ASMANEX

5 WARNINGS AND PRECAUTIONS Candida albicans infection of the mouth and pharynx. Monitor patients periodically for signs of adverse effects in the mouth and pharynx. After administration, advise patients to rinse mouth with water and spit out contents without swallowing. ( 5.1 ) Deterioration of asthma or acute episodes: ASMANEX TWISTHALER should not be used for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. ( 5.2 ) Hypersensitivity reactions including anaphylaxis, angioedema, pruritus, and rash have been reported with the use of ASMANEX TWISTHALER. Discontinue ASMANEX TWISTHALER if such reactions occur. ( 5.3 ) Potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex. More serious or even fatal course of chickenpox or measles in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections. ( 5.4 ) Risk of impaired adrenal function when transferring from oral steroids to inhaled corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to ASMANEX TWISTHALER. ( 5.5 ) Hypercorticism, suppression of hypothalamic-pituitary-adrenal (HPA) function, with very high dosages or at the regular dosage in susceptible individuals. If such changes occur discontinue ASMANEX TWISTHALER slowly. ( 5.6 ) Reduction in bone mineral density with long-term administration. Monitor patients with major risk factors for decreased bone mineral content. ( 5.7 ) Suppression of growth in children. Monitor growth routinely in pediatric patients receiving ASMANEX TWISTHALER. ( 5.8 ) Glaucoma and cataracts. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX TWISTHALER long term. ( 5.9 ) Paradoxical bronchospasm may occur with ASMANEX TWISTHALER. Treat bronchospasm immediately with a fast-acting inhaled bronchodilator and discontinue use of ASMANEX TWISTHALER. ( 5.10 ) Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with ASMANEX TWISTHALER. ( 5.11 ) 5.1 Oropharyngeal Candidiasis In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans occurred in 195 of 3007 patients treated with ASMANEX TWISTHALER. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while remaining on treatment with ASMANEX TWISTHALER therapy, but at times therapy with the ASMANEX TWISTHALER may need to be interrupted. After administration, advise patients to rinse the mouth with water and spit out contents without swallowing. 5.2 Acute Asthma Episodes ASMANEX TWISTHALER is not a bronchodilator and is not indicated for rapid relief of bronchospasm or other acute episodes of asthma. A short acting beta 2 -agonist, such as albuterol, should be available at all times to treat acute asthma symptoms. Instruct patients to contact their physician immediately if episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with ASMANEX TWISTHALER. During such episodes, patients may require therapy with oral corticosteroids. 5.3 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions including rash, pruritus, angioedema, and anaphylactic reaction have been reported with use of ASMANEX TWISTHALER. Discontinue ASMANEX TWISTHALER if such reactions occur [see Contraindications (4) and Adverse Reactions (6.2) ]. ASMANEX TWISTHALER contains small amounts of lactose, which contains trace levels of milk proteins. In postmarketing experience with ASMANEX TWISTHALER, anaphylactic reactions in patients with milk protein allergy have been reported [see Contraindications (4) and Adverse Reactions (6.2) ]. 5.4 Immunosuppression and Risk of Infections Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or who are not properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. 5.5 Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency Particular care is needed for patients who are transferred from systemically active corticosteroids to ASMANEX TWISTHALER because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function. Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although ASMANEX TWISTHALER may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity necessary for coping with these emergencies. During periods of stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to ASMANEX TWISTHALER. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during treatment with ASMANEX TWISTHALER [see Dosage and Administration (2.1) ] . Lung function (FEV 1 or PEFR), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids Transfer of patients from systemic corticosteroid therapy to ASMANEX TWISTHALER may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. Corticosteroid Withdrawal Symptoms During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function. 5.6 Hypercorticism and Adrenal Suppression ASMANEX TWISTHALER will often help control asthma symptoms with less suppression of HPA function than therapeutically similar oral doses of prednisone. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing ASMANEX TWISTHALER. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear in a small number of patients, particularly when ASMANEX TWISTHALER is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of ASMANEX TWISTHALER should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma. 5.7 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate. The clinical significance of small changes in BMD with regard to long-term outcomes is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. In a 2-year double-blind study in 103 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (baseline FEV 1 85%–88% predicted), treatment with ASMANEX TWISTHALER 220 mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD at the end of the treatment period compared to placebo. The mean change from baseline to endpoint in the lumbar spine BMD was -0.015 (-1.43%) for the ASMANEX TWISTHALER group compared to 0.002 (0.25%) for the placebo group. In another 2-year double-blind study in 87 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (baseline FEV 1 82%–83% predicted), treatment with ASMANEX TWISTHALER 440 mcg twice daily demonstrated no statistically significant changes in lumbar spine BMD at the end of the treatment period compared to placebo. The mean change from baseline to endpoint in the lumbar spine BMD was -0.018 (-1.57%) for the ASMANEX TWISTHALER group compared to -0.006 (-0.43%) for the placebo group. 5.8 Effect on Growth Orally inhaled corticosteroids, including ASMANEX TWISTHALER, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving ASMANEX TWISTHALER routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ASMANEX TWISTHALER, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4) ] . 5.9 Glaucoma and Cataracts In clinical trials, glaucoma, increased intraocular pressure, and cataracts have been reported in 8 of 3007 patients following the administration of ASMANEX TWISTHALER. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use ASMANEX TWISTHALER long term. 5.10 Paradoxical Bronchospasm As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with ASMANEX TWISTHALER, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with ASMANEX TWISTHALER should be discontinued and alternative therapy instituted. 5.11 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of ASMANEX TWISTHALER with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, cobicistat-containing products, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systemic exposure to mometasone furoate may occur [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] .