Local Effects Of Inhaled Corticosteroids In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with ARNUITY ELLIPTA. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with ARNUITY ELLIPTA continues, but at times therapy with ARNUITY ELLIPTA 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. Acute Asthma Episodes ARNUITY ELLIPTA is not indicated for the relief of acute symptoms, i.e., as rescue therapy for treatment of acute episodes of bronchospasm. An inhaled, short-acting beta2-agonist, not ARNUITY ELLIPTA, should be used to relieve acute symptoms such as shortness of breath. When prescribing ARNUITY ELLIPTA, the physician must provide the patient with an inhaled, short-acting beta2-agonist (e.g., albuterol) for treatment of acute symptoms, despite regular once-daily use of ARNUITY ELLIPTA. Instruct patients to contact their physicians immediately if episodes of asthma not responsive to bronchodilators occur during the course of treatment with ARNUITY ELLIPTA. During such episodes, patients may require therapy with oral corticosteroids. Immunosuppression Persons 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 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 infections of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Transferring Patients From Systemic Corticosteroid Therapy 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 ARNUITY ELLIPTA 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 that is necessary for coping with these emergencies. During periods of stress or a 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 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 ARNUITY ELLIPTA. Lung function (forced expiratory volume in 1 second [FEV1] 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. Transfer of patients from systemic corticosteroid therapy to ARNUITY ELLIPTA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions). 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. Hypercorticism And Adrenal Suppression ARNUITY ELLIPTA will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since ARNUITY ELLIPTA is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of ARNUITY ELLIPTA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. Because of the possibility of significant systemic absorption of inhaled corticosteroids, patients treated with ARNUITY ELLIPTA 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, particularly when fluticasone furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of ARNUITY ELLIPTA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms. Drug Interactions With Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of ARNUITY ELLIPTA with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased systemic corticosteroid adverse effects may occur [see DRUG INTERACTIONS, CLINICAL PHARMACOLOGY]. Paradoxical Bronchospasm And Upper Airway Symptoms As with other inhaled medicines, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with ARNUITY ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; ARNUITY ELLIPTA should be discontinued immediately; and alternative therapy should be instituted. Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions such as urticaria, flushing, allergic dermatitis, and bronchospasm may occur after administration of ARNUITY ELLIPTA. Discontinue ARNUITY ELLIPTA if such reactions occur. 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 ARNUITY ELLIPTA [see CONTRAINDICATIONS]. 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 outcomes, 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. Effect On Growth Orally inhaled corticosteroids, including ARNUITY ELLIPTA, may cause a reduction in growth velocity when administered to children and adolescents. Monitor the growth of children and adolescents receiving ARNUITY ELLIPTA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ARNUITY ELLIPTA, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms [see Use In Specific Populations]. Glaucoma And Cataracts Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of inhaled corticosteroids. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. Patient Counseling Information Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use). Not for Acute Symptoms Inform patients that ARNUITY ELLIPTA is not meant to relieve acute asthma symptoms and extra doses should not be used for that purpose. ARNUITY ELLIPTA is not a bronchodilator and should not be used to treat status asthmaticus or to relieve acute asthma symptoms. Advise patients to treat acute symptoms with an inhaled, short-acting beta2-agonist such as albuterol. Provide patients with such medication and instruct them in how it should be used. Instruct patients to seek medical attention immediately if they experience any of the following:
- Symptoms get worse
- Significant decrease in lung function as outlined by the physician
- Need for more inhalations than usual of inhaled, short-acting beta2-agonists
Advise patients not to increase the dose or frequency of ARNUITY ELLIPTA. The daily dosage of ARNUITY ELLIPTA should not exceed 1 inhalation. If they miss a dose, instruct patients to take their next dose at the same time they normally do. Tell patients they should not stop or reduce therapy with ARNUITY ELLIPTA without physician/provider guidance since symptoms may recur after discontinuation. Local Effects Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with ARNUITY ELLIPTA therapy, but at times therapy with ARNUITY ELLIPTA may need to be temporarily interrupted under close medical supervision. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush. Immunosuppression Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Inform patients of potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infections or ocular herpes simplex. Hypercorticism and Adrenal Suppression Advise patients that ARNUITY ELLIPTA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, instruct that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to ARNUITY ELLIPTA. Reduction in Bone Mineral Density Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk. Reduced Growth Velocity Inform patients that orally inhaled corticosteroids, including ARNUITY ELLIPTA, may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route. Ocular Effects Advise patients that long-term use of inhaled corticosteroids may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations. Hypersensitivity Reactions Including Anaphylaxis Advise patients that hypersensitivity reactions (e.g., urticaria, flushing, allergic dermatitis, bronchospasm), including anaphylaxis, may occur after administration of ARNUITY ELLIPTA. Instruct patients to discontinue ARNUITY ELLIPTA if such reactions occur. There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use ARNUITY ELLIPTA. Use Daily for Best Effect Advise patients to use ARNUITY ELLIPTA at regular intervals, since its effectiveness depends on regular use. Maximum benefit may not be achieved for 1 week or longer after starting treatment. If symptoms do not improve after 2 weeks of therapy or if the condition worsens, instruct patients to contact their physicians. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Fluticasone furoate produced no treatment-related increases in the incidence of tumors in 2-year inhalation studies in rats and mice at inhaled doses up to 9 and 19 mcg/kg/day, respectively (less than the MRHDID in adults on a mcg/m² basis). Fluticasone furoate did not induce gene mutation in bacteria or chromosomal damage in a mammalian cell mutation test in mouse lymphoma L5178Y cells in vitro. There was also no evidence of genotoxicity in the in vivo micronucleus test in rats. No evidence of impairment of fertility was observed in male and female rats at inhaled fluticasone furoate doses up to 29 and 91 mcg/kg/day, respectively (approximately equal to and 4 times, respectively, the MRHDID in adults on a mcg/m² basis). Use In Specific Populations Pregnancy Teratogenic Effects Pregnancy Category C. There are no adequate and well-controlled trials with ARNUITY ELLIPTA in pregnant women. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Because animal reproduction studies are not always predictive of human response, ARNUITY ELLIPTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking ARNUITY ELLIPTA. There were no teratogenic effects in rats and rabbits at approximately 4 times and equal to, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mcg/m² basis at maternal inhaled doses up to 91 and 8 mcg/kg/day in rats and rabbits, respectively). There were no effects on perinatal and postnatal development in rats at approximately equal to the MRHDID in adults (on a mcg/m² basis at maternal doses up to 27 mcg/kg/day). Nonteratogenic Effects Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored. Labor And Delivery There are no adequate and well-controlled human trials that have investigated the effects of ARNUITY ELLIPTA during labor and delivery. Nursing Mothers It is not known whether fluticasone furoate is excreted in human breast milk. However, other corticosteroids have been detected in human milk. Since there are no data from controlled trials on the use of ARNUITY ELLIPTA by nursing mothers, caution should be exercised when it is administered to a nursing woman. Pediatric Use The safety and efficacy in pediatric patients younger than 12 years have not been established. Effects on Growth Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. A reduction of growth velocity in children and adolescents may occur as a result of poorly controlled asthma or from use of corticosteroids, including inhaled corticosteroids. The effects of long-term treatment of children and adolescents with inhaled corticosteroids, including fluticasone furoate, on final adult height are not known. Controlled clinical trials have shown that inhaled corticosteroids may cause a reduction in growth in children. In these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appears to be related to dose and duration of exposure. This effect has been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The growth of children and adolescents receiving orally inhaled corticosteroids, including ARNUITY ELLIPTA, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including ARNUITY ELLIPTA, each patient should be titrated to the lowest dose that effectively controls his/her symptoms. A randomized, double-blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with 110 mcg of fluticasone furoate in the nasal spray formulation on growth velocity assessed by stadiometry. The systemic exposure of fluticasone furoate in this trial is lower than that of ARNUITY ELLIPTA. The subjects were 474 prepubescent children (girls aged 5 to 7.5 years and boys aged 5 to 8.5 years). Mean growth velocity over the 52-week treatment period was lower in the subjects receiving fluticasone furoate nasal spray (5.19 cm/year) compared with placebo (5.46 cm/year). The mean reduction in growth velocity was 0.27 cm/year (95% CI: 0.06, 0.48) [see WARNINGS AND PRECAUTIONS]. Geriatric Use For the 4 confirmatory trials, 71 subjects were aged 65 and older (56 of which were treated with ARNUITY ELLIPTA) and 5 were aged 75 and older (1 of which was treated with ARNUITY ELLIPTA) [see Clinical Studies]. Based on available data, no adjustment of the dosage of ARNUITY ELLIPTA in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. Clinical trials of ARNUITY ELLIPTA did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Hepatic Impairment Fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. Use ARNUITY ELLIPTA with caution in patients with moderate or severe hepatic impairment. Monitor patients for corticosteroid-related side effects [see CLINICAL PHARMACOLOGY]. Renal Impairment There were no significant increases in fluticasone furoate exposure in subjects with severe renal impairment (CrCl less than 30 mL/min) compared with healthy subjects. No dosage adjustment is required in patients with renal impairment [see CLINICAL PHARMACOLOGY]. Last reviewed on RxList: 8/28/2014
This monograph has been modified to include the generic and brand name in many instances.