TESTOSTERONE ENANTHATE

INDICATIONS AND USAGE Males Testosterone enanthate injection is indicated for replacement therapy in conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired) – Testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, or orchidectomy. Hypogonadotropic hypogonadism (congenital or acquired) – Gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation. (Appropriate adrenal cortical and thyroid hormone replacement therapy are still necessary, however, and are actually of primary importance.) If the above conditions occur prior to puberty, androgen replacement therapy will be needed during the adolescent years for development of secondary sexual characteristics. Prolonged androgen treatment will be required to maintain sexual characteristics in these and other males who develop testosterone deficiency after puberty. Safety and efficacy of testosterone enanthate injection in men with age-related hypogonadism have not been established. Delayed puberty – Testosterone enanthate injection may be used to stimulate puberty in carefully selected males with clearly delayed puberty. These patients usually have a familial pattern of delayed puberty that is not secondary to a pathological disorder; puberty is expected to occur spontaneously at a relatively late date. Brief treatment with conservative doses may occasionally be justified in these patients if they do not respond to psychological support. The potential adverse effect on bone maturation should be discussed with the patient and parents prior to androgen administration. An X-ray of the hand and wrist to determine bone age should be obtained every six months to assess the effect of treatment on the epiphyseal centers (see WARNINGS ). Females Metastatic mammary cancer – Testosterone enanthate injection may be used secondarily in women with advancing inoperable metastatic (skeletal) mammary cancer who are one to five years postmenopausal. Primary goals of therapy in these women include ablation of the ovaries. Other methods of counteracting estrogen activity are adrenalectomy, hypophysectomy, and/or antiestrogen therapy. This treatment has also been used in premenopausal women with breast cancer who have benefited from oophorectomy and are considered to have a hormone-responsive tumor. Judgment concerning androgen therapy should be made by an oncologist with expertise in this field.

DOSAGE AND ADMINISTRATION Prior to initiating testosterone enanthate injection, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. Dosage and duration of therapy with testosterone enanthate injection will depend on age, sex, diagnosis, patient’s response to treatment, and appearance of adverse effects. When properly given, injections of testosterone enanthate are well tolerated. Care should be taken to slowly inject the preparation deeply into the gluteal muscle, being sure to follow the usual precautions for intramuscular administration, such as the avoidance of intravascular injection (see PRECAUTIONS ). In general, total doses above 400 mg per month are not required because of the prolonged action of the preparation. Injections more frequently than every two weeks are rarely indicated. NOTE: Use of a wet needle or wet syringe may cause the solution to become cloudy; however this does not affect the potency of the material. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Testosterone enanthate injection is a clear, colorless to pale yellow color oily solution. Male hypogonadism : As replacement therapy, i.e., for eunuchism, the suggested dosage is 50 to 400 mg every 2 to 4 weeks. In males with delayed puberty : Various dosage regimens have been used; some call for lower dosages initially with gradual increases as puberty progresses, with or without a decrease to maintenance levels. Other regimens call for higher dosage to induce pubertal changes and lower dosage 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. Dosage is within the range of 50 to 200 mg every 2 to 4 weeks for a limited duration, for example, 4 to 6 months. X-rays should be taken at appropriate intervals to determine the amount of bone maturation and skeletal development (see INDICATIONS AND USAGE , and WARNINGS ). Palliation of inoperable mammary cancer in women : A dosage of 200 to 400 mg every 2 to 4 weeks is recommended. Women with metastatic breast carcinoma must be followed closely because androgen therapy occasionally appears to accelerate the disease.

CONTRAINDICATIONS 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 androgens, she should be apprised of the potential hazard to the fetus. This preparation is also contraindicated in patients with a history of hypersensitivity to any of its components.

WARNINGS In patients with breast cancer and in immobilized patients, androgen therapy may cause hypercalcemia by stimulating osteolysis. In patients with cancer, hypercalcemia may indicate progression of bony metastasis. If hypercalcemia occurs, the drug should be discontinued and appropriate measures instituted. 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. 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. There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as testosterone enanthate. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with testosterone enanthate and initiate appropriate workup and management . Long term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use testosterone enanthate. Testosterone can increase blood pressure which can increase cardiovascular (CV) risk over time. Monitor blood pressure periodically in men using testosterone products, especially in men with hypertension. Testosterone products are not recommended for use in patients with uncontrolled hypertension. Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic steroids. Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions (see DRUG ABUSE AND DEPENDENCE ). If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic steroids. Conversely, consider the possibility of testosterone and anabolic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. Due to sodium and water retention, 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. If the administration of testosterone enanthate is restarted, a lower dose should be used. 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 six 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.

Drug Interactions When administered concurrently, the following drugs may interact with androgens: Anticoagulants, oral – C-17 substituted derivatives of testosterone, such as methandrostenolone, have been reported to decrease the anticoagulant requirement. Patients receiving oral anticoagulant therapy require close monitoring especially when androgens are started or stopped. Antidiabetic drugs and insulin – In diabetic patients, the metabolic effects of androgens may decrease blood glucose and insulin requirements. ACTH and corticosteroids – Enhanced tendency toward edema. Use caution when giving these drugs together, especially in patients with hepatic or cardiac disease. Oxyphenbutazone – Elevated serum levels of oxyphenbutazone may result.

ADVERSE REACTIONS Endocrine and Urogenital, 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 the 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 baldness, and acne. Cardiovascular Disorders – myocardial infarction, stroke Fluid and Electrolyte Disturbances – Retention of sodium, chloride, water, potassium, calcium (see WARNINGS ), and inorganic phosphates. Gastrointestinal – Nausea, cholestatic jaundice, alterations in liver function tests; rarely, hepatocellular neoplasms, peliosis hepatis (see WARNINGS ). Hematologic – Suppression of clotting factors II, V, VII, and X; bleeding in patients on concomitant anticoagulant therapy; polycythemia. Nervous System – Increased or decreased libido, headache, anxiety, depression, and generalized paresthesia. Metabolic – Increased serum cholesterol. Vascular Disorders – venous thromboembolism Miscellaneous – Rarely, anaphylactoid reactions; inflammation and pain at injection site.

Pregnancy: Teratogenic Effects (see CONTRAINDICATIONS ).