New Combination: Mometasone furoate and formoterol fumarate dihydrate (Dulera) was approved in June for the treatment of asthma in patients ?12 years of age.
Mometasone furoate and formoterol fumarate dihydrate 100 µg/5 µg and 200 µg/5 µg for inhalation was approved by FDA in June 2010 for the treatment of asthma in patients ≥12 years of age. Mometasone is a corticosteroid demonstrating potent anti-inflammatory activity and formoterol is a long-acting selective beta2-adrenergic receptor agonist (LABA) that acts locally in the lung as a bronchodilator.
Efficacy. The efficacy of mometasone furoate and formoterol fumarate was mainly assessed in 2 multicenter, randomized, double-blind, parallel group clinical trials. The 2 trials enrolled a total of 1,509 patients ≥12 years of age with persistent asthma uncontrolled on medium- or high-dose inhaled corticosteroids (baseline forced expiratory volume in 1 second [FEV1] means of 66% to 73% of predicted normal). The first clinical trial was 26 weeks in duration and compared mometasone furoate and formoterol fumarate 100 µg/5 µg (n=191) with placebo (n=196), mometasone alone (n=192), and formoterol fumarate alone (n=202), while the second clinical trial lasted 12 weeks and compared 2 different strengths of the drug (100 µg/5 µg group, n=233 and 200 µg/5 µg group, n=255) with mometasone alone (200 µg, n=240). FEV1 area-under-the-curve (AUC) (0–12 hr) and clinically judged deteriorations in asthma/reductions in lung function (defined as a 20% decrease in FEV1; a 30% decrease in peak expiratory flow on 2 or more consecutive days; emergency treatment, hospitalization, or treatment with systemic corticosteroids or other asthma medications not allowed per protocol) were major end points evaluated in both trials. When taken together both trials demonstrated that mometasone furoate and formoterol fumarate at either dose was associated with significantly higher increases from baseline in mean FEV1 AUC (0–12 hr) compared with mometasone 100 µg alone or placebo. In addition, mometasone furoate and formoterol fumarate use resulted in fewer patients experiencing clinical deterioration compared to patients receiving mometasone 100 µg or formoterol 5 µg alone.
Safety. In clinical trials the most common adverse reactions (reported in≥3% of patients) included nasopharyngitis, sinusitis, and headache. Other adverse effects of note include oropharyngeal candidiasis, immunosuppression, hypercorticism and adrenal suppression, reduction in bone mineral density, reduced growth velocity, glaucoma and cataracts (due to mometasone), palpitations, chest pain, and tremor or nervousness (due to formoterol). Perhaps most concerning is the black box warning related to formoterol use (as with any LABA). LABAs have been found to be associated with an increased risk of asthma-related death with their use. As a result, combination products such as Dulera should only be used in patients with asthma not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, the ability to step-down therapy should be considered.