ABSTRACT
OBJECTIVE: Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria. METHODS: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo. RESULTS: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses. CONCLUSION: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.
Subject(s)
Histamine H1 Antagonists, Non-Sedating , Terfenadine , Terfenadine/analogs & derivatives , Terfenadine/pharmacokinetics , Terfenadine/pharmacology , Terfenadine/administration & dosage , Humans , Histamine H1 Antagonists, Non-Sedating/pharmacokinetics , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/pharmacology , Histamine H1 Antagonists, Non-Sedating/adverse effects , Brain/drug effects , Brain/diagnostic imaging , Brain/metabolism , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Rhinitis, Allergic/drug therapy , Urticaria/drug therapyABSTRACT
BACKGROUND: Our aim was to measure the effectiveness of oral isotretinoin with desloratadine compared with oral isotretinoin alone in treating moderate to severe acne at a tertiary care teaching hospital in North India. In this study, 90 patients with moderate to severe acne were enrolled to participate based on their fulfilling the inclusion criteria. METHODS: A randomized, assessor-blinded, parallel-arm study was conducted. Randomization was done using computer-generated tables to allocate treatments in a 1:1 ratio. A low-dose oral isotretinoin at a dose of 0.3 mg/kg/day with tab desloratadine at 5 mg/day was applied to the study group and compared against the same patients going without the dosage when controls were conducted. Follow-up was at 4, 8, and 12 weeks. RESULTS: The primary outcome was an improved global acne grading system (GAGS) score and decreased acne lesion count. SECONDARY OUTCOME: patient satisfaction with treatment. The 90 participants were randomized and 15 participants dropped out of the study, leaving 75 participants for intention to treat analysis (n = 41, n = 30). At week 12, the GAGS score and acne lesion count between the study and control groups were comparable (P > 0.05). Pruritus reported was 9.76% in the study versus 33.33% in the control group (P = 0.018). Also, 53.66% of participants reported "excellent" treatment satisfaction in the study group versus 36.67% in the control group. CONCLUSIONS: The addition of desloratadine to an isotretinoin regimen has a role in reducing disease and therapy-related pruritus in acne and leads to improved patient satisfaction.
Subject(s)
Acne Vulgaris , Dermatologic Agents , Isotretinoin , Loratadine , Patient Satisfaction , Severity of Illness Index , Humans , Isotretinoin/administration & dosage , Isotretinoin/adverse effects , Acne Vulgaris/drug therapy , Loratadine/administration & dosage , Loratadine/analogs & derivatives , Loratadine/adverse effects , Female , Male , Administration, Oral , Young Adult , Dermatologic Agents/administration & dosage , Dermatologic Agents/adverse effects , Adolescent , Adult , Drug Therapy, Combination , Single-Blind Method , Treatment Outcome , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/adverse effectsABSTRACT
We describe an unusual presentation of Bier anemic spots, cyanosis, and urticaria-like eruption (BASCULE) syndrome in a 15-year-old male, recalcitrant to low-dose anti-histamines, which subsequently responded to high-dose fexofenadine.
Subject(s)
Cyanosis , Terfenadine , Urticaria , Humans , Male , Terfenadine/analogs & derivatives , Terfenadine/therapeutic use , Adolescent , Cyanosis/etiology , Cyanosis/chemically induced , Urticaria/drug therapy , Syndrome , Histamine H1 Antagonists, Non-Sedating/therapeutic use , Histamine H1 Antagonists, Non-Sedating/adverse effectsABSTRACT
BACKGROUND: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment. OBJECTIVE: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU. METHODS: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17. RESULTS: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n = 2649, RR = 1.36, 95%CI:1.30-1.43, p < 0.00001), cure (n = 2649, RR = 1.54, 95%CI:1.42-1.66, p < 0.00001) and recurrence (n = 446, RR = 0.34, 95%CI:0.20-0.58, p < 0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n = 2317, RR = 0.76, 95% CI:0.59-0.97, p = 0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported. CONCLUSIONS: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results.
Subject(s)
Chronic Urticaria , Glycyrrhizic Acid , Histamine H1 Antagonists, Non-Sedating , Humans , Chronic Disease , Chronic Urticaria/drug therapy , Glycyrrhizic Acid/adverse effects , Glycyrrhizic Acid/therapeutic use , Histamine Antagonists/adverse effects , Histamine Antagonists/therapeutic use , Histamine H1 Antagonists/adverse effects , Histamine H1 Antagonists/therapeutic use , Histamine H1 Antagonists, Non-Sedating/adverse effects , Histamine H1 Antagonists, Non-Sedating/therapeutic useABSTRACT
OBJECTIVE: Although second-generation antihistamines have reduced sedation-related side effects compared to first-generation antihistamines, sedation may still impair motor vehicle driving performance. Moreover, receiving/making phone calls using a hands-free function can negatively affect driving performance. Therefore, herein, driving performance was evaluated using a driving simulator to gain insights into the hazards of driving by combining second-generation antihistamines and a calling task, i.e., simulated calls using a hands-free function. METHODS: In this study, 20 subjects drove in a driving simulator in the absence or presence of a calling task while taking or not taking second-generation antihistamines. Driving performances for nonemergency and emergency events were determined, and a comparative analysis of intra-individual variability when taking and not taking second-generation antihistamines was conducted. RESULTS: First, when nonemergency and emergency were examined in the absence of a calling task, no significant difference in driving performance was observed between taking and not taking second-generation antihistamines. Next, when the nonemergency event was examined in the presence of a calling task, no significant difference in driving performance was observed between taking and not taking second-generation antihistamines. However, when the emergency event was examined in the presence of a calling task, a significant difference in driving performance was observed between taking and not taking second-generation antihistamines, thus resulting in reduced driving performance. CONCLUSIONS: The new system with added calling tasks allowed the extraction of the potential risks of driving performance of second-generation antihistamines that may have been previously overlooked. This study suggests that pharmacists and other healthcare professionals may need to instruct people taking any second-generation antihistamine to focus on driving and not on subtasks that require cognitive load such as talking while driving.
Subject(s)
Automobile Driving , Histamine H1 Antagonists, Non-Sedating , Humans , Histamine H1 Antagonists, Non-Sedating/adverse effects , Accidents, Traffic , Histamine Antagonists/adverse effectsABSTRACT
Fexofenadine hydrochloride (HCl) is a second-generation, nonsedating, histamine H1-receptor antagonist used to manage seasonal allergic rhinitis and chronic idiopathic urticaria. A new oral pediatric suspension of fexofenadine HCl has been developed, with the preservative potassium sorbate replacing parabens. The objective of this phase 1 single-center, open-label, randomized, 2-treatment, full-replicated, 4-period, 2-sequence crossover study in healthy adult volunteers was to assess the bioequivalence of 30 mg of the new oral suspension of fexofenadine HCl (test) versus 30 mg of the marketed pediatric oral suspension of fexofenadine HCl (reference). The replicate design was based on the high intra-individual variability of fexofenadine (>30% on Cmax ). The study comprised 68 randomized and treated volunteers. Plasma concentrations of fexofenadine were similar following the administration of a single dose of each formulation. Cmax , AUClast , AUC, median tmax , and mean t1/2z were similar between administrations of the same fexofenadine formulation and between formulations. A high intra-individual variability was confirmed with both formulations. Bioequivalence of the test and reference fexofenadine HCl formulations was demonstrated as the 90% confidence intervals of the geometric least squares mean ratio for Cmax , AUClast , and AUC of fexofenadine were all within the bioequivalence range of 0.80-1.25. There were no serious adverse events (AEs) or study discontinuations due to treatment-emergent AEs with either fexofenadine HCl formulation. The new paraben-free fexofenadine HCl 30-mg oral suspension and marketed fexofenadine HCl 30-mg pediatric oral suspension are bioequivalent under fasting conditions, with no safety concerns and a safety profile consistent with the known profile of fexofenadine.
Subject(s)
Histamine H1 Antagonists, Non-Sedating , Terfenadine , Adult , Humans , Child , Therapeutic Equivalency , Cross-Over Studies , Terfenadine/adverse effects , Histamine H1 Antagonists , Histamine H1 Antagonists, Non-Sedating/adverse effectsABSTRACT
Background Urticaria is a common skin disease which often causes impairment in the quality of life. The ideal drug for chronic urticaria would have antihistaminic and anti-inflammatory actions. Bepotastine besilate is a recently approved novel anti-allergic agent with multiple mechanisms of action; levocetirizine is a potent and selective second-generation H1 receptor antagonist used in the treatment of urticaria. Aim To compare the efficacy and safety of bepotastine besilate versus levocetirizine in patients with chronic spontaneous urticaria. Methods The study design is a randomised, open-label, parallel-group, prospective interventional study. The study subjects were randomly assigned to either of the two groups a and b, each group had 50 patients with chronic urticaria. Statistical analyses were performed using (SPSS, version 18) for all the variables. Chi-square test was used for comparison between categorical variables. An unpaired student's t-test was done for quantitative variables. Results There was a significant decrease in mean urticaria activity score (P < 0.001), chronic urticaria quality of life (P < 0.001) and clinical global improvement (P < 0.001) in both the treatment groups but this improvement was higher in the bepotastine than in the levocetirizine group. There was no significant difference in the mean of absolute eosinophil count, C-reactive protein, aspartate transaminase, alanine transaminase from baseline to 4th week between the two study groups. Visual analogue scale showed statistically significant improvement from baseline to 4th week (P < 0.001) of follow-up but this increase was higher in levocetirizine group (0.64-4.24) than in bepotastine group (0.56-2.56) Limitations Blinding was not done. To assess the efficacy and safety of bepotastine, a larger study can be planned. Conclusion This study found that bepotastine is superior to levocetirizine and showed a statistically significant reduction in mean urticaria activity score 7, improved quality of life and clinical global improvement in patients with urticaria.
Subject(s)
Chronic Urticaria , Histamine H1 Antagonists, Non-Sedating , Urticaria , Humans , Prospective Studies , Quality of Life , Cetirizine/adverse effects , Histamine H1 Antagonists, Non-Sedating/adverse effects , Urticaria/diagnosis , Urticaria/drug therapy , Chronic Urticaria/drug therapyABSTRACT
BACKGROUND: Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent. OBJECTIVES: We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria. METHODS: We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software. RESULTS: We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo. CONCLUSIONS: Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.
Subject(s)
Chronic Urticaria , Histamine H1 Antagonists, Non-Sedating , Rhinitis, Allergic , Urticaria , Benzimidazoles , Histamine Antagonists/therapeutic use , Histamine H1 Antagonists, Non-Sedating/adverse effects , Histamine H1 Antagonists, Non-Sedating/therapeutic use , Humans , Piperidines , Randomized Controlled Trials as Topic , Rhinitis, Allergic/drug therapy , Urticaria/chemically induced , Urticaria/drug therapyABSTRACT
INTRODUCTION: The aim of this study was to determine the efficacy and safety of intensive versus standard nonsedating antihistamines (NSAs) for chronic spontaneous urticaria (CSU) patients. METHODS: An electronic search was performed on the PubMed, Embase, and the Cochrane Library databases to identify eligible randomized controlled trials (RCTs) throughout January 2021. The weighted mean difference (WMD) and relative risk (RR) with 95% confidence interval (CI) were applied to calculate the pooled outcomes for the continuous and categorical data using the random-effects model. RESULTS: Nine RCTs involving 1,996 CSU patients were selected. We found that intensive NSA was associated with greater reduction in the mean pruritus score than the standard dose of NSA (WMD: -0.13; p = 0.005). However, there was no significant difference between the intensive and standard dose of NSA in terms of the rate of response to antihistamines (RR: 1.00; p = 0.865). Finally, the use of intensive NSA was associated with a higher risk of somnolence than the use of standard NSA (RR: 3.28; 95% CI: 1.55-6.95; p = 0.002). CONCLUSION: We found that the use of intensive NSA could achieve greater reduction in the mean pruritus score, without increasing the risk of adverse events.
Subject(s)
Chronic Urticaria , Histamine H1 Antagonists, Non-Sedating , Urticaria , Chronic Urticaria/drug therapy , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Pruritus/drug therapy , Randomized Controlled Trials as Topic , Urticaria/drug therapyABSTRACT
Chronic spontaneous urticaria (CSU) is a debilitating condition, adversely affecting the patient's quality of life. Bilastine is a recently introduced, non-sedative H1-antihistamine for its treatment. We wanted to compare the effectiveness, safety, and tolerability of bilastine 20 mg vs levocetirizine 5 mg in moderate-to-severe CSU. We conducted a double-blind, randomized controlled trial with two groups: bilastine 20 mg (n = 31) and levocetirizine 5 mg (n = 27), once daily for 42 days. We included patients (18-65 years), with moderate-to-severe CSU. UAS7, VAS, and DLQI were used to assess severity of urticaria, global urticaria-induced discomfort and quality of life, respectively. DLQI was assessed at baseline (D0) and end-of-treatment (D42), while UAS7 and VAS were noted at baseline and all follow-up visits. Assessment of UAS7 alteration was our primary objective, while changes in DLQI and VAS were the secondary outcomes. Safety was assessed by recording drug-related adverse events, biochemical investigations, and electrocardiogram, along with tolerability and compliance. Both drugs significantly improved UAS7, DLQI, and VAS at end-of-treatment (D42) compared with baseline (intra-group). At the end-of-treatment, all parameters showed greater improvement with bilastine, but only UAS7 reduction was significant (bilastine > levocetirizine, P = .03). In both the groups, UAS7 and VAS improved significantly D14 onwards, and was maintained throughout the study. Sedation was significantly less with bilastine (P = .04), while neither drug showed any serious adverse-effect. Tolerability of both drugs was similar. Therefore, bilastine was found to be a more effective and less-sedative novel therapy for CSU compared to levocetirizine, with similar effect on quality of life.
Subject(s)
Chronic Urticaria , Histamine H1 Antagonists, Non-Sedating , Urticaria , Benzimidazoles , Cetirizine , Chronic Disease , Double-Blind Method , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Piperidines , Quality of Life , Treatment Outcome , Urticaria/diagnosis , Urticaria/drug therapyABSTRACT
Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.
Subject(s)
Cetirizine/pharmacokinetics , Chronic Urticaria/drug therapy , Histamine H1 Antagonists, Non-Sedating/pharmacokinetics , Rhinitis, Allergic/drug therapy , Administration, Oral , Adult , Cetirizine/administration & dosage , Cetirizine/adverse effects , Cross-Over Studies , Drug Compounding/trends , Healthy Volunteers , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Japan , Male , Middle Aged , Safety , Therapeutic EquivalencyABSTRACT
Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults and children aged ≥ 6 years. Pharmacokinetic data for children aged 6-11 years were extracted post hoc from a study in which children (2-11 years) with allergic rhinoconjunctivitis or urticaria received oral bilastine (10 mg/day). Maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC) data were compared with adult pharmacokinetic data from seven clinical studies (bilastine 20 mg/day). Safety data for children aged 6-11 years were extracted post hoc from a phase III randomized controlled trial of children (2-11 years) with allergic rhinoconjunctivitis or chronic urticaria receiving once-daily bilastine 10 mg or placebo for 12 weeks. Exposure and Cmax values were similar for children (6-11 years) and adults: median pediatric/adult ratios for AUC0-24 and Cmax were 0.93 and 0.91, respectively. There was no significant difference in the incidence of treatment-emergent adverse in children (6-11 years) receiving bilastine 10 mg or placebo.Conclusion: Pharmacokinetic and safety analyses in children aged 6-11 years support the suitability of the pediatric dose of bilastine 10 mg and confirm that the safety profiles of bilastine and placebo are similar.What is Known:⢠Bilastine, a second-generation antihistamine, is approved in Europe for the treatment of allergic rhinoconjunctivitis and urticaria in adults (20 mg/day) and children aged ≥ 6 years (10 mg/day).⢠An ontogenic model based on adult data and pharmacokinetic/pharmacodynamic simulations supported the selection of a bilastine dose of 10 mg/day in children aged 2-11 years. Bilastine 10 mg/day was shown to have a safety profile similar to that of placebo in a large phase III randomized clinical trial in children aged 2-11 years.What is New:⢠As bilastine is approved in Europe for children aged ≥6 years, the current study reports the results of two post hoc analyses of pharmacokinetic and safety data in children aged 6-11 years.⢠Analysis of pharmacokinetic and safety data in children aged 6-11 years supports the suitability of the pediatric dose of bilastine 10 mg and confirms that its safety profile is similar to that of placebo.
Subject(s)
Benzimidazoles/pharmacokinetics , Conjunctivitis, Allergic/drug therapy , Histamine H1 Antagonists, Non-Sedating/pharmacokinetics , Piperidines/pharmacokinetics , Urticaria/drug therapy , Administration, Oral , Adult , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Child , Female , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Male , Piperidines/administration & dosage , Piperidines/adverse effectsABSTRACT
H1 nonsedating antihistamines, such as desloratadine, are first-line treatment options for chronic spontaneous urticaria (CSU). However, desloratadine induces various degrees of sedation side effect in CSU patients, and no biomarkers currently exist for predicting the severity of such side effect. Herein, we evaluated the association between HRH1 gene rs901865 polymorphism and the severity of sedation side effect following desloratadine therapy in patients with CSU. We found that 20 of the 114 patients (17.50%) showed sedation side effect after desloratadine treatment, and 3 patients (2.63%) experienced serious sleepiness. The frequency of HRH1 rs901865 G allele was significantly higher in patients who experienced sedation than in patients with rs901865 A allele (p = 0.0009). Moreover, patients with the rs901865 G/G genotype suffered a more serious sedation side effect than patients with the rs901865 G/A genotype (p = 0.005). These results provide evidence that the HRH1 rs901865 G/G polymorphism is associated with severe sedation side effect after desloratadine treatment. Thus, the HRH1 rs901865 allele may potentially be used as a biomarker for predicting the severity of sedation side effect in patients suffering from CSU and treated with desloratadine.
Subject(s)
Drug-Related Side Effects and Adverse Reactions/genetics , Histamine H1 Antagonists, Non-Sedating/adverse effects , Loratadine/analogs & derivatives , Polymorphism, Single Nucleotide/genetics , Receptors, Histamine H1/genetics , Urticaria/genetics , Adult , China/epidemiology , Chronic Disease , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Humans , Loratadine/adverse effects , Male , Middle Aged , Severity of Illness Index , Sleepiness , Treatment Outcome , Urticaria/drug therapy , Urticaria/epidemiologyABSTRACT
BACKGROUND: As a new generation antihistamine, fexofenadine has been widely used in allergic diseases. However, there is still a lack of collective evidence regarding the antihistamine effects and safety profiles of fexofenadine relative to other antihistamine drugs and placebo. Therefore, we aimed to systematically evaluate the antihistamine effects and safety of fexofenadine. METHODS: An electronic literature search of randomized controlled trials (RCTs) was performed using Embase, Cochrane and PubMed from establishment to January 1st, 2018. RCTs comparing the antihistamine effects or safety (adverse events, sedative effects, and cognitive/psychomotor function) of fexofenadine with either other antihistamines or placebo for healthy subjects and patients with allergy were selected. RESULTS: Fifty-one studies of 14,551 participants met the inclusion criteria. When compared with the first-generation antihistamines, fexofenadine produced significantly lower adverse events frequency (OR = 0.446; 95% CI: 0.214 to 0.929, P = 0.031), significantly lower sedative effects frequency (OR = 0.265; 95% CI: 0.072 to 0.976, P = 0.046) and significantly less change of all cognitive/psychomotor function. When compared with the second-generation antihistamines, fexofenadine produced significantly marginal sedative effects (OR = 0.59; 95% CI, 0.38 to 0.93; P = 0.02) and significantly less change of most of the cognitive/psychomotor function. When compared with placebo, fexofenadine produced more significant antihistamine effects. CONCLUSIONS: Fexofenadine has a positive antihistamine effect, which is probably no worse than the second-generation antihistamines. Fexofenadine probably has a favorable safety profile, which is more likely better than that of the first-generation antihistamines. There is lack of data to support that fexofenadine has a better overall safety profile compared to the second-generation antihistamines, however, some presently available evidence on sedative effects and certain aspects of cognitive/psychomotor function favors fexofenadine. Therefore, fexofenadine may be worthy of recommendation for safety related workers.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Histamine H1 Antagonists, Non-Sedating/pharmacology , Terfenadine/analogs & derivatives , Cognition/drug effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/etiology , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Psychomotor Performance/drug effects , Randomized Controlled Trials as Topic , Terfenadine/adverse effects , Terfenadine/pharmacologyABSTRACT
PURPOSE: The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated. PATIENTS AND METHODS: Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software. RESULTS: Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75-107.24% and 99.98-114.69% for the maximum observed concentration, and 97.13-102.50% and 98.36-103.98% for the area under the concentration-time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported. CONCLUSION: The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers.
Subject(s)
Cetirizine/administration & dosage , Drugs, Generic/administration & dosage , Food-Drug Interactions , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Administration, Oral , Adolescent , Adult , Area Under Curve , Biological Availability , Cetirizine/adverse effects , Cetirizine/pharmacokinetics , Chromatography, High Pressure Liquid , Cross-Over Studies , Drugs, Generic/adverse effects , Drugs, Generic/pharmacokinetics , Female , Histamine H1 Antagonists, Non-Sedating/adverse effects , Histamine H1 Antagonists, Non-Sedating/pharmacokinetics , Humans , Male , Pilot Projects , Tandem Mass Spectrometry , Therapeutic Equivalency , Young AdultABSTRACT
BACKGROUND: No comparative study of antihistamines that differ in structural system has been conducted in allergic rhinitis. OBJECTIVE: This was a randomized, double-blind, crossover comparative study to verify the efficacy of antihistamines that differ in structural system. METHODS: A total of 50 patients with moderate or more severe Japanese cedar pollen-induced allergic rhinitis were randomized to receive either placebo, desloratadine 5 mg (a tricyclic), or levocetirizine 5 mg (a piperazine). One dose of the study drug was orally administered at 9 pm on the day before a pollen exposure test, which was performed for 3 h (9 a.m. to 12 p.m.) to assess symptoms in an environmental challenge chamber (ECC). Nasal and ocular symptoms were compared at an airborne pollen level of 8,000 grains/m3. The primary endpoint was mean total nasal symptom score (TNSS) from 120 to 180 min in the ECC. Subjects with a difference of ≥1 in TNSS between 2 drugs were extracted to the relevant drug-responsive group. RESULTS: The difference in TNSS from placebo was -2.42 (p < 0.0001) with levocetirizine and -1.66 (p < 0.01) with desloratadine, showing that both drugs were significantly more effective than placebo in controlling symptoms, but with no statistically significant difference between the 2 drugs. There were 12 subjects in the desloratadine-responsive group and 24 subjects in the levocetirizine-responsive group, with no contributor to response was detected. CONCLUSION: Levocetirizine tended to control nasal symptoms more effectively than desloratadine. However, the response to each antihistamine varied among individuals and the predictors to the response are unknown. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID: UMIN000029653.
Subject(s)
Cedrus/immunology , Cetirizine/therapeutic use , Histamine H1 Antagonists, Non-Sedating/therapeutic use , Loratadine/analogs & derivatives , Rhinitis, Allergic, Seasonal/drug therapy , Adult , Cetirizine/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Loratadine/adverse effects , Loratadine/therapeutic use , Male , Placebos/administration & dosage , Pollen/immunologyABSTRACT
BACKGROUND: Rupatadine is a novel H1 antihistamine with platelet-activating factor antagonist activity. Its efficacy and safety on pruritic skin diseases have been demonstrated by 10mg/day rupatadine in a two weeks clinical trial. OBJECTIVE: To investigate the long-term efficacy and safety of rupatadine in the management of pruritus, and the clinical effect of updosing to 20mg in Japanese adult and adolescent patients. METHODS: In this 52-week, multicenter, open-label clinical trial (JapicCTI-152787), 206 patients (132, eczema or dermatitis; 58, pruritus; and 16, chronic spontaneous urticaria) received the study medication. The primary efficacy endpoint was change from baseline in the total pruritus score to Week 2 by treatment with rupatadine 10mg once daily. From Week 3 to Week 52, rupatadine updosing to 20mg was allowed. RESULTS: The mean [95% CI] change from baseline to Week 2 in the total pruritus score was -1.241 [-1.450, -1.033] (paired t test, P< 0.001). The therapeutic effect persisted up to Week 52 (paired t test, P< 0.001). Adverse drug reactions (ADRs) were reported at an overall incidence of 18.0% (45 events in 37 patients). No serious or clinically significant ADRs were reported. Somnolence was the most common ADR (14.1%). CONCLUSIONS: This clinical trial demonstrated the short- and long-term benefits of rupatadine in the management of patients with chronic spontaneous urticaria, dermatitis, and pruritus. Rupatadine 10 and 20mg doses are effective for the treatment of itch in adults and adolescents, and can be used safely on a long-term basis.
Subject(s)
Chronic Urticaria/drug therapy , Cyproheptadine/analogs & derivatives , Eczema/drug therapy , Histamine H1 Antagonists, Non-Sedating/administration & dosage , Pruritus/drug therapy , Adolescent , Adult , Child , Chronic Urticaria/complications , Cyproheptadine/administration & dosage , Dose-Response Relationship, Drug , Eczema/complications , Female , Histamine H1 Antagonists, Non-Sedating/adverse effects , Humans , Japan , Male , Middle Aged , Pruritus/diagnosis , Pruritus/etiology , Severity of Illness Index , Sleepiness , Time Factors , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX). METHODS: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups. RESULTS: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group. CONCLUSION: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR.