Nasacort AQ (Triamcinolone Acetonide)

NASACORT® AQ

Rhône-Poulenc Rorer

Triamcinolone Acetonide

Corticosteroid

Action And Clinical Pharmacology: Triamcinolone acetonide is a potent anti-inflammatory steroid with strong topical and weak systemic activity. Triamcinolone acetonide 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.

When administered intranasally in therapeutic doses, it has a direct anti-inflammatory action on the nasal mucosa, the mechanism of which is not yet completely defined. The minute amount absorbed in therapeutic doses has not been shown to exert any apparent clinical systemic effects.

Corticosteroids are very effective. However, when allergic symptoms are very severe, local treatment with recommended doses (g) of any available topical corticosteroid are not as effective as treatment with larger doses (mg) of oral or parenteral formulations. Corticosteroids do not have an immediate effect on allergic signs and symptoms. An improvement of symptoms may be seen as early as the first day after initiation of treatment and full benefit may be expected in 3 to 4 days. However, symptomatic relief may not occur in some patients for as long as 2 weeks. Triamcinolone aqueous should not be continued beyond 3 weeks in the absence of significant symptomatic improvement.

Pharmacokinetics: Based upon i.v. dosing of triamcinolone acetonide phosphate ester, the half-life of triamcinolone acetonide was reported to be 88 minutes. The volume of distribution (Vd) reported was 99.5 L (SD±27.5) and clearance was 45.2 L/hour (SD±9.1) for triamcinolone acetonide. The plasma half-life of corticosteroids does not correlate well with the biologic half-life.

Pharmacokinetic characterization of the triamcinolone aqueous nasal spray formulation was determined in both normal subjects and in patients with allergic rhinitis. Single dose intranasal administration of 220 g of triamcinolone aqueous in normal adult subjects and patients demonstrated minimal absorption of triamcinolone. The mean peak plasma concentration was approximately 0.5 ng/mL (range: 0.1 to 1 ng/mL) and occurred at 1.5 hours post dose. The mean plasma drug concentration was less than 0.06 ng/mL at 12 hours, and below the assay detection limit at 24 hours. The average terminal half-life was 3.1 hours. Dose proportionality was demonstrated in normal subjects and in patients following a single intranasal dose of 110 g or 220 g triamcinolone aqueous. Following multiple doses in pediatric patients ages 6 to 12 years old receiving 440 g/day, plasma drug concentration, AUC, Cmax and Tmax were similar to those values observed in adult patients.

Triamcinolone aqueous administered intranasally has been shown to be minimally absorbed into the systemic circulation in humans. Patients with active rhinitis showed absorption similar to that found in normal volunteers.

In order to determine if systemic absorption plays a role in triamcinolone aqueous treatment of allergic rhinitis symptoms, a 2 week double-blind placebo-controlled clinical study was conducted comparing Nasacort AQ, orally ingested triamcinolone acetonide, and placebo in 297 patients with seasonal allergic rhinitis. The study demonstrated that the therapeutic efficacy of Nasacort AQ can be attributed to the topical effects of triamcinolone.

In order to evaluate the effects of systemic absorption on the Hypothalamic-Pituitary-Adrenal (HPA) axis, a clinical study was performed comparing 220 g or 440 g Nasacort AQ, or 10 mg prednisone to placebo for 42 days. Adrenal response to a 6-hour cosyntropin stimulation test clearly indicated that Nasacort AQ administered at doses of 220 g and 440 g had no effect on HPA activity versus placebo. Conversely, oral prednisone at 10 mg/day significantly reduced the response to ACTH.

A 6-week study was conducted in 80 pediatric patients to evaluate the effect of 220 g or 440 g of Nasacort AQ versus placebo on HPA function. No evidence of adrenal axis suppression was observed in the pediatric patients exposed to systemic levels of triamcinolone acetonide higher than the systemic levels observed following administration of the maximum recommended dose of Nasacort AQ Nasal Spray.

Clinical Trials: The safety and efficacy of triamcinolone aqueous nasal spray has been evaluated in 10 double-blind, placebo-controlled clinical trials in adults and children 12 years and older with seasonal or perennial allergic rhinitis. The number of patients treated with the triamcinolone aqueous nasal spray in these studies was 1 204; of these patients, 668 were males and 536 were females.

Overall, in double-blind clinical trials of 2 to 4 weeks duration, analysis of the clinical studies has demonstrated that triamcinolone aqueous nasal spray 220 g once daily (2 sprays in each nostril) when compared to placebo provides statistically significant relief of nasal symptoms including sneezing, stuffiness, discharge, and itching.

The safety and efficacy of triamcinolone aqueous nasal spray, at doses of 110 or 220 g once daily, has also been studied in 2 double blind placebo controlled trials of 2 and 12 weeks duration in children ages 4 through 12 years with seasonal and perennial allergic rhinitis. These trials included 355 males and 183 females. Triamcinolone aqueous administered at either dose resulted in statistically significant reductions of allergic rhinitis symptoms.

Indications And Clinical Uses: For the topical treatment of the symptoms of perennial and seasonal allergic rhinitis unresponsive to conventional treatment.

Regular usage is essential since maximum relief may not be obtained until after 2 to 3 days of treatment.

Contra-Indications: Hypersensitivity to any of the ingredients of the triamcinolone aqueous nasal spray, and patients with active or quiescent tuberculosis, or untreated fungal, bacterial and viral infection.

Manufacturers’ Warnings In Clinical States: In patients previously on prolonged periods or high doses of systemic steroids, the replacement with a topical corticosteroid can be accompanied by symptoms of withdrawal, e.g. joint and/or muscular pain, lassitude, and depression; in severe cases, adrenal insufficiency may occur, necessitating the temporary resumption of systemic steroid therapy. These patients should be carefully monitored for acute adrenal insufficiency in response to stress. Careful attention must be given to patients with asthma or other clinical conditions in whom a rapid decrease in systemic steroids may cause a severe exacerbation of their symptoms.

The use of triamcinolone aqueous nasal spray with alternate day systemic prednisone could increase the likelihood of hypothalamic-pituitary-adrenal (HPA) suppression compared to a therapeutic dose of either one alone. Therefore, triamcinolone aqueous nasal spray should be used with caution in patients already receiving alternate-day prednisone treatment for any disease.

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 such children, or in 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 i.v. immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Pregnancy: See Precautions.

Precautions: The replacement of a systemic steroid with triamcinolone aqueous nasal spray has to be gradual and carefully supervised by the physician. The guidelines under Dosage should be followed in all such cases.

During long-term therapy pituitary-adrenal function and hematological status should be assessed.

Patients should be informed that the full effect of triamcinolone aqueous nasal spray therapy is not achieved until 2 to 3 days of treatment have been completed. Treatment of seasonal rhinitis should, if possible, start before the exposure to allergens.

Treatment with triamcinolone aqueous nasal spray should not be stopped abruptly but tapered off gradually.

Corticosteroids may mask some signs of infection and new infections may appear. A decreased resistance to localized infections has been observed during corticosteroid therapy; this may require treatment with appropriate therapy or stopping the administration of triamcinolone aqueous nasal spray.

Glaucoma and osteoporosis are possible adverse effects associated with a long-term use of large doses of corticosteroids. The possibility of atrophic rhinitis and/or pharyngeal candidiasis should be kept in mind.

There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis. ASA should be used cautiously in conjunction with corticosteroids in hypothrombinemia.

Because of the inhibitory effect of corticosteroids on wound healing, in patients who have had recent nasal surgery or trauma, a nasal corticosteroid should be used with caution until healing has occurred. As with other nasally inhaled corticosteroids, nasal septal perforations have been reported in rare instances.

Patients should be advised to inform subsequent physicians of prior use of corticosteroids.

Until greater clinical experience has been gained, the continuous, long-term treatment of children under age 4 is not recommended.

Pregnancy: The safety of triamcinolone aqueous nasal spray in pregnancy has not been established. If used, the expected benefits should be weighed against the potential hazard to the fetus, particularly during the first trimester of pregnancy.

Like other glucocorticosteroids, triamcinolone acetonide is teratogenic to rodents and non-human primates. The relevance of these findings to humans has not yet been established. Infants born of mothers who have received substantial doses of glucocorticosteroids during pregnancy should be carefully observed for hypoadrenalism.

Lactation: Glucocorticosteroids are excreted in human milk. It is not known whether triamcinolone would be secreted in human milk, but it is suspected to be likely. The use of triamcinolone aqueous nasal spray in nursing mothers, requires that the possible benefits of the drug be weighed against the potential hazards to the infant.

Children: Triamcinolone aqueous nasal spray is not presently recommended for children younger than 4 years of age due to limited clinical data in this age group. Oral corticosteroids have been shown to cause growth suppression in children and teenagers, particularly with higher doses over extended periods. If a child or teenager on any corticosteroids appears to have growth suppression, the possibility that they are particularly sensitive to this effect of steroids should be considered.

To ensure the proper dosage and administration of the drug, the patient should be instructed by a physician or other health professional in the use of triamcinolone aqueous nasal spray (see Information for the Patient).

Adverse Reactions: In placebo-controlled, double-blind and open-label clinical studies, 1 483 adults and children 12 years and older received treatment with triamcinolone acetonide aqueous nasal spray. These patients were treated for an average duration of 50.7 days. In the controlled, seasonal trials (2 to 5 weeks duration) from which the following adverse reaction data is derived, 1 394 patients were treated with triamcinolone aqueous nasal spray for an average of 18.7 days. In the long-term, open-label study, the 172 patients enrolled received treatment for an average of 286 days duration.

The most commonly reported adverse reactions included those involving mucous membranes of the nose and throat. The 3 most prevalent adverse reactions considered to be at least possibly drug-related in adults and children 12 years and older were rhinitis (1.5%), headache (0.7%), and pharyngitis (0.3%) and in children 4 to 12 years were epistaxis (3.1%), rhinitis (1.4%) and headache (1.2%).

Children 4 to 12 years of age (n=622) were studied in 3 controlled clinical trials. Of these, 179 received 110 g/day and 215 received 220 g/day of triamcinolone aqueous nasal spray in 2-, 6-, or 12-week trials. The longest average duration of treatment for patients receiving 110 g/day was 76.3 days and 79.6 days for those receiving 220 g/day.

These adverse reactions, with the exception of epistaxis (in adults), and the exception of nasal congestion and sneezing (in children) were reported at approximately the same or lower incidence as placebo treated patients. Only 1% of the patients in the controlled trials discontinued treatment (e.g. pharyngitis, headache). In children, no patient receiving 110 g/day discontinued due to a serious adverse event and 1 patient receiving 220 g/day discontinued due to a serious event that was considered not drug-related. Overall, these studies found the adverse experience profile for triamcinolone aqueous nasal spray to be similar to placebo.

In the event of accidental overdose, an increased potential for these adverse experiences may be expected, but systemic adverse experiences are unlikely (see Overdose).

Hypersensitivity reactions including skin rash and edema of the face or tongue have been reported with other intranasal corticosteroids.

When patients are transferred to triamcinolone aqueous nasal spray from a systemic steroid, allergic conditions such as asthma or eczema may be unmasked (see Warnings).

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Like any other nasally administered corticosteroid, acute overdosing is unlikely in view of the total amount of active ingredient present. In the event that the entire contents of the bottle were administered all at once, via either oral or nasal application, clinically significant systemic adverse events would most likely not result. The patient may experience some gastrointestinal upset.

However when used chronically in excessive doses or in conjunction with other corticosteroid formulations, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of triamcinolone aqueous nasal spray should be discontinued slowly consistent with accepted procedures for discontinuation of chronic steroid therapy (see Dosage).

The restoration of hypothalamic-pituitary axis may be slow; during periods of pronounced physical stress (i.e. severe infections, trauma, surgery) a supplement with systemic steroids may be advisable.

Dosage And Administration: See Warnings.

Not recommended for children under 4 years of age.

Careful attention must be given to patients previously treated for prolonged periods with systemic corticosteroids when transferred to triamcinolone aqueous nasal spray. Initially, triamcinolone aqueous nasal spray and the systemic corticosteroid must be given concomitantly, while the dose of the latter is gradually decreased. The usual rate of withdrawal of the systemic steroid is the equivalent of 2.5 mg of prednisone every 4 days if the patient is under close supervision. If continuous supervision is not feasible, the withdrawal of the systemic steroid should be slower, approximately 2.5 mg of prednisone (or equivalent) every 10 days. If withdrawal symptoms appear, the previous dose of the systemic steroid should be resumed for a week before further decrease is attempted.

The therapeutic effects of corticosteroids, unlike those of decongestants, are not immediate. Since the effect of triamcinolone aqueous nasal spray depends on its regular use, patients must be instructed to take the nasal inhalations at regular intervals and not as with other nasal sprays, as they feel necessary.

In the presence of excessive nasal mucus secretion or edema of the nasal mucosa, the drug may fail to reach the site of action. In such cases it is advisable to use a nasal vasoconstrictor for 2 to 3 days prior to triamcinolone aqueous nasal spray therapy. Patients should be instructed on the correct method of use, which is to blow the nose, then insert the nozzle firmly into the nostril, compress the opposite nostril and actuate the spray while inspiring through the nose, with the mouth closed.

An improvement of symptoms usually becomes apparent within a few days after the start of therapy. However symptomatic relief may not occur in some patients for as long as 2 weeks. The triamcinolone aqueous nasal spray should not be continued beyond 3 weeks in the absence of significant symptomatic improvement.

Adults and Children 12 years of age and older: The recommended starting dose is 220 g as 2 sprays in each nostril once daily.

It is always desirable to titrate an individual patient to the minimum effective dose to reduce the possibility of side effects. Therefore, when the maximum benefit has been achieved and symptoms have been controlled, reducing the dose to 110 g (1 spray in each nostril once/day) has been shown to be effective in maintaining control of the allergic rhinitis symptoms in patients who were initially controlled at 220 g/day (see Precautions, Warnings, Information for the Patient, and Adverse Effects).

Children 4 to 12 years of age: The recommended starting dose is 110 g/day given as 1 spray in each nostril once a day. Patients who do not achieve maximum symptom control may benefit from a dose of 220 g given as 2 sprays in each nostril once a day. Once symptoms are controlled, patients can be maintained on 110 g (1 spray in each nostril) once daily.

Availability And Storage: Each actuation releases approximately triamcinolone acetonide 55 g from the nasal actuator to the patient (estimated from in vitro testing) in an unscented, thixotrophic, water-based formulation. Nonmedicinal ingredients: benzalkonium chloride, carboxymethylcellulose, dextrose, disodium EDTA, hydrochloric acid, microcrystalline cellulose, polysorbate 80, purified water and sodium hydroxide. Non-chlorofluorocarbon (CFC) containing-metered dose pump spray which will provide 120 actuations. After 120 actuations, the amount delivered per actuation may not be consistent and the unit should be discarded. It is supplied with a nasal adapter and patient instructions including a check-off form to track usage. Each bottle contains triamcinolone acetonide 9.075 mg. Store at controlled room temperature (15 to 30°C).

NASACORT® AQ Rhône-Poulenc Rorer Triamcinolone Acetonide Corticosteroid

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