Mometasone Furoate and Formoterol Fumarate Inhalation Aerosol (Dulera®)
Pharmacology Update
Mometasone Furoate and Formoterol Fumarate Inhalation Aerosol (Dulera®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
A third inhaled corticosteroid and long-acting beta-agonist combination has been approved by the FDA, joining currently marked combinations fluticasone/salmeterol (Advair Diskus®) and budesonide/formoterol (Symbicort®). Mometasone furoate and formoterol fumarate is marketed by Schering as Dulera®.
Indications
Mometasone furoate (MF)/formoterol (F) is indicated for the treatment of asthma in patients 12 years of age and older.1
Dosage
The recommended dose is 2 inhalations twice daily. Each inhalation contains 100 mg or 200 mg of mometasone furoate and 5 mg of formoterol.
Potential Advantages
Patients with persistent asthma not well controlled on a medium dose of inhaled steroid or high dose of inhaled steroid showed improved asthma control with the combination of MF/F compared to MF alone.1-3
Potential Disadvantages
Long-acting beta-agonists appear to increase the risk of asthma-related intubation and death, even if used in combination with an inhaled corticosteroid.4
Comments
Mometasone furoate is corticosteroid with high affinity for the corticosteroid receptor and low systemic exposure.5 Its potency is similar to fluticasone propionate. Formoterol is a long-acting beta-agonist similar to salmeterol. The safety and efficacy of MF/F was shown in two randomized, double-blind, parallel group trials.1-3 In the first 26-week study, eligible subjects were ≥ 12 years of age with persistent asthma on a stable regimen, had symptoms not well controlled on medium dose inhaled steroid, and had a FEV1 between 60% and 90% of predicted. After a run-in period of MF (200 mg twice daily) of 2-3 weeks, patients were then randomized to MF/F (100 mg/10 mg; n = 191), MF (100 mg; n = 192), F (5 mg; n = 202), or placebo (n = 196) twice daily.1,3 Efficacy was assessed by pulmonary function (FEV1 AUC0-12h) and coprimary endpoints were time to first asthma deterioration on MF/F compared to F and bronchodilatory effect of MF/F compared to MF. At the end of treatment, mean FEV1 AUC0-12h values were 3.2, 1.3, 1.6 and 0.5 Lx hr for MF/F, MF, F, and placebo, respectively. MF/F was significantly better than MF, F, and placebo. Lung function improved more rapidly with MF/F than MF or placebo. Percents of subjects that showed clinically judged deterioration in asthma or reduction in lung function were 30%, 34%, 54%, and 56% for MF/F, MF, F, and placebo, respectively (P < 0.001 MF/F and MF vs F and placebo).
The second study was a 12-week study of similar design involving subjects with a history of deterioration requiring treatment with oral corticosteroids and receiving a high daily dose of inhaled steroids.1,2 Subjects were randomized to MF/F (200 mg/5 mg; n = 255), MF/F (100 mg/5 mg; n = 233), or MF (200 mg; n = 240) twice daily. Mean changes in FEV1 AUC0-12h were 4.19, 3.59, and 2.04 Lx hr, respectively. Both doses of MF/F were statistically different than MF. The percents of asthma deterioration were 12%, 12%, and 18% for MF/F, MF, and F, respectively.
Clinical Implications
Due to safety concerns regarding long-acting beta-agonists, the FDA is requiring a risk management strategy (REMS) and class labeling for all long-acting beta-agonists.6 The current recommendation is that long-acting beta-agonists be used only in combination with an asthma controller and be used for the shortest duration of time possible. In addition, it should not be used long term in patients whose asthma cannot be controlled on controller medication. However, the use in combination with a controller may not completely eliminate the risk. In an analysis of pooled clinical trial data involving 36,588 participants, the authors reported an association with an increase in risk of asthma-related intubation and death, regardless of concomitant inhaled corticosteroid use.4 For combination compared to inhaled corticosteroid alone, the odds ratio is 3.65 (95% confidence interval, 1.39-9.55). While there are limitations with this meta-analysis, particularly with the small number of events per trial as evidenced by the wide confidence interval, the potential risk should not be overlooked.
References
1. Dulera Prescribing Information. Whitehouse Station, NJ: Schering Corporation; June 2010.
2. Einstein SF, et al. Twelve-week efficacy and safety study of mometasone furoate/formoterol 200/10 mug and 400/10 mug combination treatments in patients with persistent asthma previously receiving high-dose inhaled corticosteroids. Allergy Asthma Proc 2010;31: 280-289.
3. Nathan RA, et al. Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 mug combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids. Allergy Asthma Proc 2010;31:269-279.
4. Saltpeter SR, et al. Long-acting beta-agonists with and without inhaled corticosteroids and catastrophic asthma events. Am J Med 2010;123:322-328.e2.
5. McCormack PL, Plosker GL. Inhaled mometasone furoate: A review of its use in persistent asthma in adults and adolescents. Drugs 2006;66:1151-1168.
6. Long-acting Beta Agonists: New Safe Use Requirements. Available at: www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedical Products/ucm201003.htm. Accessed Aug. 10, 2010.
A third inhaled corticosteroid and long-acting beta-agonist combination has been approved by the FDA, joining currently marked combinations fluticasone/salmeterol (Advair Diskus®) and budesonide/formoterol (Symbicort®). Mometasone furoate and formoterol fumarate is marketed by Schering as Dulera®Subscribe Now for Access
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