brand asmanex twisthaler 220 mcg #60

Uses

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Bronchospasm

Asthma

Mometasone furoate is used for the long-term prevention of bronchospasm in patients with asthma.

Current guidelines include recommendations for assessing asthma severity and asthma control as principal components for effective management of asthma. Assessment of asthma severity is used principally to determine initial therapy; once therapy is initiated, asthma control is assessed to guide decisions about adjusting or maintaining therapy using a stepped-care approach.

In the stepped-care approach to antiasthmatic drug therapy, current asthma management guidelines and most clinicians recommend initiation of a controller drug such as an anti-inflammatory agent, preferably a low-dose orally inhaled corticosteroid (e.g., 88-264, 88-176, or 176 mcg of fluticasone propionate [or its equivalent] daily via a metered-dose inhaler in adolescents and adults, children 5-11 years of age, or children 4 years of age or younger, respectively) as first-line therapy for persistent asthma (i.e., patients with daytime symptoms of asthma more than twice per week, but less than once daily, and nocturnal symptoms of asthma 3 or 4 times per month), supplemented by as-needed use of a short-acting, inhaled β₂-agonist. For equivalent orally inhaled dosages of corticosteroids, .

According to current asthma management guidelines, therapy with a long-acting β₂-agonist such as salmeterol or formoterol generally is recommended in adults and adolescents who have moderate persistent asthma and daily asthmatic symptoms that are inadequately controlled following addition of low-dose inhaled corticosteroids to as-needed inhaled β₂-agonist treatment. However, the National Asthma Education and Prevention Program (NAEPP) recommends that the beneficial effects of long-acting β₂-agonists should be weighed carefully against the increased risk (although uncommon) of severe asthma exacerbations and asthma-related deaths associated with daily use of such agents. Current asthma management guidelines also state that an alternative, but equally preferred option for management of moderate persistent asthma that is not adequately controlled with a low dosage of inhaled corticosteroid is to increase the maintenance dosage to a medium dosage (e.g., exceeding 264 but not more than 440 mcg of fluticasone propionate [or its equivalent] daily via a metered-dose inhaler in adults and adolescents).

Maintenance therapy with an inhaled corticosteroid at medium or high dosages (e.g., exceeding 440 mcg of fluticasone propionate in adults and adolescents or 352 mcg of the drug in children 5-11 years of age [or its equivalent] daily via a metered-dose inhaler) and adjunctive therapy with a long-acting inhaled β₂-agonist is the preferred treatment according to current asthma management guidelines for adults and children 5 years of age or older with severe persistent asthma (i.e., continuous daytime asthma symptoms, nighttime symptoms 7 times per week).

If asthma symptoms in patients with moderate to severe asthma are very poorly controlled (i.e., at least 2-3 exacerbations per year requiring oral corticosteroids), a short course of an oral corticosteroid (3-10 days) may be added to gain prompt control of asthma. Regular use of oral corticosteroids as add-on therapy in adults and children 5 years of age or older with severe asthma who are inadequately controlled with a high-dose inhaled corticosteroid, intermittent oral corticosteroid therapy, and a long-acting inhaled β₂-agonist bronchodilator is suggested, based on consensus and clinical experience. A short (2-week) course of oral corticosteroids may be considered to confirm clinical response prior to implementing long-term oral corticosteroid therapy. Once long-term oral corticosteroid therapy is initiated, the lowest possible effective dosage (i.e., alternate-day or once-daily administration) should be used, and the patient should be monitored carefully for adverse effects. Once asthma is well controlled, repeated attempts should be made to reduce the oral corticosteroid dosage.

Well-controlled clinical studies have shown that oral inhalation of mometasone relieves symptoms of bronchial asthma and improves pulmonary function. Optimum symptomatic relief may require at least 1-2 weeks of continuous mometasone oral inhalation therapy. In corticosteroid-dependent patients, use of mometasone oral inhalation therapy may permit a substantial reduction in the daily maintenance dosage, or discontinuance, of the systemic corticosteroid.

In several studies in patients with mild to moderate asthma who were receiving short-acting β₂-adrenergic agonists alone, mometasone furoate (220 mcg once or twice daily or 440 mcg once daily) produced greater improvements in pulmonary function (e.g., morning predose forced expiratory volume in 1 second [FEV₁], morning or evening peak expiratory flow rate [PEFR]) than placebo. In adolescents and adults with mild to moderate asthma who were receiving inhaled corticosteroids, substitution of mometasone furoate (220 or 440 mcg once daily; 110, 220, or 440 mcg twice daily) for the previous inhaled corticosteroid (at existing or reduced dosage) maintained or improved pulmonary function (e.g., as assessed by morning predose FEV₁). In pediatric patients 4-11 years of age with mild to moderate asthma who were receiving inhaled corticosteroids, substitution of mometasone furoate (110 mcg once or twice daily) for the previous inhaled corticosteroid improved pulmonary function (e.g., change in percentage of predicted FEV₁ from baseline to end point).

In a 12-week, double-blind, placebo-controlled study in patients with severe persistent asthma who were receiving chronic oral therapy with prednisone (approximately 12 mg daily) usually in conjunction with inhaled corticosteroids, discontinuance of prednisone therapy was achieved in 40 or 0% of patients receiving mometasone furoate 440 mcg twice daily or placebo, respectively, following discontinuance of any previous inhaled corticosteroid therapy. At the study end point, prednisone dosage was decreased by 46% in patients receiving mometasone furoate 440 mcg twice daily and increased by 164% in those receiving placebo.

Orally inhaled mometasone should not be used for the primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required.(See Cautions: Contraindications.) Mometasone oral inhalation is not a bronchodilator, and patients should be warned that the drug should not be used for rapid relief of bronchospasm or other acute episodes of bronchospasm.(See Advice to Patients.)

For EENT and topical uses, and , respectively.

Dosage and Administration

General

Dosage of mometasone furoate should be adjusted carefully according to individual requirements and response. The recommended initial and maximum dosages of mometasone furoate in adults and adolescents 12 years of age or older are based on previous asthma therapy. The lowest effective dosage of mometasone should be used, particularly in children and adolescents, since inhaled corticosteroids have the potential to affect growth.(See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Administration

Mometasone furoate inhalation powder is administered by oral inhalation using the Twisthaler breath-actuated dry powder inhalation device. Children should use the Twisthaler under adult supervision as instructed by a clinician.

Removal of the cap of the Twisthaler device (by twisting in a counterclockwise direction) loads a single dose of drug from the drug storage unit into the inhalation channel, making the dose available for administration via inhalation through the mouthpiece. A dose counter will decrease by 1 each time the cap is removed.

Before inhaling the dose, the patient should exhale as completely as possible; the patient should not exhale into the Twisthaler device. The patient should then place the mouthpiece of the inhaler between the lips and inhale quickly and deeply through the inhaler. Patients should not cover the ventilation holes on either side of the inhaler while inhaling the dose. The patient should remove the inhaler from the mouth, hold the breath for a few seconds (i.e., about 10 seconds), then exhale slowly. Patients may not taste, smell, or feel the released powder; therefore, extra doses should not be taken unless otherwise instructed by a clinician. Rinsing the mouth after inhalation of mometasone is advised to minimize potential systemic or local adverse effects. Patients should wipe the mouthpiece dry with a dry cloth or tissue. The Twisthaler device may be closed and reloaded for the next dose by twisting the cap in a clockwise direction until a click is heard. The inhaler should not be washed but should be stored in a dry place. The inhaler should be discarded when every inhalation has been used (when the dose indicator reads ''00'') or 45 days after removal from its foil overwrap pouch, whichever comes first.

When mometasone is administered once daily, the dose should be administered in the evening for optimal efficacy.

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

The dose of mometasone furoate administered as an oral inhalation powder is expressed as the nominal (labeled) dose contained in the Twisthaler device. The actual amount of drug delivered to the lungs depends on factors such as the patient's inspiratory flow. Based on standardized in vitro testing at a flow rate of 30 and 60 L/minute at a constant volume of 2 L, each actuation of the Twisthaler inhaler labeled as containing 220 or 110 mcg of mometasone furoate delivers 200 or 100 mcg of mometasone furoate, respectively, from the mouthpiece. In adults and adolescents 12 years of age or older with asthma of varying severity, mean peak inspiratory flow through the Twisthaler device was 69 L/minute. Mean peak inspiratory flow through the Twisthaler device in pediatric patients 5-8 or 9-12 years of age exceeded 50 or 60 L/minute, respectively.

Asthma

Safety and efficacy of mometasone furoate dosages exceeding those recommended by the manufacturer have not been established.

In children 4-11 years of age, the recommended initial and maximum dosage of mometasone furoate is 110 mcg once daily in the evening, regardless of prior therapy.(See Dosage and Administration: Administration.) Data from a randomized study in such children indicate no additional improvement in lung function with a dosage of 110 mcg twice daily.

The recommended initial dosage of mometasone furoate for adults and adolescents 12 years of age or older who have received or are receiving monotherapy with bronchodilators or inhaled corticosteroids is 220 mcg once daily in the evening. If control of asthma is inadequate after 2 weeks of therapy at the initial dosage in such adults and adolescents, higher dosages may provide additional asthma control; the maximum recommended dosage in these patients is 440 mcg daily, given once daily in the evening or in 2 divided doses.

In adults and adolescents 12 years of age and older who are currently receiving oral corticosteroids, the recommended initial and maximum dosage is 440 mcg twice daily. In order to minimize the potential effects on growth in children and adolescents, dosage of mometasone furoate should be titrated to the lowest effective dosage.

Conversion to Orally Inhaled Therapy in Patients Receiving Systemic Corticosteroids

When orally inhaled corticosteroids are administered to patients receiving systemic corticosteroids, the patient's asthma should be reasonably stable before oral inhalation therapy begins. Initially, mometasone furoate inhalation powder is given concurrently with the maintenance dosage of the systemic corticosteroid. Reduction of the systemic corticosteroid dosage should be initiated at least 1 week after starting mometasone furoate oral inhalation, and dosage reductions should not exceed 2.5 mg daily of prednisone (or its equivalent) each week.Particular care is needed in gradually withdrawing systemic corticosteroids following long-term therapy with these drugs, since death due to adrenal insufficiency has occurred in some individuals in whom systemic corticosteroids were withdrawn too rapidly.(See Withdrawal of Systemic Corticosteroids under Warnings/Precautions: Warnings, in Cautions.)

Cautions

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required.

Known hypersensitivity to mometasone furoate or any ingredient (e.g., lactose) in the formulation. Patients with a history of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not be given mometasone furoate since lactose is used in the manufacture of the dry powder.

Warnings/Precautions

Warnings

Withdrawal of Systemic Corticosteroids

Systemic corticosteroid therapy should be withdrawn gradually in patients being switched from systemic corticosteroids to less systemically available orally inhaled corticosteroids. Patients should be monitored during dosage reduction for objective signs and symptoms of adrenal insufficiency (e.g., fatigue, lassitude, weakness, nausea, vomiting, hypotension) since life-threatening adrenal insufficiency could occur. Lung function (forced expiratory volume in 1 second [FEV₁] or peak expiratory flow rate [PEFR]), adjunctive β₂-adrenergic agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic corticosteroid therapy.In most patients, several months are required for total recovery of HPA function following withdrawal of systemic corticosteroid therapy. Patients who have been maintained on a corticosteroid dosage equivalent to 20 mg or more of prednisone daily may be most susceptible to adrenal insufficiency, particularly when systemic corticosteroids have been almost completely withdrawn. These patients should be carefully monitored during and for a number of months after withdrawal of systemic corticosteroids for corticosteroid withdrawal symptoms (e.g., joint pain, muscular pain, lassitude, depression); acute adrenal insufficiency during exposure to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with acute electrolyte loss; or symptomatic exacerbation of allergic conditions previously controlled by systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

In patients who have been withdrawn from systemic corticosteroids, reinitiation of systemic corticosteroid therapy will likely be necessary during periods of stress or severe asthmatic attack. Since glucocorticoids can reduce HPA-axis response to stress, supplementation with a systemic corticosteroid in patients undergoing such stress is recommended. Recommended dosages of orally inhaled mometasone provide less than normal physiologic amounts of glucocorticoid systemically and do not provide mineralocorticoid activity sufficient for coping with these emergencies.

Immunosuppressed Patients

Patients who are taking immunosuppressant drugs have increased susceptibility to infections compared with healthy individuals, and certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients. Patients receiving corticosteroids who are potentially immunosuppressed and who have not had these diseases or been properly vaccinated should be warned of the risk of exposure to certain infections (e.g., chickenpox, measles) and take particular care to avoid exposure. If exposure to varicella (chickenpox) or measles occurs in susceptible individuals, administration of varicella zoster immune globulin (VZIG) or pooled IM immunoglobulin (IG), respectively, may be indicated. If chickenpox develops, treatment with an antiviral agent may be considered. It is not known how the dosage, route, and duration of administration of a corticosteroid, or the contribution of the underlying disease and/or prior corticosteroid therapy, affect the risk of developing a disseminated infection. For additional information, and also , in the Corticosteroids General Statement 68:04.

Bronchospasm

As with other inhaled drugs for asthma, bronchospasm may occur, resulting in an immediate increase in wheezing following oral inhalation of mometasone. If bronchospasm occurs, appropriate treatment (e.g., use of a rapid-acting inhaled β₂-adrenergic agonist) should be instituted immediately, and mometasone therapy should be discontinued.

Acute Exacerbations of Asthma

Orally inhaled mometasone should not be used as a bronchodilator and is not indicated for emergency use (e.g., status asthmaticus) or relief of acute bronchospasm. Acute asthma symptoms should be treated with a short-acting β₂-agonist bronchodilator. If inadequate control of symptoms persists with supplemental β₂-agonist bronchodilator therapy, prompt reevaluation of asthma therapy is required. Such reevaluation may include initiating systemic corticosteroids.

Sensitivity Reactions

Cases of allergic reaction, facial edema, urticaria, hypersensitivity, and throat tightness have been reported with mometasone furoate oral inhalation therapy in clinical trials and during postmarketing experience.

General Precautions

Infections

Localized candidal infections of the mouth and pharynx have been reported in patients receiving orally inhaled mometasone therapy. When infection occurs, appropriate local or systemic treatment of the infection may be necessary and interruption of orally inhaled mometasone therapy may be required. Inhaled corticosteroid therapy should be used with caution, if at all, in patients with clinical or asymptomatic Mycobacterium tuberculosis infections of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.

Ophthalmic Effects

Glaucoma, increased intraocular pressure, and cataracts have been reported rarely in patients receiving orally inhaled corticosteroids. Careful monitoring is recommended in patients who have a change in vision and in those with a history of increased intraocular pressure, glaucoma, and/or cataracts.

Systemic Corticosteroid Effects

Because minimal absorption of mometasone into circulation occurs at recommended dosages, manifestations of hypercorticism and HPA axis suppression could occur when recommended dosages are exceeded over prolonged periods of time or in particularly sensitive individuals. If such changes occur, the dosage of mometasone should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroid dosage and management of asthma symptoms. Particular care should be taken in monitoring patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

Musculoskeletal Effects

Long-term use of orally inhaled corticosteroids, including mometasone, may affect normal bone metabolism, resulting in a loss of bone mineral density. Although appreciable reduction in lumbar spine bone mineral density was noted in a 2-year study in adults receiving 220 mcg of mometasone furoate twice daily, this adverse effect was not confirmed in another 2-year study in adults receiving 440 mcg of the drug twice daily. The manufacturer of mometasone states that patients with major risk factors for decreased bone mineral density, such as family history of osteoporosis, prolonged immobilization, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, corticosteroids), should be monitored and treated using established standards of care.

Specific Populations

Pregnancy

Category C. Hypoadrenalism may occur in infants of mothers receiving substantial oral corticosteroid dosages during pregnancy. These infants should be carefully monitored.

Lactation

It is not known whether mometasone is distributed into milk; however, other corticosteroids are distributed into milk. Caution is advised if mometasone is administered in nursing women.

Pediatric Use

Safety and efficacy of mometasone oral inhalation powder have not been established in children younger than 4 years of age.

Use of corticosteroids may lead to suppression of growth in children and adolescents. Therefore, pediatric patients receiving prolonged therapy with orally inhaled mometasone should be monitored periodically (e.g., via stadiometry) for possible adverse effects on growth and development. The benefits of corticosteroid therapy should be weighed against the possibility of growth suppression and the availability of safe and effective alternative therapies. Pediatric patients should be maintained on the lowest possible dosage of mometasone that controls asthma symptoms.

Geriatric Use

Although no overall differences in safety and efficacy of orally inhaled mometasone were observed relative to younger adults, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

Common Adverse Effects

Adverse effects occurring in at least 3% of adults and adolescents 12 years of age or older who had been on bronchodilators and/or inhaled corticosteroids and who received mometasone in controlled clinical trials include headache, allergic rhinitis, pharyngitis, upper respiratory tract infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, dyspepsia, myalgia, abdominal pain, and nausea.

Adverse effects occurring in at least 3% of children 4-11 years of age who had been on bronchodilators and/or inhaled corticosteroids and who received mometasone in controlled clinical trials include fever, allergic rhinitis, upper respiratory tract infection, abdominal pain, and vomiting.

Drug Interactions

Drugs Affecting Hepatic Microsomal Enzymes

Drugs that Inhibit Isoenzyme CYP3A4

Since mometasone furoate is principally metabolized in the liver by the cytochrome P-450 (CYP) 3A4 isoenzyme, concomitant use with drugs that are potent inhibitors (e.g., ketoconazole) of the CYP3A4 isoenzyme may result in increased plasma mometasone concentrations.