There have been no reports of acute overdosage with the androgens.
Androgens are contraindicated in men with carcinomas of the breast or with known or suspected carcinomas of the prostate, and in women who are or may become pregnant. When administered to pregnant women, androgens cause virilization of the external genitalia of the female fetus. This virilization includes clitoromegaly, abnormal vaginal development, and fusion of genital folds to form a scrotal-like structure. The degree of masculinization is related to the amount of drug given and the age of the fetus, and is most likely to occur in the female fetus when the drugs are given in the first trimester. If the patient becomes pregnant while taking these drugs, she should be apprised of the potential hazard to the fetus.
Female: The most common side effects of androgen therapy are amenorrhea and other menstrual irregularities, inhibition of gonadotropin secretion and virilization, including deepening of the voice and clitoral enlargement. The latter usually is not reversible after androgens are discontinued. When administered to a pregnant woman androgens cause virilization of external genitalia of the female fetus.
Male: Gynecomastia, and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages (see CLINICAL PHARMACOLOGY).
Skin and appendages: Hirsutism, male pattern of baldness, and acne.
Fluid and Electrolyte Disturbances: Retention of sodium, chloride, water, potassium, calcium and inorganic phosphates.
Gastrointestinal: Nausea, cholestatic jaundice, alterations in liver function tests, rarely hepatocellular neoplasms and peliosis hepatis (see WARNINGS).
Hematologic: Suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy and polycythemia.
Nervous System: Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia.
Metabolic: Increased serum cholesterol.
Miscellaneous: Rarely anaphylactoid reactions.
Drug abuse and DependenceMethyltestosterone Capsules are classified as a schedule III Controlled Substance under the Anabolic Steroids Act of 1990.
In patients with breast cancer, androgen therapy may cause hypercalcemia by stimulating osteolysis. In this case, the drug should be discontinued.
Prolonged use of high doses of androgens has been associated with the development of peliosis hepatis and hepatic neoplasms including hepatocellular carcinoma. (See PRECAUTIONS, Carcinogenesis). Peliosis hepatis can be a life-threatening or fatal complication.
Cholestatic hepatitis and jaundice occur with 17-alpha-alkylandrogens at a relatively low dose. If cholestatic hepatitis with jaundice appears or if liver function tests become abnormal, the androgen should be discontinued and the etiology should be determined. Drug-induced jaundice is reversible when the medication is discontinued.
Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hypertrophy and prostatic carcinoma.
Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required.
Gynecomastia frequently develops and occasionally persists in patients being treated for hypogonadism.
Androgen therapy should be used cautiously in healthy males with delayed puberty. The effect on bone maturation should be monitored by assessing bone age of the wrist and hand every 6 months. In children, androgen treatment may accelerate bone maturation without producing compensatory gain in linear growth. This adverse effect may result in compromised adult stature. The younger the child the greater the risk of compromising final mature height.
This drug has not been shown to be safe and effective for the enhancement of athletic performance. Because of the potential risk of serious adverse health effects, this drug should not be used for such purpose.
PRECAUTIONS GeneralWomen should be observed for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly and menstrual irregularities). Discontinuation of drug therapy at the time of evidence of mild virilism is necessary to prevent irreversible virilization. Such virilization is usual following androgen use at high doses. A decision may be made by the patient and the physician that some virilization will be tolerated during treatment for breast carcinoma.
Laboratory TestsAndrogens 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 Animal DataTestosterone 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 the liver in rats.
Human DataThere 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.
PregnancyTeratogenic effects. Pregnancy Category X (See CONTRAINDICATIONS).
Nursing MothersIt 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 UseAndrogen 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 six months by an X-ray of hand and wrist (See INDICATIONS AND USAGE and WARNINGS).
Methyltestosterone capsules are administered orally. The suggested dosage for androgens varies depending on the age, sex, and diagnosis of the individual patient. Dosage is adjusted according to the patient's response and the appearance of adverse reactions.
Replacement therapy in androgen-deficient males is 10 to 50 mg of Methyltestosterone daily. Various dosage regimens have been used to induce pubertal changes in hypogonadal males, some experts have advocated lower dosages initially, gradually increasing the dose as puberty progresses with or without a decrease to maintenance levels. Other experts emphasize that higher dosages are needed to induce pubertal changes and lower dosages can be used for maintenance after puberty. The chronological and skeletal ages must be taken into consideration both in determining the initial dose and in adjusting the dose.
Doses used in delayed puberty generally are in the lower range of that given above, and for a limited duration, for example 4 to 6 months.
Women with metastatic breast carcinoma must be followed closely because androgen therapy occasionally appears to accelerate the disease. Thus, many experts prefer to use the shorter acting androgen preparations rather than those with prolonged activity for treating breast carcinoma, particularly during the early stages of androgen therapy. The dosage of Methyltestosterone for androgen therapy in breast carcinoma in females is from 50-200 mg daily.
