Testosterone - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Androgens, antiandrogens

Included in the formulation

Andriol TK®

capsules inwards

Organon, N.V. Netherlands

Androgel

gel externally

Bezen Mengyufekchuring Belgium Belgium

Nebido®

solution w / m

Bayer Pharma AG Germany

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

VED

ONLS

АТХ:

G.03.B.A Derivatives of 3-oxoandrostene

G.03.B.A.03 Testosterone

Pharmacodynamics:The main androgen. Physiological effects are due to the combined effect of testosterone itself and its metabolites with androgenic (dihydrotestosterone) and estrogenic (estradiol) activity. In target organs (prostate gland, seminal vesicles, skin and others) is restored 5a-reductase up to 5a-dihydrotestosterone, which specifically interacts with the androgen receptors on the cell surface and penetrates into the nucleus. In some tissues (including the hypothalamus) it turns into estradiol.

The main effects of testosterone: androgenic (growth and development of genital organs, stimulation of their activity, manifestation of secondary sexual characteristics, providing erectile function), anabolic (maintenance of muscle mass and regulation of adipose tissue mass, stimulation of synthesis of organ-specific proteins in the kidneys, liver, sebaceous and sweat glands, maintenance of bone density), antigonotrophic (inhibition of gonadotropin secretion), reproductive (maintenance of spermatogenesis), psychophysiological (providing sexual attraction, forming a stereotype of sexual behavior, mood, psycho-stimulating effect), hematopoietic (stimulation of the production of erythropoietin in the kidneys, erythropoiesis in the red bone marrow).

In men with hypogonadism, androgen therapy leads to a clinically significant increase in the concentration in the plasma of testosterone, dihydrotestosterone, androstenedione, a decrease in the content of sex hormone binding globulin (SHGG), luteinizing and follicle-stimulating hormone, and in men with primary (hypergonadotropic) hypogonadism normalizes the concentration of gonadotropin. The sexual function improves, the libido increases, the fat mass decreases, the fat-free body weight increases, the mineral density of bone tissue increases, and the psychophysiological state improves.

Pharmacokinetics:Absorption of testosterone from mucous membranes and skin is high and depends on the dosage form. It is used in the form of testosterone undecanoate (inside, intramuscularly) and active testosterone (skin).

About 98% of circulating testosterone binds to GSH and albumin.Only the free fraction of testosterone is considered biologically active. Biotransformation to inactive metabolites occurs in the liver. After the administration of labeled testosterone, about 90% of the radioactivity is determined in the urine in the form of glucuronide and sulfate acid conjugates. Urine-specific foods include androsterone and etiocholanolone. 6% of the active substance after passage of the entero-hepatic circulation is found in feces.

Testosterone, formed from testosterone undecanoate as a result of cleavage of the ester bond, is metabolized and excreted from the body in the same ways as the endogenous testosterone. Undecanoic acid is metabolized by β-oxidation in the same way as other aliphatic carboxylic acids.

Features of pharmacokinetics for various routes of administration

After taking inwards a significant portion of testosterone (in the form of undecanoate ether) is absorbed into the small intestine and enters the lymphatic system, thereby partially avoiding the primary passage through the liver. From the lymphatic system of testosterone, undecanoate enters the plasma. In plasma and tissues, as a result of hydrolysis, natural male sex hormones are released testosterone and dihydrotestosterone.

A single dose of 80-160 mg of testosterone undecanoate leads to a clinically significant increase in the total plasma concentration of testosterone, the maximum concentrationis approximately 40 nmol / L and is achieved 4-5 hours after administration. Increased concentration of testosterone is retained for at least 8 hours. Half-life - 10 to 100 minutes.

After intramuscular injection testosterone undecanoate is gradually released from the depot form (oily solution) and is almost completely cleaved by serum esterases to testosterone and undecanoic acid. The next day there is an increase in serum testosterone concentration.

According to two studies, in men with hypogonadism after a single intramuscular injection of 1000 mg of testosterone undecanoate, the mean maximum concentrationtestosterone, comprising 45 and 24 nmol / L, are determined at 7 and 14 days, respectively. Postmaximum levels of testosterone decrease with a half-life period of approximately 53 days.

After repeated intramuscular injections of 1000 mg of testosterone undecanoate to men with hypogonadism with an interval between injections of 10 weeks, the equilibrium concentration was reached between the 3rd and 5th injections.Mean values of the maximum and minimum concentrations of testosterone in the equilibrium state were about 42 and 17 nmol / L, respectively. Post-maximal serum testosterone levels were reduced with a half-life of approximately 90 days, which corresponds to the release rate of the substance from the depot.

When skin application the degree of absorption of testosterone is from 9 to 14% of the applied dose. After absorption through the skin testosterone enters the systemic circulation at relatively constant concentrations during a 24-hour cycle. Daily fluctuations in testosterone concentrations have the same amplitude as circadian changes in the content of endogenous testosterone. External application of testosterone allows to avoid the peak distribution in the blood, arising from the injection method of its administration. In contrast to oral androgen therapy, external application of testosterone does not cause an increase in the concentrations of steroids in the liver above physiological norms.

The use of 50 mg of testosterone externally causes an average increase in plasma concentration of approximately 2.5 ng / ml (8.7 nmol / L).After discontinuation of treatment, testosterone concentration begins to decrease approximately 24 hours after the last use. Concentration returns to the baseline level approximately 72-96 hours after the last dose. The main active metabolites of testosterone for its dermal application are dihydrotestosterone and estradiol.

Indications:Hormone replacement therapy for violations associated with testosterone deficiency: post-stroke syndrome, eurychidism, hypopituitarism, endocrine impotence, some forms of infertility associated with impaired spermatogenesis, menopausal symptoms in men (decreased libido and physical activity, deterioration of overall health), masculinization in transsexuals.

Testosterone therapy is indicated in men with osteoporosis caused by androgen deficiency.

ICD-10

IV.E20-E35.E23.0 Hypopituitarism

IV.E20-E35.E25 Adrenogenital disorders

IV.E20-E35.E29 Testicular dysfunction

IV.E20-E35.E29.1 Hypofunction of the testes

V.F50-F59.F52.2 Insufficiency of the genital reaction

XIII.M80-M85.M81.9 Osteoporosis, unspecified

XIII.M80-M85.M82.1 * Osteoporosis in endocrine disorders (E00-E34 +)

XIV.N40-N51.N46 Male infertility

XIV.N40-N51.N50.8 Other specific diseases of male genital organs

Contraindications:Hypersensitivity, verified or suspected carcinoma of the prostate or breast, hypercalcemia associated with malignant tumors, liver tumors (currently or in history), pregnancy and lactation.

Carefully:Latent or severe heart failure, renal dysfunction, arterial hypertension, apnea syndrome, epilepsy, migraine (currently or in the anamnesis); benign prostatic hypertrophy.

Use with caution in boys in the prepubertal period (risk of premature closure of the epiphyses and accelerated puberty).

Pregnancy and lactation:Contraindicated in pregnancy (possible masculinization of the fetus) and during lactation.

Action category for the fetus by FDA - H.

Dosing and Administration:The dose is selected individually, depending on the route of administration and the clinical effect.

Inside

As a rule, the initial dose for adults is 120-160 mg per day for 2-3 weeks, maintaining a dose of 40-120 mg per day. To improve the absorption should be taken with food.

Intramuscularly

1000 mg of testosterone undecanoate once every 10-14 weeks. This injection frequency ensures the maintenance of a sufficient level of testosterone, its cumulation does not occur. Before the start of treatment it is recommended to determine the content of testosterone in the serum. At the end of the interval between injections, the level of testosterone should also be assessed. If it is lower than normal, this may indicate a need to reduce the interval between injections. At high concentrations, the feasibility of increasing this interval should be considered.

Outwardly

The recommended dose of testosterone (50 mg) in the form of a gel is applied to the skin of the shoulders, forearms and / or stomach once a day at about the same time (preferably in the morning). The individual daily dose can be adjusted depending on the clinical and laboratory parameters, but should not exceed 100 mg of testosterone per day. Correction of the dosing regimen should be performed stepwise - 25 mg of testosterone per day.

Side effects:Have boys in prepubertal period: premature puberty; premature closure of bone growth zones; increased frequency of erections and an increase in the size of the penis.

In men: priapism; increased sexual arousal; oligospermia; decrease in ejaculate volume.

In all patients: sodium and water retention, polycythemia.

Common adverse reactions associated with androgen therapy

In the presence of neoplasms of benign, malignant and vague (including cysts and polyps) - prostate cancer (progression of subclinical prostate cancer).

From the side of the circulatory and lymphatic systems: polycythemia.

From the side of metabolism: fluid retention.

From the side of the central nervous system: dizziness, headache.

Mental disorders: depression, nervousness, mood disorders, increased or decreased libido.

From the side of the cardiovascular system: arterial hypertension.

From the gastrointestinal tract, liver and bile ducts: nausea, diarrhea, pain or discomfort in the abdomen, impaired liver function.

From the musculoskeletal system and connective tissue: pain in the legs, myalgia.

From the skin and subcutaneous tissue: itching, acne, with external application - skin reactions at the site of application: (irritation, erythema).

On the part of the reproductive system and mammary glands: gynecomastia, oligospermia, priapism, an increase in the size of the prostate.

Laboratory indicators: abnormalities in liver function parameters, changes in lipid profile (decrease in HDL, LDL, triglycerides in blood plasma), increase in the concentration of specific antigen of the prostate.

Overdose:When you receive Inside: symptoms: - violations of the gastrointestinal tract: treatment: gastric lavage, symptomatic therapy.

When intramuscular introduction: treatment - suspension of therapy or dose reduction.

When outdoor application of cases of overdose is not fixed.

Interaction:Inducers of microsomal liver enzymes can be reduced, and inhibitors of these enzymes can increase the concentration of testosterone. It may be necessary to adjust its dose when combined with such drugs.

Androgens can increase glucose tolerance and reduce the need for insulin or other hypoglycemic agents in patients with diabetes mellitus. Such patients should undergo a special examination before androgen treatment, periodically during and after treatment.

Androgens can enhance the action of anticoagulants coumarinovogo number. It should be constantly monitor prothrombin time, if necessary - reduce the dose of anticoagulants.

The use of testosterone simultaneously with ACTH or GCS can enhance the formation of edema, especially in patients with liver or cardiovascular disease, as well as in patients predisposed to edema.

Androgens can reduce the concentration of thyroxine-binding globulin, as a result of which the content of total T₄ in serum and binding increases T₃ and T₄. At the same time, the levels of free thyroid hormones remain unchanged, and there are no clinical manifestations of a violation of its function.

Special instructions:When appointing testosterone inwards or intramuscularly patients need regular rectal examination of the prostate (to exclude benign hyperplasia, asymptomatic prostate cancer, prostate carcinoma), and to determine hematocrit and hemoglobin level (to exclude polycythaemia). Boys in the prepubescent period should monitor body growth and sexual development (due to the risk of premature closure of the epiphyses of long tubular bones and accelerated puberty).

In patients with hypogonadism receiving testosterone treatment, especially in obese and chronic respiratory diseases, the risk of developing sleep apnea increases.

Some categories of patients should be monitored (especially the elderly):

1) patients with tumors (breast cancer, hypernephroma, bronchial cancer and bone metastases), in whom spontaneous hypercalcemia may occur, including with androgen therapy. Hypercalcemia may indicate a positive tumor response to hormone therapy. However, first you should treat hypercalcemia, and after restoring the normal concentration of calcium, you can resume hormone therapy;

2) patients with existing diseases of the heart, kidney, liver, or with cardiac, renal or hepatic insufficiency, in which treatment with androgens can lead to edema with or without chronic heart failure. In such cases, treatment with androgens should be stopped immediately;

3) patients with diabetes mellitus, who testosterone can increase glucose tolerance;

4) patients taking anticoagulants, whose effect can enhance testosterone.

Testosterone use in athletes

Athletes participating in competitions under the control of the World Anti-Doping Agency (WADA) should, before starting testosterone treatment, read the rules of WADA, since taking androgen can affect the results of anti-doping control. Do not use testosterone to increase sports performance, this represents a serious health risk.

In case of androgen-dependent side effects, treatment should be discontinued. After their disappearance it is necessary to resume treatment with lower doses. The use of exogenous testosterone can affect the results of some laboratory tests.

Outwardly androgen therapy should be prescribed only if testosterone deficiency is accompanied by such clinical manifestations as regression of secondary sexual characteristics, changes in body structure, asthenia, decreased libido, erectile dysfunction, and so on, and do not use for the treatment of male infertility or erectile dysfunction, not related to testosterone deficiency.If a patient develops a severe local reaction, treatment should be discontinued. The patient should be informed that when the testosterone is prescribed, there is a potential for it to be transferred to another person. To ensure the safety of the partner, the patient must: observe the interval between dermal application of testosterone and sexual intercourse, wear clothing covering the place of application during the contact, or take a shower before sexual intercourse.

In the case of a partner's pregnancy, the patient needs to be more careful about the observance of precautionary measures. Pregnant women should avoid any contact of testosterone with the skin. In case of contact, the woman should be washed as soon as possible with water and soap, the skin area on which the gel has fallen. In contact with children, patients who use testosterone externally, it is recommended to wear clothing covering the place of application of testosterone.

Androgen therapy does not affect the ability to drive vehicles and work with mechanisms.

Instructions

Testosterone (Testosteronum)