mometasone inhaled/formoterol (Rx)

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)

Vision blurred

Contraindications

Hypersensitivity

Primary treatment for acute bronchospasm, status asthmaticus, or exercise-induced bronchospasm

Cautions

Risk of LABAs used as monotherapy

• Use of LABAs as monotherapy (without inhaled corticosteroids) for asthma is associated with an increased risk of asthma-related death
• Data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patient
• These findings are considered a class effect of LABA monotherapy
• When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone

Fungal infections

• Localized infections of the mouth and pharynx with Candida albicans reported; if oropharyngeal candidiasis develops, treat with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment; at times therapy may need to be interrupted
• To reduce risk of oropharyngeal candidiasis, after dosing, advise patients to rinse their mouth with water and spit out the contents without swallowing

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

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals; 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

Because of possibility of systemic absorption of inhaled corticosteroids, patients should be observed carefully for any evidence of systemic corticosteroid effects; particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response

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; consider referral to an ophthalmologist in patients who develop ocular symptoms or use therapy long term

Risk of systemic eosinophilic conditions, some consistent with Churg-Strauss syndrome

Risk of transient hypokalemia; supplementation may not be necessary

Exercise caution when considering coadministration with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, telithromycin); consider benefit of coadministration versus potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side effects

Prolonged treatment with corticosteroids associated with development of Kaposi sarcoma; consider discontinuing therapy if it occurs

Psychiatric disturbances reported with corticoid use; therapy may exacerbate preexisting psychiatric conditions

Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex infections may occur; more serious or even fatal course of chickenpox or measles can occur in susceptible patients; use with caution in patients with these infections because of potential for worsening of these infections

Risk of impaired adrenal function when transferring from oral steroids; taper patients slowly from systemic corticosteroids if transferring to inhaler

Hypercorticism and adrenal suppression; may occur with very high dosages or at regular dosage in susceptible individuals

Decreases in bone mineral density; monitor patients with major risk factors for decreased bone mineral content

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.

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%)

Oral Inhalation Preparation

Priming

• Prime inhaler before first use or when inhaler is unused for >5 days
• Release 4 test puffs into air, away from face
• Remove cap; shake well for 5 sec before each test puff

Instructions

• Check mouthpiece for objects before use
• Make sure canister is fully inserted
• Shake well before each use

Oral Inhalation Administration

For oral inhalation only

Remove cap; place middle or index finger on canister top while placing thumb underneath mouthpiece

Breathe out fully through your mouth, expelling as much air from lungs as possible; hold inhaler upright, placing the mouthpiece fully into the mouth, closing your lips around it

While pushing firmly on canister top, continue breathing in slowly until lungs are full; avoid breathing out

Hold breath as comfortably possible, up to 10 sec

Remove inhaler from mouth; breathe through nose while keeping lips closed

Repeating dose

• Wait at least 30 seconds prior preceding second puff
• Shake well prior to use; repeat steps (see under Oral Inhalation Administration)
• Replace the cap after use
• When finished administering 2 puffs, rinse mouth out with water (do not swallow water)

Cleaning

Wash and dry mouthpiece at least weekly

When mouthpiece becomes blocked, wash mouthpiece thoroughly

Storage

Store at room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)