Cytadren may cause adrenocortical hypofunction, especially under conditions of stress, such as surgery, trauma, or acute illness. Patients should be carefully monitored and given hydrocortisone and mineralocorticoid supplements as indicated. Dexamethasone should not be used. (See PRECAUTIONS, Drug Interactions.)
Cytadren also may suppress aldosterone production by the adrenal cortex and may cause orthostatic or persistent hypotension. The blood pressure should be monitored in all patients at appropriate intervals. Patients should be advised of the possible occurrence of weakness and dizziness as symptoms of hypotension, and of measures to be taken should they occur.
The effects of Cytadren may be potentiated if it is taken in combination with alcohol.
Cytadren can cause fetal harm when administered to a pregnant woman. In the earlier experience with the drug in about 5000 patients, two cases of pseudohermaphroditism were reported in female infants whose mothers were treated with Cytadren and concomitant anticonvulsants. Normal pregnancies have also occurred in patients treated with Cytadren.
When administered to rats at doses 1/2 and 1 1/4 times the maximum daily human dose, Cytadren caused a decrease in fetal implantation, an increase in fetal deaths, and a variety of teratogenic effects. The compound also caused pseudohermaphroditism in rats treated with approximately 3 times the maximum daily human dose. If this drug must be used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus.
This drug should be administered only by physicians familiar with its use and hazards. Therapy should be initiated in a hospital. (See DOSAGE AND ADMINISTRATION.)
Information for Patients
Patients should be warned that drowsiness may occur and that they should not drive, operate potentially dangerous machinery, or engage in other activities that may become hazardous because of decreased alertness.
Patients should also be warned of the possibility of hypotension and its symptoms (see WARNINGS).
Hypothyroidism may occur in association with Cytadren; hence, appropriate clinical observations should be made and laboratory studies of thyroid function performed as indicated. Supplementary thyroid hormone may be required.
Hematologic abnormalities in patients receiving Cytadren have been reported (see ADVERSE REACTIONS). Therefore, baseline hematologic studies should be performed, followed by periodic hematologic evaluation.
Since elevations in SGOT, alkaline phosphatase, and bilirubin have been reported, appropriate clinical observations and regular laboratory studies should be performed before and during therapy.
Serum electrolyte levels should be determined periodically.
Cytadren accelerates the metabolism of dexamethasone; therefore, if glucocorticoid replacement is needed, hydrocortisone should be prescribed.
Aminoglutethimide diminishes the effect of coumarin and warfarin.
Carcinogenesis, Mutagenesis, Impairment of Fertility
A 2-year carcinogenicity study of Cytadren conducted in rats at doses of 10-60 mg/kg/day (approximately 0.04 to 0.2 times the maximum daily therapeutic dose based on surface area, mg/m2) revealed a highly statistically significant dose-related trend in the incidence of benign and malignant neoplasms of the adrenal cortex and thyroid follicular cells in both sexes. A borderline statistically significant increase (0.05 level) in ovarian tubular adenomas was observed at 60 mg/kg/day. Urinary bladder papillomas also showed a statistically significant dose-related trend in males.
Cytadren affects fertility in female rats (see WARNINGS). The relevance of these findings to humans is not known.
Pregnancy Category D
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Cytadren, 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.
Safety and effectiveness in pediatric patients have not been established (see CLINICAL STUDIES IN CHILDREN).