AllerNaze

ALLERNAZE- triamcinolone acetonide spray, metered
Lupin Pharmaceuticals

For Intranasal Use Only

DESCRIPTION:

Triamcinolone acetonide, the active ingredient of AllerNaze , is a corticosteroid with the chemical name, 9α-Fluoro-11β,16α, 17, 21-tetrahydroxypregna-1,4-diene-3, 20-dione cyclic 16, 17-acetal with acetone (C24 H31 FO6 ). Its structural formula is:

Structural Formula for Triamcinolone Acetonide

Triamcinolone acetonide, USP, is a white crystalline powder, with a molecular weight of 434.51. It is practically insoluble in water, and sparingly soluble in dehydrated alcohol, in chloroform and in methanol. It has a melting point temperature range between 292° and 294°C.

AllerNaze is a metered-dose manual spray pump in an amber polyethylene terephthalate (PET) bottle with 0.05% w/v triamcinolone acetonide in a solution containing citric acid, edetate disodium, polyethylene glycol 3350, propylene glycol, purified water, sodium citrate, and 0.01% benzalkonium chloride as a preservative. AllerNaze pH is 5.3.

After initial priming (three sprays) of the AllerNaze metered pump delivery system, each spray will deliver 50 mcg of triamcinolone acetonide. If the pump was not used for more than 14 days, reprime with 3 sprays or until a fine mist is observed. Each 15 mL bottle contains 7.5 mg of triamcinolone acetonide to deliver 120 metered sprays. After 120 sprays, the amount of triamcinolone acetonide delivered per spray may not be consistent and the bottle should be discarded.

CLINICAL PHARMACOLOGY:

Triamcinolone acetonide is a more potent derivative of triamcinolone. Triamcinolone acetonide is approximately eight times more potent than prednisone in animal models of inflammation. The clinical significance of this is unclear.

Although the precise mechanism of corticosteroid antiallergic action is unknown, 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. histamines, eicosanoids, leukotrienes, and cytokines) involved in inflammation.

Pharmacokinetics:

Absorption:

The pharmacokinetics of triamcinolone acetonide solution was evaluated in a single-dose study conducted in 24 patients with perennial allergic rhinitis. Following a single intranasal dose of 400 mcg of triamcinolone acetonide (twice the recommended starting dose of triamcinolone acetonide solution), the mean C max of the drug was 1.12 ng/mL (SD = 0.38) with a median T max of 0.5 hours (range: 0.08 — 1.0).

A pharmacokinetic study to demonstrate dose proportionality was conducted in patients with perennial allergic rhinitis. The C max and AUC of the 200 and 400 mcg doses increased less than proportionally when compared to the 100 mcg dose. Following multiple dosing (100 or 200 or 400 mcg QD for 7 days), there was no evidence of drug accumulation.

Distribution:

The volume of distribution (Vd) reported was 99.5 L (SD = 27.5).

Metabolism:

In animal studies using rats and dogs, three metabolites of triamcinolone acetonide have been identified. They are 6β-hydroxytriamcinolone acetonide, 21-carboxytriamcinolone acetonide and 21-carboxy-6β-hydroxytriamcinolone acetonide. All three metabolites are expected to be substantially less active than the parent compound due to (a) the dependence of anti-inflammatory activity on the presence of a 21-hydroxyl group, (b) the decreased activity observed upon 6-hydroxylation, and (c) the markedly increased water solubility favoring rapid elimination. There appeared to be some quantitative differences in the metabolites among species. No differences were detected in metabolic pattern as a function of route of administration.

Elimination:

After a single intranasal dose of 400 mcg of triamcinolone acetonide (twice the recommended starting dose of triamcinolone acetonide solution), the mean observed elimination half-life was 2.26 hours (SD=0.77). Based upon intravenous dosing of triamcinolone acetonide phosphate ester, the half-life of triamcinolone acetonide was reported to be 88 minutes. The reported clearance was 45.2 L/hour (SD=9.1) for triamcinolone acetonide.

Special Populations

Age:

The effect of age, specifically in geriatric and pediatric patients, on the pharmacokinetics of triamcinolone acetonide has not been studied.

Gender:

Gender did not significantly influence the pharmacokinetics of triamcinolone acetonide solution.

Race:

The effect of race on the pharmacokinetics of triamcinolone acetonide solution has not been studied.

Renal/Hepatic Insufficiency:

No specific pharmacokinetic studies have been conducted in renally or hepatically impaired subjects.

Drug-Drug Interactions:

No specific drug-drug interactions have been investigated.

Pharmacodynamics:

A small (approximately 5 to 7 patients per treatment group), parallel trial was conducted to assess the effect of triamcinolone acetonide solution on the Hypothalamic-Pituitary-Adrenal (HPA) axis. Patients with allergic rhinitis were treated for six weeks with 400 mcg, 800 mcg, or 1600 mcg total daily doses of triamcinolone acetonide solution, 10 mg oral prednisone once daily, or placebo. Adrenal response to a six-hour cosyntropin stimulation test suggests that intranasal triamcinolone acetonide solution 400 mcg/day for six weeks did not measurably affect adrenal activity. Triamcinolone acetonide solution treatment arms using doses of 800 and 1600 mcg/day demonstrated a trend toward dose-related suppression of HPA response. However, this decrease did not reach statistical significance, whereas 10 mg daily oral prednisone did.

CLINICAL TRIALS:

The efficacy of triamcinolone acetonide solution has been evaluated in 746 patients with seasonal or perennial allergic rhinitis who completed 8 controlled clinical trials.

In total, 1187 patients have been treated with triamcinolone acetonide solution in the clinical development program. Three adequate and well controlled multi-center trials involving 541 patients with seasonal allergic rhinitis who received doses of triamcinolone acetonide solution ranging from 50 mcg to 400 mcg once daily were conducted. These trials evaluated the total nasal symptom scores that included stuffiness, rhinorrhea, itching, and sneezing.

The results showed that patients who received ≥ 200 mcg daily of the active drug had statistically significant relief in the total nasal symptom score compared to those receiving placebo.

In one clinical trial that examined efficacy after 2 days of 200 or 400 mcg triamcinolone acetonide solution treatment, only the 400 mcg dose showed statistically significant improvement over placebo in the nasal symptoms of seasonal allergic rhinitis.

INDICATIONS AND USAGE:

AllerNaze is indicated for the treatment of the nasal symptoms of seasonal and perennial allergic rhinitis in adults and children 12 years of age or older.

CONTRAINDICATIONS:

AllerNaze is contraindicated in patients with a hypersensitivity to any of its ingredients.

WARNINGS:

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

Patients who are on immunosuppressant drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in children or adults on immunosuppressant doses of corticosteroids. In children, or adults who have not had these diseases, particular care should be taken to avoid exposure. If exposed, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

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