Label: TESTOSTERONE CYPIONATE injection

Testosterone Cypionate Injection, USP, for intramuscular injection, contains testosterone cypionate which is the oil-soluble 17 (beta)- cyclopentylpropionate ester of the androgenic hormone testosterone.

Testosterone cypionate is a white or creamy white crystalline powder, odorless or nearly so and stable in air. It is insoluble in water, freely soluble in alcohol, chloroform, dioxane, ether, and soluble in vegetable oils.

The chemical name for testosterone cypionate is androst-4-en-3-one, 17-(3-cyclopentyl-1-oxopropoxy)-, (17β)-. Its molecular formula is C 27H 40O 3, and the molecular weight 412.61.

The structural formula is represented below:

Testosterone Cypionate Injection, USP, is available as 200 mg/mL testosterone cypionate.

Each mL of the 200 mg/mLsolution contains:

Endogenous androgens are responsible for normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include growth and maturation of the prostate, seminal vesicles, penis, and scrotum; development of male hair distribution, such as beard, pubic, chest, and axillary hair; laryngeal enlargement, vocal cord thickening, and alterations in body musculature and fat distribution. Drugs in this class also cause retention of nitrogen, sodium, potassium, and phosphorous, and decreased urinary excretion of calcium. Androgens have been reported to increase protein anabolism and decrease protein catabolism. Nitrogen balance is improved only when there is sufficient intake of calories and protein.

Androgens are responsible for the growth spurt of adolescence and for eventual termination of linear growth, brought about by fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of the growth process. Androgens have been reported to stimulate production of red blood cells by enhancing production of erythropoietic stimulation factor.

During exogenous administration of androgens, endogenous testosterone release is inhibited through feedback inhibition of pituitary luteinizing hormone (LH). At large doses of exogenous androgens, spermatogenesis may also be suppressed through feedback inhibition of pituitary follicle stimulating hormone (FSH).

There is a lack of substantial evidence that androgens are effective in fractures, surgery, convalescence, and functional uterine bleeding.

Testosterone Cypionate Injection is indicated for replacement therapy in the male in conditions associated with symptoms of deficiency or absence of endogenous testosterone.

1. Primary hypogonadism (congenital or acquired) - testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome; or orchidectomy.

2. Hypogonadotropic hypogonadism (congenital or acquired) - gonadotropin or LHRH deficiency, or pituitary-hypothalamic injury from tumors, trauma, or radiation.

Safety and efficacy of testosterone cypionate in men with "age-related hypogonadism" (also referred to as "late-onset hypogonadism") have not been established.

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 testosterone cypionate.

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.

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.

Special senses: Rare cases of central serous chorioretinopathy (CSCR).

Miscellaneous: Inflammation and pain at the site of intramuscular injection.

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

Prior to initiating testosterone cypionate, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

Testosterone Cypionate Injection is for intramuscular use only.

It should not be given intravenously. Intramuscular injections should be given deep in the gluteal muscle.

The suggested dosage for Testosterone Cypionate Injection 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.

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.

For replacement in the hypogonadal male, 50 mg to 400 mg should be administered every two to four weeks.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Warming and shaking the vial should redissolve any crystals that may have formed during storage at temperatures lower than recommended.

Testosterone Cypionate Injection, USP, is available as follows:

200 mg/mL

Rx only

Manufactured for:
Wilshire Pharmaceuticals, Inc.
Atlanta, GA 30328

Manufactured by:
Pharmaceutics International, Inc. (Pii)
Cockeysville, MD 21030

Rev. 02/2019

TST-PI-01