Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. The precise mechanism through which fluticasone furoate affects rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. Specific effects of fluticasone furoate demonstrated in in vitro and in vivo models included activation of the glucocorticoid response element, inhibition of pro-inflammatory transcription factors such as NFkB, and inhibition of antigen-induced lung eosinophilia in sensitized rats. Fluticasone is also found to increase airway retention of long-acting beta adrenergic agonist, thus potentiating its beneficial effects for the treatment of asthma.
Avamys® is used to treat symptoms of allergic rhinitis including stuffy, runny or itchy nose, sneezing, and watery, itchy or red eyes. The effects are usually felt within the first day, although some people will not feel the effects until several days after first taking it.
Systemic and local corticosteroid use may result in the following:
Adults and Adolescents Aged 12 Years and Older
Overall adverse reactions were reported with approximately the same frequency by patients treated with VERAMYST Nasal Spray and those receiving placebo. Less than 3% of patients in clinical trials discontinued treatment because of adverse reactions. The rate of withdrawal among patients receiving VERAMYST Nasal Spray was similar or lower than the rate among patients receiving placebo.
There were no differences in the incidence of adverse reactions based on gender or race. Clinical trials did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger subjects.
Pediatric Patients Aged 2 to 11 Years
In the 3 clinical trials in pediatric patients aged 2 to < 12 years, overall adverse reactions were reported with approximately the same frequency by patients treated with VERAMYST Nasal Spray and those receiving placebo
There were no differences in the incidence of adverse reactions based on gender or race. Pyrexia occurred more frequently in children aged 2 to < 6 years compared with children aged 6 to < 12 years.
Long-term (52-Week) Safety Trial
In a 52-week, placebo-controlled, long-term safety trial, 605 patients (307 females and 298 males aged 12 years and older) with perennial allergic rhinitis were treated with VERAMYST Nasal Spray 110 mcg once daily for 12 months and 201 were treated with placebo nasal spray. While most adverse reactions were similar in type and rate between the treatment groups, epistaxis occurred more frequently in patients who received VERAMYST Nasal Spray (123/605, 20%) than in patients who received placebo (17/201, 8%). Epistaxis tended to be more severe in patients treated with VERAMYST Nasal Spray. All 17 reports of epistaxis that occurred in patients who received placebo were of mild intensity, while 83, 39, and 1 of the total 123 epistaxis events in patients treated with VERAMYST Nasal Spray were of mild, moderate, and severe intensity, respectively. No patient experienced a nasal septal perforation during this trial.
Immune System Disorders
Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria.
Respiratory, Thoracic, and Mediastinal Disorders
Rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness, and nasal septal perforation.
Administer VERAMYST Nasal Spray by the intranasal route only. Prime VERAMYST Nasal Spray before using for the first time by shaking the contents well and releasing 6 sprays into the air away from the face. When VERAMYST Nasal Spray has not been used for more than 30 days or if the cap has been left off the bottle for 5 days or longer, prime the pump again until a fine mist appears. Shake VERAMYST Nasal Spray well before each use.
Titrate an individual patient to the minimum effective dosage to reduce the possibility of side effects.
Adults And Adolescents Aged 12 Years And Older
The recommended starting dosage is 110 mcg once daily administered as 2 sprays (27.5 mcg/spray) in each nostril. When the maximum benefit has been achieved and symptoms have been controlled, reducing the dosage to 55 mcg (1 spray in each nostril) once daily may be effective in maintaining control of allergic rhinitis symptoms.
Children Aged 2 To 11 Years
The recommended starting dosage in children is 55 mcg once daily administered as 1 spray (27.5 mcg/spray) in each nostril. Children not adequately responding to 55 mcg may use 110 mcg (2 sprays in each nostril) once daily. Once symptoms have been controlled, dosage reduction to 55 mcg once daily is recommended.
Fluticasone furoate is cleared by extensive first-pass metabolism mediated by CYP3A4. In a drug interaction trial of intranasal fluticasone furoate and the CYP3A4 inhibitor ketoconazole given as a 200-mg once-daily dose for 7 days, 6 of 20 subjects receiving fluticasone furoate and ketoconazole had measurable but low levels of fluticasone furoate compared with 1 of 20 receiving fluticasone furoate and placebo. Based on this trial and the low systemic exposure, there was a 5% reduction in 24-hour serum cortisol levels with ketoconazole compared with placebo. The data from this trial should be carefully interpreted because the trial was conducted with ketoconazole 200 mg once daily rather than 400 mg, which is the maximum recommended dosage. Therefore, caution is required with the coadministration of VERAMYST Nasal Spray and ketoconazole or other potent CYP3A4 inhibitors.
Based on data with another glucocorticoid, fluticasone propionate, metabolized by CYP3A4, coadministration of VERAMYST Nasal Spray with the potent CYP3A4 inhibitor ritonavir is not recommended because of the risk of systemic effects secondary to increased exposure to fluticasone furoate. High exposure to corticosteroids increases the potential for systemic side effects, such as cortisol suppression.
Enzyme induction and inhibition data suggest that fluticasone furoate is unlikely to significantly alter the cytochrome P450-mediated metabolism of other compounds at clinically relevant intranasal dosages.
Avamys® is best stored at room temperature away from direct light and moisture. To prevent drug damage, you should not store Avamys® in the bathroom or the freezer. There may be different brands of Avamys® that may have different storage needs. It is important to always check the product package for instructions on storage, or ask your pharmacist. For safety, you should keep all medicines away from children and pets.
Local Nasal Effects
Epistaxis and Nasal Ulceration
In clinical trials of 2 to 52 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
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
Postmarketing cases of nasal septal perforation have been reported in patients following the intranasal application of 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 (IOP), glaucoma, and/or cataracts.
Glaucoma and cataract formation was evaluated with intraocular pressure measurements and slit lamp examinations in 1 controlled 12-month trial in 806 adolescent and adult patients aged 12 years and older and in 1 controlled 12-week trial 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 trials. However, in the 12-month trial 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 ( ≥ 21 mmHg). In the same trial, 7 patients (6 treated with VERAMYST Nasal Spray 110 mcg once daily and 1 patient treated with placebo) had cataracts identified during the trial that were not present at baseline.
Hypersensitivity Reactions, Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria, may occur after administration of VERAMYST Nasal Spray. Discontinue VERAMYST Nasal Spray if such reactions occur
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, 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 Cytochrome P450 3A4 Inhibitors
Coadministration with ritonavir is not recommended because of the risk of systemic effects secondary to increased exposure to fluticasone furoate. Use caution with the coadministration of VERAMYST Nasal Spray and other potent cytochrome P450 3A4 (CYP3A4) inhibitors, such as ketoconazole
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
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling
Local Nasal Effects
Inform patients that treatment with VERAMYST Nasal Spray may lead to adverse reactions, which include epistaxis and nasal ulceration. Candida infection may also occur with treatment with VERAMYST Nasal Spray. In addition, nasal corticosteroids are associated with nasal septal perforation and impaired wound healing. Advise patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma to not use VERAMYST Nasal Spray until healing has occurred
Cataracts and Glaucoma
Inform patients that glaucoma and cataracts are associated
with nasal and inhaled corticosteroid use. Instruct patients to inform their
healthcare providers if a change in vision is noted while using VERAMYST Nasal
Hypersensitivity Reactions, Including Anaphylaxis
Inform patients that hypersensitivity reactions, including
anaphylaxis, angioedema, rash, and urticaria, may occur after administration of
VERAMYST Nasal Spray. Instruct patients to discontinue use of VERAMYST Nasal
Spray if such reactions occur
Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their healthcare providers without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex
Effect on Growth
Advise parents that VERAMYST Nasal Spray may slow growth in
children. A child taking VERAMYST Nasal Spray should have his/her growth
Use Daily for Best Effect
Instruct patients to use VERAMYST Nasal Spray on a regular once-daily basis for optimal effect. VERAMYST Nasal Spray, like other corticosteroids, does not have an immediate effect on rhinitis symptoms. Although significant improvement is usually achieved within 24 hours in patients with seasonal allergic rhinitis and 4 days in patients with perennial allergic rhinitis, maximum benefit may not be reached for several days. Instruct the patient to not increase the prescribed dosage but contact the healthcare provider if symptoms do not improve or if the condition worsens.
Keep Spray Out of Eyes
Inform patients to avoid spraying VERAMYST Nasal Spray in their eyes.
Potential Drug Interactions
Advise patients that coadministration of VERAMYST Nasal Spray and ritonavir is not recommended and to be cautious if coadministering with ketoconazole.