AZMACORT®
Rhône-Poulenc Rorer
Triamcinolone Acetonide
Corticosteroid
Action And Clinical Pharmacology: Triamcinolone is a potent anti-inflammatory steroid with strong topical and weak systemic activity. When inhaled at therapeutic dosages, it has a direct anti-inflammatory action on the bronchial mucosa. Since the minute amounts absorbed do not exert any significant systemic effect, inhaled triamcinolone can replace oral steroids with the elimination of the untoward effects of systemic therapy.
Indications And Clinical Uses: Only for patients requiring chronic treatment with corticosteroids for symptomatic control of bronchial asthma. Such patients would include: steroid-dependent asthmatic patients to replace oral medication with this product through gradual withdrawal of systemic corticosteroids and selected patients who are inadequately controlled on a nonsteroid regimen and in whom steroid therapy has been withheld because of concern over potential adverse effects.
Contra-Indications: For the primary treatment of status asthmaticus or other acute asthmatic episodes where intensive therapeutic measures are required, or in patients with moderate to severe bronchiectasis.
Hypersensitivity to any of the ingredients of this preparation contraindicates its use.
It is also contraindicated in active or quiescent untreated pulmonary tuberculosis or untreated fungal, bacterial or viral infections.
Manufacturers’ Warnings In Clinical States: Particular care is needed in patients who are transferred from systemic corticosteroids to Azmacort, because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to aerosolized steroids in recommended doses. After withdrawal from systemic corticosteroids, a number of months is usually required for recovery of hypothalamic pituitary-adrenal (HPA) function.
For some patients who received large doses of oral steroids for long periods of time before therapy with inhaled triamcinolone was initiated, recovery was delayed for 1 year or longer. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery or infection, particularly gastroenteritis or other conditions with acute electrolyte loss. Although inhaled triamcinolone may provide control of asthmatic symptoms during these episodes, it supplies systemically only normal physiological amounts of corticosteroid in recommended doses and does not provide the increased systemic steroid needed for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have recently been withdrawn from systemic corticosteroids should be instructed to resume systemic steroids (in large doses) immediately and to contact their physician for further instructions. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthmatic attack.
To assess the risk of adrenal insufficiency in emergency situations, routine tests of adrenal cortical function, including measurement of early morning and evening cortisol levels, should be performed periodically in all patients. An early morning resting cortisol level may be accepted as normal only if it falls at or near the normal mean level.
Localized infections with C. albicans have occurred infrequently in the mouth and pharynx. These areas should be examined by the treating physician at each patient visit. The percentage of positive mouth and throat cultures for C. albicans did not change during a year of continuous therapy. The incidence of clinically apparent infection was low (2.5%). The development of pharyngeal and laryngeal candidiasis is cause for concern because the extent of its penetration of the respiratory tract is unknown. These infections may require treatment with appropriate antifungal therapy and/or discontinuance or treatment with inhaled triamcinolone, depending on the severity of the infection. Azmacort is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm.
Patients should be instructed to contact their physician immediately when episodes of asthma not responsive to bronchodilators occur during the course of treatment with inhaled triamcinolone. During such episodes, patients may require systemic corticosteroid therapy.
There is no evidence that control of asthma can be achieved by the administration of inhaled triamcinolone in amounts greater than the recommended doses, which appear to be the therapeutic equivalent of approximately 10 mg/day of oral prednisone.
Theoretically, the use of inhaled corticosteroids with alternate day oral prednisone therapy should be accompanied by more HPA suppression than a therapeutically equivalent regimen of either alone.
Transfer of patients from systemic steroid therapy to inhaled triamcinolone may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema.
Precautions: It is essential that the patient be instructed that inhaled triamcinolone is a preventative agent which must be taken at regular intervals and is not to be used during an asthmatic attack.
During withdrawal from oral steroids, some patients may experience symptoms of systemically active steroid withdrawal, e.g., joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement of respiratory function (see Dosage). Although steroid withdrawal effects are usually transient and not severe, severe and even fatal exacerbations of asthma can occur if the previous daily oral corticosteroid requirement significantly exceeded 10 mg/day of prednisone or equivalent.
In responsive patients, inhaled corticosteroids will often permit control of asthmatic symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since triamcinolone is absorbed into the circulation and can be systemically active, the beneficial effects of the drug in minimizing or preventing HPA dysfunction may be expected only when recommended dosages are not exceeded.
Suppression of HPA function has been reported in volunteers who received 4 000 g daily of triamcinolone. In addition, suppression of HPA function has been reported in some patients who have received recommended doses for as little as 6 to 12 weeks. Since the response of HPA function to inhaled corticosteroids is highly individualized, the physician should consider this information when treating patients.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with such drugs should be observed carefully for evidence of systemic corticosteroid effects including suppression of growth in children. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of a decrease in adrenal function.
The long-term effects of triamcinolone in human subjects are not completely known, therefore during long-term therapy pituitary-adrenal function and hematological status should be periodically assessed.
While there have been no clinical reports of adverse experience, the local effects of the agent on developmental or immunologic processes in the mouth, pharynx, trachea and lung are also unknown.
The potential effects of inhaled triamcinolone on acute, recurrent, or chronic pulmonary infections, including active or quiescent tuberculosis, are not known. For this reason, since systemic administration of corticosteroids may mask some signs of fungal, bacterial or viral infection, the same caution should be observed when treating patients with inhaled triamcinolone. The potential effects of the long-term administration on lung or other tissues are unknown. However, pulmonary infiltrates with eosinophilia have occurred in patients receiving other inhaled corticosteroids.
Pregnancy: Triamcinolone has been shown to be teratogenic in rats and rabbits when given in doses comparable to the highest recommended dose for human use (approximately 0.032 mg/kg/day). Administration by aerosol inhalation to pregnant rats and rabbits produced embryotoxic and fetotoxic effects which were compared to those produced by administration by other routes.
Teratogenic effects in both species included a low incidence of cleft palate and/or internal hydrocephaly and axial skeletal defects. These findings represent known effects of glucocorticoids in laboratory animals.
There are no well-controlled studies in pregnant women. Experience with other dosage forms of triamcinolone does not include positive evidence of adverse effects on the fetus. However, since such experience cannot exclude the possibility of fetal damage, the drug should be used during pregnancy only if the benefit clearly justifies the potential risk to the fetus. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for hypoadrenalism.
Lactation: It is not known whether this drug is excreted in human milk. Because of the potential for tumorigenicity shown by triamcinolone in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Corticosteroids may mask some signs of infections and new infections may appear. A decreased resistance to localized infection has been observed during corticosteroid therapy. During long-term therapy, pituitary-adrenal function and hematological status should be periodically assessed.
Fluorocarbon propellants may be hazardous if they are deliberately abused. Inhalation of high concentrations of aerosol sprays has brought about toxic cardiovascular effects and even death, especially under conditions of hypoxia. However, evidence attests to the safety of aerosols when used properly and with adequate ventilation.
There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.
ASA should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Patients should be advised to inform subsequent physicians of the prior use of corticosteroids.
To ensure the proper dosage and administration of the drug, the patient must be instructed by a physician or other health professional in the use of the inhaler.
Adequate oral hygiene is of primary importance in minimizing overgrowth of microorganisms such as C. albicans (see Dosage).
Adverse Reactions: Oral candidiasis has been reported (see Warnings). In addition, some patients receiving inhaled triamcinolone have experienced hoarseness, dry throat, irritated throat and dry mouth. Increased wheezing and cough have been infrequently reported, as has facial edema. These adverse effects have generally been mild and transient. Symptoms of rhinitis and eczema may become apparent during therapy after withdrawal of systemic corticosteroids.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage may cause systemic steroid effects such as adrenal suppression and hypercorticism. Decreasing the dose will diminish these effects.
Dosage And Administration: All patients should be instructed that Azmacort must be used on a regular daily basis rather than prn. Reliable dosage delivery cannot be assured after 240 actuations and patients should be cautioned against longer use of individual canisters.
Patients must be instructed in the correct method of using the inhaler (see Information for the Patient).
Good oral hygiene including rinsing of the mouth after inhalation is recommended.
Adults: The usual adult dosage is 2 inhalations (approximately 400 g) given 3 to 4 times a day. The maximal daily intake should not exceed 16 inhalations (3 200 g) for adults. Higher initial doses (12 to 16 inhalations/day) may be advisable in patients with more severe asthma, with dosage when being adjusted downward according to patient response. In some patients maintenance can be accomplished when the total daily dose is given on a twice a day schedule.
Each actuation releases approximately 200 g of triamcinolone from the metered valve, of which approximately 100 g are delivered from the mouthpiece (in vitro testing). The dosages expressed in this product monograph are based on 200 g of drug being released from the metered valve upon each actuation.
Children 6 to 12 years of age: The usual dosage is 1 to 2 inhalations (200 to 400 g) given 3 to 4 times a day according to the response of the patient. The maximal daily intake should not exceed 12 inhalations (2 400 g) in children 6 to 12 years of age. Insufficient clinical data exist with respect to the administration of Azmacort to children below the age of 6. The long-term effects of inhaled steroids on growth are still under evaluation.
Patients receiving bronchodilators by inhalation should be advised to use them before using this product, in order to enhance penetration of triamcinolone into the bronchial tree. After use of an aerosol bronchodilator, several minutes should elapse before use of inhaled triamcinolone in order to reduce potential toxicity from inhaled fluorocarbon propellants in the 2 aerosols.
Different considerations must be given to the following groups of patients in order to obtain the full therapeutic benefit of inhaled triamcinolone.
Patients not receiving systemic steroids: The use of Azmacort is straightforward in patients inadequately controlled with nonsteroidal medications, but in whom systemic steroid therapy has been withheld because of concern for potential adverse reactions. In patients who respond to inhaled triamcinolone, an improvement in pulmonary function is usually apparent within 1 to 2 weeks of the start.
Patients receiving systemic steroids: In those patients dependent on systemic steroids, transfer to Azmacort and subsequent management may be more difficult because recovery from impaired adrenal function is usually slow. Such suppression has been known to last for up to 12 months or longer. Clinical studies, however, have demonstrated that Azmacort may be effective in the management of these asthmatic cases and may permit replacement or significant reduction in dosage of the systemic corticosteroids.
The patient’s asthma should be reasonably stable before treatment with inhaled triamcinolone is started. Initially, the inhaler should be used concurrently with the usual maintenance dose of systemic steroid. After approximately 1 week, gradual withdrawal of the systemic steroid is started with an initial reduction in dosage, and close supervision.
The next reduction is made after an interval of 1 or 2 weeks, depending on response of the patient. Generally, these decrements should not exceed 2.5 mg of prednisone or its equivalent. If continuous supervision is not feasible, the withdrawal of the systemic steroid should be slower. A slow rate of withdrawal cannot be overemphasized. During this process, some patients may experience systemic symptoms of active steroid withdrawal, e.g., joint and/or muscle pain, lassitude and depression, despite maintenance or even improvement in respiratory function. Such patients should be encouraged to continue with the inhaler but should be watched carefully for objective signs of adrenal insufficiency, such as hypotension and weight loss. If evidence of adrenal insufficiency occurs, the systemic steroid dose should be boosted temporarily and thereafter, further withdrawal should continue more slowly. No clinical studies have been conducted evaluating Azmacort with alternate day prednisone regimens. However, based on the results of such a study with another corticosteroid inhaler, these products are generally not recommended for chronic use with alternate day prednisone regimens (see Warnings).
During periods of stress or a severe asthma attack, withdrawal patients will require supplementary treatment with systemic steroids.
Exacerbations of asthma which can occur during the course of treatment with inhaled triamcinolone, should be treated with a short course of systemic steroid and gradually tapered as the symptoms subside. There is no evidence that control of asthma can be achieved by the administration of inhaled triamcinolone in amounts greater than the recommended doses.
Under stressful conditions or when the patient has a severe exacerbation of bronchial asthma, after complete withdrawal of the systemic steroid, use of the latter must be resumed in order to avoid relative adrenocortical insufficiency. There are some patients who cannot completely discontinue the oral corticosteroid. In these cases, a minimum maintenance dosage should be given in addition to inhaled triamcinolone.
Availability And Storage: Each metered-dose aerosol unit contains: a microcrystalline suspension of triamcinolone acetonide 60 mg. Nonmedicinal ingredients: alcohol and dichlorodifluoromethane. Each actuation releases approximately 200 g triamcinolone acetonide, of which approximately 100 g are delivered from the unit (in vitro testing). Canisters of at least 240 oral inhalations. The device should not be used after 240 inhalations, since the amount delivered thereafter may be less than consistent. Boxes of 1 supplied with an oral adapter and patient’s leaflet of instructions.
Store at room temperature. Caution: container may explode if heated. Contents under pressure. Do not place in hot water or near radiators, stoves or other sources of heat. Even when empty do not puncture or incinerate containers or store at temperatures over 50°C.
AZMACORT® Rhône-Poulenc Rorer Triamcinolone Acetonide Corticosteroid
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