warnings and cautions
5 WARNINGS AND PRECAUTIONS Local Nasal Adverse Reactions: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma. ( 5.1 ) Glaucoma and Cataracts may occur with long-term use. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use XHANCE long-term. ( 5.2 ) Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur. ( 5.3 ) Immunosuppression and Risk of Infection: potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; 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. ( 5.4 ) Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly. ( 5.5 ) Assess for decrease in bone mineral density initially and periodically thereafter. ( 5.7 ) 5.1 Local Nasal Adverse Reactions Epistaxis, Nasal Erosions and Ulcerations In placebo-controlled clinical trials of 16 weeks duration, epistaxis, nasal erosions, and nasal ulcerations were reported more frequently in patients treated with XHANCE than those who received placebo [see Adverse Reactions ( 6.1 )] . Nasal Septal Perforation Nasal septal perforations have been reported in patients following the nasal application of XHANCE. In placebo-controlled clinical trials of 16 weeks duration, nasal septal perforation was reported in 1 (0.3%) patient treated with XHANCE compared with none treated with placebo. The patient had a prior history of nasal/sinus surgery. Three (0.3%) patients treated with XHANCE in uncontrolled, open-label trials of 3 to 12 months duration developed nasal septal perforations. As with any long term topical treatment of the nasal cavity, patients using XHANCE over several months or longer should be examined periodically for possible changes in the nasal mucosa. If a septal perforation is noted, discontinue XHANCE. Avoid spraying XHANCE directly on the septum. Candida Infection In clinical trials with XHANCE, localized infections with Candida albicans have been observed. Eight (0.9%) patients in uncontrolled, open-label trials of 3 to 12 months duration developed Candida albicans infections (nasal, pharyngeal, esophageal or intestinal). If such an infection develops, it may require treatment with appropriate local therapy and discontinuation of XHANCE. Patients using XHANCE should be examined periodically for evidence of Candida infection in the nasal and oropharyngeal mucosa. Impaired Wound Healing Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcerations, nasal surgery, or nasal trauma should avoid using XHANCE until healing has occurred. 5.2 Glaucoma and Cataracts Nasal and inhaled corticosteroids, including fluticasone propionate, may result in the development of glaucoma and/or cataracts. In placebo-controlled clinical trials of 16 weeks duration, cataracts were reported in 4 (1.2%) patients treated with XHANCE, compared with 3 (1.9%) patients treated with placebo. Among these patients, 2 patients treated with XHANCE reported subcapsular cataracts compared with none treated with placebo. Eleven patients (1.2%) in uncontrolled, open-label trials of 3 to 12 months duration developed new or worsening cataracts, of which none were subcapsular. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure (IOP), glaucoma, and/or cataracts. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use XHANCE long-term. 5.3 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. XHANCE is contraindicated in patients with known hypersensitivity to fluticasone propionate or any of the ingredients of XHANCE. Discontinue XHANCE if such reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) occur [see Contraindications ( 4 ) and Adverse Reactions ( 6.1 )] . 5.4 Immunosuppression and Risk of Infection Persons who are using drugs that suppress the immune system, such as corticosteroids, including XHANCE, are more susceptible to infections than healthy individuals and may experience a worsening of existing infections. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible adults using corticosteroids. In such adults who have not had these diseases or 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) 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. Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex [see Adverse Reactions ( 6.1 )] . 5.5 Hypercorticism and Adrenal Suppression Hypercorticism and adrenal suppression may occur when nasal corticosteroids, such as XHANCE, are used at higher than recommended dosages or in susceptible individuals at recommended dosages. Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, recommended dosages of XHANCE should not be exceeded to avoid hypothalamic-pituitary-adrenal (HPA) dysfunction. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of pulmonary treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing XHANCE. Patients treated with XHANCE should be observed carefully for any evidence of systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis). If such effects occur, the dosage of XHANCE should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of nasal symptoms should be considered. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response. The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression). After withdrawal from systemic corticosteroids, a number of months are required for recovery of HPA function. Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress such as trauma, surgery, infection (particularly gastroenteritis), or other conditions associated with severe electrolyte loss. In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms [see Adverse Reactions ( 6.1 ) and Clinical Pharmacology ( 12.2 )] . 5.6 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, conivaptan, lopinavir, voriconazole) with XHANCE is not recommended because increased systemic corticosteroid adverse effects may occur [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )] . 5.7 Reduction in Bone Mineral Density Decreases in bone mineral density (BMD) have been observed with long-term oral inhalation of products containing corticosteroids into the lungs. 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, postmenopausal status, tobacco use, advanced age, poor nutrition, 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. A 2-year trial in 160 patients (females aged 18 to 40 years, males aged 18 to 50 years) with asthma receiving chlorofluorocarbon (CFC)-propelled fluticasone propionate inhalation aerosol 88 or 440 mcg twice daily demonstrated no statistically significant changes in BMD at any time point (24, 52, 76, and 104 weeks of double-blind treatment) as assessed by dual-energy x-ray absorptiometry at lumbar regions L1 through L4. 5.8 Effect on Growth Nasal corticosteroids, including XHANCE, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of XHANCE has not been established in pediatric patients [see Use in Specific Populations ( 8.4 )] .