antihistamine drug should be tried in perennial allergic rhinitis if the first fails.

Non-sedating antihistamines have been used in the treatment of allergic rhinoconjunctivitis. Recommended dosage of loratadine (CAS 79794-75-5) is 10 mg once daily, whereas terfenadine (CAS 50679-08-8) until recently has been recommended as 60 mg twice daily. 105 patients took part in this double-blind 3-week controlled study comparing loratadine 10 mg once daily to terfenadine 120 mg once daily. Patient's daily symptom score and physician's assessment of symptoms, treatment effect and anterior rhinoscopy were evaluated as well as an objective parameter, nasal peak flow. In addition nasal peak flow was compared to patient's symptom score of stuffiness. A significant treatment effect in both treatment groups was found but there was no statistically significant difference between the two groups. Correlation between patient's feeling of stuffiness and nasal peak flow was significant. It is concluded that loratadine 10 mg once daily is as effective as terfenadine 120 mg once daily in controlling allergic rhinoconjunctivitis, and that patients' feeling of stuffiness correlates well to nasal peak flow.

This double-blind, double-dummy, parallel-group study was undertaken in 40 patients with seasonal allergic rhinoconjunctivitis during the 1990 hay fever season. The patients were randomized and treated for seven days with either 120 mg terfenadine or 10 mg loratadine, each drug taken once daily in the morning. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching, and itchy, watery, red eyes was evaluated before and at the end of treatment. The global severity of symptoms was ranked daily by the patient on a diary card. Both treatment groups experienced a significant improvement of symptoms after treatment (p < 0.01), without any significant difference between the two study drugs. Terfenadine and loratadine significantly improved symptom severity by 69 and 55% compared with the baseline values, respectively. Headache and fatigue were reported in three loratadine-treated patients, and sedation in one patient. No side effects were observed in patients receiving terfenadine. This study confirmed that terfenadine 120 mg once daily is a safe and effective treatment for hay fever.