Depo-Testosterone

• 1.
• Known hypersensitivity to the drug 2.
• Males with carcinoma of the breast 3.
• Males with known or suspected carcinoma of the prostate gland 4.
• Women who are pregnant (see PRECAUTIONS, Pregnancy ) 5.
• Patients with serious cardiac, hepatic or renal disease (see 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-α 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 DEPO-Testosterone (testosterone cypionate).
• 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 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.
• 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 liver and kidneys’ 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.
• 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:
• 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.
• Drug/Laboratory test Interferences Androgens may decrease levels of thyroxine-binding globulin, resulting in decreased total T 4 serum levels and increased resin uptake of T 3 and T 4 .
• 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 The use of testosterone in women who are pregnant is contraindicated.
• See WARNINGS .
• Nursing mothers DEPO-Testosterone 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.
• 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.

• Teratogenic Effects The use of testosterone in women who are pregnant is contraindicated.
• Testosterone is teratogenic and may cause fetal harm.
• Testosterone is known to cause virilization of the female fetus when administrated to pregnant women.
• Benzyl alcohol can cross the placenta.
• See WARNINGS .
• DEPO-Testosterone is not recommended for use in nursing mothers.

• 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.

There have been no reports of acute overdosage with the androgens.

• Controlled Substance DEPO-Testosterone Injection contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female
• adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men:
• transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women:
• hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents:
• premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors:
• Taking greater dosages than prescribed
• Continued drug use despite medical and social problems due to drug use
• Spending significant time to obtain the drug when supplies of the drug are interrupted
• Giving a higher priority to drug use than other obligations
• Having difficulty in discontinuing the drug despite desires and attempts to do so
• Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented.
• DEPO-Testosterone Injection contains testosterone, a Schedule III controlled substance in the Controlled Substances Act.