Long-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in DULERA, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Data from a large placebo-controlled US trial that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol [see WARNINGS AND PRECAUTIONS].
Systemic and local corticosteroid use may result in the following:
- Candida albicans infection [see WARNINGS AND PRECAUTIONS]
- Immunosuppression [see WARNINGS AND PRECAUTIONS]
- Hypercorticism and adrenal suppression [see WARNINGS AND PRECAUTIONS]
- Growth effects in pediatrics [see WARNINGS AND PRECAUTIONS]
- Glaucoma and cataracts [see WARNINGS AND PRECAUTIONS]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience
The safety data described below is based on 3 clinical trials which randomized 1913 patients 12 years of age and older with asthma, including 679 patients exposed to DULERA for 12 to 26 weeks and 271 patients exposed for 1 year. DULERA was studied in two placebo- and active-controlled trials (n=781 and n=728, respectively) and in a long-term 52-week safety trial (n=404). In the 12 to 26-week clinical trials, the population was 12 to 84 years of age, 41% male and 59% female, 73% Caucasians, 27% non-Caucasians. Patients received two inhalations twice daily of DULERA (100 mcg/5 mcg or 200 mcg/5 mcg), mometasone furoate MDI (100 mcg or 200 mcg), formoterol MDI (5 mcg) or placebo. In the long-term 52-week active-comparator safety trial, the population was 12 years to 75 years of age with asthma, 37% male and 63% female, 47% Caucasians, 53% non-Caucasians and received two inhalations twice daily of DULERA 100 mcg/5 mcg or 200 mcg/5 mcg, or an active comparator.
The incidence of treatment emergent adverse reactions associated with DULERA in Table 2 below is based upon pooled data from 2 clinical trials 12 to 26 weeks in duration in patients 12 years and older treated with two inhalations twice daily of DULERA (100 mcg/5 mcg or 200 mcg/5 mcg), mometasone furoate MDI (100 mcg or 200 mcg), formoterol MDI (5mcg) or placebo.
Table 2: Treatment-Emergent Adverse Reactions in
DULERA Groups Occurring at an Incidence of ≥ 3% and More Commonly than
|Adverse Reactions||DULERA*||Mometasone Furoate*||Formoterol*||Placebo*|
|100 mcg/5 mcg
n=424 n (%)
|200 mcg/5 mcg
n=255 n (%)
n=192 n (%)
n=240 n (%)
n=202 n (%)
|n=196 n (%)|
|Nasopharyngitis||20 (4.7)||12 (4.7)||15 (7.8)||13 (5.4)||13 (6.4)||7 (3.6)|
|Sinusitis||14 (3.3)||5 (2.0)||6 (3.1)||4 (1.7)||7 (3.5)||2 (1.0)|
|Headache||19 (4.5)||5 (2.0)||10 (5.2)||8 (3.3)||6 (3.0)||7 (3.6)|
|Average Duration of Exposure (days)||116||81||165||79||131||138|
|*All treatments were administered as two inhalations twice daily.|
Oral candidiasis has been reported in clinical trials at an incidence of 0.7% in patients using DULERA 100 mcg/5 mcg, 0.8 % in patients using DULERA 200 mcg/5 mcg and 0.5 % in the placebo group.
Long-Term Clinical Trial Experience
In a long-term safety trial in patients 12 years and older treated for 52 weeks with DULERA 100 mcg/5 mcg (n=141), DULERA 200 mcg/5 mcg (n=130) or an active comparator (n=133), safety outcomes in general were similar to those observed in the shorter 12 to 26 week controlled trials. No asthma-related deaths were observed. Dysphonia was observed at a higher frequency in the longer term treatment trial at a reported incidence of 7/141 (5%) patients receiving DULERA 100 mcg/5 mcg and 5/130 (3.8%) patients receiving DULERA 200 mcg/5 mcg. No clinically significant changes in blood chemistry, hematology, or ECG were observed.
The following adverse reactions have been reported during post-approval use of DULERA or post-approval use with inhaled mometasone furoate or inhaled formoterol fumarate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorders: atrial fibrillation, angina pectoris, ventricular extrasystoles, tachyarrhythmia
Investigations: electrocardiogram QT prolonged, blood pressure increased (including hypertension)
Read the Dulera (mometasone furoate, formoterol fumarate dihydrate inhalation) Side Effects Center for a complete guide to possible side effects »
In clinical trials, concurrent administration of DULERA and other drugs, such as short-acting beta2-agonist and intranasal corticosteroids have not resulted in an increased frequency of adverse drug reactions. No formal drug interaction studies have been performed with DULERA. The drug interactions of the combination are expected to reflect those of the individual components.
Inhibitors of Cytochrome P450 3A4
The main route of metabolism of corticosteroids, including mometasone furoate, a component of DULERA, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally inhaled mometasone furoate increased. Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, mometasone furoate. Caution should be exercised when considering the coadministration of DULERA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see WARNINGS AND PRECAUTIONS and CLINICAL PHARMACOLOGY].
If additional adrenergic drugs are to be administered by any route, they should be used with caution because the pharmacologically predictable sympathetic effects of formoterol, a component of DULERA, may be potentiated.
Concomitant treatment with xanthine derivatives may potentiate any hypokalemic effect of formoterol, a component of DULERA.
Concomitant treatment with diuretics may potentiate the possible hypokalemic effect of adrenergic agonists. The ECG changes and/or hypokalemia that may result from the administration of non-potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of DULERA with non-potassium-sparing diuretics.
Monoamine oxidase inhibitors, tricyclic antidepressants, and drugs known to prolong the QTc interval
DULERA should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the action of formoterol, a component of DULERA, on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias.
Beta-adrenergic receptor antagonists
Beta-adrenergic receptor antagonists (beta-blockers) and formoterol may inhibit the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta2-agonists, such as formoterol, a component of DULERA, but may produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
Last reviewed on RxList: 2/1/2013
This monograph has been modified to include the generic and brand name in many instances.
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