Triamcinolone Acetonide

Proprietary name: Azmacort
Established name: Triamcinolone acetonide
Route of administration: RESPIRATORY (INHALATION) (C38216)
Active ingredients (moiety): Triamcinolone acetonide (Triamcinolone)

#	Strength	Form	Inactive ingredients
1	60 MILLIGRAM	AEROSOL, METERED (C42960)	Dehydrated alcohol, dichlorodifluoromethane

Triamcinolone acetonide, USP, the active ingredient in Azmacort® (triamcinolone acetonide inhalation aerosol) Inhalation Aerosol, is a corticosteroid with a molecular weight of 434.5 and with the chemical designation 9- Fluoro-11β,16α,17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with acetone. (C24H31FO6).

Azmacort (triamcinolone acetonide inhalation aerosol) Inhalation Aerosol is a metered-dose aerosol unit containing a microcrystalline suspension of triamcinolone acetonide in the propellant dichlorodifluoromethane and dehydrated alcohol USP 1% w/w. Each canister contains 60 mg triamcinolone acetonide. The canister must be primed prior to the first use. After an initial priming of 2 actuations, each actuation delivers 200 mcg triamcinolone acetonide from the valve and 75 mcg from the spacer-mouthpiece under definedin vitro test conditions. The canister will remain primed for 3 days. If the canister is not used for more than 3 days, then it should be reprimed with 2 actuations. There are at least 240 actuations in one Azmacort (triamcinolone acetonide inhalation aerosol) Inhalation

Aerosol canister. After 240 actuations, the amount delivered per actuation may not be consistent and the unit should be discarded.

#	Name	Strength	Dosage Form	Appearance	Package Type	Package Qty	NDC
1	Azmacort	60MILLIGRAM	AEROSOL METERED (C42960)		INHALER (C16738)	6 MILLIGRAM	60598-061-60

Azmacort Inhalation Aerosol contains 60 mg triamcinolone acetonide in a 20 gram package which delivers at least 240 actuations. It is supplied with a white plastic actuator, a white plastic spacer-mouthpiece and patient's leaflet of instructions: box of one. NDC 60598-061-60. Each actuation delivers 200 mcg triamcinolone acetonide from the valve and 75 mcg from the spacer-mouthpiece under defined in vitro test conditions.

Avoid spraying in eyes.

For best results, the canister should be at room temperature before use.

Shake well before using.

CONTENTS UNDER PRESSURE. Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator. Keep out of reach of children unless otherwise prescribed. Store at Controlled Room Temperature 20 to 25°C (68 to 77°F) [see USP].

Note: The indented statement below is required by the Federal government's Clean Air Act for all products containing or manufactured with chlorofluorocarbons (CFCs):

WARNING: Contains CFC-12, a substance which harms public health and the environment by destroying ozone in the upper atmosphere.

A notice similar to the above WARNING has been placed in the "Information For The Patient" portion of this package insert under the Environmental Protection Agency's (EPA's) regulations. The patient's warning states that the patient should consult his or her physician if there are questions about alternatives.

Azmacort (triamcinolone acetonide)Inhalation Aerosol is a registered trademark. ©2007 Kos Pharmaceuticals, Inc. Manufactured for: Kos Pharmaceuticals, Inc. Cranbury, NJ 08512. FDA rev date: 3/13/2008

Synthetic glucocorticoid; virtually no mineralocorticoid activity.c j

Contraindications

• Known hypersensitivity to triamcinolone or any ingredient in the formulation.a g h j

• Oral or parenteral administration in presence of systemic fungal infections.d e j (See Increased Susceptibility to Infection under Cautions.)

• Concurrent administration of live virus vaccines in patients receiving immunosuppressive dosages of glucocorticoids (oral or parenteral formulations).g h (See Immunosuppression under Cautions.)

• IM administration for conditions prone to bleeding (e.g., ITP).d g h

• Oral inhalation for primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures are required.a

• Epidural administration in patients with local or systemic infection; individuals with bleeding disorders or receiving concurrent anticoagulant therapy (e.g., warfarin, heparin, antiplatelet agents); patients with known hypersensitivity to local anesthetic agents, contrast agents, or glucocorticoids; and patients who experienced complications with prior glucocorticoid injections.

Warnings/Precautions

Warnings

Nervous System Effects

May precipitate mental disturbances ranging from euphoria, insomnia, mood swings, depression and anxiety, and personality changes to frank psychoses.d e g h j Use may aggravate emotional instability or psychotic tendencies.d e g h j

Use with caution in patients with seizure disorders and patients with myasthenia gravis receiving anticholinesterase therapy.b d

Aseptic meningitis, arachnoiditis, exacerbation of pain, spinal cord trauma, subdural injection, intracranial air injection, increased intracranial pressure, nerve injury, seizures, bladder or bowel dysfunction, paraparesis or paralysis, sensory disturbances, and brain damage reported following epidural and/or intrathecal glucocorticoid injection. Unclear whether these effects involved improper needle placement or were related to administration of the drug and/or preservatives.

Serious, potentially permanent, and sometimes fatal adverse neurologic events (e.g., spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke, seizures, nerve injury, brain edema) reported rarely, often within minutes to 48 hours following epidural glucocorticoid injection given either with or without fluoroscopic guidance.1000 1001 1002 1003

FDA states efficacy and safety of epidural glucocorticoid administration not established; not FDA-labeled for this use.1000 1001 (See Advice to Patients.)

Adrenocortical Insufficiency

When given in supraphysiologic doses for prolonged periods, glucocorticoids may cause decreased secretion of endogenous corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency).b

The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of glucocorticoid therapy.b

Acute adrenal insufficiency (even death) may occur if the drugs are withdrawn abruptly or if patients are transferred from systemic glucocorticoid therapy to local (e.g., inhalation) therapy.b a

Withdraw triamcinolone very gradually following long-term therapy with pharmacologic dosages.b (See Discontinuance of Therapy under Dosage and Administration.)

Adrenal suppression may persist up to 12 months in patients who receive large dosages for prolonged periods.a b With recommended dosages administered by oral inhalation, suppression of the HPA axis has occurred within 6–12 weeks in some patients.

Until recovery occurs, signs and symptoms of adrenal insufficiency may develop if subjected to stress (e.g., surgery, trauma, infection) and replacement therapy may be required.b Since mineralocorticoid secretion may be impaired, sodium chloride and/or a mineralocorticoid should also be administered.b

If the disease flares up during withdrawal, dosage may need to be increased and followed by a more gradual withdrawal.b

Immunosuppression

Increased susceptibility to infections secondary to glucocorticoid-induced immunosuppression. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients.a d e g h j (See Increased Susceptibility to Infection under Warnings.)

Administration of live virus vaccines, including smallpox, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids.d e g j h If inactivated or killed vaccines are administered to such patients, the expected antibody response may not be obtained.g May undertake immunization procedures in patients receiving glucocorticoids as replacement therapy (e.g., Addison’s disease).g h (See Specific Drugs and Laboratory Tests under Interactions.)

Increased Susceptibility to Infection

Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.g

Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections in any organ system, may be associated with glucocorticoids alone or in combination with other immunosuppressive agents.

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.

Do not use, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives.b

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.a

Children and any adult who are not likely to have been exposed to varicella or measles should avoid exposure to these infections while receiving glucocorticoids.a g

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG, acyclovir).a

Fatal outcome (e.g., in those developing hemorrhagic varicella) may not always be avoided even if appropriate therapy is initiated aggressively.

Immunosuppression may result in activation of latent infection or exacerbation of intercurrent infections (e.g., those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia, Ameba).

Use with great care in patients with known or suspected Strongyloides (threadworm) infection. Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

May exacerbate fungal infections and should not be used in the presence of such infections unless needed to control drug reactions.g

Some clinicians recommend avoidance of glucocorticoid inhalation therapy when risk of activating bronchopulmonary mycoses appears high, as in patients with bronchiectasis or inadequate immunologic responses.b

Not effective and can have detrimental effects in the management of cerebral malaria.b

Can reactivate tuberculosis.j Include chemoprophylaxis in patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy.b j Observe closely for evidence of reactivation.d Restrict use in active tuberculosis to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate chemoprophylaxis.d j

Can reactivate latent amebiasis.g Exclude possible amebiasis in any patient who has been in the tropics or who has unexplained diarrhea prior to initiating therapy.g

Rarely, epidural abscess reported following epidural glucocorticoid injection; infectious complications (e.g., bacterial meningitis) also reported.

Musculoskeletal Effects

Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism that may occur during prolonged therapy with glucocorticoids.b d These adverse effects may be especially serious in geriatric or debilitated patients.b A high-protein diet may help to prevent adverse effects associated with protein catabolism.b

An acute, generalized myopathy can occur with the use of high doses of glucocorticoids, particularly in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) or in patients receiving concomitant therapy with neuromuscular blocking agents (e.g., pancuronium).g d e

Possible tendon rupture, particularly of the Achilles tendon.

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy.

To minimize the risk of glucocorticoid-induced bone loss, the smallest possible effective dosage and duration should be used. Topical and inhaled preparations should be used whenever possible.

Before initiating glucocorticoid therapy in postmenopausal women, consider that they are especially prone to osteoporosis.b

Withdraw glucocorticoids if osteoporosis develops, unless their use is life-saving.b

Glucocorticoid-induced bone loss can be both prevented and treated. Obtain baseline measurement of bone mass density (BMD) at the lumbar spine and/or hip when initiating long-term (e.g., >6 months) glucocorticoid therapy and initiate appropriate preventive therapy. Longitudinal measurements may be repeated as often as every 6 months to detect possible bone loss. Less frequent (e.g., annually) follow-up probably is sufficient in patients who are receiving therapy to prevent bone loss.

Skeletal wasting is most rapid during the initial 6 months of therapy; trabecular bone is affected to a greater degree than is cortical bone.

Calcium and vitamin D supplementation, bisphosphonate (e.g., alendronate, risedronate), and a weight-bearing exercise program that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects.

Calcitonin may be considered as second-line therapy for patients who refuse or do not tolerate bisphosphonate therapy or in whom the drugs are contraindicated.

Fluid and Electrolyte Disturbances

Sodium retention with resultant edema, potassium loss, and elevation of BP may occur but is less common with triamcinolone than with average or large doses of cortisone or hydrocortisone.j Risk is increased with high-dose synthetic glucocorticoids for prolonged periods.b j Edema and CHF (in susceptible patients) may occur.b

Dietary salt restriction and potassium supplementation may be necessary.b d e g h j

Increased calcium excretion and possible hypocalcemia.c j

Ocular Effects

Prolonged use may result in posterior subcapsular and nuclear cataracts (particularly in children), exophthalmos, and/or increased IOP which may result in glaucoma or may occasionally damage the optic nerve.b j

Increased risk of ocular hypertension or open-angle glaucoma observed in patients receiving the maximum dosage of oral inhalation for 3 or more months.

May enhance the establishment of secondary fungal and viral infections of the eye.j

Do not use in patients with active ocular herpes simplex infections for fear of corneal perforation.b g h

Transient blindness, amblyopia, acute retinal necrosis syndrome, intraocular hemorrhage, and cortical blindness have occurred following epidural glucocorticoid injection.1001 1002 1003

Endocrine and Metabolic Effects

Administration over a prolonged period may produce various endocrine disorders including hypercorticism (cushingoid state) and amenorrhea or other menstrual difficulties.a b e

May decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus, especially in patients predisposed to diabetes mellitus.b If glucocorticoid therapy is required in patients with diabetes mellitus, changes in insulin or oral antidiabetic agent dosage or diet may be necessary.b

Administer by epidural injection with caution in patients with diabetes mellitus.

Exaggerated glucocorticoid response in patients with hypothyroidism.b e

Cardiovascular Effects

Possible association between use of glucocorticoids and left ventricular free-wall rupture; use with extreme caution in patients with recent MI.b g

Use with caution in patients with CHF or hypertension.e g

Administer by epidural injection with caution in patients with CHF.

Respiratory Effects

Bronchospasm,a and/or wheezing may occur with oral inhalation therapy.a

If bronchospasm occurs, treat immediately with a short-acting bronchodilator, and discontinue treatment with triamcinolone acetonide and institute alternative therapy.a

Unknown long-term, systemic, and local effects of the drug in humans, particularly developmental or immunologic processes in the mouth, pharynx, trachea, and lung.a

Sensitivity Reactions

Some commercially available injections of triamcinolone contain benzyl alcohol as a preservative.d e g h Administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates (gasping syndrome).b g

Anaphylactic or anaphylactoid reactions have occurred with parenteral corticosteroids.e d e Take appropriate precautionary measures prior to administration, especially in patients with a history of allergy to any drug.e

General Precautions

Monitoring

Prior to initiation of long-term glucocorticoid therapy, perform baseline ECGs, BP, chest and spinal radiographs, glucose tolerance tests, and evaluations of HPA-axis function in all patients.b d

Perform upper GI radiographs in patients predisposed to GI disorders, including those with known or suspected peptic ulcer disease or appreciable dyspepsia.b d

During long-term therapy, perform periodic height, weight, chest and spinal radiographs, hematopoietic, electrolyte, glucose tolerance, and ocular and BP evaluations.

Because systemic absorption possible with orally inhaled corticosteroids, carefully observe patients for systemic effects.a

GU Effects

Increased or decreased motility and number of sperm in some men.b h

GI Effects

Corticosteroids should be used with caution in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or those with recent intestinal anastomoses.d g j

Use with caution in patients with active or latent peptic ulcer.d g Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving corticosteroids.b g Suggest concurrent administration of antacids between meals to prevent peptic ulcer formation in patients receiving high dosages of corticosteroids.b

Hematologic Effects

Cortisone reported rarely to increase blood coagulability and to precipitate intravascular thrombosis, thromboembolism, and thrombophlebitis; use corticosteroids with caution in patients with thromboembolic disorders.b d e

Specific Populations

Pregnancy

Category C.a g h

Fluoroscopy (recommended for ensuring proper needle placement for epidural injections) is contraindicated in pregnant women.

Lactation

Distributed into milk.g h Caution if used in nursing women.g h

Pediatric Use

Insufficient experience with triamcinolone acetonide IM injection or inhalation aerosol in children <6 years of age; use not recommended.a d

With long-term use, may delay growth and maturation in children and adolescents.b h j Monitor carefully the growth and development of pediatric patients receiving prolonged corticosteroid therapy.b Titrate dosage to the lowest effective level.b h Weigh potential growth effects of prolonged therapy against the clinical benefits and availability of treatment alternatives.h

Glucocorticoid-induced osteoporosis and associated fractures are common in children and adolescents receiving long-term systemic therapy. In addition, may prevent achievement of peak bone mass during adolescence by inhibiting bone formation. Methods for monitoring bone mineralization (e.g., dual-energy x-ray absorptiometry [DXA]) in children and adolescents are similar to those in adults.

Ensure children and adolescents consistently ingest, either through diet or supplementation, adequate calcium and vitamin D.

Do not use preparations containing benzyl alcohol in newborn infants.g h

Geriatric Use

Triamcinolone acetonide: Insufficient experience with oral inhalation in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a (See Special Populations under Dosage and Administration.)

Triamcinolone hexacetonide: No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.g h

With prolonged therapy, muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones may occur.b May be especially serious in geriatric or debilitated patients.b (See Musculoskeletal Effects under Cautions.)

Before initiating glucocorticoid therapy in postmenopausal women, consider that such women are especially prone to osteoporosis.b Use with caution in patients with osteoporosis.b (See Musculoskeletal Effects under Cautions.)

Hepatic Impairment

Exaggerated glucocorticoid response in patients with cirrhosis.b j

Renal Impairment

Use with caution in patients with renal insufficiency, acute glomerulonephritis, or chronic nephritis.d g j

Common Adverse Effects

With oral inhalation, sinusitis, pharyngitis, headache, flu syndrome, back pain.a

Associated with long-term therapy: bone loss, cataracts, indigestion, muscle weakness, back pain, bruising, oral candidiasis.k l