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The Australasian Journal of Dermatology Aug 2018Derivatives of hydrocortisone, such as mometasone furoate, a (2') furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve... (Review)
Review
Derivatives of hydrocortisone, such as mometasone furoate, a (2') furoate-17 ester with chlorine substitutions at positions 9 and 21, have been designed to improve efficacy and reduce the incidence of adverse effects. An extensive literature search of MEDLINE, Embase and other databases was conducted to review the safety and efficacy of various formulations of topical mometasone furoate. Mometasone furoate exhibits high potency with greater anti-inflammatory activity and a longer duration of action than betamethasone. In clinical trials, mometasone furoate shows comparable or significantly better efficacy, depending on the comparator, in all indications studied in both adults and children. It is well tolerated with only transient, mild to moderate local adverse effects. It is characterised by low systemic availability due to its high lipophilicity, low percutaneous absorption and rapid hepatic biotransformation, and consequently has no significant effect on the hypothalamic-pituitary-adrenal axis. The molecular biotransformation of mometasone furoate in the skin results in a lower affinity with dermal cells than epidermal cells, which contributes to its low atrophogenicity. Sensitisation to mometasone furoate is low. Overall, mometasone furoate is a highly efficacious potent corticosteroid with a low risk of both local and systemic adverse effects.
Topics: Administration, Topical; Betamethasone; Dermatologic Agents; Humans; Mometasone Furoate
PubMed: 29411351
DOI: 10.1111/ajd.12762 -
JAMA Pediatrics Mar 2023Obstructive sleep-disordered breathing (SDB) in children is characterized by snoring and difficulty breathing during sleep. SDB affects at least 12% of otherwise healthy... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Obstructive sleep-disordered breathing (SDB) in children is characterized by snoring and difficulty breathing during sleep. SDB affects at least 12% of otherwise healthy children and is associated with significant morbidity. Evidence from small clinical trials suggests that intranasal corticosteroids improve SDB as measured by polysomnography; however, the effect on symptoms and quality of life is unclear.
OBJECTIVE
To determine whether intranasal mometasone furoate is more effective than intranasal saline for improving symptoms and quality of life in children with SDB.
DESIGN, SETTING, AND PARTICIPANTS
The MIST trial was a multicenter, randomized, double-blind, placebo-controlled trial, recruiting participants from June 8, 2018, to February 13, 2020. Children aged 3 to 12 years who were referred to a specialist for significant SDB symptoms were included; exclusions were previous adenotonsillectomy, body mass index greater than the 97th percentile, and severe SDB. Randomization was stratified by site, and data were analyzed on an intention-to-treat basis from October 28, 2020, to September 25, 2022.
INTERVENTIONS
Participants were randomly assigned to receive mometasone furoate, 50 μg, or sodium chloride (saline), 0.9%, 1 spray per nostril daily, dispensed in identical bottles.
MAIN OUTCOMES AND MEASURES
The primary outcome was resolution of significant SDB symptoms (ie, reduction to a level no longer requiring referral to a specialist as per the American Academy of Pediatrics guidelines) at 6 weeks, measured by parental report of symptoms using the SDB Score.
RESULTS
A total of 276 participants (mean [SD] age, 6.1 [2.3] years; 146 male individuals [53%]) were recruited, 138 in each treatment arm. Resolution of significant SDB symptoms occurred in 56 of 127 participants (44%) in the mometasone group and 50 of 123 participants (41%) in the saline group (risk difference, 4%; 95% CI, -8% to 16%; P = .51) with 26 participants lost to follow-up and missing values managed by multiple imputation. The main adverse effects were epistaxis, affecting 12 of 124 participants (9.7%) in the mometasone group and 18 of 120 participants (15%) in the saline group, and nasal itch/irritation, affecting 12 of 124 participants (9.7%) in the mometasone group and 22 of 120 participants (18%) in the saline group.
CONCLUSIONS AND RELEVANCE
Results of this randomized clinical trial suggest that there was no difference in treatment effect between intranasal mometasone and saline for the management of SDB symptoms. The results suggest that almost one-half of children with SDB could be initially managed in the primary care setting and may not require referral to specialist services, as is currently recommended.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ANZCTRN12618000448246.
Topics: Male; Humans; Child; Mometasone Furoate; Quality of Life; Nasal Sprays; Australia; Administration, Intranasal; Pruritus; Saline Solution; Sleep Apnea Syndromes; Treatment Outcome
PubMed: 36648937
DOI: 10.1001/jamapediatrics.2022.5258 -
Expert Review of Respiratory Medicine Jan 2022Fixed-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) combinations and add-on therapies as needed are the mainstay for maintenance therapy in asthma.... (Review)
Review
INTRODUCTION
Fixed-dose long-acting beta2-agonist (LABA)/inhaled corticosteroid (ICS) combinations and add-on therapies as needed are the mainstay for maintenance therapy in asthma. However, more than 40% of patients have an inadequately controlled disease. The development of triple fixed-dose combinations consisting of long-acting muscarinic antagonist (LAMA)/LABA/ICS has paved the way for a new approach to reach therapeutic goals of an optimal control of symptoms and an effective prevention of future exacerbations.
AREAS COVERED
A search was conducted on PubMed (MEDLINE), using the MeSH terms [asthma] + [indacaterol] + [glycopyrronium] +[mometasone furoate] + [treatment], until October 2021. Original data from clinical trials, prospective and retrospective studies and reviews were selected. Clinical studies with IND/MF/GLY (Enerzair Breezhaler) are summarized, and its place in current asthma therapy is examined.
EXPERT OPINION
Triple therapy has been shown to be an effective and safe therapeutic option for asthma patients who remain uncontrolled despite ICS/LABA combination. The recently approved single-inhaler indacaterol/glycopyrronium/mometasone fixed dose combination has demonstrated to significantly reduce exacerbations, improve FEV, symptoms and quality of life compared to ICS/LABA, including, salmeterol/fluticasone combination. Moreover, once-daily dosing may improve adherence.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Asthma; Clinical Trials as Topic; Drug Combinations; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Prospective Studies; Quality of Life; Quinolones; Retrospective Studies
PubMed: 34783265
DOI: 10.1080/17476348.2021.2005585 -
Expert Opinion on Investigational Drugs Aug 2016Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing,... (Review)
Review
INTRODUCTION
Asthma is a common respiratory disease characterized by airway inflammation, bronchoconstriction and airway hyperresponsiveness and symptoms such as coughing, wheezing, shortness of breath and chest tightness. Allergic rhinitis is a common comorbidity in asthma and glucocorticoids are the key stone in the treatment of both diseases. Mometasone furoate is a potent synthetic steroid with a very high receptor affinity and a low bioavailability and shown to be superior compared to other inhaled corticosteroids. It is not clear whether the use of mometasone furoate nasal spray (MFNS) is associated with an improvement in asthma control.
AREAS COVERED
This current paper reviews the current knowledge on the effect of mometasone furoate nasal spray in the treatment of asthma and includes clinical trials in which both subjective and objective outcomes are assessed.
EXPERT OPINION
To date, only few clinical studies have investigated the effect of nasal steroids in the treatment of asthma. The studies investigating the effect of MFNS report contradicting results, although the most well-designed study to answer this question finds no improvement in asthma control. Thus, it seems unlikely that asthma guidelines will be influenced by the current knowledge on the effect of MFNS in the treatment of asthma.
Topics: Administration, Intranasal; Anti-Allergic Agents; Asthma; Glucocorticoids; Humans; Mometasone Furoate; Nasal Sprays; Treatment Outcome
PubMed: 27218300
DOI: 10.1080/13543784.2016.1192124 -
Ugeskrift For Laeger Sep 1991
Review
Topics: Administration, Topical; Anti-Inflammatory Agents; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols
PubMed: 1926632
DOI: No ID Found -
Expert Review of Clinical Pharmacology Dec 2018: Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host... (Review)
Review
: Chronic rhinosinusitis (CRS) is a broad heterogeneous inflammatory disorder of the nose and paranasal sinuses, resulting from the dysfunctional interplay between host immunity, defective epithelial barrier, and environmental factors. CRS with nasal polyps (CRSwNP) is considered a more severe clinical phenotype with greater burden of symptoms and higher relapse rate, especially with comorbid asthma or aspirin sensitivity. Available treatment options after endoscopic sinus surgery (ESS) - systemic corticosteroids or revision surgery - have significant risks and limitations. : Bioabsorbable, steroid-eluting implants have been studied extensively for the ability to dilate and re-establish sinus patency by the localized, controlled delivery of topical corticosteroids to diseased sinonasal lining and nasal polyps. This review provides a comprehensive, up to date analysis of the literature regarding a novel, office-based, mometasone furoate (MF) sinus implant that may treat patients with recurrent CRSwNP after ESS. : Clinical evidence has demonstrated the safety and efficacy of steroid-eluting implant in the reduction of polyp size, symptom burden, and the need for revision sinus surgery. MF sinus implants may play an important role in the management of patients with recurrent polyposis after sinus surgery.
Topics: Anti-Inflammatory Agents; Chronic Disease; Drug Implants; Endoscopy; Humans; Mometasone Furoate; Nasal Polyps; Paranasal Sinuses; Recurrence; Rhinitis; Sinusitis
PubMed: 30457411
DOI: 10.1080/17512433.2018.1549485 -
American Journal of Health-system... Nov 2001
Topics: Anti-Inflammatory Agents; Humans; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Seasonal
PubMed: 11760915
DOI: 10.1093/ajhp/58.22.2140 -
Pulmonary Pharmacology & Therapeutics Oct 2021Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate (MF/IND) and mometasone furoate/indacaterol acetate/glycopyrronium bromide... (Review)
Review
Dose bridging data for mometasone furoate in once-daily fixed-dose inhaled combinations of mometasone furoate/indacaterol and mometasone furoate/ indacaterol/glycopyrronium in patients with asthma.
Once-daily (o.d.) fixed-dose combinations of mometasone furoate/indacaterol acetate (MF/IND) and mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY), both delivered via the Breezhaler® device, are approved for the maintenance treatment of asthma. Across these fixed-dose combinations, while the doses of bronchodilators remain the same, the nominal doses of mometasone furoate in micrograms differ. This article presents the steps followed in bridging the mometasone furoate doses at the corresponding dose strengths in the mometasone furoate formulation delivered via the Twisthaler® and mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulations delivered via the Breezhaler®. These were: (i) bridging the mometasone furoate doses in the Twisthaler® (previously approved) to mometasone furoate doses in the Breezhaler®; (ii) bridging the mometasone furoate doses in the Breezhaler® to mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation. Following this stepwise approach, it was determined that mometasone furoate 80 μg o.d. (medium-dose strength) and 160 μg o.d. (high-dose strength) in mometasone furoate/indacaterol acetate/glycopyrronium bromide formulation provided comparable inhaled corticosteroid efficacy to mometasone furoate 160 μg o.d. (medium-dose strength) and 320 μg o.d. (high-dose strength) in the mometasone furoate/indacaterol acetate formulation, respectively. These doses were used in the PLATINUM Phase III clinical program that investigated the efficacy and safety of mometasone furoate/indacaterol acetate and mometasone furoate/indacaterol acetate/glycopyrronium bromide combinations in patients with asthma.
Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Drug Combinations; Glycopyrrolate; Humans; Indans; Mometasone Furoate; Quinolones; Treatment Outcome
PubMed: 34329722
DOI: 10.1016/j.pupt.2021.102068 -
Pulmonary Pharmacology & Therapeutics Dec 2022To investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
To investigate the pharmacokinetics and effects on the hypothalamic-pituitary-adrenal (HPA) axis of mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF).
METHODS
Study 1: Fourteen healthy participants received inhaled and intravenous MF (inhaled dose via Twisthaler) and FP (inhaled dose via Diskus), both given at 400 μg, using a randomised, single-dose, four-way crossover design. Study 2: Twenty-seven participants with mild to moderate asthma, who discontinued their corticosteroid medication for 5 days to obtain a baseline 24 h serum cortisol, received inhaled MF Twisthaler and FP Diskus, both given at 400 μg twice daily (BID), using a randomised, 14-day repeat dose, two-way crossover design. Study 3: Forty-four healthy participants were randomised to a double-blind, placebo-controlled, five-period crossover study where the following treatments were administered via the inhaled route for 7 days: FP Diskus (250, 500, 1000 μg BID), FF Diskus (100, 200, 400, 800, 1600 μg once daily [QD]) or placebo Diskus. In each study, 24-h serial blood samples were collected and assayed to assess concentrations of MF, 6β-hydroxy mometasone, mometasone, FP, FF and cortisol. Pharmacokinetic and serum cortisol parameters were estimated as geometric means and 95% confidence intervals (CI).
RESULTS
Study 1: For intravenous MF and FP, respectively: absolute bioavailability was 11.4% (95% CI: 7.5, 17.6) and 7.8% (6.3, 9.6); plasma clearance was 47 L/h (41, 52) and 60 L/h (52, 69); half-life was 7.4 h (6.9, 8.0) and 7.2 h (6.5, 8.0); and volume of distribution was 499 L (439, 567) and 623 L (557, 698). Inhalation of single dose MF or FP did not significantly affect serum cortisol (<10% reduction from baseline), whereas intravenous administration of MF or FP each changed serum cortisol by approximately -50% from baseline. Study 2: For MF and FP, respectively: area under the curve up to the last measurable concentration on Day 1 was 421 pg h/mL (270, 659) and 248 pg h/mL (154, 400), and on Day 14 was 1092 pg h/mL (939, 1269) and 591 pg h/mL (501, 696); absolute bioavailability was 12.8% (11.2, 14.2) and 8.9% (7.7, 10.2). On Day 14, 24-h serum cortisol change from baseline was -35% (-44%, -26%) and -18% (-28%, -5%) for MF and FP, respectively; the reduction was significantly greater for MF than FP (ratio for geometric adjusted mean serum cortisol concentration: 1.28 [1.04, 1.56]). Low plasma concentrations of 6β-hydroxy mometasone were detected after intravenous dosing (Study 1) and after multiple inhaled dosing (Study 2); mometasone was not detected in any samples. Study 3: Inhaled FP and FF had similar systemic bioavailability estimates (12.0% [11.0, 13.2] and 15.0% [12.0, 17.3], respectively), but a differential effect on the HPA axis which was in agreement with the known 1.7-fold higher glucocorticoid receptor-binding affinity of FF versus FP. However, for FP 250 μg BID and FF 100, 200 and 400 μg QD, reduction in serum cortisol was not significantly different from placebo. For higher doses, FP 500 and 1000 μg BID, and FF 800 and 1600 μg QD, changes in serum cortisol concentration relative to placebo were -30%, -70%, -41% and -90%, respectively. Repeat inhaled dosing of FP 1000 μg/day (within the therapeutic dose range) resulted in comparable cortisol suppression to MF in the therapeutic range (30% reduction); whereas for FF this occurred at more than 3-fold above the therapeutic dose range (644 μg/day).
CONCLUSIONS
Single inhaled and intravenous doses of MF and FP (400 μg) resulted in similar bioavailability and reductions in serum cortisol. Repeat dosing of inhaled MF and FP in the therapeutic range (800 μg/day) resulted in greater systemic exposure for MF, and a 35% reduction in serum cortisol that was 2-fold greater than for FP. The higher glucocorticoid receptor-binding affinity and bioavailability, lower clearance and the presence of active metabolites may contribute to the greater systemic exposure and effect on cortisol for MF. Repeat dosing of inhaled FP and FF resulted in similar systemic bioavailability but differed in terms of the dose required for comparable cortisol suppression to MF in the therapeutic range. Unlike FP and FF, MF has active metabolites that may contribute to its systemic effects, while device/formulation performance differences also exist between MF-containing products.
Topics: Humans; Fluticasone; Mometasone Furoate; Hypothalamo-Hypophyseal System; Cross-Over Studies; Receptors, Glucocorticoid; Pituitary-Adrenal System; Androstadienes; Administration, Inhalation; Hydrocortisone; Double-Blind Method
PubMed: 36243386
DOI: 10.1016/j.pupt.2022.102171 -
Expert Opinion on Pharmacotherapy Aug 2009Mometasone furoate has been available for clinical use, starting with a dermatologic preparation, for nearly 20 years. An inhaled format of the drug for management of... (Review)
Review
Mometasone furoate has been available for clinical use, starting with a dermatologic preparation, for nearly 20 years. An inhaled format of the drug for management of asthma had been in development during the last decade and has been available for clinical use for 6 years as a dry powder inhaler delivering either 100 mcg or 200 mcg per dose. It has a long half-life and is suitable for daily dosing. The drug is approved for use in the USA for the treatment of asthma in patients aged 4 years or over. Mometasone furoate is a topically potent glucocorticoid with a favorable risk-benefit profile. A wide variety of randomized clinical trials have shown the drug to have a clinically beneficial effect on asthma comparable to fluticasone propionate, and to permit the reduction or withdrawal of oral glucocorticoid therapy in patients with asthma. Mometasone furoate has approximately 1% oral bioavailability but does produce systemic glucocorticoid effects from the drug released from the lung and its metabolites. These effects are minimal when mometasone is used appropriately at low or moderate doses.
Topics: Administration, Inhalation; Adult; Anti-Allergic Agents; Asthma; Biological Availability; Child; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Mometasone Furoate; Pregnadienediols
PubMed: 19618993
DOI: 10.1517/14656560903078428