warnings and cautions
5 WARNINGS AND PRECAUTIONS Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation. ( 5.1 ) Deterioration of asthma and acute episodes: Do not use for relief of acute symptoms. Patients require immediate re-evaluation during rapidly deteriorating asthma. ( 5.2 ) Immunosuppression: Potential worsening of existing tuberculosis, fungal, bacterial, viral, parasitic infections or ocular herpes simplex. Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.3 ) Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from systemic corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to ArmonAir Digihaler. ( 5.4 ) Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue ArmonAir Digihaler slowly. ( 5.5 ) Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. ( 5.7 ) Monitor growth of pediatric patients. ( 5.8 ) Close monitoring for glaucoma and cataracts is warranted. ( 5.9 ) Paradoxical bronchospasm: Discontinue ArmonAir Digihaler and institute alternative therapy if paradoxical bronchospasm occurs. ( 5.10 ) 5.1 Oropharyngeal Candidiasis In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with fluticasone propionate MDPI. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with ArmonAir Digihaler continues, but at times therapy with ArmonAir Digihaler may need to be interrupted. Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis. 5.2 Acute Asthma Episodes ArmonAir Digihaler is not indicated for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta 2 -agonist, not ArmonAir Digihaler, should be used to relieve acute symptoms such as shortness of breath. When prescribing ArmonAir Digihaler, the physician must provide the patient with an inhaled, short-acting beta 2 -agonist (e.g., albuterol) for treatment of acute symptoms, despite regular twice-daily use of ArmonAir Digihaler. Instruct patients to contact their physicians immediately if episodes of asthma not responsive to bronchodilators occur during the course of treatment with ArmonAir Digihaler. During such episodes, patients may require therapy with oral corticosteroids. 5.3 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 patients who have not had these diseases or who have not been 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 a patient is exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (see the respective Prescribing Information for VZIG and IG). 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 infections of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. 5.4 Transferring Patients from Systemic Corticosteroid Therapy HPA Suppression/Adrenal Insufficiency Particular care is needed for patients who are transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma 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 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 ArmonAir Digihaler 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 that is necessary for coping with these emergencies. During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction. These patients should also be instructed to carry a medical identification warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack. Patients requiring systemic corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to ArmonAir Digihaler. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with ArmonAir Digihaler. Lung function (mean forced expiratory volume in 1 second [FEV 1 ] or morning peak expiratory flow [AM PEF]), beta‑agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic 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 ArmonAir Digihaler may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, 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, depression) despite maintenance or even improvement of respiratory function. 5.5 Hypercorticism and Adrenal Suppression ArmonAir Digihaler will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since ArmonAir Digihaler is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of ArmonAir Digihaler in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing ArmonAir Digihaler. Because of the possibility of significant systemic absorption of inhaled corticosteroids, patients treated with ArmonAir Digihaler 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. It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, the dosage of ArmonAir Digihaler should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and for management of asthma symptoms. 5.6 Hypersensitivity Reactions, Including Anaphylaxis Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of ArmonAir Digihaler. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder products containing lactose; therefore, patients with severe milk protein allergy should not use ArmonAir Digihaler [see Contraindications ( 4 )]. 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. The clinical significance of small changes in BMD with regard to long‑term consequences, such as fracture, 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, oral corticosteroids) should be monitored and treated with established standards of care. 5.8 Effect on Growth Orally inhaled corticosteroids, including ArmonAir Digihaler, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving ArmonAir Digihaler routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ArmonAir Digihaler, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration ( 2 ) and Use in Specific Populations ( 8.4 )]. 5.9 Glaucoma and Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids, including fluticasone propionate. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. 5.10 Paradoxical Bronchospasm As with other inhaled medicines, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with ArmonAir Digihaler, it should be treated immediately with an inhaled, short-acting bronchodilator; ArmonAir Digihaler should be discontinued immediately; and alternative therapy should be instituted. 5.11 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ArmonAir Digihaler is not recommended because increased systemic corticosteroid adverse effects may occur [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . 5.12 Eosinophilic Conditions and Churg-Strauss Syndrome In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with Churg‑Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other inhaled corticosteroids in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.