Inhaled Mometasone Furoate

Inhaled mometasone furoate (Asmanex®) is a synthetic corticosteroid indicated for the first-line maintenance prophylactic therapy of persistent asthma in adults and adolescents. It is formulated for delivery via a breath-actuated dry powder inhaler (DPI) [Twisthaler®]

Inhaled mometasone furoate delivered by DPI is effective in treating patients with persistent asthma. It improves pulmonary function and health-related quality of life, reduces symptoms and decreases oral corticosteroid requirements in severe disease. It is a potent anti-inflammatory agent and is at least as clinically effective as other inhaled corticosteroids. Inhaled mometasone furoate is equally effective in controlling asthma when administered in two divided doses or as a single daily dose. Once-daily administration of mometasone furoate 200μg in the evening was more effective than administration of the same dosage in the morning. The drug is well tolerated, with low systemic bioavailability and minimal systemic activity. Therefore, it is an effective and convenient option for controller therapy of persistent asthma in adults and adolescents.

Mometasone furoate binds to the corticosteroid receptor in vitro with greater affinity than dexamethasone, triamcinolone acetonide, budesonide and fluticasone propionate. Studies with human cells in vitro indicate that mometasone furoate has anti-inflammatory potency similar to that of fluticasone propionate and generally greater than that of triamcinolone acetonide, beclomethasone dipropionate or budesonide. Mometasone furoate 50 or 100μg delivered by DPI twice daily for 2 weeks in patients with mild asthma significantly reduced bronchial hyper-responsiveness induced by adenosine monophosphate or allergen. Inhaled mometasone furoate 400–1600 μg/day for 28 days was capable of suppressing plasma cortisol in patients with mild to moderate persistent asthma, but to a significantly lower extent than seen with oral prednisone. Mometasone furoate therapy for 2 years reduced bone mineral density; an effect that reached statistical significance over placebo in one of two studies.

The systemic exposure to mometasone furoate delivered by DPI was low, with plasma concentrations often below the lower limit of quantification (0.05 μg/L) following administration of a single 400μg dose. The bioavailability of singledose inhaled mometasone furoate in healthy volunteers was originally estimated at 0.96%, but more recently was estimated at 5.3%. Most of the inhaled dose of mometasone furoate is swallowed and excreted unchanged in faeces. Any drug that is absorbed appears to undergo extensive metabolism in the liver and is excreted mainly in the bile. The time to peak plasma concentration was approximately 2 hours. The elimination half-life after intravenous administration was 4.5 hours.

In patients with mild to moderate asthma previously treated with either short-acting β₂-adrenoceptor agonists (SABAs) alone or inhaled corticosteroids, mometasone furoate 400μg delivered by DPI once daily in the morning or evening, mometasone furoate 200μg twice daily or mometasone furoate 200μg once daily in the evening for 12 weeks were consistently superior (p < 0.01) to placebo for the primary endpoint of improvement from baseline in forced expiratory volume in 1 second. Mometasone furoate 200μg once daily in the morning was not significantly better than placebo in two of three studies.

In patients previously treated with SABAs, once-daily administration of mometasone furoate 400μg delivered by DPI in the morning for 12 weeks was similar in efficacy to mometasone furoate 200μg twice daily. Mometasone furoate 400μg once daily in the morning generally produced greater improvements in most parameters than mometasone furoate 200μg once daily in the morning.

In patients previously treated with inhaled corticosteroids, mometasone furoate 200μg once daily by DPI in the evening for 12 weeks was similar in efficacy to mometasone furoate 400μg once daily (morning or evening) and to mometasone furoate 200μg twice daily, and was superior to mometasone furoate 200μg once daily in the morning.

Mometasone furoate 400 or 800μg twice daily delivered by DPI for 12 weeks in patients dependent on oral corticosteroids significantly reduced the daily prednisone requirement compared with placebo and permitted complete discontinuation of prednisone in 37–40% of patients. Following a 9-month extension phase, 76% of evaluable patients had discontinued prednisone after 12 months of therapy.

In 8-to 12-week comparative trials in patients with moderate asthma previously maintained on inhaled corticosteroids, mometasone furoate 200μg twice daily by DPI generally improved lung function more than mometasone furoate 100μg twice daily, while mometasone furoate 400μg twice daily did not provide additional benefit over that with 200μg twice daily.

Mometasone furoate 100μg twice daily delivered by DPI was similar in efficacy to beclomethasone dipropionate 200μg twice daily delivered by metered dose inhaler (MDI) and budesonide 400μg twice daily delivered by DPI. Mometasone furoate 200μg twice daily or 400μg once daily in the evening had similar efficacy to fluticasone propionate 250μg twice daily delivered by DPI or MDI. Mometasone furoate 200 or 400μg twice daily were superior to budesonide 400μg twice daily, while mometasone furoate 400μg once daily in the morning was superior to budesonide 400μg once daily in the morning.

Treatment with inhaled mometasone furoate for 12 weeks significantly improved patients’ health-related quality of life as determined both by a general health questionnaire and an asthma-specific instrument.

Inhaled mometasone furoate was generally well tolerated in clinical trials. Most adverse events were of mild to moderate intensity and occurred with frequencies similar to those with placebo. The most common adverse events were headache, allergic rhinitis, pharyngitis and upper respiratory tract infections. The nature, incidence and severity of treatment-related adverse events with inhaled mometasone furoate were similar to those with inhaled beclomethasone dipropionate, budesonide and fluticasone propionate. In trials assessing cortisol activity, there was no evidence of hypothalamic-pituitary-adrenal axis suppression by inhaled mometasone furoate at therapeutic dosages (≤800 μg/day).