Bioavailability assessment of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously

Introduction and Objectives: Allergic rhinitis is a condition with high global prevalence most effectively treated with antihistamines and antileukotrienes. This study aimed to evaluate the bioequivalence of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously. Materials and Methods: An open, randomized, 2×2 crossover study was performed in 78 healthy volunteers. Fexofenadine–montelukast tablets containing 120 mg and 10 mg, respectively, were used as the test treatment, and 120 mg fexofenadine tablets and 10 mg montelukast tablets were used as the reference treatment. Concentrations of fexofenadine and montelukast in plasma were determined by protein precipitation and analysis by liquid chromatography/mass spectrometry or liquid chromatography tandem mass spectrometry. Results: The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612–102.144 for area under the curve of the plasma concentration after administration to the last concentration (AUC0-t), 88.471–102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC0–∞), and 91.413–108.544 for the maximum plasma concentration (Cmax). For montelukast, they were 96.418–108.416 for AUC0-t, 93.273–106.642 for AUC0-∞ and 94.749–110.178 for Cmax. The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%–125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses. No adverse events were recorded during the study. Conclusions: This study has shown the bioequivalence of the combined fixed-dose tablet, which may be considered a new alternative for the treatment of allergic rhinitis (AU)

Eficacia y seguridad de la combinación de fexofenadina con montelukast en el tratamiento de la rinitis alérgica / Efficacy and safety of combined therapy of fexofenadine and montelukast for the treatment of allergic rhinitis

El propósito de este trabajo fue revisar la literatura científica que evalúa la eficacia y seguridad de las monoterapias de fexofenadina y montelukast, la terapia combinada (fija o en asociación) de montelukast - fexofenadina, así como de montelukast con otros antihistamínicos de segunda generación en el tratamiento de la rinitis alérgica. Se realizó una estrategia de búsqueda bibliográfica de múltiples etapas, en donde se identificaron estudios basados en ensayos clínicos y estudios no aleatorizados (ensayo controlado no aleatorizado, controlado antes-después, de series de tiempo interrumpidas, con controles históricos, de cohorte, de casos y controles, estudio transversal, y series de casos) en pacientes con rinitis alérgica, en las bases de datos MEDLINE/ PubMed, Scopus, Web of Science, Biblioteca Cochrane, Redalyc y Colección BVS y debido a la cantidad de resultados obtenidos se incluyó la búsqueda en Hinari. Con base en esta revisión se concluye que las combinaciones de antihistamínicos de segunda generación y antagonistas de leucotrienos y, en particular, la combinación fija de fexofenadina ­ montelukast es eficaz, segura y favorece la adherencia al tratamiento, y a largo plazo también ayuda a alcanzar el objetivo terapéutico.

The purpose of this work was to review the scientific literature that evaluates the efficacy and safety of monotherapies of fexofenadine and montelukast, the combined therapy (fixed-dose or separate drug combinations) of montelukast-fexofenadine, as well as the use of montelukast together with other second-generation antihistamines in the treatment of allergic rhinitis. A multistage literature search strategy was designed, including clinical trials and non-randomized studies (non-randomized controlled trial, controlled before-after study, interrupted time series study, historical control study, cohort study, case-control study, crosssectional study, and case series) evaluating patients with allergic rhinitis. The databases MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library, Redalyc, BVS Collection, and, due to the number of results obtained, Hinari were included. Based on this review, the conclusion is that the combinations of secondgeneration antihistamines with leukotriene antagonists and, in particular, the fixed combination of fexofenadine-montelukast are effective, safe and promote treatment adherence. In the long term, they also help achieve therapeutic goals.