PRECAUTIONS GENERAL Pellet implantation is much less flexible for dosage adjustment than is oral administration of or intramuscular injections of oil solutions or aqueous suspensions. Therefore, great care should be used when estimating the amount of testosterone needed. In the face of complications where the effects of testosterone should be discontinued, the pellets would have to be removed. INFORMATION FOR THE PATIENT The physician should instruct patients to report any of the following side effects of androgens: Adult or adolescent males: Too frequent or persistent erections of the penis. Any nausea, vomiting, changes in skin color, ankle swelling. Implantation site infection and/or pellet extrusion can occur and may be associated with implant site induration, inflammation, fibrosis, bleeding, bruising, wound drainage, pain, itching, and pellet extrusion. (see WARNINGS and ADVERSE REACTIONS). Any male adolescent patient receiving androgens for delayed puberty should have bone development checked every 6 months. LABORATORY TESTS Because of the hepatotoxicity associated with the use of 17-alpha-alkylated androgens, liver function tests should be obtained periodically. Periodic (every 6 months) x-ray examinations of the bone age should be made during treatment of prepubertal males to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers. Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens. DRUG INTERACTIONS Anticoagulants. C-17 substituted derivatives of testosterone, such as methandrostenolone have been reported to decrease the anticoagulant requirements of patients receiving oral anticoagulants. Patients receiving oral anticoagulant therapy require close monitoring, especially when androgens are started or stopped. Oxyphenbutazone. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone. Insulin. In diabetic patients the metabolic effects of androgens may decrease blood glucose and insulin requirements. DRUG/LABORATORY TEST INTERFERENCES Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T4 serum levels and increased resin uptake of T3 and T4. Free thyroid hormone levels remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY Animal Data. Testosterone has been tested by subcutaneous injection and implantation in mice and rats. The implant induced cervical-uterine tumors in mice, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of liver in rats. Human Data. There are rare reports of hepatocellular carcinoma in patients receiving long-term therapy with androgens in high doses. Withdrawal of the drugs did not lead to regression of the tumors in all cases. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma. PREGNANCY Teratogenic Effects. Pregnancy Category X (see CONTRAINDICATIONS). NURSING MOTHERS It is not known whether androgens are 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 androgens, 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. PEDIATRIC USE Androgen therapy should be used very cautiously in children and only by specialists who are aware of the adverse effects on bone maturation. Skeletal maturation must be monitored every 6 months by an x-ray of the hand and wrist (see INDICATIONS AND USAGE and WARNINGS).