Testosterone enanthate

Name: Testosterone enanthate

Other names

  • testosterone cypionate
  • testosterone enanthate
  • testosterone undecanoate

Side effects

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.

Drug Abuse And Dependence

DELATESTRYL® (Testosterone Enanthate Injection, USP) is classified as a controlled substance under the Anabolic Steroids Control Act of 1990 and has been assigned to Schedule III.

Introduction

Androgenic anabolic steroid hormone; the principal endogenous androgen.a

Uses for Testosterone Enanthate

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Male Hypogonadism

Management of congenital or acquired primary hypogonadism such as that resulting from orchiectomy or from testicular failure caused by cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals.117 133 135 157 161 162 a

Management of congenital or acquired hypogonadotropic hypogonadism such as that resulting from idiopathic gonadotropin or gonadotropin-releasing hormone (luteinizing hormone-releasing hormone) deficiency or from pituitary-hypothalamic injury caused by tumors, trauma, or radiation.117 133 135 157 161 162 a Used in the treatment of hypogonadotropic hypogonadism only in patients uninterested in or unable to achieve fertility.f

Considered the androgen of choice for the treatment of androgen deficiency (e.g., hypogonadism) and AIDS wasting in HIV-infected men.126

May be used to stimulate puberty when the diagnosis is well established in carefully selected males with delayed puberty (designated an orphan drug by FDA for this use).a 162

Some experts (e.g., American College of Rheumatology) recommend that men who develop low serum testosterone concentrations (<300 ng/mL) while receiving long-term corticosteroid therapy receive testosterone replacement therapy in an attempt to treat hypogonadism and possibly reduce the risk of corticosteroid-induced osteoporosis†.122

Safety and efficacy of testosterone replacement therapy in men with late-onset hypogonadism (i.e., low testosterone concentrations related to aging) not established.133 175 Further study needed to elucidate the role of testosterone replacement therapy in treatment of this condition.176

Not indicated for the treatment of erectile dysfunction† in men with normal testosterone concentrations.158

Breast Cancer

Palliative treatment of androgen-responsive, advanced, inoperable, metastatic (skeletal) breast cancer in women who are 1–5 years postmenopausal and in premenopausal women who have benefited from oophorectomy.a 162

Poorly tolerated (see Virilization under Cautions); other hormonal agents (e.g., tamoxifen, anastrozole, letrozole, exemestane) currently are preferred for this use.d e

Misuse and Abuse

Has been misused and abused by athletes, bodybuilders, weight lifters, and others to enhance athletic performance or physique†.100 101 102 103 104 105 106 107 108 109 110 111 112 114 115 116 120

Medical and sports experts (e.g., International Olympic Committee) consider such use to be inappropriate and unacceptable because of known adverse effects and potential long-term sequelae and because such use by athletes is contrary to the rules and ethical principles of athletic competition.101 102 107 114 115 116

Stability

Storage

Buccal (Transmucosal)

Extended-release Tablets

20–25°C.161 Protect from heat and moisture.161

Topical

Gel

25°C (may be exposed to 15–30°C).135 157

Transdermal System

20–25°C.133 Protect from excessive heat.133

Parenteral

Injection

20–25°C.117 162 Protect from light;117 do not freeze.a

A precipitate may form if testosterone cypionate or testosterone enanthate injection is stored at low temperatures; the precipitate will dissolve after shaking and warming to room temperature.117 162

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Injection

Use of a wet needle or syringe may cause testosterone enanthate solutions to become cloudy; potency is not affected.162

Testosterone Enanthate Description

Testosterone Enanthate Injection, USP provides Testosterone Enanthate, USP, a derivative of the primary endogenous androgen testosterone, for intramuscular administration. In their active form, androgens have a 17-beta-hydroxy group. Esterification of the 17-beta-hydroxy group increases the duration of action of testosterone; hydrolysis to free testosterone occurs in vivo. Each mL of sterile, colorless to pale yellow, solution provides 200 mg Testosterone Enanthate, USP in sesame oil with 5 mg chlorobutanol (chloral derivative) as a preservative.

Testosterone Enanthate, USP is designated chemically as androst-4-en-3-one, 17-[(1-oxoheptyl)-oxy]-, (17β)-. Structural formula:

Pharmacokinetics

Testosterone esters are less polar than free testosterone. Testosterone esters in oil injected intramuscularly are absorbed slowly from the lipid phase; thus Testosterone Enanthate can be given at intervals of two to four weeks.

Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about two percent is free. Generally, the amount of this sex-hormone binding globulin (SHBG) in the plasma will determine the distribution of testosterone between free and bound forms, and the free testosterone concentration will determine its half-life.

About 90 percent of a dose of testosterone is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about six percent of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver. Testosterone is metabolized to various 17-keto steroids through two different pathways. There are considerable variations of the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.

In responsive tissues, the activity of testosterone appears to depend on reduction to dihydrotestosterone (DHT), which binds to cytosol receptor proteins. The steroid-receptor complex is transported to the nucleus where it initiates transcription events and cellular changes related to androgen action.

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 injection. 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 injection 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 injection.

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 Abuse and Dependence

Controlled Substance

Testosterone Enanthate 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 of 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.

Principal Display Panel

NDC 0143-9750-01
Testosterone
Enanthate
Injection, USP
CIII
1,000 mg/5 mL
(200 mg/mL)
STERILE
For Intramuscular Use Only
Rx ONLY
5 mL Multiple Dose Vial
Each mL contains 200 mg Testosterone Enanthate, USP in sesame oil
with 5 mg chlorobutanol (chloral derivative) as preservative.
USUAL DOSAGE: See package insert.
Store at 20º to 25ºC (68º to 77ºF) [See USP Controlled Room Temperature].
Warming and rotating the vial between the palms of the hands will
redissolve any crystals that may have formed during storage at low
temperatures.

Testosterone Enanthate 
Testosterone Enanthate injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0143-9750
Route of Administration INTRAMUSCULAR DEA Schedule CIII    
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Testosterone Enanthate (TESTOSTERONE) Testosterone Enanthate 200 mg  in 1 mL
Inactive Ingredients
Ingredient Name Strength
SESAME OIL  
CHLOROBUTANOL 5 mg  in 1 mL
Packaging
# Item Code Package Description
1 NDC:0143-9750-01 5 mL in 1 VIAL, MULTI-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA091120 09/18/2012
Labeler - West-Ward Pharmaceuticals Corp (001230762)
Establishment
Name Address ID/FEI Operations
HIKMA FARMACEUTICA (PORTUGAL), S.A 452742943 ANALYSIS(0143-9750), LABEL(0143-9750), MANUFACTURE(0143-9750), PACK(0143-9750)
Revised: 11/2016   West-Ward Pharmaceuticals Corp
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