The following observations relevant to systemic absorption were made in clinical studies. In one uncontrolled study a statistically significant decrease in responsiveness to metyrapone was noted in 15 adult steroid-independent patients treated with mg of flunisolide per day (the maximum recommended dose) for 3 months. A small but statistically significant drop in eosinophils from % to % of total circulating leucocytes was noted in another study in children who were not taking oral corticosteroids simultaneously. A 5% incidence of menstrual disturbances was reported during open studies, in which there were no control groups for comparison.
High doses of inhaled glucocorticoids may decrease the formation of bone and increase the breakdown (resorption) of bone leading to weak bones and fractures. Very high doses may cause suppression of the body's ability to make its own natural glucocorticoid in the adrenal glands. It is possible that patients with suppression of their adrenal glands may need increased amounts of glucocorticoids by the oral or intravenous route during periods of high physical stress such as illnesses when increased amounts of glucocorticoids are needed by the body.