Veramyst Information
Veramyst (Fluticasone) Dosage And Administration
Administer Veramyst (Fluticasone) Nasal Spray by the intranasal route only. Prime Veramyst (Fluticasone) 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 (Fluticasone) 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 (Fluticasone) Nasal Spray well before each use.
Veramyst (Fluticasone) Dosage Forms And Strengths
Veramyst (Fluticasone) Nasal Spray is a nasal spray suspension. Each spray (50 microliters) delivers 27.5 mcg of fluticasone furoate.
Veramyst (Fluticasone) Contraindications
Veramyst (Fluticasone) Nasal Spray is contraindicated in patients with hypersensitivity to any of its ingredients .
Veramyst (Fluticasone) Warnings And Precautions
Impaired Wound Healing:
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 (Fluticasone) 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 (
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.
Hypercorticism and Adrenal Suppression:
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.
Veramyst (Fluticasone) Adverse Reactions
Systemic and local corticosteroid use may result in the following:
The safety data described below reflect exposure to Veramyst (Fluticasone) Nasal Spray in 1,563 patients with seasonal or perennial allergic rhinitis in 9 controlled clinical trials of 2 to 12 weeks’ duration. The data from adults and adolescents are based upon 6 clinical trials in which 768 patients with seasonal or perennial allergic rhinitis (473 females and 295 males aged 12 years and older) were treated with Veramyst (Fluticasone) Nasal Spray 110 mcg once daily for 2 to 6 weeks. The racial distribution of adult and adolescent patients receiving Veramyst (Fluticasone) Nasal Spray was 82% white, 5% black, and 13% other. The data from pediatric patients are based upon 3 clinical trials in which 795 children with seasonal or perennial rhinitis (352 females and 443 males aged 2 to 11 years) were treated with Veramyst (Fluticasone) Nasal Spray 55 or 110 mcg once daily for 2 to 12 weeks. The racial distribution of pediatric patients receiving Veramyst (Fluticasone) Nasal Spray was 75% white, 11% black, and 14% other.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults and Adolescents Aged 12 Years and Older:
Table 1 displays the common adverse reactions (>1% in any patient group receiving Veramyst (Fluticasone) Nasal Spray) that occurred more frequently in patients aged 12 years and older treated with Veramyst (Fluticasone) Nasal Spray compared with placebo-treated patients.
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:
There were no differences in the incidence of adverse reactions based on gender or race. Pyrexia occurred more frequently in children aged 2 to
Long-Term (52-Week) Safety Trial:
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use of Veramyst (Fluticasone) Nasal Spray. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone furoate or a combination of these factors.
Immune System Disorders:
Respiratory, Thoracic, and Mediastinal Disorders:
Veramyst (Fluticasone) Drug Interactions
Fluticasone furoate is cleared by extensive first-pass metabolism mediated by CYP3A4. In a drug interaction study 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 study 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 study should be carefully interpreted because the study 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 (Fluticasone) Nasal Spray and ketoconazole or other potent CYP3A4 inhibitors.
Based on data with another glucocorticoid, fluticasone propionate, metabolized by CYP3A4, coadministration of Veramyst (Fluticasone) 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.
Veramyst (Fluticasone) Use In Specific Populations
Teratogenic Effects:
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/m 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/m basis).
There are no adequate and well-controlled studies in pregnant women. Veramyst (Fluticasone) Nasal Spray should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects:
Controlled clinical trials with Veramyst (Fluticasone) Nasal Spray included 1,224 patients aged 2 to 11 years and 344 adolescent patients aged 12 to 17 years . The safety and effectiveness of Veramyst (Fluticasone) Nasal Spray in children younger than 2 years 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 (Fluticasone) 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 (Fluticasone) Nasal Spray, each patient’s dose should be titrated to the lowest dosage that effectively controls his/her symptoms.
The potential for Veramyst (Fluticasone) Nasal Spray to cause growth suppression in susceptible patients or when given at higher than recommended dosages cannot be ruled out.
Veramyst (Fluticasone) Overdosage
Chronic overdosage may result in signs/symptoms of hypercorticism . There are no data on the effects of acute or chronic overdosage with Veramyst (Fluticasone) Nasal Spray. Because of low systemic bioavailability and an absence of acute drug-related systemic findings in clinical studies (with dosages of up to 440 mcg/day for 2 weeks [4 times the maximum recommended daily dose]), overdose is unlikely to require any therapy other than observation.
Intranasal administration of up to 2,640 mcg/day (24 times the recommended adult dose) of fluticasone furoate was administered to healthy human volunteers for 3 days. Single- and repeat-dose studies with orally inhaled fluticasone furoate doses of 50 to 4,000 mcg have shown decreased mean serum cortisol at doses of 500 mcg or higher. The oral median lethal dose in mice and rats was >2,000 mg/kg (approximately 74,000 and 147,000 times, respectively, the maximum recommended daily intranasal dose in adults and 52,000 and 105,000 times, respectively, the maximum recommended daily intranasal dose in children, on a mcg/m basis).
Acute overdosage with the intranasal dosage form is unlikely since 1 bottle of Veramyst (Fluticasone) Nasal Spray contains approximately 3 mg of fluticasone furoate, and the bioavailability of fluticasone furoate is
Veramyst (Fluticasone) Description
Fluticasone furoate, the active component of Veramyst (Fluticasone) Nasal Spray, is a synthetic fluorinated corticosteroid having the chemical name (6α,11β,16α,17α)-6,9-difluoro-17-{[(fluoro-methyl)thio]carbonyl}-11-hydroxy-16-methyl-3-oxoandrosta-1,4-dien-17-yl 2-furancarboxylate and the following chemical structure:
Fluticasone furoate is a white powder with a molecular weight of 538.6, and the empirical formula is CHFOS. It is practically insoluble in water.
Veramyst (Fluticasone) Nasal Spray is an aqueous suspension of micronized fluticasone furoate for topical administration to the nasal mucosa by means of a metering (50 microliters), atomizing spray pump. After initial priming , each actuation delivers 27.5 mcg of fluticasone furoate in a volume of 50 microliters of nasal spray suspension. Veramyst (Fluticasone) Nasal Spray also contains 0.015% w/w benzalkonium chloride, dextrose anhydrous, edetate disodium, microcrystalline cellulose and carboxymethylcellulose sodium, polysorbate 80, and purified water. It has a pH of approximately 6.
Veramyst (Fluticasone) Clinical Pharmacology
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 furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is approximately 29.9 times that of dexamethasone and 1.7 times that of fluticasone propionate. The clinical relevance of these findings is unknown.
Adrenal Function:
Clinical Trials Specifically Designed to Assess Hypothalamic-Pituitary-Adrenal Axis Effect:
The second 6-week study conducted in children aged 2 to 11 years was of similar design to the adult study, including adrenal function assessments, but did not include a prednisone positive-control arm. Patients were treated once daily with Veramyst (Fluticasone) Nasal Spray 110 mcg or placebo nasal spray. After 6 weeks of treatment, there was a change in the mean 24-hour urinary cortisol excretion in the group treated with Veramyst (Fluticasone) Nasal Spray (n = 43) of 0.49 mcg/day compared with 1.92 mcg/day in the placebo group (n = 41), with a difference between the group treated with Veramyst (Fluticasone) Nasal Spray and the placebo group of -1.43 mcg/day (95% CI: -5.21, 2.35). For serum cortisol levels, after 6 weeks, there was a change from baseline in mean (0-24 hours) of -0.34 and -0.23 mcg/dL for the group treated with Veramyst (Fluticasone) Nasal Spray (n = 48) and for the placebo group (n = 47), respectively, with a difference between the group treated with Veramyst (Fluticasone) Nasal Spray and the placebo group of -0.11 mcg/dL (95% CI: -0.88, 0.66).
Additional Hypothalamic-Pituitary-Adrenal Axis Assessments:
In the 12-week safety and efficacy trial in children aged 2 to 11 years with perennial allergic rhinitis, Veramyst (Fluticasone) Nasal Spray 55 mcg (n = 185) and Veramyst (Fluticasone) Nasal Spray 110 mcg (n = 185) were compared with placebo nasal spray (n = 188). Adrenal function was assessed by measurement of 24-hour urinary free cortisol in a subset of patients who were aged 6 to 11 years (103 to 109 patients per group) before and after 12 weeks of treatment. After 12 weeks of treatment, there was a decrease in mean 24-hour urinary cortisol excretion from baseline in the group treated with Veramyst (Fluticasone) Nasal Spray 55 mcg (n = 109) of -2.93 mcg/day and in the group treated with Veramyst (Fluticasone) Nasal Spray 110 mcg (n = 103) of -2.07 mcg/day compared with an increase in the placebo group (n = 107) of 0.08 mcg/day. The difference from placebo in mean change from baseline in 24-hour urinary cortisol excretion for the group treated with Veramyst (Fluticasone) Nasal Spray 55 mcg was -3.01 mcg/day (95% CI: -6.16, 0.13) and -2.14 mcg/day (95% CI: -5.33, 1.04) for the group treated with Veramyst (Fluticasone) Nasal Spray 110 mcg.
When the results of the HPA axis assessments described above are taken as a whole, an effect of intranasal fluticasone furoate on adrenal function cannot be ruled out, especially in pediatric patients.
Cardiac Effects:
Absorption:
Absolute bioavailability was evaluated in 16 male and female subjects following supratherapeutic dosages of fluticasone furoate (880 mcg given intranasally at 8-hour intervals for 10 doses, or 2,640 mcg/day). The average absolute bioavailability was 0.50% (90% CI: 0.34%, 0.74%).
Due to the low bioavailability by the intranasal route, the majority of the pharmacokinetic data was obtained via other routes of administration. Studies using oral solution and intravenous dosing of radiolabeled drug have demonstrated that at least 30% of fluticasone furoate is absorbed and then rapidly cleared from plasma. Oral bioavailability is on average 1.26%, and the majority of the circulating radioactivity is due to inactive metabolites.
Distribution:
Binding of fluticasone furoate to human plasma proteins is greater than 99%.
Metabolism:
Elimination:
Population Pharmacokinetics:
Hepatic Impairment:
Renal Impairment:
Veramyst (Fluticasone) How Supplied/storage And Handling
Veramyst (Fluticasone) Nasal Spray, 27.5 mcg per spray, is supplied in a brown glass bottle enclosed in a nasal device with a nozzle and a mist-release button to actuate the spray in a box of 1 (NDC 0173-0753-00) with FDA-Approved Patient Labeling (see Patient Instructions for Use for proper actuation of the device). Each bottle contains a net fill weight of 10 g of white, liquid suspension and will provide 120 metered sprays. After priming , each spray delivers a fine mist containing 27.5 mcg of fluticasone furoate in 50 microliters of formulation through the nozzle. The contents of the bottle can be viewed through an indicator window. Shake the contents well before each use. The correct amount of medication in each spray cannot be assured before the initial priming and after 120 sprays have been used, even though the bottle is not completely empty. The nasal device should be discarded after 120 sprays have been used.
Veramyst (Fluticasone) Patient Counseling Information
See FDA-Approved Patient Labeling.
Patients should be advised that coadministration of Veramyst (Fluticasone) Nasal Spray and ritonavir is not recommended and to be cautious if coadministrating with ketoconazole.
GlaxoSmithKline
Research Triangle Park, NC 27709
©2011, GlaxoSmithKline. All rights reserved.
October 2011
VRM:8PI
Veramyst (Fluticasone)
Veramyst (Fluticasone)
