DESCRIPTION

Fluticasone propionate, the active component of Fluticasone Propionate Nasal Spray, USP.., is a synthetic corticosteroid having the chemical name -(fluoromethyl) 6α,9-difluoro-11β-17-dihydroxy- 16α-methyl-3-oxoandrosta-1,4- diene-17β-carbothioate, 17-propionate and the following chemical structure: S

*

Fluticasone propionate is a White powder with a molecular weight of 500.6, and the empirical formula is C H F O S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide và dimethylformamide, và slightly soluble in methanol & 95% ethanol. 253135

Fluticasone Propionate Nasal Spray, USP., 50 mcg is an aqueous suspension of microfine fluticasone propionate for topical administration to lớn the nasal mucosa by means of a metering, atomizing spray pump. Fluticasone Propionate Nasal Spray, USP., also contains benzalkonium chloride (0.02% w/w), carboxymethylcelluthất bại sodium,dextrose, microcrystalline celluthua kém, phenylethyl alchol (0.25% w/w), polysorbate 80, và purified water và has a pH between 5.8 and 6.8.

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It is necessary to lớn prime the pump before first use or after a period of non-use (1 week or more). After initial priming (6 actuations), each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter. Each 16-g bottle of Fluticasone Propionate Nasal Spray, USP, provides 120 metered sprays. After 120 metered sprays, the amount of fluticasone propionate delivered per actuation may not be consistent và the unit should be discarded.


CLINICAL PHARMACOLOGY

Mechanism of Action:

Fluticasone propionate is a synthetic, trifluorinated corticosteroid with anti-inflammatory activity. In vitro dose response studies on a cloned human glucocorticoid receptor system involving binding and ren expression afforded một nửa responses at 1.25 and 0.17 nM concentrations, respectively. Fluticasone propionate was 3-fold lớn 5-fold more potent than dexamethasone in these assays. Data from the McKenzie vasoconstrictor assay in man also support its potent glucocorticoid activity.

In preclinical studies, fluticasone propionate revealed progesterone-lượt thích activity similar lớn the natural hormone. However, the clinical significance of these findings in relation to lớn the low plasma levels (see ) is not known. Pharmacokinetics

The precise mechanism through which fluticasone propionate affects allergic rhinitis symptoms is not known. Corticosteroids have sầu been shown to lớn have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, và lymphocytes) & mediators (e.g., histamine, eicosanoids, leukotrienes, & cytokines) involved in inflammation. In 7 trials in adults, Fluticasone Propionate Nasal Spray,USPhường, has decreased nasal mucosal eosinophils in 66% (35% for placebo) of patients and basophils in 39% (28% for placebo) of patients. The direct relationship of these finding khổng lồ long-term symptom relief is not known.

Fluticasone Propionate Nasal Spray, USPhường, lượt thích other corticosteroids, is an agent that does not have an immediate effect on allergic symptoms. A decrease in nasal symptoms has been noted in some patients 12 hours after initial treatment with Fluticasone Propionate Nasal Spray, USP. Maximum benefit may not be reached for several days. Similarly, when corticosteroids are discontinued, symptoms may not return for several days.


Pharmacokinetics


Absorption

The activity of Fluticasone Propionate Nasal Spray, USPhường, is due lớn the parent drug, fluticasone propionate. Indirect calculations indicate that fluticasone propionate delivered by the intranasal route has an absolute bioavailability averaging less than 2%. After intranasal treatment of patients with allergic rhinitis for 3 weeks, fluticasone propionate plasma concentrations were above sầu the cấp độ of detection (50 pg/mL) only when recommended doses were exceeded and then only in occasional samples at low plasma levels. Due lớn the low bioavailability by the intranasal route, the majority of the pharmacokinetic data was obtained via other routes of administration. Studies using oral dosing of radiolabeled drug have demonstrated that fluticasone propionate is highly extracted from plasma and absorption is low. Oral bioavailability is negligible, và the majority of the circulating radioactivity is due to an inactive metabolite.


Distribution

Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid và consistent with its high lipid solubility & tissue binding. The volume of distribution averaged 4.2 L/kilogam.

The percentage of fluticasone propionate bound lớn human plasma proteins averaged 91% with no obvious concentration relationship. Fluticasone propionate is weakly and reversibly bound to lớn erythrocytes and freely equilibrates between erythrocytes & plasma. Fluticasone propionate is not significantly bound khổng lồ human transcortin.


Metabolism

The total blood clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total. The only circulating metabolite detected in man is the 17β-carboxylic acid derivative sầu of fluticasone propionate, which is formed through the cytochrome P450 3A4 pathway. This inactive metabolite had less affinity (approximately 50%,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro và negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.


Elimination

Following intravenous dosing, fluticasone propionate showed polyexponential kinetics và had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.


Special Populations

Fluticasone Propionate Nasal Spray, USPhường, was not studied in any special populations, and no gender-specific pharmacokinetic data have been obtained.


Drug Interactions

Fluticasone propionate is a substrate of cytochrome P450 3A4. Coadministration of fluticasone propionate and the highly potent cytochrome P450 3A4 inhibitor ritonavir is not recommended based upon a multiple- dose, crossover drug interaction study in 18 healthy subjects. Fluticasone propionate aqueous nasal spray (200 mcg once daily) was coadministered for 7 days with ritonavir (100 mg twice daily). Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (max(0-t)max(0-t)

Caution should be exercised when other potent cytochrome P450 3A4 inhibitors are coadministered with fluticasone propionate. In a drug interaction study, coadministration of orally inhaled fluticasone propionate (1,000 mcg) & ketoconazole (200 mg once daily) resulted in increased fluticasone propionate exposure & reduced plasma cortisol AUC, but had no effect on urinary excretion of cortisol.

In another multiple-dose drug interaction study, coadministration of orally inhaled fluticasone propionate (500 mcg twice daily) and erythromycin (333 mg 3 times daily) did not affect fluticasone propionate pharmacokinetics.


Pharmacodynamics

In a trial khổng lồ evaluate the potential systemic and topical effects of Fluticasone Propionate Nasal Spray, USP, on allergic rhinitis symptoms, the benefits of comparable drug blood levels produced by Fluticasone Propionate Nasal Spray, USPhường, and oral fluticasone propionate were compared. The dosages used were 200 mcg of Fluticasone Propionate Nasal Spray, USP, the nasal spray vehicle (plus oral placebo), & 5 & 10 mg of oral fluticasone propionate (plus nasal spray vehicle) per day for 14 days. Plasma levels were undetectable in the majority of patients after intranasal dosing, but present at low levels in the majority after oral dosing. Fluticasone Propionate Nasal Spray, USPhường., was significantly more effective sầu in reducing symptoms of allergic rhinitis than either the oral fluticasone propionate or the nasal vehicle. This trial demonstrated that the therapeutic effect of Fluticasone Propionate Nasal Spray, USPhường, can be attributed khổng lồ the topical effects of fluticasone propionate.

In another trial, the potential systemic effects of Fluticasone Propionate Nasal Spray, USPhường, on the hypothalamic-pituitaryadrenal (HPA) axis were also studied in allergic patients. Fluticasone Propionate Nasal Spray, USP, given as 200 mcg once daily or 400 mcg twice daily was compared with placebo or oral prednisone 7.5 or 15 mg given in the morning. Fluticasone Propionate Nasal Spray, USP, at either dosage for 4 weeks did not affect the adrenal response to lớn 6-hour cosyntropin stimulation, while both dosages of oral prednisone significantly reduced the response to cosyntropin.


CLINICAL TRIALS

A total of 13 randomized, double-blind, parallel-group, multicenter, vehicle placebo-controlled clinical trials were conducted in the United States in adults & pediatric patients (4 years of age & older) to investigate regular use of Fluticasone Propionate Nasal Spray, USPhường, in patients with seasonal or perennial allergic rhinitis. The trials included 2,633 adults (1,439 men và 1,194 women) with a mean age of 37 (range, 18 to lớn 79 years). A total of 440 adolescents (405 boys và 35 girls), mean age of 14 (range, 12 to lớn 17 years), and 500 children (325 boys and 175 girls), mean age of 9 (range, 4 lớn 11 years) were also studied. The overall racial distribution was 89% Trắng, 4% black, và 7% other. These trials evaluated the total nasal symptom scores (TNSS) that included rhinorrhea, nasal obstruction, sneezing, và nasal itching in known allergic patients who were treated for 2 khổng lồ 24 weeks. Subjects treated with Fluticasone Propionate Nasal Spray, USP exhibited significantly greater decreases in TNSS than vehicle placebo-treated patients. Nasal mucosal basophils and eosinophils were also reduced at the kết thúc of treatment in adult studies; however, the clinical significance of this decrease is not known.

There were no significant differences between fluticasone propionate regimens whether administered as a single daily dose of 200 mcg (two 50-mcg sprays in each nostril) or as 100 mcg (one 50-mcg spray in each nostril) twice daily in 6 clinical trials. A clear dose response could not be identified in clinical trials. In 1 trial, 200 mcg/day was slightly more effective than 50 mcg/day during the first few days of treatment; thereafter, no difference was seen.

Two randomized, double-blind, parallelgroup, multicenter, vehicle placebo-controlled 28-day trials were conducted in the United States in 732 patients (243 given Fluticasone Propionate Nasal Spray, USP) 12 years of age và older to investigate “as-needed” use of Fluticasone Propionate Nasal Spray, USP (200 mcg) in patients with seasonal allergic rhinitis. Patients were instructed to lớn take the study medication only on days when they thought they needed the medication for symptom control, not khổng lồ exceed 2 sprays per nostril on any day, & not more than once daily. “Asneeded” use was prospectively defined as average use of study medication no more than 75% of study days. Average use of study medications was 57% to 70% of days for all treatment arms. The studies demonstrated significantly greater reduction in TNSS (sum of nasal congestion, rhinorrhea, sneezing, & nasal itching) with Fluticasone Propionate Nasal Spray, USP, 200 mcg compared to placebo. The relative difference in efficacy with as-needed use as compared khổng lồ regularly administered doses was not studied.

Three randomized, double-blind, parallel- group, vehicle placebo-controlled trials were conducted in 1,191 patients lớn investigate regular use of Fluticasone Propionate Nasal Spray, USP, in patients with perennial nonallergic rhinitis. These trials evaluated the patient-rated TNSS (nasal obstruction, postnasal drip, rhinorrhea) in patients treated for 28 days of doubleblind therapy and in 1 of the 3 trials for 6 months of open-label treatment. Two of these trials demonstrated that patients treated with Fluticasone Propionate Nasal Spray, USP, at a dosage of 100 mcg twice daily exhibited statistically significant decreases in TNSS compared with patients treated with vehicle.


Individualization of Dosage

Patients should use Fluticasone Propionate Nasal Spray, USP, at regular intervals for optimal effect.

Adult patients may be started on a 200-mcg once-daily regimen (two 50-mcg sprays in each nostril once daily). An alternative sầu 200-mcg/day dosage regimen can be given as 100 mcg twice daily (one 50-mcg spray in each nostril twice daily).

Individual patients will experience a variable time to onphối & different degree of symptom relief. In 4 randomized, doubleblind, vehicle placebo-controlled, parallel- group allergic rhinitis studies and 2 studies of patients in an outdoor “park” setting (park studies), a decrease in nasal symptoms in treated subjects compared to lớn placebo was shown khổng lồ occur as soon as 12 hours after treatment with a 200-mcg dose of Fluticasone Propionate Nasal Spray, USP.. Maximum effect may take several days. Regular-use patients who have sầu responded may be able to be maintained (after 4 khổng lồ 7 days) on 100 mcg/day (1 spray in each nostril once daily).

Some patients (12 years of age & older) with seasonal allergic rhinitis may find as-needed use of Fluticasone Propionate Nasal Spray, USP.. (not khổng lồ exceed 200 mcg daily) effective for symptom control (see ). Greater symptom control may be achieved with scheduled regular use. Efficacy of asneeded use of Fluticasone Propionate Nasal Spray, USP, has not been studied in pediatric patients under 12 years of age with seasonal allergic rhinitis, or patients with perennial allergic or nonallergic rhinitis. CLINICAL TRIALS

Pediatric patients (4 years of age and older) should be started with 100 mcg (1 spray in each nostril once daily). Treatment with 200 mcg (2 sprays in each nostril once daily or 1 spray in each nostril twice daily) should be reserved for pediatric patients not adequately responding khổng lồ 100 mcg daily. Once adequate control is achieved, the dosage should be decreased lớn 100 mcg (1 spray in each nostril) daily.

Maximum total daily doses should not exceed 2 sprays in each nostril (total dose, 200 mcg/day). There is no evidence that exceeding the recommended dose is more effective sầu.


INDICATIONS AND USAGE

Fluticasone Propionate Nasal Spray, USP.., is indicated for the management of the nasal symptoms of seasonal and perennial allergic & nonallergic rhinitis in adults and pediatric patients 4 years of age và older.

Safety và effectiveness of Fluticasone Propionate Nasal Spray, USPhường, in children below 4 years of age have sầu not been adequately established.


CONTRAINDICATIONS

Fluticasone Propionate Nasal Spray, USP, is contraindicated in patients with a hypersensitivity khổng lồ any of its ingredients.


WARNINGS

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, và in addition some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, & depression. Patients previously treated for prolonged periods with systemic corticosteroids & transferred khổng lồ topical corticosteroids should be carefully monitored for adễ thương adrenal insufficiency in response to bao tay. In those patients who have sầu asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms.

The concomitant use of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis.

A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations (see và ). During postsale use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate & ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome và adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to lớn the patient outweighs the risk of systemic corticosteroid side effects. CLINICAL PHARMACOLOGY: Drug InteractionsPRECAUTIONS: Drug Interactions

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox & measles, for example, can have sầu 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 been properly immunized, particular care should be taken khổng lồ avoid exposure. How the dose, route, & 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 lớn the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If exposed khổng lồ 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.

Avoid spraying in eyes.


General

Intranasal corticosteroids may cause a reduction in growth velothành phố when administered to pediatric patients (see ). Rarely, immediate hypersensitivity reactions or liên hệ dermatitis may occur after the administration of Fluticasone Propionate Nasal Spray, USPhường. Rare instances of wheezing, nasal septum perforation, cataracts, glaucoma, và increased intraocular pressure have been reported following the intranasal application of corticosteroids, including fluticasone propionate. PRECAUTIONS: Pediatric use

Use of excessive doses of corticosteroids may lead khổng lồ signs or symptoms of hypercorticism and/or suppression of HPA function.

Although systemic effects have sầu been minimal with recommended doses of Fluticasone Propionate Nasal Spray, USPhường, potential risk increases with larger doses. Therefore, larger than recommended doses of Fluticasone Propionate Nasal Spray, USP, should be avoided.

When used at higher than recommended doses or in rare individuals at recommended doses, systemic corticosteroid effects such as hypercorticism & adrenal suppression may appear. If such changes occur, the dosage of Fluticasone Propionate Nasal Spray, USP.., should be discontinued slowly consistent with accepted procedures for discontinuing oral corticosteroid therapy.

In clinical studies with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with albicans has occurred only rarely. When such an infection develops, it may require treatment with appropriate local therapy và discontinuation of treatment with Fluticasone Propionate Nasal Spray, USP.. Patients using Fluticasone Propionate Nasal Spray, USPhường., over several months or longer should be examined periodically for evidence of Candida infection or other signs of adverse effects on the nasal mucosa. Candida

Intranasal 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 inhibitory effect of corticosteroids on wound healing, patients who have sầu experienced recent nasal septal ulcers, nasal surgery, or nasal trauma should not use a nasal corticosteroid until healing has occurred.


Information for patients

Patients being treated with Fluticasone Propionate Nasal Spray, USPhường, should receive sầu the following information & instructions. This information is intended to aid them in the safe và effective sầu use of this medication. It is not a disclosure of all possible adverse or intended effects.

Patients should be warned lớn avoid exposure khổng lồ chickenpox or measles &, if exposed, lớn consult their physician without delay.

Patients should use Fluticasone Propionate Nasal Spray, USP, at regular intervals for optimal effect. Some patients (12 years of age & older) with seasonal allergic rhinitis may find as-needed use of 200 mcg once daily effective sầu for symptom control (see ). CLINICAL TRIALS

A decrease in nasal symptoms may occur as soon as 12 hours after starting therapy with Fluticasone Propionate Nasal Spray, USPhường. Results in several clinical trials indicate statistically significant improvement within the first day or two of treatment; however, the full benefit of Fluticasone Propionate Nasal Spray, USPhường, may not be achieved until treatment has been administered for several days. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens.

For the proper use of Fluticasone Propionate Nasal Spray, USPhường, & khổng lồ attain maximum improvement, the patient should read và follow carefully the patient’s instructions accompanying the sản phẩm.


Drug interactions

Fluticasone propionate is a substrate of cytochrome P450 3A4. A drug interaction study with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations (see ). During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate và ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome và adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to lớn the patient outweighs the risk of systemic corticosteroid side effects. CLINICAL PHARMACOLOGY: Drug Interactions

In a placebo-controlled, crossover study in 8 healthy volunteers, coadministration of a single dose of orally inhaled fluticasone propionate (1,000 mcg; 5 times the maximum daily intranasal dose) with multiple doses of ketoconazole (200 mg) lớn steady state resulted in increased plasma fluticasone propionate exposure, a reduction in plasma cortisol AUC, & no effect on urinary excretion of cortisol. Caution should be exercised when Fluticasone Propionate Nasal Spray, USPhường, is coadministered with ketoconazole and other known potent cytochrome P450 3A4 inhibitors.


Carcinogenesis, mutagenesis, impairment of fertility

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to lớn 1,000 mcg/kilogam (approximately đôi mươi times the maximum recommended daily intranasal dose in adults and approximately 10 times the maximum recommended daily intranasal dose in children on a mcg/m basis) for 78 weeks or in rats at inhalation doses up khổng lồ 57 mcg/kg (approximately 2 times the maximum recommended daily intranasal dose in adults and approximately equivalent to the maximum recommended daily intranasal dose in children on a mcg/m basis) for 104 weeks. 22

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the mouse micronucleus chạy thử.

No evidence of impairment of fertility was observed in reproductive studies conducted in male và female rats at subcutaneous doses up khổng lồ 50 mcg/kg (approximately 2 times the maximum recommended daily intranasal dose in adults on a mcg/m basis). Prostate weight was significantly reduced at a subcutaneous dose of 50 mcg/kilogam. 2


Teratogenic effects

Pregnancy Category C. Subcutaneous studies in the mouse & rat at 45 & 100 mcg/kilogam, respectively (approximately equivalent to lớn and 4 times, respectively, the maximum recommended daily intranasal dose in adults on a mcg/m basis) revealed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, và retarded cranial ossification. 2

In the rabbit, fetal weight reduction và cleft palate were observed at a subcutaneous dose of 4 mcg/kilogam (less than the maximum recommended daily intranasal dose in adults on a mcg/m basis). 2

However, no teratogenic effects were reported at oral doses up to 300 mcg/kg (approximately 25 times the maximum recommended daily intranasal dose in adults on a mcg/m basis), of fluticasone propionate to the rabbit. No fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration (see ). 2CLINICAL PHARMACOLOGY

Fluticasone propionate crossed the placenta following oral administration of 100 mcg/kg lớn rats và 300 mcg/kilogam khổng lồ rabbits (approximately 4 và 25 times, respectively, the maximum recommended daily intranasal dose in adults on a mcg/m basis). 2

There are no adequate & well-controlled studies in pregnant women. Fluticasone propionate should be used during pregnancy only if the potential benefit justifies the potential risk khổng lồ the fetus.

Experience with oral corticosteroids since their introduction in pharmacosúc tích, as opposed lớn physiongắn gọn xúc tích, doses suggests that rodents are more prone khổng lồ teratogenic effects from corticosteroids than humans. In addition, because there is a natural increase in corticosteroid production during pregnancy, most women will require a lower exogenous corticosteroid dose và many will not need corticosteroid treatment during pregnancy.


Nursing mothers

It is not known whether fluticasone propionate is excreted in human breast milk. However, other corticosteroids have been detected in human milk. Subcutaneous administration khổng lồ lactating rats of 10 mcg/kg of tritiated fluticasone propionate (less than the maximum recommended daily intranasal dose in adults on a mcg/m basis) resulted in measurable radioactivity in the milk. Since there are no data from controlled trials on the use of intranasal fluticasone propionate by nursing mothers, caution should be exercised when Fluticasone Propionate Nasal Spray, USP, is administered khổng lồ a nursing woman. 2


Pediatric use

Six hundred fifty (650) patients aged 4 to 11 years & 440 patients aged 12 khổng lồ 17 years were studied in US clinical trials with Fluticasone Propionate Nasal Spray, USP.. The safety & effectiveness of Fluticasone Propionate Nasal Spray, USP.., in children below 4 years of age have not been established.

Controlled clinical studies have shown that intranasal corticosteroids may cause a reduction in growth velothành phố in pediatric patients. This effect has been observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velothành phố 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 this reduction in growth velothành phố 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 Fluticasone Propionate Nasal Spray, USP, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained & the risks/benefits of treatment alternatives. To minimize the systemic effects of intranasal corticosteroids, including Fluticasone Propionate Nasal Spray, USPhường, each patient should be titrated lớn the lowest dose that effectively controls his/her symptoms.

A 1-year placebo-controlled clinical growth study was conducted in 150 pediatric patients (ages 3 khổng lồ 9 years) to lớn assess the effect of Fluticasone Propionate Nasal Spray, USPhường (single daily dose of 200 mcg, the maximum approved dose) on growth velocity. From the primary population of 56 patients receiving Fluticasone Propionate Nasal Spray, USPhường & 52 receiving placebo, the point estimate for growth velocity with Fluticasone Propionate Nasal Spray, USP. was 0.14 cm/year lower than that noted with placebo (95% confidence interval ranging from 0.54 cm/year lower than placebo khổng lồ 0.27 cm/year higher than placebo). Thus, no statistically significant effect on growth was noted compared to placebo. No evidence of clinically relevant changes in HPA axis function or bone mineral mật độ trùng lặp từ khóa was observed as assessed by 12-hour urinary cortisol excretion & dual-energy x-ray absorptiometry, respectively.

The potential for Fluticasone Propionate Nasal Spray, USPhường, lớn cause growth suppression in susceptible patients or when given at higher doses cannot be ruled out.


Geriatric use

A limited number of patients 65 years of age and older (n = 129) or 75 years of age and older (n = 11) have sầu been treated with Fluticasone Propionate Nasal Spray, USP.., in US và non-US clinical trials. While the number of patients is too small lớn permit separate analysis of efficacy và safety, the adverse reactions reported in this population were similar lớn those reported by younger patients.


ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, tương tác Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

In controlled US studies, more than 3,300 patients with seasonal allergic, perennial allergic, or perennial nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical studies have sầu been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by patients treated with the vehicle itself. The complaints did not usually interfere with treatment. Less than 2% of patients in clinical trials discontinued because of adverse events; this rate was similar for vehicle placebo và active comparators.

Systemic corticosteroid side effects were not reported during controlled clinical studies up to 6 months’ duration with Fluticasone Propionate Nasal Spray, USPhường. If recommended doses are exceeded, however, or if individuals are particularly sensitive or taking Fluticasone Propionate Nasal Spray, USP, in conjunction with administration of other corticosteroids, symptoms of hypercorticism, e.g., Cushing syndrome, could occur.

The following incidence of comtháng adverse reactions (>3%, where incidence in fluticasone propionate-treated subjects exceeded placebo) is based upon 7 controlled clinical trials in which 536 patients (57 girls & 108 boys aged 4 to 11 years, 137 female & 234 male adolescents & adults) were treated with Fluticasone Propionate Nasal Spray, USPhường, 200 mcg once daily over 2 khổng lồ 4 weeks và 2 controlled clinical trials in which 246 patients (119 female và 127 male adolescents và adults) were treated with Fluticasone Propionate Nasal Spray, USP, 200 mcg once daily over 6 months. Also included in the table are adverse events from 2 studies in which 167 children (45 girls and 122 boys aged 4 to 11 years) were treated with Fluticasone Propionate Nasal Spray, USP, 100 mcg once daily for 2 to lớn 4 weeks.

Overall Adverse Experiences With >3% Incidence on Fluticasone Propionate in Controlled Clinical Trials With Fluticasone Propionate Nasal Spray, USPhường, in Patients ≥4 Years With Seasonal or Perennial Allergic Rhinitis
Adverse Experience

Vehicle Placebo

(n=758)

%

Fluticasone Propionate Nasal Spray, USP

100 mcg Once Daily

(n=167)

%

Fluticasone Propionate Nasal Spray, USP

200 mcg Once Daily

(n=782)

%

Headache14.66.616.1
Pharyngitis7.26.07.8
Epistaxis5.46.06.9
Nasal burning/nasal irritation2.62.43.2
Nausea/vomitting2.04.82.6
Asthma symptoms2.97.23.3
Cough2.83.63.8

Other adverse events that occurred in ≤3% but ≥1% of patients and that were more comtháng with fluticasone propionate (with uncertain relationship lớn treatment) included: blood in nasal mucus, runny nose, abdominal pain, diarrhea, fever, flu-lượt thích symptoms, aches và pains, dizziness, bronchitis.


Observed During Clinical Practice

Practice: In addition to adverse events reported from clinical trials, the following events have been identified during postapproval use of intranasal fluticasone propionate in clinical practice. Because they are reported voluntarily from a population of unknown kích thước, estimates of frequency cannot be made. These events have sầu been chosen for inclusion due to lớn either their seriousness, frequency of reporting, or causal connection to lớn fluticasone propionate or a combination of these factors.


General

Hypersensitivity reactions, including angioedema, skin rash, edema of the face và tongue, pruritus, urticaria, bronchospasm, wheezing, dyspnea, and anaphylaxis/anaphylactoid reactions, which in rare instances were severe.


Ear, Nose, & Throat

Alteration or loss of sense of taste and/or smell và, rarely, nasal septal perforation, nasal ulcer, sore throat, throat irritation và dryness, cough, hoarseness, and voice changes.


Eye

Dryness & irritation, conjunctivitis, blurred vision, glaucoma, increased intraocular pressure, and cataracts. Cases of growth suppression have sầu been reported for intranasal corticosteroids, including Fluticasone Propionate Nasal Spray, USP (see ). PRECAUTIONS: Pediatric Use


OVERDOSAGE

Chronic overdosage may result in signs/symptoms of hypercorticism (see ). Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate twice daily for 7 days to lớn healthy human volunteers was well tolerated. Single oral doses up to lớn 16 mg have sầu been studied in human volunteers with no axinh đẹp toxic effects reported. Repeat oral doses up lớn 80 mg daily for 10 days in volunteers và repeat oral doses up lớn 10 mg daily for 14 days in patients were well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active & placebo treatment groups. Axinh đẹp overdosage with this dosage khung is unlikely since 1 bottle of Fluticasone Propionate Nasal Spray, USP, contains approximately 8 mg of fluticasone propionate. PRECAUTIONS

The oral & subcutaneous median lethal doses in mice và rats were >1,000 mg/kg (>20,000 và >41,000 times, respectively, the maximum recommended daily intranasal dose in adults & >10,000 and >trăng tròn,000 times, respectively, the maximum recommended daily intranasal dose in children on a mg/m basis). 2


DOSAGE AND ADMINISTRATION

Patients should use Fluticasone Propionate Nasal Spray, USPhường, at regular intervals for optimal effect.


Adults

The recommended starting dosage in is 2 sprays (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 200 mcg). The same dosage divided into 100 mcg given twice daily (e.g., 8 a.m. and 8 p.m.) is also effective sầu. After the first few days, patients may be able khổng lồ reduce their dosage khổng lồ 100 mcg (1 spray in each nostril) once daily for maintenance therapy. Some patients (12 years of age và older) with seasonal allergic rhinitis may find as-needed use of 200 mcg once daily effective sầu for symptom control (see ). Greater symptom control may be achieved with scheduled regular use. adultsCLINICAL TRIALS


Adolescents & Children (4 Years of Age and Older)

Patients should be started with 100 mcg (1 spray in each nostril once daily). Patients not adequately responding khổng lồ 100 mcg may use 200 mcg (2 sprays in each nostril). Once adequate control is achieved, the dosage should be decreased to lớn 100 mcg (1 spray in each nostril) daily.

The maximum total daily dosage should not exceed 2 sprays in each nostril (200 mcg/day). (See ). CLINICAL TRIALS: Individualization of Dosage

Fluticasone Propionate Nasal Spray, USP, is not recommended for children under 4 years of age.


Directions for Use

Illustrated patient’s instructions for proper use accompany each package of Fluticasone Propionate Nasal Spray, USPhường.


PATIENT INSTRUCTIONS FOR USE

Please read this leaflet carefully before you start khổng lồ take your medicine. It provides a summary of information on your medicine. For further information ask your doctor or pharmacist.


WHAT YOU SHOULD KNOW ABOUT RHINITIS

Rhinitis is a word that means inflammation of the lining of the nose. If you suffer from rhinitis, your nose becomes stuffy & runny. Rhinitis can also make your nose itchy, và you may sneeze a lot. Rhinitis can be caused by allergies lớn pollen, animals, molds, or other materials-or it may have a nonallergic cause.


WHAT YOU SHOULD KNOW ABOUT FLUTICASONE PROPIONATE NASAL SPRAY, USP

Your doctor has prescribed Fluticasone Propionate Nasal Spray, USPhường, a medicine that can help treat your rhinitis. Fluticasone Propionate Nasal Spray, USP, contains fluticasone propionate, which is a synthetic corticosteroid. Corticosteroids are natural substances found in the body toàn thân that help fight inflammation. When you spray Fluticasone Propionate Nasal Spray, USPhường, inkhổng lồ your nose, it helps to reduce the symptoms of allergic reactions và the stuffiness, runniness, itching, & sneezing that can bother you.


THINGS TO REMEMBER ABOUT FLUTICASONE PROPIONATE NASAL SPRAY, USP

1. Shake gently before using.

2. Use your nasal spray as directed by your doctor. The directions are on the pharmacy label.

3. Keep your nasal spray . out of the reach of children


BEFORE USING YOUR NASAL SPRAY

If you are pregnant (or intending khổng lồ become pregnant),If you are breastfeeding a baby,If you are allergic khổng lồ Fluticasone Propionate Nasal Spray, USP.., or any other nasal corticosteroid,If you are taking a medicine containing ritonavir (commonly used khổng lồ treat HIV infection or AIDS).

In some circumstances, this medicine may not be suitable & your doctor may wish to lớn give sầu you a different medicine. Make sure that your doctor knows what other medicines you are taking. TELL YOUR DOCTOR BEFORE STARTING TO TAKE THIS MEDICINE.


USING YOUR NASAL SPRAY

Follow the instructions shown in the rest of this leaflet. If you have sầu any problems, tell your doctor or pharmacist.It is important that you use it as directed by your doctor. The pharmacist¡¦s label will usually tell you what dose khổng lồ take và how often. If it doesn¡¦t, or you are not sure, ask your doctor or pharmacist.

DOSAGE

For , the usual starting dose is . Sometimes your doctor may recommover using 1 spray in each nostril twice a day (morning & evening). You should not use more than a total of 2 sprays in each nostril daily. After you have sầu begun lớn feel better, 1 spray in each nostril daily may be adequate for you. ADULTS2 sprays in each nostril once daily

For (4 years of age và older), the usual starting dosage is . Sometimes your doctor may recommend using 2 sprays in each nostril daily. Then, after you have sầu begun khổng lồ feel better, 1 spray in each nostril daily may be adequate for you. ADOLESCENTS & CHILDREN1 spray in each nostril once daily

DO NOT use more of your medicine or take it more often than your doctor advises.Fluticasone Propionate Nasal Spray, USPhường, may begin to work within 12 hours of the first dose, but it takes several days of regular use to lớn reach its greatest effect. It is important that you use Fluticasone Propionate Nasal Spray, USPhường., as prescribed by your doctor. Best results will be obtained by using the spray on a regular basis. If symptoms disappear, liên hệ your doctor for further instructions.If you also have itchy, watery eyes, you should tell your doctor. You may be given an additional medicine to lớn treat your eyes. Be careful not khổng lồ confuse them, particularly if the second medicine is an eye drop.If you miss a dose, just take your regularly scheduled next dose when it is due. DO NOT DOUBLE the dose.

BEFORE USING

1. Shake the bottle gently and then remove the cap (Figure 1).

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Figure 1

2. It is necessary khổng lồ prime the pump inkhổng lồ the air the first time it is used, or when you have not used it for a week or more. To prime the pump, hold the bottle as shown with the nasal applicator pointing away from you & with your forefinger và middle finger on either side of the nasal applicator và your thumb underneath the bottle. When you prime the pump for the first time, press down and release the pump 6 times (Figure 2). The pump is now ready for use. If the pump is not used for 7 days, prime until a fine spray appears.

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Figure 2


USING THE SPRAY

3. Blow your nose khổng lồ clear your nostrils

4. Cthất bại one nostril. Tilt your head forward slightly and, keeping the bottle upright, carefully insert the nasal applicator inkhổng lồ the other nostril (Figure 3).

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Figure 3

5. Start to lớn breathe in through your nose, và WHILE BREATHING IN press firmly and quickly down once on the applicator to release the spray. To get a full actuation, use your forefinger and middle finger khổng lồ spray while supporting the base of the bottle with your thumb. Avoid spraying in eyes. Breathe gently inwards through the nostril (Figure 4).

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Figure 4

6. Breathe out through your mouth.

7. If a second spray is required in that nostril, repeat steps 4 through 6.

8. Repeat steps 4 through 7 in the other nostril.

9. Wipe the nasal applicator with a clean tissue & replace the cap (Figure 5).

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Figure 5

10. Do not use this bottle for more than the labeled number of sprays even though the bottle is not completely empty. Before you throw the bottle away, you should consult your doctor khổng lồ see if a refill is needed. Do not take extra doses or stop taking Fluticasone Propionate Nasal Spray, USP, without consulting your doctor.


CLEANING

Your nasal spray should be cleaned at least once a week. To vị this:

1. Remove sầu the cap & then gently pull upwards to lớn không tính phí the nasal applicator.

2. Wash the applicator và cap under warm tap water. Allow to dry at room temperature, then place the applicator and cap baông chồng on the bottle.

3. If the nasal applicator becomes blocked, it can be removed as above and left khổng lồ soak in warm water. Rinse with cold tap water, dry, & refit. Do not try lớn unbloông xã the nasal applicator by inserting a pin or other sharp object.


STORING YOUR NASAL SPRAY

Keep your Fluticasone Propionate Nasal Spray, USPhường, . out of the reach of childrenAvoid spraying in eyes.Store between 4° và 30°C (39°F and 86°F).Do not use your Fluticasone Propionate Nasal Spray, USP, after the expiration date shown on the label and box.

REMEMBER: This medicine has been prescribed for you by your doctor. DO NOT give sầu this medicine to anyone else.


FURTHER INFORMATION

The leaflet does not contain the complete information about your medicine. . If you have sầu any questions, or are not sure about something, then you should ask your doctor or pharmacist

You may want to read this leaflet again. Please DO NOT THROW IT AWAY until you have finished your medicine.

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured by:

Hi-Tech Pharmacal Co., Inc.

Xem thêm: Hiện Tượng Bóng Đè Khi Ngủ, Mẹo Để Thoát Khỏi Tình Trạng Bóng Đè Khi Ngủ

Amityville, N.Y. 11701

Made in U.S.A.

Rev. 700:05 8/11


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