FDA label b8a2a78a-67b3-50a5-e053-2a95a90ad9a7

Warnings Hypercalcemia may occur in immobilized patients. If this occurs, the drug should be discontinued. Prolonged use of high doses of androgens (principally the 17-a alkyl-androgens) has been associated with development of hepatic adenomas, hepatocellular carcinoma, and peliosis hepatis —all potentially life-threatening complications. Geriatric patients treated with androgens may be at an increased risk of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking. 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 cypionate. 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 cypionate 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 cypionate. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease. Gynecomastia may develop and occasionally persists in patients being treated for hypogonadism. The preservative benzyl alcohol has been associated with serious adverse events, including the “gasping syndrome”, and death in pediatric patients. Although normal therapeutic doses of this product ordinarily deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome”, the minimum amount of benzyl alcohol at which toxicity may occur is not known. The risk of benzyl alcohol toxicity depends on the quantity administered and the hepatic capacity to detoxify the chemical. Premature and low-birth weight infants may be more likely to develop toxicity. 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. Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic 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 androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

Precautions General Patients with benign prostatic hypertrophy may develop acute urethral obstruction. Priapism or excessive sexual stimulation may develop. Oligospermia may occur after prolonged administration or excessive dosage. If any of these effects appear, the androgen should be stopped and if restarted, a lower dosage should be utilized. Testosterone cypionate should not be used interchangeably with testosterone propionate because of differences in duration of action. Testosterone cypionate is not for intravenous use. Information for Patients Patients should be instructed to report any of the following: nausea, vomiting, changes in skin color, ankle swelling, too frequent or persistent erections of the penis. Laboratory Tests Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. Serum cholesterol may increase during androgen therapy. Drug Interactions Androgens may increase sensitivity to oral anticoagulants. Dosage of the anticoagulant may require reduction in order to maintain satisfactory therapeutic hypoprothrombinemia. Concurrent administration of oxyphenbutazone and androgens may result in elevated serum levels of oxyphenbutazone. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, 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 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 the 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 of developing prostatic hypertrophy and prostatic carcinoma although conclusive evidence to support this concept is lacking. Pregnancy Teratogenic Effects Pregnancy Category X (See CONTRAINDICATIONS). Benzyl alcohol can cross the placenta. See WARNINGS. Nursing Mothers Testosterone cypionate injection is not recommended for use in nursing mothers. Pediatric Use Safety and effectiveness in pediatric patients below the age of 12 years have not been established.

Adverse Reactions The following adverse reactions in the male have occurred with some androgens: Endocrine and urogenital: Gynecomastia and excessive frequency and duration of penile erections. Oligospermia may occur at high dosages. Skin and appendages: Hirsutism, male pattern of baldness, seborrhea, and acne. Cardiovascular Disorders: Myocardial infarction, stroke. 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. Allergic: Hypersensitivity, including skin manifestations and anaphylactoid reactions. Vascular Disorders: Venous thromboembolism. Miscellaneous: Inflammation and pain at the site of intramuscular injection. To report SUSPECTED ADVERSE REACTIONS, contact Actavis Pharma Inc. at 1-800-272-5525or FDA at 1-800-FDA-1088 or www.fda.‌gov/‌medwatch.