2.1 Adults and Adolescents 12 Years of Age and Older

The recommended starting and maximum dose is 220 mcg per day as two sprays in each nostril once daily. Titrate an individual patient to the minimum effective dose to reduce the possibility of side effects. When the maximum benefit has been achieved and symptoms have been controlled, reducing the dose to 110 mcg per day (one spray in each nostril once a day) has been shown to be effective in maintaining control of the allergic rhinitis symptoms.

2.2 Children 2 to 12 Years of Age

2.3 Administration Information

5.1 Local Nasal Effects

5.2 Glaucoma and Cataracts

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.

5.3 Immunosuppression

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 exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If 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 develops, treatment with antiviral agents may be considered.

Corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis 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.

5.4 Hypothalamic-Pituitary-Adrenal Axis Effects

5.5 Effect on Growth

Corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth routinely of pediatric patients receiving triamcinolone acetonide nasal spray. To minimize the systemic effects of intranasal corticosteroids, including triamcinolone acetonide nasal spray, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms [see Use in Specific Populations (8.4)].

6.1 Clinical Trials Experience

In placebo-controlled, double-blind, and open-label clinical studies, 1483 adults and children 12 years and older received treatment with triamcinolone acetonide nasal spray. These patients were treated for an average duration of 51 days. In the controlled trials (2-5 weeks duration) from which the following adverse reaction data are derived, 1394 patients were treated with triamcinolone acetonide nasal spray for an average of 19 days. In a long-term, open-label study, 172 patients received treatment for an average duration of 286 days. Adverse reactions from 12 studies in adults and adolescent patients 12 to 17 years of age receiving triamcinolone acetonide nasal spray 27.5 mcg to 440 mcg once daily are summarized in Table 1.

In clinical trials, nasal septum perforation was reported in one adult patient who received triamcinolone acetonide nasal spray.

A total of 602 children 6 to 12 years of age were studied in 3 double-blind, placebo-controlled clinical trials. Of these, 172 received 110 mcg/day and 207 received 220 mcg/day of triamcinolone acetonide nasal spray for two, six, or twelve weeks. The longest average durations of treatment for patients receiving 110 mcg/day and 220 mcg/day were 76 days and 80 days, respectively. One percent of patients treated with triamcinolone acetonide were discontinued due to adverse experiences. No patient receiving 110 mcg/day and one patient receiving 220 mcg/day discontinued due to a serious adverse event. A similar adverse reaction profile was observed in pediatric patients 6 to 12 years of age as compared to adolescents and adults with the exception of epistaxis which occurred in less than 2% of the children studied. Adverse reactions from 2 studies in children 4 to 12 years of age receiving triamcinolone acetonide nasal spray 110 mcg once daily are summarized in Table 2.

A total of 474 children 2 to 5 years of age were studied in a 4-week double-blind, placebo-controlled clinical trial. Of these, 236 received 110 mcg/day of triamcinolone acetonide nasal spray for a mean duration of 28 days. No patient discontinued due to a serious adverse event. Adverse reactions from the single placebo-controlled study in children 2 to 5 years of age receiving triamcinolone acetonide nasal spray 110 mcg once daily are summarized in Table 3.

In the event of accidental overdose, an increased potential for these adverse experiences may be expected, but acute systemic adverse experiences are unlikely. [see Overdosage (10)]

6.2 Post-Marketing Experience

In addition to the adverse drug reactions reported during clinical studies and listed above, the following adverse events have been identified during post-approval use of triamcinolone acetonide nasal spray. Because these events 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. Events that have been reported during post-marketing experience include: nasal discomfort and congestion, sneezing, alterations of taste and smell, nausea, insomnia, dizziness, fatigue, dyspnea, decreased blood cortisol, cataract, glaucoma, increased ocular pressure, pruritus, rash, and hypersensitivity.

8.1 Pregnancy

8.3 Nursing Mothers

It is not known whether triamcinolone acetonide is excreted in human milk. Because other corticosteroids are excreted in human milk, caution should be exercised when triamcinolone acetonide nasal spray is administered to nursing women.

8.4 Pediatric Use

The safety and effectiveness of triamcinolone acetonide nasal spray has been evaluated in 464 children 2 to 5 years of age, 518 children 6 to 12 years of age, and 176 adolescents 12 to 17 years of age [see Clinical Studies (14)]. The safety and effectiveness of triamcinolone acetonide nasal spray in children below 2 years of age 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 of 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 triamcinolone acetonide 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 triamcinolone acetonide nasal spray, each patient's dose should be titrated to the lowest dosage that effectively controls his/her symptoms.

The potential for triamcinolone acetonide nasal spray to cause growth suppression in susceptible patients and when given at higher than recommended dosages cannot be ruled out.

8.5 Geriatric Use

Clinical studies of triamcinolone acetonide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

12.1 Mechanism of Action

Triamcinolone acetonide is a synthetic fluorinated corticosteroid with approximately 8 times the potency of prednisone in animal models of inflammation.

Although the precise mechanism of corticosteroid antiallergic action is unknown, 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.

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

Based upon intravenous dosing of triamcinolone acetonide phosphate ester in adults, 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 acetonide nasal spray formulation was determined in both normal adult subjects and patients with allergic rhinitis. Single dose intranasal administration of 220 mcg of triamcinolone acetonide nasal spray in normal adult subjects and patients demonstrated minimal absorption of triamcinolone acetonide. 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 (the minimum LOQ of the assay was 0.025 ng/mL) at 24 hours. The average terminal half-life was 3.1 hours. The range of mean AUC0–∞ values was 1.4 ng∙hr/mL to 4.7 ng∙hr/mL between doses of 110 mcg to 440 mcg in both patients and healthy volunteers. Dose proportionality was demonstrated in both normal adult subjects and in allergic rhinitis patients following single intranasal doses of 110 mcg or 220 mcg triamcinolone acetonide nasal spray. The Cmax and AUC0-∞ of the 440 mcg dose increased less than proportionally when compared to 110 and 220 mcg doses.

Following multiple dose administration of triamcinolone acetonide 440 mcg once daily in pediatric patients 6 to 12 years of age, plasma drug concentrations, AUC0-∞, Cmax and Tmax were similar to those values observed in adult patients receiving the same dose. Intranasal administration of triamcinolone acetonide 110 mcg once daily in pediatric patients 2 to 5 year of age exhibited similar systemic exposure to that achieved in adult patients 20 to 40 years of age with intranasal administration of triamcinolone acetonide at a dose of 220 mcg once daily. Based on the population pharmacokinetic modeling, the apparent clearance and volume of distribution following intranasal administration of triamcinolone acetonide in pediatric patients 2 to 5 years of age were found to be approximately half of that in adults.

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.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

In a two-year study in rats, triamcinolone acetonide caused no treatment-related carcinogenicity at oral doses up to 1 mcg/kg (less than the maximum recommended daily intranasal dose in adults and children on a mcg/m2 basis, respectively). In a two-year study in mice, triamcinolone acetonide caused no treatment-related carcinogenicity at oral doses up to 3 mcg/kg (less than the maximum recommended daily intranasal dose in adults and children on a mcg/m2 basis, respectively).

No evidence of mutagenicity was detected from in vitro tests (a reverse mutation test in Salmonella bacteria and a forward mutation test in Chinese hamster ovary cells) conducted with triamcinolone acetonide.

In male and female rats, triamcinolone acetonide caused no change in pregnancy rate at oral doses up to 15 mcg/kg (less than the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). Triamcinolone acetonide caused increased fetal resorptions and stillbirths and decreases in pup weight and survival at doses of 5 mcg/kg and above (less than the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). At 1 mcg/kg (less than the maximum recommended daily intranasal dose in adults on a mcg/m2 basis), it did not induce the above mentioned effects.

13.2 Animal Toxicology and/or Pharmacology

Triamcinolone acetonide was teratogenic in rats, rabbits, and monkeys. In rats, triamcinolone acetonide was teratogenic at inhalation doses of 20 mcg/kg and above (approximately 7/10 of the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). In rabbits, triamcinolone acetonide was teratogenic at inhalation doses of 20 mcg/kg and above (approximately 2 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). In monkeys, triamcinolone acetonide was teratogenic at an inhalation dose of 500 mcg/kg (approximately 37 times the maximum recommended daily intranasal dose in adults on a mcg/m2 basis). Dose-related teratogenic effects in rats and rabbits included cleft palate and/or internal hydrocephaly and axial skeletal defects, whereas the effects observed in the monkey were cranial malformations.

Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed.

16.1 How Supplied

Triamcinolone Acetonide Nasal Spray, 55 mcg per spray, is supplied in a white high-density polyethylene container with a metered-dose pump unit, white nasal adapter, and patient instructions.

NDC 0093-2085-17

The contents of one 16.5 gram bottle provide 120 actuations. After 120 actuations, the amount of triamcinolone acetonide delivered per actuation may not be consistent and the unit should be discarded. Each actuation delivers 55 mcg triamcinolone acetonide from the nasal actuator after an initial priming of 5 sprays [see Administration Information (2.3)].

In the Patient Package Information, patients are provided with a check-off form to track usage [see Patient Counseling Information (17)].

WARNING: KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

16.2 Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

17.1 Local Nasal Effects

Patients should be informed that treatment with triamcinolone acetonide nasal spray may lead to adverse reactions, which include epistaxis and nasal ulceration. Candida infection may also occur with treatment with triamcinolone acetonide nasal spray. In addition, nasal corticosteroids are associated with nasal septal perforation and impaired wound healing. Patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use triamcinolone acetonide nasal spray until healing has occurred [see Warnings and Precautions (5.1)].

17.2 Cataracts and Glaucoma

Patients should be informed that glaucoma and cataracts are associated with nasal and inhaled corticosteroid use. Patients should inform his/her healthcare provider if a change in vision is noted while using triamcinolone acetonide nasal spray [see Warnings and Precautions (5.2)].

17.3 Immunosuppression

Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to consult their physician without delay. Patients should be informed of potential worsening of existing tuberculosis, fungal, bacterial, viral or parasitic infections, or ocular herpes simplex [see Warnings and Precautions (5.3)].

17.4 Use Daily for Best Effect

Patients should use triamcinolone acetonide nasal spray on a regular once-daily basis for optimal effect. It is also important to shake the bottle well before each use. Do not blow your nose for 15 minutes after using the spray. Triamcinolone acetonide nasal spray, like other corticosteroids, does not have an immediate effect on rhinitis symptoms. Although improvement in some patient symptoms may be seen within the first day of treatment, maximum benefit may not be reached for up to one week. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens.

17.5 Keep Spray Out of Eyes

Patients should be informed to avoid spraying triamcinolone acetonide nasal spray in their eyes.

17.6 Patient Package Information

IMPORTANT: Please read these instructions carefully before using your triamcinolone acetonide nasal spray.

Manufactured in Israel by:

Perrigo Israel Pharmaceuticals Ltd.
Industrial Zone, Yeruham 80500, Israel
Manufactured for:
TEVA Pharmaceuticals USA
Sellersville, PA 18960

Rev. A 9/2012

Triamcinolone Acetonide Nasal Spray 0.055 mg/spray Carton Text

NDC 0093-2085-17

TRIAMCINOLONE
ACETONIDE
Nasal Spray
0.055 mg/spray

FOR INTRANASAL USE ONLY
SHAKE WELL BEFORE USING

Attention Pharmacist: DISPENSE WITH
INFORMATION FOR THE PATIENT.

Rx only

One 16.5g Spray Bottle
120 Metered Actuations

TEVA