, Volume 56, Issue 4, pp 725-745
Date: 27 Nov 2012

Mometasone Furoate

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Summary

Abstract

Mometasone furoate is a synthetic corticosteroid which has been evaluated for intranasal use in the treatment of adults and children with allergic rhinitis. In several large, well-controlled clinical trials, mometasone furoate 200μg administered once daily as an aqueous intranasal spray was significantly more effective than placebo in controlling the symptoms associated with moderate to severe seasonal or perennial allergic rhinitis. Mometasone furoate was as effective as twice-daily beclomethasone dipropionate or once-daily fluticasone propionate in the treatment of perennial allergic rhinitis, and was as effective as twice-daily beclomethasone dipropionate and slightly more effective than once-daily oral loratadine in the treatment of seasonal allergic rhinitis. Mometasone furoate was also as effective as twice-daily beclomethasone dipropionate or once-daily budesonide, and significantly more effective than placebo in the prophylaxis of seasonal allergic rhinitis. The onset of action of mometasone furoate was approximately 7 hours in patients with seasonal allergic rhinitis.

Mometasone furoate was as well tolerated as beclomethasone dipropionate, fluticasone propionate and budesonide in clinical trials, with an overall incidence of adverse events similar to placebo. Adverse events were generally mild to moderate and of limited duration. The most common adverse events associated with mometasone furoate therapy were nasal irritation and/or burning, headache, epistaxis and pharyngitis. Intranasal or oral mometasone furoate had no detectable effect on hypothalamic-pituitary-adrenal axis function in studies of ≤1 year in duration.

Conclusions: Mometasone furoate is a well tolerated intranasal corticosteroid with minimal systemic activity and an onset of action of ≤7 hours. It is effective in the prophylaxis and treatment of seasonal allergic rhinitis and the treatment of perennial allergic rhinitis in patients with moderate to severe symptoms.

Pharmacodynamic Properties

Mometasone furoate is a synthetic glucocorticoid which inhibits both the early and late phases of the allergic response. It inhibits the influx of inflammatory cells to the nasal mucosa in patients with allergic rhinitis, and inhibits the expression of the inflammatory mediators histamine, leukotrienes, interleukin-1 (IL-1 ), IL-4, IL-5, IL-6, IL-8, interferon-γ and tumour necrosis factor-α according to in vivo and in vitro studies. In patients with allergic rhinitis who received mometasone furoate once daily for 12 months, the influx of inflammatory cells to the nasal mucosa was inhibited and the phenotype of the nasal epithelium improved compared to baseline. When administered orally as a single dose or intranasally in a once-daily regimen for up to 1 year, mometasone furoate did not suppress hypothalamic-pituitary-adrenal axis function in healthy volunteers, or in children or adults with allergic rhinitis.

Pharmacokinetic Properties

Systemic absorption of intranasal mometasone furoate is minimal. With a single intranasal dose of mometasone furoate 400μg, bioavailability was ≤0.1% and peak plasma concentration (Cmax) was below the limit of quantification (50 ng/L) of the assay used. Mometasone furoate undergoes extensive hepatic metabolism and is excreted as metabolites mainly in the bile. When mometasone furoate 1mg was administered intravenously, the effective plasma elimination half-life was 5.8 hours.

Therapeutic Use

In 2- to 12-week, multicentre, double-blind, randomised trials involving adults or children, aqueous mometasone furoate 200μg administered once daily as an intranasal spray (100μg to each nostril) was significantly more effective than placebo in the treatment of perennial allergic rhinitis and in the treatment and prophylaxis of seasonal allergic rhinitis, based on subjective parameters including reduction in total nasal symptom scores (TNSS) and reduction in total symptom scores and, in 2 studies, objective parameters including total airway resistance. Mometasone furoate was equivalent in efficacy to beclomethasone dipropionate and fluticasone propionate in the treatment of moderate to severe perennial allergic rhinitis in adult patients: the average reduction of TNSS values compared to baseline ranged from 21 to 37% with once-daily mometasone furoate 200μg, 23 and 30% with twice-daily beclomethasone dipropionate 168 or 200μg, 39% with once-daily fluticasone propionate 200μg and 13 to 22% with placebo in 3 different studies.

In the treatment of adult patients with moderate to severe seasonal allergic rhinitis, mometasone furoate was more effective than placebo and as effective as beclomethasone dipropionate: the average reduction in TNSS was 47 to 71% with once-daily mometasone furoate 200μg, 64% with twice-daily beclomethasone dipropionate 200μg and 27 to 46% with placebo in 3 studies. In 1 study, mometasone furoate was slightly more effective than loratadine; the average reduction in TNSS from baseline was 32% with once-daily mometasone furoate 200μg, 22% with once-daily loratadine 10mg and 15% with placebo. In children with seasonal allergic rhinitis, once-daily mometasone furoate 100 or 200μg was more effective than placebo and as effective as twice-daily beclomethasone dipropionate 84μg; TNSS were reduced by approximately 35% with each of the active treatments and 24% with placebo. Mometasone furoate was also more effective than placebo and was as effective as beclomethasone dipropionate or budesonide in the prophylaxis of seasonal allergic rhinitis in adults: the proportion of days with minimal symptoms after the start of the pollen season was 81 and 83% with once-daily mometasone furoate 200μg, 77% with twice-daily beclomethasone dipropionate 168μg, 82% with once-daily budesonide 400μg and 63 and 64% with placebo.

When the nasal symptoms of congestion, rhinorrhoea, sneezing and itching in patients with either perennial or seasonal allergic rhinitis were considered individually, the trends observed were similar to those observed for TNSS. Prompt relief from symptoms was noted in many patients with seasonal allergic rhinitis; mometasone furoate was effective at ≤7 hours in a significant number of patients compared with placebo in 1 study.

Tolerability

In clinical trials, the overall incidence of adverse events was generally similar for adult patients with allergic rhinitis who received mometasone furoate, other intranasal corticosteroids or placebo. Events were usually mild to moderate in severity and of short duration. The most common adverse events reported included epistaxis, nasal burning and/or irritation, headache and pharyngitis. Epistaxis was more common in patients treated with mometasone furoate or other intranasal corticosteroids compared with placebo recipients. Of adverse events considered related to treatment, epistaxis was reported by 6 to 19%, nasal burning and/or irritation by 3 to 6%, headache by 6 to 10% and pharyngitis by 2 to 6% of patients who received mometasone furoate. The corresponding figures in patients who received placebo were 3 to 11%, 5 to 11%, 7 to 9% and 4 to 5%.

In clinical trials, no significant changes in vital signs or clinical laboratory test results were associated with mometasone furoate.

In children aged 3 to 12 years, the overall incidence of adverse events was similar with mometasone furoate and placebo in 2 randomised, placebo-controlled trials.

Dosage and Administration

Intranasal mometasone furoate is indicated for the treatment and prophylaxis of seasonal allergic rhinitis, and for the treatment of perennial allergic rhinitis in patients aged ≥12 years. The recommended dosage is 200μg once daily. For prophylaxis of seasonal allergic rhinitis, it is recommended that patients initiate treatment with mometasone furoate 2 to 4 weeks before the start of the pollen season.

Various sections of the manuscript reviewed by: W.J. Fokkens, Department of Otorhinolaryngology, Erasmus University Medical Centre, Rotterdam, The Netherlands; S.M. Gawchik, Asthma and Allergy Associates, Crozer-Chester Medical Center, Upland, Pennsylvania, USA; P.A. Greenberger, Division of Allergy-Immunology, Northwestern Memorial Hospital and Northwestern University Medical School, Chicago, Illinois, USA; J.R. Hebert, Centre de Recherche, Rhumatologie et Immunologie, Le Centre Hospitalier de l’Université Laval, Quebec, Quebec, Canada; H.F. Krause, Department of Otorhinolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; W.J. Metzger, East Carolina University School of Medicine, Greenville, North Carolina, USA; N. Mygind, Department of Otolaryngology, Rigshospitalet, Copenhagen, Denmark; G.K. Scadding, Royal National Throat, Nose and Ear Hospital, London, England; F.J. Zijlstra, Department of Immunopharmacology, Erasmus University, Rotterdam, The Netherlands.

Data Selection

Sources: Medical literature published in any language since 1966 on mometasone furoate, identified using AdisBase (a proprietary database of Adis International, Auckland, New Zealand), Medline and EMBASE. Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: AdisBase search terms were ‘mometasone’ and ‘SCH-32088’. Medline and EMBASE search term was ‘mometasone’. Searches were last updated 11 September 1998.
Selection: Studies in patients with allergic rhinitis who received mometasone furoate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.
Index terms: Mometasone furoate, allergic rhinitis, pharmacokinetics, pharmacodynamics, therapeutic use.