Mometasone and Formoterol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol, for oral inhalation:

Dulera: Mometasone furoate 100 mcg and formoterol fumarate dihydrate 5 mcg per inhalation (8.8 g, 13 g)

Dulera: Mometasone furoate 200 mcg and formoterol fumarate dihydrate 5 mcg per inhalation (8.8 g, 13 g)

Pharmacology

Mechanism of Action

Formoterol: Relaxes bronchial smooth muscle by selective action on beta₂ receptors with little effect on heart rate. Formoterol has a long-acting effect.

Mometasone: A corticosteroid which controls the rate of protein synthesis, depresses the migration of polymorphonuclear leukocytes/fibroblasts, and reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.

Use: Labeled Indications

Asthma: Treatment of asthma in patients ≥5 years of age

Limitations of use: Not indicated for the relief of acute bronchospasm.

Use: Off Label

Chronic obstructive pulmonary disease (COPD) (stable)yes

Based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 update to the guidelines for the management of COPD, long-term monotherapy with inhaled corticosteroids is not recommended. Regular treatment with inhaled corticosteroids has been shown to increase the risk of pneumonia, especially in those with severe disease. Per the 2018 GOLD guideline update, combining two long-acting bronchodilators (ie, long-acting beta agonist [LABA] and long-acting antimuscarinic [LAMA]) is more effective in reducing exacerbations than monotherapy or the combination of inhaled corticosteroid and LABA. If symptoms are inadequately controlled on a bronchodilator regimen, addition of an inhaled corticosteroid may be considered. Triple inhaled therapy of inhaled corticosteroid/LAMA/LABA has been shown to improve lung function, symptoms, and health status and reduces exacerbations compared to inhaled corticosteroid/LABA or LAMA monotherapy GOLD 2018.

Contraindications

Hypersensitivity to mometasone, formoterol, or any component of the formulation; status asthmaticus or other acute episodes of asthma.

Canadian labeling: Additional contraindications (not in US labeling): Cardiac tachyarrhythmias; untreated systemic fungal, bacterial, viral or parasitic infections, active tuberculous infection of the respiratory tract, or ocular herpes simplex.

Documentation of allergenic cross-reactivity for corticosteroids and/or sympathomimetics are limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Asthma: Note: The recommended starting dose is based upon asthma severity and previous asthma therapy (including inhaled corticosteroid dosage); may increase dose after 2 weeks of therapy in patients who are not adequately controlled. Titrate to the lowest effective dose once asthma is controlled. The maximum dose is based on the formoterol component; to increase the dose of the inhaled glucocorticoid component, a separate inhaler with a higher mometasone dose per inhalation must be prescribed.

Oral inhalation: Metered-dose inhaler: Two inhalations twice daily of mometasone 100 mcg/formoterol 5 mcg or mometasone 200 mcg/formoterol 5 mcg (maximum dose: mometasone 200 mcg/formoterol 5 mcg [2 inhalations] twice daily).

Chronic obstructive pulmonary disease (stable) (off-label use): Oral inhalation: Metered-dose inhaler: Mometasone 200 mcg/formoterol 10 mcg to mometasone 400 mcg/formoterol 10 mcg twice daily (Doherty 2012; GOLD 2018).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Patients receiving mometasone/formoterol twice daily should not use additional formoterol or other inhaled, long-acting beta-2 agonists (eg, arformoterol, salmeterol) for any other reason. The maximum dose is based on the formoterol component; to increase the dose of the inhaled glucocorticoid component, a separate inhaler with a higher mometasone dose per inhalation must be prescribed.

Asthma, maintenance treatment: Note: Initial dose is based on previous asthma therapy, current control, and risk of exacerbation; may increase dose after 2 weeks of therapy in patients who are not adequately controlled; to increase the dose of the inhaled glucocorticoid component, a separate inhaler with a higher mometasone dose per inhalation must be prescribed; titrate to the lowest effective dose once asthma is controlled:

Children 5 years to <12 years: Note: Do not administer more than 2 inhalations twice daily.

Mometasone 50 mcg/formoterol 5 mcg: Oral inhalation: 2 inhalations twice daily.

Children ≥12 years and Adolescents: Note: Do not administer more than 2 inhalations twice daily.

Mometasone 100 mcg/formoterol 5 mcg: Oral inhalation: 2 inhalations twice daily.

Mometasone 200 mcg/formoterol 5 mcg: Oral inhalation: 2 inhalations twice daily.

Administration

Oral inhalation: Metered-dose inhaler: For oral inhalation only; administer every morning and evening, ~12 hours apart. Prior to first use, prime inhaler by releasing 4 test sprays into the air; shake well before each spray. Inhaler must be reprimed if not used for >5 days; shake well before each use. Discard inhaler after the labeled number of inhalations have been used. Use canister only with provided actuator; do not use with canisters or actuators from other products. Do not remove the canister from the actuator; the correct amount of medication may not be discharged; the dose counter may not function properly; reinsertion may cause the dose counter to count down by 1 and discharge a puff.

Delivery of dose: Place mouthpiece between lips and inhale deeply and hold breath for up to 10 seconds (or as long as you comfortably can); do not exhale through inhaler. Wait ≥30 seconds prior to the second inhalation dose; may use with or without spacer. Rinse mouth/oropharynx with water and spit out rinse solution (without swallowing) after each use. Do not wash inhaler with water; clean mouthpiece using a dry wipe every 7 days.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F); temperatures above 49°C (120°F) may cause bursting. Contents under pressure; do not puncture, incinerate, or store near heat or open flame. Discard inhaler after the labeled number of inhalations have been used (the dose counter will read “0”). The 120-actuation inhaler may be stored in any position; store the 60-actuation inhaler with the mouthpiece down or in a horizontal position after priming.

Drug Interactions

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta2-Agonists (Long-Acting): May enhance the adverse/toxic effect of other Beta2-Agonists (Long-Acting). Avoid combination

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Formoterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Formoterol. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

Cosyntropin: Corticosteroids (Orally Inhaled) may diminish the diagnostic effect of Cosyntropin. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Orally Inhaled). Management: Orally inhaled fluticasone propionate with a strong CYP3A4 inhibitor is not recommended. Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Desmopressin: Corticosteroids (Orally Inhaled) may enhance the hyponatremic effect of Desmopressin. Avoid combination

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Inhalational Anesthetics: May enhance the arrhythmogenic effect of Formoterol. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loop Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Long-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting beta₂ agonists for 36 hours before methacholine use. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Theophylline Derivatives: May enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Orally Inhaled) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tobacco (Smoked): May diminish the therapeutic effect of Corticosteroids (Orally Inhaled). Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

Also see individual agents.

1% to 10%:

Central nervous system: Voice disorder (adolescents and adults: 4% to 5%), headache (≥3%)

Infection: Influenza (children: ≥3%)

Respiratory: Nasopharyngitis (adolescents and adults: 5%), upper respiratory tract infection (children: ≥3%), sinusitis (adolescents and adults: 2% to 3%)

<1%, postmarketing, and/or case reports: Anaphylaxis, angina pectoris, angioedema, atrial fibrillation, blurred vision, cardiac arrhythmia, exacerbation of asthma, hyperglycemia, hypertension, hypokalemia, hypotension, oropharyngeal candidiasis, paradoxical bronchospasm, prolonged QT interval on ECG, pruritus, severe hypotension, skin rash, tachyarrhythmia, type I hypersensitivity reaction, type IV hypersensitivity reaction, ventricular premature contractions

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving ≥20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. Do not use this product to transfer patients from oral corticosteroid therapy.
• Asthma-related deaths: The use of long-acting beta-2 agonists (LABAs) as monotherapy is associated with an increased risk of asthma-related deaths. In a large, randomized, placebo-controlled US trial, salmeterol was associated with an increase in asthma-related deaths (SMART 2006); risk is considered a class effect of LABA monotherapy. Additional data from other clinical trials suggest LABA monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. However, data from large randomized, double-blind, active-controlled trials do not show a significant increase in the risk of serious asthma-related events (including hospitalizations, intubations, and death) in adult, adolescent, and pediatric (aged 4 to 11 years) patients when fixed-dose LABAs are used with inhaled corticosteroids combined in a single inhaler compared with inhaled corticosteroid monotherapy. In addition, patients receiving fluticasone/salmeterol had fewer severe asthma exacerbations compared with patients receiving fluticasone alone (Peters 2016; Stempel 2016a; Stempel 2016b). Current guidelines recommend the use of an inhaled corticosteroid before adding an LABA (GINA 2018; NIH/NHLBI 2007). Assess patients at regular intervals once asthma control is maintained on combination therapy to determine if step-down therapy is appropriate (without loss of asthma control), and the patient can be maintained on an inhaled corticosteroid only. LABAs are not appropriate in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.
• Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.
• Hypersensitivity reactions: Immediate hypersensitivity reactions (allergic dermatitis, angioedema, bronchospasm, flushing, rash, urticaria) have been reported.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines. Avoid use if possible in patients with ocular herpes; active or quiescent tuberculosis infections of the respiratory tract; or untreated viral, fungal, or bacterial or parasitic systemic infections. Exposure to chickenpox or measles should be avoided; if the patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin or pooled intravenous immunoglobulin, may be indicated; if chickenpox develops, treatment with antiviral agents may be considered. If exposure to measles, prophylaxis with pooled intramuscular immunoglobulin may be indicated.
• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert 2002).
• Oral candidiasis: Local oropharyngeal Candida infections have been reported; if this occurs, treat appropriately while continuing mometasone/formoterol therapy. Patients should be instructed to mouth/oropharynx with water (without swallowing) and spit out rinse solution after each use.
• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.
• Serious effects/fatalities: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
• Vasculitis: Rare cases of vasculitis (eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]) or other systemic eosinophilic conditions can occur; often associated with decrease and/or withdrawal of oral corticosteroid therapy following initiation of inhaled corticosteroid.

Disease-related concerns:

• Asthma: Supplemental steroids (oral or parenteral) may be needed during stress or severe asthma attacks. Not to be used in status asthmaticus or for the relief of acute bronchospasm.
• Bone density: Use with caution in patients with major risk factors for decreased bone mineral count such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (eg, anticonvulsants or oral corticosteroids); high doses and/or long-term use of inhaled corticosteroids have been associated with decreases in bone mineral density.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, or hypertension); beta agonists may cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta-2 agonists may also increase risk of arrhythmias and ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. Use with caution following acute myocardial infarction; corticosteroids have been associated with myocardial rupture.
• Diabetes: Use with caution in patients with diabetes mellitus; beta-2 agonists may increase serum glucose and aggravate ketoacidosis; corticosteroids may alter glucose production/regulation leading to hyperglycemia.
• Gastrointestinal disease: Use corticosteroids with caution in patients with GI diseases (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.
• Hepatic impairment: Monitor patients with hepatic impairment; may lead to accumulation of mometasone.
• Hypokalemia: Use with caution in patients with hypokalemia; beta-2 agonists may decrease serum potassium (transient), possibly through intracellular shunting.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred, especially during initial treatment with corticosteroids.
• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Consider routine eye exams in chronic users.
• Pheochromocytoma: Use with caution in patients with pheochromocytoma; beta agonists may stimulate the sympathetic nervous system.
• Seizure disorders: Use with caution in patients with seizure disorders; beta agonists may result in CNS stimulation/excitation.
• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: LABAs may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Orally inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients (~1 centimeter per year [range 0.3 to 1.8 cm per year] and related to dose and duration of exposure). To minimize the systemic effects of orally inhaled corticosteroids, each patient should be titrated to the lowest effective dose. Growth should be routinely monitored in pediatric patients.

Other warnings/precautions:

• Appropriate use: Do not use for acute bronchospasm. Short-acting beta-2 agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Do not initiate in patients with significantly worsening or acutely deteriorating asthma.
• Discontinuation of systemic corticosteroid therapy: Withdraw systemic corticosteroid therapy with gradual tapering of dose. Monitor lung function, beta agonist use, asthma symptoms, and for signs and symptoms of adrenal insufficiency (fatigue, lassitude, weakness, nausea and vomiting, hypotension) during withdrawal.

Monitoring Parameters

FEV₁, peak flow meter, and/or other pulmonary function tests; monitor growth in pediatric patients, symptom relief, monitor for increased use if short-acting beta₂-adrenergic agonists (may be a sign of asthma deterioration); HPA axis suppression; bone mineral density; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium; eye exams (chronic users)

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted with this combination. See individual agents.

Patient Education

What is this drug used for?

• It is used to treat asthma. This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

Frequently reported side effects of this drug

• Throat irritation
• Nasal irritation
• Flu-like symptoms
• Common cold symptoms

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Chest pain
• Fast heartbeat
• Abnormal heartbeat
• Anxiety
• Vision changes
• Tremors
• Seizures
• Severe dizziness
• Passing out
• Severe headache
• Trouble sleeping
• Severe nausea
• Vomiting
• Thrush
• Eye pain
• Severe eye irritation
• Flushing
• Loss of strength and energy
• Trouble breathing
• Wheezing
• Coughing
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.