Dosing and uses of Dulera (mometasone inhaled/formoterol)
Adult dosage forms and strengths
mometasone/formoteroL
aerosoL
- (100mcg/5mcg)/actuation
- (200mcg/5mcg)/actuation
Asthma
200 mcg/10 mcg (2 actuations of 100 mcg/5 mcg) PO via metered-dose inhaler q12hr; for more severe asthma, 400 mcg/10 mcg (2 actuations of 200 mcg/5 mcg) PO q12hr; not to exceed 800 mcg/20 mcg daily
Dosing Considerations
Patients on inhaled medium-dose corticosteroids: 200 mcg/10 mcg (2 actuations of 100 mcg/5 mcg) PO q12hr; not to exceed 400 mcg/20 mcg daily
Patients on inhaled high-dose corticosteroids: 400 mcg/10 mcg (2 actuations of 200 mcg/5 mcg) PO q12hr; not to exceed 800 mcg/20 mcg daily
Administration
Prime before first use by releasing 4 test sprays into air, shaking well for 5 seconds before each spray; repeat priming if inhaler is unused for >5 days or has been dropped
After inhalation, rinse mouth with water without swallowing
Pediatric dosage forms and strengths
mometasone/formoteroL
aerosoL
- (100mcg/5mcg)/actuation
- (200mcg/5mcg)/actuation
Asthma
<12 years: Safety and efficacy not established
≥12 years: 200 mcg/10 mcg (2 actuations of 100 mcg/5 mcg) PO via metered-dose inhaler q12hr; for more severe asthma, 400 mcg/10 mcg (2 actuations of 200 mcg/5 mcg) PO q12hr; not to exceed 800 mcg/20 mcg daily
Dosing Considerations
Patients on inhaled medium-dose corticosteroids: 200 mcg/10 mcg (2 actuations of 100 mcg/5 mcg) PO q12hr; not to exceed 400 mcg/20 mcg daily
Patients on inhaled high-dose corticosteroids: 400 mcg/10 mcg (2 actuations of 200 mcg/5 mcg) PO q12hr; not to exceed 800 mcg/20 mcg daily
≥12 years: If response is inadequate after 2 weeks, switching to higher-strength formulation may provide additional asthma controL
Dulera (mometasone inhaled/formoterol) adverse (side) effects
1-10%
Nasopharyngitis (4.7%)
Headache (2-4.5%)
Sinusitis (2-3.3%)
<1%
Oral candidiasis
Postmarketing Reports
Cardiac: Angina pectoris, cardiac arrhythmias (eg, atrial fibrillation, ventricular extrasystoles, tachyarrhythmia), QT prolongation, elevated blood pressure (including hypertension)
Metabolic, nutritional: Hypokalemia, hyperglycemia
Respiratory, thoracic, mediastinal: Asthma aggravation (potentially including cough, dyspnea, wheezing, bronchospasm)
Warnings
Black box warnings
Long-acting beta agonists (LABAs), such as formoterol, may increase risk of asthma-related deaths; therefore, they should be used only as additional therapy for patients whose disease is not adequately controlled on other asthma-control medications (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including formoteroL
Because of risk, use of formoterol without concomitant long-term asthma-control medication (eg, inhaled corticosteroid) is contraindicated
Once asthma control is achieved or maintained, assess at regular intervals; step down therapy (eg, discontinue LABA) if possible without loss of asthma control, and maintain on long-term asthma-control medication (eg, inhaled corticosteroid)
Do not use formoterol if asthma is adequately controlled on low- or medium-dose inhaled corticosteroids
Controlled clinical trials suggest that LABAs increase risk of asthma-related hospitalization in pediatric and adolescent patients; if such patients require addition of LABA to inhaled corticosteroid, use fixed-dose combination product containing both inhaled corticosteroid and LABA to ensure adherence
Contraindications
Hypersensitivity
Primary treatment for acute bronchospasm, status asthmaticus, or exercise-induced bronchospasm
Cautions
Increased risk of asthma-related hospitalization and deaths (see Black box warnings)
Do not use to treat acutely deteriorating asthma or acute symptoms; additionally, increased inhaled short-acting beta agonist (SABA) use is marker of deteriorating asthma
Do not use in combination with additional LABA, because of risk of overdose
Localized Candida albicans infections develop in mouth and pharynx in some patients; to reduce risk, mouth must be rinsed after inhalation
Risk of more serious or fatal course of chickenpox or measles exists in susceptible patients (eg, unvaccinated or immunologically unexposed individuals); care must be taken to avoid exposure
Particular care is needed in switching patients from systemic to inhaled corticosteroids; potentially fatal adrenal insufficiency may occur before or afterward; taper withdrawal gradually
During stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should resume PO corticosteroids immediately
Excessive use may suppress hypothalamic-pituitary-adrenal function; monitor closely, especially postoperatively or during periods of stress
Risk of paradoxical bronchospasm, which may be life-threatening; discontinue, and treat immediately with inhaled SABA
Cardiovascular and central nervous system (CNS) effects may occur as consequences of excess beta-adrenergic stimulation; may result in asthma-related death; caution must be exercised in patients with cardiovascular (eg, aneurysm, pheochromocytoma) or convulsive disorders or thyrotoxicosis
Long-term administration of corticosteroids may decrease in bone mineral density; monitor patients at risk
May decrease growth velocity in children
Risk of cataracts, glaucoma, and increased intraocular pressure
Risk of systemic eosinophilic conditions, some consistent with Churg-Strauss syndrome
Risk of transient hypokalemia; supplementation may not be necessary
Pregnancy and lactation
Pregnancy: There are no randomized clinical studies in pregnant women; there are clinical considerations with use in pregnant women In women with poorly or moderately controlled asthma, there is increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate; pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma controL
Lactation: There are no available data on the presence of mometasone furoate, or formoterol fumarate in human milk; the effects on the breastfed child, or the effects on milk production; The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Dulera (mometasone inhaled/formoterol)
Mechanism of action
Mometasone: Glucocorticoid; elicits local anti-inflammatory effects on respiratory tract with minimal systemic absorption
Formoterol: Long-acting selective beta2-adrenergic agonist with rapid onset of action; acts locally as bronchodilator; stimulates intracellular adenyl cyclase, which results in increased cyclic adenosine monophosphate levels, causing relaxation of bronchial smooth muscle and inhibition of release of mast cell mediators
Absorption
Peak plasma time: Mometasone, 1-2 hr; formoterol, 0.5-2 hr
Peak plasma concentration: Mometasone, 20-60 pg/mL; formoterol, 22-125 pg/mL
Distribution
Protein bound: Mometasone, 98-99%; formoterol, 31-38%
Vd: Mometasone, 152 L
Metabolism
Metabolized in liver by CYP3A4 (mometasone); glucuronidation and O-demethylation followed by conjugation (CYP2D6, CYP2C19, CYP2C9, and CYP2A6 involved in O-demethylation)
Elimination
Half-life: Mometasone, 25 hr; formoterol, 9-11 hr
Total body clearance: Mometasone, 12.5 mL/min/kg; formoterol, 217 mL/min/kg
Excretion (mometasone): Urine (8%), feces (74%)
Excretion (formoterol): Urine (59-62%), feces (32-34%)
