Untoward effects have been reported in about 2 out of 3 patients with Cushing’s syndrome who were treated for 4 or more weeks with Cytadren as the only adrenocortical suppressant.
The most frequent and reversible side effects were drowsiness (approximately 1 in 3 patients), morbilliform skin rash (1 in 6 patients), nausea and anorexia (each approximately 1 in 8 patients), and dizziness (about 1 in 20 patients). The dizziness was possibly caused by lowered vascular resistance or orthostasis. These reactions often disappear spontaneously with continued therapy.
Other Effects Observed
Hematologic: Single instances of neutropenia, leukopenia (patient received concomitant o,p' -DDD), pancytopenia (patient received concomitant 5-fluorouracil), and agranulocytosis occurred in 4 of 27 patients with Cushing’s syndrome caused by adrenal carcinoma who were treated for at least 4 weeks. In 1 patient with adrenal hyperplasia, hemoglobin levels and hematocrit decreased during the course of treatment with Cytadren. From the earlier experience with the drug used as an anticonvulsant in 1,214 patients, transient leukopenia was the only hematologic effect and was reported once; Coombs’-negative hemolytic anemia also occurred once. In approximately 300 patients with nonadrenal malignancy, 1 in 25 showed some degree of anemia, and 1 in 150 developed pancytopenia during treatment with Cytadren.
Endocrine: Adrenal insufficiency occurred in about 1 in 30 patients with Cushing’s syndrome who were treated with Cytadren for 4 or more weeks. This insufficiency tended to involve glucocorticoids as well as mineralocorticoids. Hypothyroidism is occasionally associated with thyroid enlargement and may be detected or confirmed by measuring plasma levels of the thyroid hormone. Masculinization and hirsutism have occasionally occurred in females, as has precocious sexual development in males.
Central Nervous System: Headache was reported in about 1 in 20 patients.
Cardiovascular: Hypotension, occasionally orthostatic, occurred in 1 in 30 patients receiving Cytadren. Tachycardia occurred in 1 in 40 patients.
Gastrointestinal and Liver: Vomiting occurred in 1 in 30 patients. Isolated instances of abnormal findings on liver function tests were reported. Suspected hepatotoxicity occurred in less than 1 in 1000 patients.
Skin: In addition to rash (1 in 6 patients, and often reversible with continued therapy), pruritus was reported in 1 in 20 patients. These may be allergic or hypersensitive reactions. Urticaria has occurred rarely.
Miscellaneous: Fever was reported in several patients who were treated with Cytadren for less than 4 weeks; some of these patients also received other drugs. Myalgia occurred in 1 in 30 patients. Pulmonary hypersensitivity, including allergic alveolitis and interstitial alveolar infiltrates, has occurred rarely.