Testopel

Name: Testopel

Why is this medication prescribed?

Testosterone cypionate (Depo-Testosterone), testosterone enanthate (Delatestryl), testosterone undecanoate (Aveed), and testosterone pellet (Testopel) are forms of testosterone injection used to treat symptoms of low testosterone in men who have hypogonadism (a condition in which the body does not produce enough natural testosterone). Testosterone is used only for men with low testosterone levels caused by certain medical conditions, including disorders of the testicles, pituitary gland, (a small gland in the brain), or hypothalamus (a part of the brain) that cause hypogonadism. Your doctor will order certain lab tests to check your testosterone levels to see if they are low before you begin to use testosterone injection. Testosterone enanthate (Delatestryl) and testosterone pellet (Testopel) are also used to stimulate puberty in males with delayed puberty. Testosterone enanthate (Delatestryl) injection may be used in certain women with a type of breast cancer called mammary cancer that has spread to other parts of the body. Testosterone should not be used to treat the symptoms of low testosterone in men who have low testosterone due to aging ('age related hypogonadism'). Testosterone is in a class of medications called androgenic hormones. Testosterone is a hormone produced by the body that contributes to the growth, development, and functioning of the male sexual organs and typical male characteristics. Testosterone injection works by supplying synthetic testosterone to replace the testosterone that is normally produced naturally in the body. When used to treat breast cancer, testosterone works by stopping the release of estrogen.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

Side effects

The following adverse reactions have been identified during post-approval use of testosterone replacement therapy, including TESTOPEL®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Implantation Site Infection and Pellet Extrusion: (see WARNINGS)

Endocrine and Urogenital, 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 of baldness, 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.

Metabolic. Increased serum cholesterol.

Vascular Disorders: Venous thromboembolism (see WARNINGS).

Miscellaneous. Rarely anaphylactoid reactions.

Testopel Drug Class

Testopel is part of the drug class:

  • 3 oxoandrosten 4 derivatives

Testopel Precautions

Serious side effects have been reported with topical testosterone including the following:

  • Swelling of the hands, feet, ankles, and lower legs
  • Breathing problems, especially during sleep
  • Excessive frequency or duration of penile erections in males
  • Difficulty urinating or changes in urination habits
  • Changes in skin color
  • Liver dysfunction or liver cancer

Serious side effects have been reported with injectable testosterone including the following:

  • Virilization in women, which includes amenorrhea or menstrual irregularities, deepening of the voice, clitoral enlargement
  • Sexual changes or dysfunction in males, which includes breast enlargement and excessive frequency or duration of penile erections

Do not take testosterone if you:

  • are allergic to testosterone or to any of its ingredients
  • are a male with breast or prostate cancer
  • are a woman who is or may become pregnant

Testopel - Clinical Pharmacology

Endogenous androgens are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution such as beard, pubic, chest and axillary hair, laryngeal enlargements, vocal cord thickening, alterations in body musculature and fat distribution. Drugs in this class can also cause retention of nitrogen, sodium, potassium, phosphorus, 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 the eventual termination of linear growth which is brought about by the fusion of the epiphyseal growth centers. In children, exogenous androgens accelerate linear growth rates, but may cause a disproportionate advancement in bone maturation. Use over long periods may result in fusion of the epiphyseal growth centers and termination of growth process. Androgens have been reported to stimulate the production of red blood cells by enhancing the production of erythropoietic stimulating 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.

PHARMACOKINETICS

Testosterone in plasma is 98 percent bound to a specific testosterone-estradiol binding globulin, and about 2 percent is free. Generally, the amount of this sex-hormone binding globulin in the plasma will determine the distribution of testosterone between the free and bound forms, and the free testosterone concentration will determine its half-life.

About 90 percent of a dose of testosterone is excreted as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6 percent of a dose is excreted in 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 as reported in the literature, ranging from 10-100 minutes.

In many tissues the activity of testosterone appears to depend on reduction to dihydrotestosterone, 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.

Adverse Reactions

The following adverse reactions have been identified during post-approval use of testosterone replacement therapy, including Testopel®. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Implantation Site Infection and Pellet Extrusion: (see WARNINGS)  

Endocrine and Urogenital, 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 of baldness, 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.

Metabolic. Increased serum cholesterol.

Vascular Disorders: Venous thromboembolism (see WARNINGS)

Miscellaneous. Rarely anaphylactoid reactions.

Drug Abuse and Dependence

Controlled Substance

Testopel® 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.

Testopel Dosage and Administration

Prior to initiating, Testopel® (testosterone pellets) 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.

The suggested dosage for androgens varies depending on the age, and diagnosis of the individual patient. Dosage is adjusted according to the patient’s response and the appearance of adverse reactions. The dosage guideline for the testosterone pellets for replacement therapy in androgen-deficient males is 150mg to 450mg subcutaneously every 3 to 6 months. Various dosage regimens have been used to induce pubertal changes in hypogonadal males; some experts have advocated lower doses initially, gradually increasing the dose as puberty progresses, with or without a decrease in 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.

Dosages in delayed puberty generally are in the lower range of that listed above and, for a limited duration, for example 4 to 6 months.

The number of pellets to be implanted depends upon the minimal daily requirements of testosterone propionate determined by a gradual reduction of the amount administered parenterally. The usual dosage is as follows: implant two 75mg pellets for each 25mg testosterone propionate required weekly. Thus when a patient requires injections of 75mg per week, it is usually necessary to implant 450mg (6 pellets). With injections of 50mg per week, implantation of 300mg (4 pellets) may suffice for approximately three months. With lower requirements by injection, correspondingly lower amounts may be implanted. It has been found that approximately one-third of the material is absorbed in the first month, one-fourth in the second month and one-sixth in the third month. Adequate effect of the pellets ordinarily continues for three to four months, sometimes as long as six months.

For Healthcare Professionals

Applies to testosterone: buccal film extended release, compounding powder, intramuscular solution, nasal gel, subcutaneous implant, transdermal cream, transdermal film extended release, transdermal gel, transdermal ointment, transdermal solution

General

The most frequently reported side effects with this drug are edema, acne, site pain, injection site erythema, cough or dyspnea during or immediately after injection.

The most frequently reported side effects with testosterone (the active ingredient contained in Testopel) topical are skin reaction (16.1%) and allergic contact dermatitis (up to 37%).[Ref]

Dermatologic

Very common (10% or more): Testosterone topical: Skin reaction (16.1%), burn-like blisters (12%), itching, allergic contact dermatitis (up to 37%)
Common (1% to 10%): Acne, induration, burning
Uncommon (0.1% to 1%): Alopecia, erythema, rash (including rash popular), pruritus, dry skin, folliculitis (testosterone (the active ingredient contained in Testopel) topical)
Frequency not reported: Seborrhea, urticaria, male pattern baldness, hirsutism injection site inflammation
Postmarketing reports: Angioedema, angioneurotic edema, hyperhidrosis, discolored hair, leukocytoclastic vasculitis[Ref]

Endocrine

Very common (10% or more): Accelerated growth
Common (1% to 10%): Increased estradiol, hypogonadism
Uncommon (0.1% to 1%): Increased blood testosterone (the active ingredient contained in Testopel) Frequency not reported: Signs of virilization in women (e.g., hoarseness, acne, hirsutism, menstrual irregularity, clitoral enlargement, and alopecia), precocious puberty (in prepubertal males)
Postmarketing reports: Hyperparathyroidism, prolactin increased, testosterone increased[Ref]

Gastrointestinal

Very common (10% or more): Testosterone (the active ingredient contained in Testopel) buccal film: Gingivitis (32.6%)
Common (1% to 10%): Diarrhea, oily stools (due to IM injection oily solvent); Testosterone topical: Gastroesophageal reflux disease, gastrointestinal bleeding, gum or mouth irritation (9.2%), taste bitter, gum pain, gum tenderness, gum edema, taste perversion
Uncommon (0.1% to 1%): Nausea
Rare (less than 0.1%): Abdominal pain
Frequency not reported: Abdominal disorder, intraabdominal hemorrhage
Postmarketing reports: Vomiting; Testosterone buccal film: Dry mouth, gingival swelling, lip swelling, mouth ulceration, stomatitis[Ref]

The majority of gum-related adverse events were transient.[Ref]

Local

Very common (10% or more): Testosterone topical: Application site pruritus (up to 37%), application site blistering (12%)
Common (1% to 10%): Injection site pain, injection site discomfort, injection site pruritus, erythema, injection site hematoma, injection site irritation, injection site inflammation; injection site reaction; Topical testosterone (the active ingredient contained in Testopel) Application site erythema, application site warmth, application site irritation, application site vesicles, application site exfoliation, application site burning, application site induration, bullae at application site, mechanical irritation at application site, rash at application site, contamination of application site
Postmarketing reports: Injection site abscess, procedural pain, application site swelling (topical testosterone)[Ref]

Cardiovascular

Common (1% to 10%): Hot flush, hypertension
Uncommon (0.1% to 1%): Cardiovascular disorder
Frequency not reported: Venous thromboembolism
Postmarketing reports: Angina pectoris, cardiac arrest, cardiac failure, coronary artery disease, coronary artery occlusion, myocardial infarction, tachycardia, cerebral infarction, cerebrovascular accident, circulatory collapse, deep venous thrombosis, syncope, thromboembolism, thrombosis, venous insufficiency, stroke[Ref]

Genitourinary

Common (1% to 10%): Abnormal prostate examination, benign prostate hyperplasia (BPH), ejaculation disorder, prostatitis
Uncommon (0.1% to 1%): Prostate induration, prostatic disorder, testicular pain, decreased urine flow, urinary retention, urinary tract disorder, nocturia, dysuria
Rare (less than 0.1%): Micturition disorders, epididymitis, bladder irritability, impotence, inhibition of testicular function and testicular atrophy
Frequency not reported: Oligospermia, priapism, benign prostatic hyperplasia (prostatic growth to eugonadal state), excessive frequency and duration of erections; Pediatrics: Precocious sexual development, an increased frequency of erections, phallic enlargement
Postmarketing reports: Prostate infection, calculus urinary, dysuria, hematuria, urinary tract disorder, pollakiuria[Ref]

Hematologic

Common (1% to 10%): Polycythemia, hematocrit increased
Uncommon (0.1% to 1%): Increased red blood cell count, increased hemoglobin, prolonged activated partial thromboplastin time, prolonged prothrombin time
Frequency not reported: Blood and lymphatic system disorders, suppression of clotting factors II, V, VII, and X, bleeding in patients on concomitant anticoagulant therapy
Postmarketing reports: Thrombocytopenia, anemia[Ref]

Metabolic

Common (1% to 10%): Weight increased, appetite increased, fluid retention (sodium, chloride, water, potassium, calcium, and inorganic phosphates)
Uncommon (0.1% to 1%): Increased glycosylated hemoglobin, hypercholesterolemia, increased triglyceride
Frequency not reported: Abnormal lipids (decrease in serum LDL, HDL, and triglycerides), metabolism and nutrition disorders, hypercalcemia
Postmarketing reports: Hypoglycemia, diabetes mellitus, fluid retention, hyperlipidemia, hypertriglyceridemia, blood glucose increased[Ref]

Musculoskeletal

Common (1% to 10%): Back pain, hemarthrosis (testosterone (the active ingredient contained in Testopel) topical)
Uncommon (0.1% to 1%): Arthralgia, pain in extremity, muscle spasm, muscle strain, myalgia, musculoskeletal stiffness, increased creatine phosphokinase
Frequency not reported: Pediatrics: Premature epiphyseal closure, increased bone formation
Postmarketing reports: Musculoskeletal chest pain, musculoskeletal pain, myalgia, osteopenia, osteoporosis, systemic lupus erythematosus[Ref]

Nervous system

Common (1% to 10%): Headache, vertigo (topical testosterone (the active ingredient contained in Testopel)
Uncommon (0.1% to 1%): Migraine, tremor, dizziness
Frequency not reported: Nervousness, paresthesia
Postmarketing reports: Cerebrovascular insufficiency, reversible ischemic neurological deficiency, transient ischemic attack, amnesia[Ref]

Oncologic

Common (1% to 10%): Prostatic specific antigen (PSA) increased, prostate cancer
Uncommon (0.1% to 1%): Prostatic intraepithelial neoplasia
Rare (less than 0.1%): Neoplasms benign, malignant, and unspecified (including cysts and polyps)[Ref]

Other

Common (1% to 10%): Fatigue, hyperhidrosis; chills, body pain, smell disorder
Uncommon (0.1% to 1%): Breast induration, breast pain, sensitive nipples, gynecomastia, increased estradiol, increased testosterone (the active ingredient contained in Testopel) asthenia, night sweats
Rare (less than 0.1%): Fever, malaise
Frequency not reported: Edema
Postmarketing reports: Sudden hearing loss, tinnitus, Influenza like illness[Ref]

Psychiatric

Common (1% to 10%): Irritability, insomnia, mood swings, aggression,
Uncommon (0.1% to 1%): Depression, emotional disorder, restlessness, increased libido, decreased libido
Frequency not reported: Hostility, anxiety
Postmarketing reports: Korsakoff's psychosis nonalcoholic, male orgasmic disorder, restlessness, sleep disorder[Ref]

Respiratory

Common (1% to 10%): Sinusitis, nasopharyngitis, upper respiratory tract infection, bronchitis
Uncommon (0.1% to 1%): Cough, dyspnea, snoring, dysphonia
Rare (less than 0.1%): Pulmonary microembolism (POME) (cough, dyspnea, malaise, hyperhidrosis, chest pain, dizziness, paresthesia, or syncope) caused by oily solutions
Frequency not reported: Sleep apnea
Postmarketing reports: Chest pain, asthma, chronic obstructive pulmonary disease, hyperventilation, obstructive airway disorder, pharyngeal edema, pharyngolaryngeal pain, pulmonary embolism, respiratory distress, rhinitis, sleep apnea syndrome[Ref]

Signs and symptoms of pulmonary microemboli may occur during or immediately after the injections and are reversible.[Ref]

Hepatic

Uncommon (0.1% to 1%): Abnormal LFT, increased AST
Rare (less than 0.1%): Abnormal hepatic function
Frequency not reported: Jaundice, benign liver tumor, malignant liver tumor, liver enlargement, peliosis hepatitis
Postmarketing reports: ALT increased, AST increased, bilirubin increased, transaminases increased, gamma-glutamyltransferase increased[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity reactions
Frequency not reported: Anaphylactic reactions
Postmarketing reports: Anaphylactic shock[Ref]

Ocular

Uncommon (0.1% to 1%): Testosterone (the active ingredient contained in Testopel) topical: Lacrimation increased
Postmarketing reports: Testosterone topical: Intraocular pressure increased, vitreous detachment[Ref]

Renal

Postmarketing reports: Nephrolithiasis, renal colic, renal pain[Ref]

Some side effects of Testopel may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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