Nasacort HFA (Aerosol, Metered)
Recommended Doses:<br/>Adults and Adolescents 12 years of age and older: The recommended starting dose of Nasacort HFA Nasal Aerosol is 220 mcg per day given as 2 sprays (55 mcg/spray) in each nostril once daily. If needed, the dose may be increased to 440 mcg per day given as 4 sprays (55 mcg/spray) in each nostril once daily. Once the maximal effect has been achieved, it is always desirable to titrate the patient to the minimum effective dose.<br/>Children 6 through 11 years of age: The recommended dose of Nasacort HFA Nasal Aerosol is 220 mcg per day given as 2 sprays (55 mcg/spray) in each nostril once daily. Once the maximal effect has been achieved, it is always desirable to titrate the patient to the minimum effective dose. Safety and effectiveness have not been established in pediatric patients below the age of 6 years .<br/>Directions for Use: Illustrated PATIENT'S INSTRUCTIONS FOR USE accompanies each package.
Triamcinolone acetonide, USP, the active ingredient in Nasacort HFA Nasal Aerosol, is a glucocorticosteroid with a molecular weight of 434.5, the chemical designation 9-Fluoro-11��,16��,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone (CHFO), and the following chemical structure: Triamcinolone acetonide is a white to cream-colored crystalline powder, practically insoluble in water, very soluble in dehydrated alcohol, chloroform, and methyl alcohol. Nasacort HFA Nasal Aerosol is a metered-dose aerosol unit containing a microcrystalline suspension of triamcinolone acetonide in tetrafluoroethane (HFA-134a) and dehydrated alcohol USP 0.7% w/w. Each canister contains 15 mg of triamcinolone acetonide. The canister must be primed with 3 actuations prior to the first use or after a period of non-use (3 days). After priming, each actuation meters 100 mcg of triamcinolone acetonide in 65 mg of suspension from the valve and delivers 55 mcg of triamcinolone acetonide from the nasal actuator to the patient. If the product is not used for more than 3 days, it should be re-primed with 3 actuations. Each 9.3 g canister of Nasacort HFA Nasal Aerosol provides 100 metered sprays. After 100 metered sprays, this amount of medication delivered per actuation may not be consistent and the unit should be discarded. Patients are provided with a check-off card to track usage as part of the PATIENT'S INSTRUCTIONS FOR USE tear-off sheet.
Triamcinolone acetonide, a synthetic glucocorticosteroid, is a more potent derivative of triamcinolone. Although triamcinolone itself is approximately 1 to 2 times as potent as prednisone in animal models of inflammation, triamcinolone acetonide is approximately 8 times more potent than prednisone. The clinical relevance of in vitro or animal models of potency comparison is unknown. The precise mechanism of corticosteroid action on allergic rhinitis is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation. Nasacort HFA Nasal Aerosol, like other corticosteroids, does not have an immediate effect on allergic rhinitis signs and symptoms. When corticosteroids are discontinued, symptoms may not recur for several days.<br/>Pharmacokinetics:<br/>Absorption: Triamcinolone acetonide is absorbed into the systemic circulation in humans following intranasal administration. In a study involving 24 patients with allergic rhinitis and 24 healthy subjects, absorption of triamcinolone from the nasal mucosa was similar. Following a single intranasal administration of 440 mcg of Nasacort HFA Nasal Aerosol to healthy subjects, the mean maximum triamcinolone acetonide plasma concentration of 0.2 (SD��0.1) ng/mL was observed at 3.8 (SD��2.4) hours postdosing.<br/>Distribution: Based on an intravenous dose of 2 mg of triamcinolone acetonide phosphate ester in 12 healthy subjects, the mean volume of distribution (Vd) was 103.4 L (SD��58.7). The binding of triamcinolone acetonide to plasma proteins is relatively low, and remains consistent over a wide plasma triamcinolone acetonide concentration range (0.03���3.2 ng/mL). Based on an ex vivo study, the overall mean percent bound to plasma protein was approximately 68% (SD��4.3%).<br/>Metabolism: The metabolism and excretion of triamcinolone acetonide were both rapid and extensive with no parent compound being detected in plasma after 24 hours post oral [C]-triamcinolone radiolabeled dose. The disposition and metabolic profile of [C]-triamcinolone acetonide in human plasma, urine, and feces was evaluated in 6 healthy male subjects. Three major metabolites in plasma were 6��-hydroxytriamcinolone acetonide, triamcinolone acetonide-21-oic acid, and 6��-hydroxytriamcinolone acetonide-21-oic acid. Two major metabolites in the urine were 6��-hydroxytriamcinolone acetonide and its derivative following further oxidation (possibly 6-oxo-triamcinolone acetonide or 11-oxo-triamcinolone acetonide). A trace amount of triamcinolone acetonide-21-oic acid was also found in urine. Primary metabolites in the feces were the same as those in plasma. All three major metabolites in the plasma had no activity as determined by in vitro studies.<br/>Elimination: Based on an intravenous dose of 2 mg of triamcinolone acetonide phosphate ester in 12 healthy subjects, the mean half-life of triamcinolone acetonide was 2 hours (SD��0.7), and the mean clearance was 37.3 L/hour (SD��12.8). Following a single intranasal administration of 440 mcg of triamcinolone acetonide in 24 healthy subjects, the mean half-life was 5.4 hours (SD��4.1). However, this value probably reflects lingering absorption of triamcinolone acetonide. Following a single 800 mcg oral dose of radiolabeled [C]-triamcinolone acetonide in 6 healthy subjects, urinary and fecal excretion accounted for approximately 90% of the oral [C]-radiolabeled dose. Of the recovered [C]-radioactivity, approximately 40% and 60% were found in the urine and feces, respectively. Urinary excretion of [C]-radioactivity was essentially complete within 24 hours post-dose with most of the fecal elimination completed between 48 and 96 hours post-dose. The plasma half-life of corticosteroids does not correlate well with the duration of the drug's activity.<br/>Special Populations: Formal pharmacokinetic studies using intranasal triamcinolone acetonide were not carried out in any special populations. The effects of renal impairment, hepatic impairment, age, or gender on the pharmacokinetics of triamcinolone acetonide following intranasal administration have not been investigated.<br/>Pharmacodynamics: Several studies were performed to determine if systemic absorption played a role in the response to triamcinolone acetonide in the treatment of allergic rhinitis. An open-label, multiple-dose study was conducted comparing intranasal CFC and depot intramuscular formulations of triamcinolone acetonide in 25 adult patients with seasonal or perennial allergic rhinitis. The doses used were based on bioavailability studies of each formulation. The intranasal CFC formulation was administered at a dose of 440 mcg once daily for 42 days, and the 4 mg depot intramuscular formulation was administered once a week for 42 days. Weekly injection yielded sustained plasma levels throughout the dosing interval while daily intranasal administration resulted in daily peak and trough concentrations, the mean of which was 3.5 times below the mean plasma levels achieved with intramuscular administration. Both intranasal and intramuscular triamcinolone acetonide were clinically effective on allergic rhinitis symptoms. This suggests that triamcinolone acetonide is both systemically and topically active. The potential systemic effects of triamcinolone acetonide aqueous formulation (Nasacort AQ Nasal Spray) on the hypothalamic-pituitary-adrenal (HPA) axis were studied in 64 patients with allergic rhinitis. Nasacort AQ Nasal Spray administered to adults at doses of 220 or 440 mcg once daily was compared to placebo or 10 mg prednisone administered as oral capsules for 42 days. Plasma cortisol concentrations were not affected in patients treated with either placebo or Nasacort AQ Nasal Spray in response to a 6-hour cosyntropin stimulation test, while oral prednisone significantly reduced the response to cosyntropin. In another trial, the potential systemic effects of triamcinolone acetonide CFC formulation (Nasacort Nasal Inhaler) on the HPA axis were studied in 64 patients with allergic rhinitis. Nasacort Nasal Inhaler administered to adults at doses of 220 or 440 mcg once daily was compared to placebo or 10 mg prednisone once daily administered as oral capsules for 42 days. Plasma cortisol concentrations, 24-hour urinary 17-OHCS, and 24-hour urinary free cortisol concentrations were not affected in patients treated with either placebo or Nasacort Nasal Inhaler in response to a 6-hour cosyntropin stimulation test, while oral prednisone significantly reduced the response to cosyntropin for plasma cortisol concentrations and24-hour urinary 17-OHCS concentrations. A study was conducted evaluating plasma cortisol response 30 and 60 minutes after cosyntropin stimulation in 80 pediatric patients aged 6 to 12 years with allergic rhinitis who received 220 mcg or 440 mcg (twice the maximum recommended daily dose) of Nasacort AQ Nasal Spray daily for 6 weeks. No abnormal response to cosyntropin infusion (peak serum cortisol<18 mcg/dL) was observed after 6 weeks of dosing at 440 mcg per day.<br/>Clinical Trials: The determination of efficacy and safety of Nasacort HFA Nasal Aerosol is based on the clinical program linking Nasacort HFA Nasal Aerosol to Nasacort Nasal Inhaler (triamcinolone acetonide CFC formulation), and by extrapolation from the known efficacy and safety of the Nasacort Nasal Inhaler. The clinical program of Nasacort HFA Nasal Aerosol included 2 studies conducted in the United States involving 1176 patients 12 to 83 years of age with allergic rhinitis, of whom 729 patients were treated with Nasacort HFA Nasal Aerosol. One study was a 2-week, double-blind, parallel-group, placebo-controlled trial comparing Nasacort HFA Nasal Aerosol to Nasacort Nasal Inhaler (triamcinolone acetonide CFC formulation) in 780 patients 18 years of age and older with seasonal allergic rhinitis. The design incorporated 2 doses of Nasacort Nasal Inhaler that were known to be effective (110 mcg and 440 mcg once daily), and 2 doses of Nasacort HFA Nasal Aerosol (110 mcg and 440 mcg once daily). Another study was a 12-month, open-label safety study in 396 patients 12 years of age and older with perennial allergic rhinitis. The dose of Nasacort HFA Nasal Aerosol was 220 mcg once daily for the first 2 weeks and 440 mcg once daily for the remainder of the study. In the 2-week, double-blind study, Nasacort HFA Nasal Aerosol and Nasacort Nasal Inhaler (triamcinolone acetonide CFC formulation) were comparable, and both formulations showed a significant reduction in symptoms of allergic rhinitis (see table below). There were no significant differences in the effectiveness of Nasacort HFA Nasal Aerosol across subgroups of patients defined by gender, age, or race.<br/>Individualization of Dosage: Individual patients will experience a variable time to onset and degree of symptom relief when using Nasacort HFA Nasal Aerosol. After starting patients on appropriate doses of Nasacort HFA Nasal Aerosol it is recommended that the effect be assessed in 4 to 7 days. If adequate relief has not been obtained by a reasonable time, alternate forms of treatment should be considered. The maximum total daily dose should not exceed 440 mcg (4 sprays in each nostril) in patients 12 years of age and older and 220 mcg (2 sprays in each nostril) in patients 6 through 11 years of age. There is no evidence that exceeding the recommended dose is more effective. In general, it is always desirable to titrate an individual patient to the minimum effective dose to reduce the possibility of side effects.
Nasacort HFA Nasal Aerosol is contraindicated in patients with a hypersensitivity to any of the ingredients.
Nasacort HFA Nasal Aerosol is supplied with an aerosol canister which provides 100 metered dose actuations. The correct amount of medication delivered per actuation cannot be assured after 100 actuations have been dispensed, after which the unit should be discarded. Each actuation delivers 55 mcg triamcinolone acetonide through the nasal actuator. The Nasacort HFA Nasal Aerosol canister and accompanying nasal actuator are designed to be used together. The Nasacort HFA Nasal Aerosol canister should not be used with other nasal actuators and the supplied nasal actuator should not be used with other products' canisters. Nasacort HFA Nasal Aerosol is supplied with a molecular sieve sachet as a propellant adsorbent and a white plastic protective cap, and enclosed in a foil laminate overwrap pouch. Patient instructions are also provided. Net weight of the canister contents is 9.3 grams. NDC 0075-9403-43
Nasacort HFA (Aerosol, Metered)
Clinical Trials: A total of 1176 patients with allergic rhinitis were enrolled in placebo-controlled and open-label clinical studies of Nasacort HFA Nasal Aerosol. In the placebo-controlled trial, 220 patients were treated with Nasacort HFA Nasal Aerosol for an average of 15 days (range 1���19 days). No changes in mucous membranes were noted from physical and visual examinations during this trial. Adverse events occurring with an incidence of 3% or greater and more commonly with Nasacort HFA Nasal Aerosol arms compared to placebo irrespective of drug relationship are presented in the following table: Of the 396 patients enrolled in the 12-month open-label study, 75% received treatment for greater than 6 months. In this study, patients were treated with Nasacort HFA Nasal Aerosol at 220 mcg once daily for the first 2 weeks and 440 mcg once daily for remainder of the study. Adverse events that were considered possibly or probably related to Nasacort HFA Nasal Aerosol and reported at an incidence of 3% or greater included: headache, epistaxis, nasal septum discomfort, rhinitis, nasal burning, and sneezing. In the open-label study only 2% of patients receiving recommended doses discontinued due to nasal adverse effects. In the rest of the patients the nasal adverse events usually did not interfere with treatment. Seven of the 18 patients who reported nasal septum discomfort had objective evidence of ulceration, abrasion, erosion, or excoriation of the nasal septum, and 22 of the 396 (5.5%) enrolled patients developed nasal septum disorders, of whom 8 had evidence of ulceration, erosion, or excoriation of the septum, and 14 had epistaxis. It is advisable for patients who experience nasal septum discomfort to re-evaluate their technique in the application of Nasacort HFA Nasal Aerosol to minimize deposition of drug onto the septum. If recommended doses are exceeded, or if individuals taking Nasacort HFA Nasal Aerosol are particularly sensitive or take the drug in conjunction with other corticosteroids, symptoms of hypercorticism, e.g., Cushing syndrome, could occur. In the event of accidental overdose, an increased potential for these adverse experiences may be expected, but systemic adverse experiences are unlikely .<br/>Observed During Clinical Practice: In addition to adverse events reported from clinical trials, the following events have been identified during use of Nasacort Nasal Inhaler (triamcinolone acetonide CFC formulation) in clinical practice: nasal septal perforation, infection of the nose and pharynx with Candida albicans, cataracts, glaucoma, increased intraocular pressure, wheezing, rash, pruritus, urticaria, dizziness, paresthesia, dry mouth, nausea, coughing, dyspnea, and allergic reaction. Because they were reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or possible causal connection to triamcinolone acetonide or a combination of these factors.
Nasacort HFA Nasal Aerosol is indicated for the treatment of the nasal symptoms of allergic rhinitis (seasonal and perennial) in adults and children 6 years of age and older. Safety and effectiveness of Nasacort HFA Nasal Aerosol in children below 6 years of age have not been adequately established.