Pharmacy & Therapeutics - March 2008 - (Page 150) Pharmaceutical Approval Update Mar vin M. Goldenberg, PhD, RPh, MS Ciclesonide (Alvesco) Inhalation Aerosol Manufacturer: Nycomed US, Florham Park, N.J. Indication: Ciclesonide, an inhaled corticosteroid, is indicated for the maintenance treatment of asthma as prophylactic therapy in adults and adolescents 12 years of age and older. It is not indicated for the relief of acute bronchospasm. Drug Class: The active component in the 80-mcg and 160-mcg inhalation aerosols is ciclesonide, a non-halogenated glucocorticoid having the chemical name pregna-1,4diene-3,20-dione,16,17-[[(R)-cyclohexyl methylene]bis(oxy)]11-hydroxy-21-(2-methyl-1-oxopropoxy)-,(11β,16α). Uniqueness of Drug: As a prodrug, ciclesonide is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) after it is inhaled through the mouth. Des-ciclesonide has antiinflammatory activity with affinity for glucocorticoid receptors that is 120 times greater than the parent compound and 12 times greater than dexamethasone. The clinical significance of these findings is unknown. Warnings and Precautions: Local Effects. In clinical trials, localized infections of the mouth and pharynx with Candida albicans developed in 32 of 3,038 patients receiving ciclesonide. Of the 32 reported cases, 20 occurred in 1,394 patients using a total daily dose of 320 mcg or higher. Most candidal infections were mild to moderate. These infection should be treated with appropriate local or systemic (oral antifungal) therapy, and patients should continue with ciclesonide. At certain times, however, ciclesonide therapy may need to be interrupted. Patients should rinse the mouth after inhaling ciclesonide. Acute Asthma Episodes. Ciclesonide is not a bronchodilator, and it is not indicated for the rapid relief of bronchospasm or other acute episodes of asthma. Patients should contact a physician immediately if asthma does not respond to their usual doses of bronchodilators during treatment with ciclesonide. During such episodes, patients may need oral corticosteroids. Immunosuppression. Persons who are using drugs that suppress the immune system are more susceptible than healthy individuals to infection. Chickenpox and measles, for example, can be more serious or even fatal in susceptible children or adults using corticosteroids. For children or adults who have not had these diseases or who have not been properly immunized, particular care should be taken to avoid exposure. It is not known how the dose, route, or duration of corticosteroid administration affects a person’s risk of developing a disseminated infection or whether underlying disease or prior corticosteroid treatment contributes to the risk. If a patient is exposed to chickenpox, prophylaxis with varicella zoster imThe author is President of Pharmaceutical and Scientific Services at MarvinMGoldenberg, LLC, in Westfield, N.J. His e-mail address is marvinmgoldenberg@verizon.net. mune globulin may be indicated. If a patient has been exposed to measles, prophylaxis with pooled intramuscular (IM) immunoglobulin may be indicated. If chickenpox develops, antiviral agents may be considered. Inhaled corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract; untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. Switching from Systemic Corticosteroid Therapy. Particular care is needed for patients who are switched from systemically active corticosteroids to ciclesonide. Deaths caused by adrenal insufficiency have occurred in asthmatic patients during and after their transfer from systemic corticosteroid therapy to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, several months are required to recover hypothalamic–pituitary–adrenal (HPA) function. Patients who have been previously maintained on a dose of 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when systemic corticosteroids have been almost completely withdrawn. 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 associated with severe electrolyte loss. Ciclesonide helps control asthma symptoms during these episodes, but when it is used in doses as recommended, it supplies less than normal physiological amounts of corticosteroid systemically and does not provide the mineralocorticoid activity that is necessary for coping with these emergencies. During periods of stress or during a severe asthma attack, patients who have withdrawn from systemic corticosteroid therapy should resume oral corticosteroids in large doses immediately and should contact a physician for fur ther instruction. They should carry a medical identification card indicating that they might need supplementary systemic corticosteroids during these emergencies. Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroids after switching to ciclesonide. Reducing the need for prednisone can be accomplished by lowering the daily prednisone dose by 2.5 mg on a weekly basis during ciclesonide therapy. Lung function, the use of betaagonists, and asthma symptoms should be carefully monitored while oral corticosteroids are being tapered. Patients should be observed for signs and symptoms of asthma and adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension. Switching patients from systemic steroid therapy to ciclesonide may unmask allergic conditions that had previously been suppressed by the steroids, for example, rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions. During withdrawal from oral steroids, some patients may experience symptoms of systemically active steroid withdrawal, such as 150 P&T® • March 2008 • Vol. 33 No. 3
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