WARNINGS AND PRECAUTIONS
Local Nasal Effects
Epistaxis and Nasal Ulceration
In clinical studies of 2 to52 weeks’ duration, epistaxis and nasal ulcerations were observed more frequently and some epistaxis events were more severe in patients treated with VERAMYST Nasal Spray than those who received placebo [see Adverse Reaction s (6)].
Evidence of localized infections of the nose with Candida albicans was seen on nasal exams in 7 of 2,745 patients treated with VERAMYST Nasal Spray during clinical trials and was reported as an adverse event in 3 patients. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of VERAMYST Nasal Spray. Therefore, patients using VERAMYST Nasal Spray over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa.
Nasal Septal Perforation
Instances of nasal septal perforation have been reported in patients following the intranasal application of corticosteroids. There were no instances of nasal septal perforation observed in clinical studies with VERAMYST Nasal Spray.
Impaired Wound Healing
Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use VERAMYST Nasal Spray until healing has occurred.
Glaucoma and Cataracts
Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
Glaucoma and cataract formation was evaluated with intraocular pressure measurements and slit lamp examinations in 1 controlled 12-month study in 806 adolescent and adult patients aged 12 years and older and in 1 controlled 12-week study in 558 children aged 2 to 11 years. The patients had perennial allergic rhinitis and were treated with either VERAMYST Nasal Spray (110 mcg once daily in adult and adolescent patients and 55 or 110 mcg once daily in pediatric patients) or placebo. Intraocular pressure remained within the normal range (<21 mmHg) in ≥98% of the patients in any treatment group in both studies. However, in the 12-month study in adolescents and adults, 12 patients, all treated with VERAMYST Nasal Spray 110 mcg once daily, had intraocular pressure measurements that increased above normal levels (≥21mmHg). In the same study, 7 patients (6 treated with VERAMYST Nasal Spray 110 mcg once daily and 1 patient treated with placebo) had cataracts identified during the study that were not present at baseline.
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 children or adults who have not had these diseases or 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) 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 or measles develops, treatment with antiviral agents may be considered.
Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; untreated local or systemic fungal or bacterial infections; systemic viral or parasitic infections; or ocular herpes simplex because of the potential for worsening of these infections.
Hypothalamic-Pituitary-Adrenal Axis Effects
Hypercorticism and Adrenal Suppression
When intranasal steroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of VERAMYST Nasal Spray should be discontinued slowly, consistent with accepted procedures for discontinuing oral corticosteroid therapy.
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, and depression. 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. In those 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.
Use of CYP3A Inhibitors
Co-administration with ritonavir is not recommended because of the risk of systemic effects secondary to increased exposure to fluticasone furoate. Use caution with the co-administration of VERAMYST Nasal Spray and other potent CYP3A4 inhibitors, such as ketoconazole [see Drug Interactions (7)].
Effect on Growth
Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving VERAMYST Nasal Spray. To minimize the systemic effects of intranasal corticosteroids, including VERAMYST Nasal Spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations].
USE IN SPECIFIC POPULATIONS
Pregnancy Category C. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels.
There were no teratogenic effects in rats and rabbits at inhaled fluticasone furoate dosages of up to 91 and 8 mcg/kg/day, respectively (approximately 7 and 1 times, respectively, the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). There was also no effect on pre- or post-natal development in rats treated with up to 27 mcg/kg/day by inhalation during gestation and lactation (approximately 2 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis).
There are no adequate and well-controlled studies in pregnant women. VERAMYST Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully monitored.
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 intranasal fluticasone furoate by nursing mothers, caution should be exercised when VERAMYST Nasal Spray is administered to a nursing woman.
Controlled clinical trials with VERAMYST Nasal Spray included 1,224 patients aged 2 to 11 years and 344 adolescent patients aged 12 to 17 years [see Clinical Studies]. The safety and effectiveness of VERAMYST Nasal Spray in children below 2 years of age have not been established.
Controlled clinical studies have shown that intranasal corticosteroids may cause a reduction in growth velocity in pediatric patients. 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 pediatric patients than some commonly used tests of HPA axis function. The long-term effects of reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving intranasal corticosteroids, including VERAMYST Nasal Spray, 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/benefits of treatment alternatives. To minimize the systemic effects of intranasal corticosteroids, including VERAMYST Nasal Spray, each patient’s dose should be titrated to the lowest dosage that effectively controls his/her symptoms.
The potential for VERAMYST Nasal Spray to cause growth suppression in susceptible patients or when given at higher than recommended dosages cannot be ruled out.
Clinical studies of VERAMYST Nasal Spray did not include sufficient numbers of subjects aged 65 years 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.
Use VERAMYST Nasal Spray with caution in patients with severe hepatic impairment [see Pharmacokinetics].
No dosage adjustment is required in patients with renal impairment [see Pharmacokinetics].