Efficacy and Safety of Montelukast Plus Fexofenadine Fixed Dose Combination in Allergic Rhinitis : Results of Post-Marketing Study In India.

Background:Allergic rhinitis is one of the most common conditions in clinical practice. Motelukast and second generation antihistamine fexofenadine are routinely used in the management of allergic rhinitis. Individually both drugs have been found to be effective in allergic rhinitis. Fixed dose combination of montelukast 10 mg plus fexofenadine 120 mg is available in India is also used in the treatment of allergic rhinitis. Objective: To evaluate the efficacy and safety of montelukast and fexofenadine fixed dose combination in the management of patients with allergic rhinitis. Material and methods: Post marketing observational study was conducted in 809 patients from all over India. All the patients were treated with montelukast 10 mg plus fexofenadine 120 mg fixed dose combination once daily for 14 days. The primary outcome criteria was the change in total symptom score (Sum of total nasal symptom score and total ocular symptom score) at the end of study compared to baseline. The secondary outcome criteria included change in total nasal symptom score (nasal congestion, rhinorrhea, nasal itching, and sneezing) and total ocular symptom score (Itching/burning eyes, tearing/ watering eyes and eye redness) at the end of study compared to baseline and physician’s and patient’s global assessment for efficacy and tolerability. The patients were evaluated at baseline, day 7 and day 14 for efficacy evaluation while the safety parameters were assessed at screening and day 14. Results: The fixed dose combination of fexofenadine plus montelukast was significantly effective in reducing total symptom score, total nasal symptom score and total ocular symptom score (p<0.0001 for all parameters). The global assessment of efficacy evaluation by both patient and investigators demonstrated “excellent to good” efficacy in >95% of patients. Most of the study population reported “good” tolerability with the fixed drug combination. No adverse events were reported in the study. Conclusion: The fixed dose combination of fexofenadine plus montelukast was found to be efficacious and well tolerated in allergic rhinitis in Indian adult patients.

The efficacy and safety of 30 mg fexofenadine HCl bid in pediatric patients with allergic rhinitis.

Allergic rhinitis is one of the most common chronic disorders in children. It is also one of the most common causes of absence from school. This study reports on the efficacy and safety of a twice-daily oral dose of fexofenadine HCl 30 mg in Asian children aged 6-11 years diagnosed with seasonal or perennial allergic rhinitis. A total of 100 children with a history of allergic rhinitis for more than one year and a positive prick skin test response to at least one of the common aeroallergens in Thailand were enrolled in this multi-center, open-label, non comparative study. The severity of individual symptoms such as sneezing, rhinitis, etc. and adverse events were recorded in diary cards by the patients in form of scores as well as by the investigator at each visit. The total symptom score (TSS) with or without blocked nose at baseline, week 1 and week 2 was recorded. The TSS was defined as the sum of the individual symptom scores except for the nasal blockage score, as nasal blockage was not expected to respond to antihistamine treatment. Only patients with a total symptom score > or = 6 were included in the study. There was a statistically significant improvement at p < 0.01 for the TSS with or without blocked nose and for each symptom score such as blocked nose, sneezing, rhinorrhea, itchy nose/palate and/or throat, and itchy/watery/red eyes from baseline to week 1 and week 2. Additionally, there was a statistically significant improvement between week 1 and week 2 for itchy nose/palate and/or throat and itchy/watery/red eyes (p < 0.05). The Kappa measure of agreement was statistically significant at p < 0.001 between investigator's and patient's/parent's assessment, indicating the same degree of satisfaction with the overall effectiveness of the treatment. Fexofenadine 30 mg bid is effective in reducing the total symptom score of allergic rhinitis including blocked nose and is generally well tolerated. It is not cardiotoxic and is safe for pediatric patients as young as 6 years of age.

Multicenter study of the efficacy and safety of fexofenadine 60 mg. twice daily in 108 Thai patients with chronic idiopathic urticaria.

Fexofenadine is a non-sedating antihistamine indicated for relieving symptoms from allergic conditions with a rapid onset of action without cardiotoxic risks. Controlled studies showed that fexofenadine 180 mg daily provides significant relief of symptoms of chronic idiopathic urticaria (CIU). The purpose of this study was to demonstrate the efficacy and safety of fexofenadine 60 mg twice daily in Thai patients with CIU in a multicenter trial. Patients were assigned to receive twice daily doses of fexofenadine 60 mg for 6 weeks. Patients rated symptom severity every night, investigators rated patients' signs and symptoms at recruitment and at 1, 3 and 6 weeks. Ninety eight out of 108 patient (90.7%) completed the study. The patients reported 95 per cent improvement and, of those, 91 per cent had very favorable responses (excellent 15%, very good 42%, good 30%, fair 8%). The objective assessment by their physicians paralleled those responses. Fexofenadine provided a rapid clinical response that was significantly superior to before treatment in relieving symptoms of CIU (p < 0.001). Adverse events occurred in 20 cases (18.5%), mostly mild headache and drowsiness. Fexofenadine 60 mg twice daily provides effective relief of the symptoms of CIU with minimal adverse events.

A non-comparative trial of the efficacy and safety of fexofenadine for treatment of perennial allergic rhinitis.

An open-label, non-comparative study was performed in three Otolaryngology centers in Bangkok, Thailand, to assess the efficacy, safety and tolerability of fexofenadine in Thai patients with perennial allergic rhinitis. Altogether 101 perennial allergic rhinitis patients were included, 33 males and 68 females. Mean age was 33 years, average duration of symptoms was 6 years. All patients received fexofenadine hydrochloride 120 mg once daily (OD) in the morning for 2 weeks. Patients recorded their allergy symptoms daily using a 5 point rating scales in the diary card. At the end of 2 weeks, patients and investigators assessed the overall efficacy of treatment. Adverse events and onset of symptom relief were also recorded by every patient. Blood test and ECG were performed before and after treatment in one center (Siriraj Hospital). Total symptom scores and nasal scores decreased significantly from a baseline at 1 week and 2 weeks after treatment (p < 0.05). The mean onset of symptom relief was 2 hours and 12 minutes. The global assessment of the treatment by patients and investigators showed significant concordance. There was no significant change in either the vital signs, laboratory tests or ECG. The incidence of treatment related adverse events was 8% but all were mild and easily tolerated. Drowsiness was reported from only one patient. This study suggests that fexofenadine 120 mg once daily was an effective, safe and well tolerated treatment for perennial allergic rhinitis in Thai patients.

The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a group of workers in the Netherlands was later rectified by the same group. Clinically speaking, the cardiovascular safety of fexofenadine has been convincingly demonstrated at various dose levels and various time intervals, alone and together with other drugs of potential toxigenicity. All things put together, it appears reasonable to conclude that fexofenadine is free from cardiovascular ADRs of clinical significance. It could also be concluded that cardiac side-effects of antihistamines is not a class effect.

Comparaçäo da azelastina spray nasal e terfenadina no tratamento da rinite alérgica perene / Comparison of azelastine nasal spray and terfenadine in the treatment of perennial allergic rhinitis

Um total de 54 pacientes com rinite alérgica perene foram tratados com ou azelastina spray nasal 0,14 mg/narina duas vezes ao dia (0,56 mg/dia) ou terfenadrina 60 mg uma vez ao dia. O tratamento teve a duraçäo de duas semanas. Os sintomas da rinite foram avaliados de acordo com uma escala de 4 pontos (0=ausente, 3=grave). O escore total de sintomas de rinite foi derivado da soma dos escores de sintomas individuais. Os sintomas foram avaliados na vista pré-tratamento e após as semanas 1 e 2. Comparado à vista pré-tratamento o escore total de sintomas de rinite, para ambos os grupos, azelastina e terfenadina, foi menor em cada avaliaçäo durante o tratamento, näo havendo diferenças significantes entre os grupos. Ao fim do estudo o investigador classificou a eficácia como sendo "boa" ou "excelente" em 64,3 por cento dos pacientes do grupo azelastina e 73,1 por cento do grupo terfenadina. Ambos os tratamentos foram bem tolerados e nenhum efeito adverso grave foi relatado. Concluindo, azelastina intranasal mostrou ser täo eficaz como a terfenadina oral no alívio dos sintomas da rinite alérgica perene.

Eficacia e inocuidad de loratadina vs terfenadina en el tratamiento de niños con rinitis alérgica perenne: capacidad para inhibir la respuesta cutánea positiva después del tratamiento antihistamínico / Efficacy and innocuity of loratidine vs terfenadine in the treatment of children with perennial allergic rhinitis

Se estudiaron 104 pacientes (estudiantes de la Facultad Medicina de la UANL), con síntomas de rinitis alérgica perenne de los que sólo se seleccionaron 30; siete pacientes se trataron con loratadina 10 mg, ocho con loratadina 20 mg, 15 con terfenadina 120 mg por día durante 21 días. Tanto la loratadina a 20 mg como la terfenadina 120 mg demostraron una reducción estadisticamente significativa (P> 0.0005) en el control de síntomas. Dos pacientes informaron que tuvieron reacciones adversas con terfenadina, por lo que abandonaron el estudio. La terfenadina fue más eficaz que loratadina en la disminución de la reactividad cutánea

Loratadina vs terfenadina en rinitis alérgica perenne: capacidad para inhibir la respuesta cutánea / Loratadine vs terfenadine in perenneal allergic rhinitis

Se estudiaron 104 pacientes con síntomas de rinitis alérgica perenne de los que se seleccionó a 30. siete se trataron con loratadina 10 mg, ocho con loratadina 20 mg, 15 con terfenadina 120 mg por día durante 21 días. Tanto loratadina 20 mg como terfenadina 120 mg demostraron una reducción estadísticamente significativa (P) en el control de los síntomas. Dos pacientes tuvieron reacciones adversas con terfenadina y abandonaron el estudio. La terfenadina fue más eficaz que la loratadina en la disminución de la reactividad cutánea

Pharmacodynamic bioequivalence: evaluation of different brands of terfenadine hydrochloride.

Terfenadine is a selective histamine H1 receptor antagonist which binds preferentially to peripheral receptors in vivo and is devoid of central nervous system depressant activity and thus has an improved adverse effect profile (1). Hence, terfenadine may be considered to be a first line agent in the treatment of allergic rhinitis and chronic urticaria. In man terfenadine is rapidly absorbed following a single oral dose and a peak terfenadine plasma concentration is reached within 1-2 hr after the drug administration (2). The present study was carried out to compare the bioequivalence of two terfenadine hydrochloride preparations marketed by Kopran Chem. Co. and Marrel Dow U.K. (Triludan) by evaluating their ability to inhibit the skin reaction to intradermally injected histamine (3).