Particular care is needed in patients who are transferred from systemically active corticosteroids to Azmacort Inhalation Aerosol 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 have received large doses of oral steroids for long periods of time before therapy with Azmacort Inhalation Aerosol is initiated, recovery may be delayed for one year or longer. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infections, particularly gastroenteritis or other conditions with acute electrolyte loss. Although Azmacort Inhalation Aerosol may provide control of asthmatic symptoms during these episodes, in recommended doses it supplies only normal physiological amounts of corticosteroid systemically and does NOT provide the increased systemic steroid which is necessary for coping with these emergencies.
During periods of stress or a severe asthmatic attack, patients who have been recently withdrawn from systemic corticosteroids should be instructed to resume systemic steroids (in large doses) immediately and to contact their physician for further instruction. 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 asthma attack.
Localized infections with Candida 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 Candida albicans did not change during a year of continuous therapy. The incidence of clinically apparent infection is low (2.5%). These infections may disappear spontaneously or may require treatment with appropriate antifungal therapy or discontinuance of treatment with Azmacort Inhalation Aerosol.
Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chickenpox and measles, for example, can have a more serious or even fatal course in children 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 intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Azmacort Inhalation Aerosol is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm.
As with other inhaled asthma medications, bronchospasm may occur with an immediate increase in wheezing following dosing. If bronchospasm occurs following use of Azmacort Inhalation Aerosol, it should be treated immediately with a fast-acting inhaled bronchodilator. Treatment with Azmacort Inhalation Aerosol should be discontinued and alternative treatment should be instituted.
Patients should be instructed to contact their physician immediately when episodes of asthma which are not responsive to bronchodilators occur during the course of treatment with Azmacort Inhalation Aerosol. During such episodes, patients may require therapy with systemic corticosteroids.
The use of Azmacort Inhalation Aerosol with systemic prednisone, dosed either daily or on alternate days, could increase the likelihood of HPA suppression compared to a therapeutic dose of either one alone. Therefore, Azmacort Inhalation Aerosol should be used with caution in patients already receiving prednisone treatment for any disease.
Transfer of patients from systemic steroid therapy to Azmacort Inhalation Aerosol may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema.
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 AND ADMINISTRATION.) Although steroid withdrawal effects are usually transient and not severe, severe and even fatal exacerbation of asthma can occur if the previous daily oral corticosteroid requirement had 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 acetonide is absorbed into the circulation and can be systemically active, the beneficial effects of Azmacort Inhalation Aerosol 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 4000 mcg daily of triamcinolone acetonide by oral inhalation. 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.
When used at excessive doses or at recommended doses in a small number of susceptible individuals, systemic corticosteroid effects such as hypercorticoidism and adrenal suppression may appear. If such changes occur, Azmacort Inhalation Aerosol should be discontinued slowly, consistent with accepted procedures for reducing systemic steroid therapy and for management of asthma symptoms.
Azmacort Inhalation Aerosol should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, parasitic, or viral infections; or ocular herpes simplex.
The long-term local and systemic effects of Azmacort Inhalation Aerosol in human subjects are still not fully known. While there has been no clinical evidence of adverse experiences, the effects resulting from chronic use of Azmacort Inhalation Aerosol on developmental or immunologic processes in the mouth, pharynx, trachea, and lung are unknown.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with these drugs should be observed carefully for any 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.
Information for Patients: Patients being treated with Azmacort Inhalation Aerosol should receive the following information and instructions. This information is intended to aid them in the safe and effective use of this medication. It is not a complete disclosure of all possible adverse or intended effects.
Patients should use Azmacort Inhalation Aerosol at regular intervals as directed. Results of clinical trials indicate that significant improvement in asthma may occur by 1 week, but maximum benefit may not be achieved for 2 weeks or more. The patient should not increase the prescribed dosage but should contact the physician if symptoms do not improve or if the condition worsens.
In clinical studies and post-marketing experience with Azmacort Inhalation Aerosol, local infections of the oropharynx with Candida albicans have occurred. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral antifungal) therapy while remaining on treatment with Azmacort Inhalation Aerosol. However, at times therapy with Azmacort Inhalation Aerosol may need to be interrupted.
Patients should be instructed to track their use of Azmacort Inhalation Aerosol and to dispose of the canister after 240 actuations since reliable dose delivery cannot be assured after 240 doses.
Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice.
Carcinogenesis, Mutagenesis, Impairment of Fertility: No evidence of treatment-related carcinogenicity was demonstrated after two years of once daily gavage of triamcinolone acetonide at doses of 0.05, 0.2, and 1.0 mcg/kg (approximately 0.02, 0.07, and 0.4% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) in the rat and 0.1, 0.6, and 3.0 mcg/kg (approximately 0.02, 0.1, and 0.6% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) in a mouse.
Mutagenesis studies with triamcinolone acetonide have not been carried out.
No evidence of impaired fertility was manifested when oral doses of up to 15.0 mcg/kg (8% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) were administered to female and male rats. However, triamcinolone acetonide at oral doses of 8 mcg/kg (approximately 4% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) caused dystocia and prolonged delivery and at oral doses of 5.0 mcg/kg (approximately 2.5% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) and above caused increases in fetal resorptions and stillbirths and decreases in pup body weight and survival. At a lower dose of 1.0 mcg/kg (approximately 0.5% of the maximum recommended human daily inhalation dose on a mcg/m2 basis) it did not induce the above mentioned effects.
Pregnancy: Pregnancy Category C. Triamcinolone acetonide has been shown to be teratogenic at inhalational doses of 20, 40, and 80 mcg/kg in rats (approximately 0.1, 0.2, and 0.4 times the maximum recommended human daily inhalation dose on a mcg/m2 basis, respectively), in rabbits at the same doses (approximately 0.2, 0.4, and 0.8 times the maximum recommended human daily inhalation dose on a mcg/m2 basis, respectively) and in monkeys, at an inhalational dose of 500 mcg/kg (approximately 5 times the maximum recommended human daily inhalation dose 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 teratogenic effects observed in the monkey were CNS and/or cranial malformations. There are no adequate and well controlled studies in pregnant women. Triamcinolone acetonide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Experience with oral glucocorticoids since their introduction in pharmacologic as opposed to physiologic doses suggests that rodents are more prone to teratogenic effects from glucocorticoids than humans. In addition, because there is a natural increase in glucocorticoid production during pregnancy, most women will require a lower exogenous steroid dose and many will not need glucocorticoid treatment during pregnancy.
Nonteratogenic Effects: Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Such infants should be carefully observed.
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 Azmacort Inhalation Aerosol is administered to nursing women.
Pediatric Use: Safety and effectiveness have not been established in pediatric patients below the age of 6. 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 corticosteroid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of steroids should be considered.
Geriatric Use: Clinical studies of Azmacort Inhalation Aerosol 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.