Nebido® [Testosterone undecanoate]

Pharmacological properties

Testosterone undecanoate is an ester of natural androgen, testosterone. active form - testosterone is formed as a result of cleavage of the side chain.

Testosterone is the most important androgen in the male body and is synthesized mainly in the testes and to a lesser extent in the adrenal cortex.

Testosterone is responsible for the formation of male sexual characteristics during prenatal development, in early childhood, as well as during puberty, and over time - for supporting the male phenotype and androgen-dependent functions (e.g. spermatogenesis, sex glands), and also performs some functions, for example, in the skin , muscles, skeleton bones, kidneys, liver, bone marrow and central nervous system.

Insufficient testosterone secretion causes the development of hypogonadism in men, which is characterized by low concentrations of testosterone in the blood serum. Symptoms associated with hypogonadism in patients also include impotence, decreased sex drive, fatigue, depression, lack of, underdevelopment, or regression of secondary sexual characteristics, as well as an increased risk of osteoporosis. Exogenous androgens are prescribed to increase insufficient levels of endogenous testosterone, as well as to eliminate the corresponding symptoms of hypogonadism.

Depending on the target organ, the range of testosterone is mainly androgenic (for example, the prostate gland, seminal vesicles, epididymis) or protein-anabolic (muscles, bones, blood-forming system, kidneys, liver).

The effect of testosterone in some organs appears after conversion of testosterone to peripheral tissues into estradiol, which subsequently binds to estrogen receptors in the nuclei of target cells (for example, the pituitary gland, adipose tissue, brain, bones, and Leydig testicular cells).

In men with hypogonadism, the use of androgens reduces body fat mass, increases lean body mass, muscle strength, and also prevents bone loss. Androgens can improve sexual function, as well as have a positive psychotropic effect by improving mood.

Nebido is a depot drug that is administered in oil and contains testosterone undecanoate, as a result of which the effect of the first passage through the liver is absent. After a / m injection of testosterone undecanoate in the form of an oil solution, this compound is gradually released from the depot and is almost completely cleaved by serum esterases into testosterone and undecanoic acid. An increase in the concentration of testosterone in serum relative to basal values ​​can be determined the very next day after the injection.

During two separate studies, average maximum testosterone concentrations of 24 and 45 nmol / L were determined after 14 and 7 days, respectively, after a single IM injection of 1000 mg of testosterone undecanoate in patients with hypogonadism. Postmaximal testosterone levels decreased with a half-life of approximately 53 days.

In male blood serum, about 98% of circulating testosterone binds to sex steroid-binding globulin (SHGS) and albumin. Only the free fraction of testosterone is considered biologically active. After iv infusion of testosterone in elderly patients, the apparent volume of distribution was determined at about 1 l / kg.

Testosterone resulting from the breakdown of the testosterone undecanoate ester is metabolized and excreted from the body in the same ways as endogenous testosterone. Undecanoic acid is metabolized via β-oxidation in the same way as other aliphatic carboxylic acids.

Testosterone undergoes significant metabolism in the liver and beyond.After the administration of labeled testosterone, about 90% of the radioactivity was excreted in the urine in the form of glucuronide and sulfate acid conjugates, and 6% (after undergoing intrahepatic circulation) in feces. Products excreted in the urine include androsterone and etiocholanolone.

After repeated intramuscular injections of 1000 mg of testosterone undecanoate in patients with hypogonadism, an equilibrium concentration was reached between the 3rd and 5th injections at a 10-week interval between injections. The average maximum and average minimum concentrations of testosterone in equilibrium were approximately 42 and 17 nmol / L, respectively. The postmaximal serum testosterone level decreased with a half-life of approximately 90 days, which corresponds to the rate of release of the substance from the depot.

Indications

Testosterone treatment of primary and secondary hypogonadism in men.

Application

Nebido injection (1 ampoule contains 1000 mg of testosterone undecanoate) is carried out once every 10-14 weeks. at such a frequency of injections, an adequate level of testosterone is maintained and the substance does not accumulate.

Injections should be carried out very slowly. The drug is intended for IM injection only. Care must be taken to ensure that the substance that is introduced does not enter the vessel.

Before starting treatment, you should determine the level of testosterone in the blood serum. The first interval between injections can be shortened, but should be at least 6 weeks. Equilibrium concentration at such a loading dose is achieved quickly.

In the intervals between injections, it is recommended from time to time to measure the level of testosterone in the blood serum. If this level is below normal, this fact may indicate the need to reduce the interval between injections. At high concentrations, consideration should be given to the advisability of lengthening this interval. The interval between injections should remain within the recommended range, which is 10-14 weeks.

Contraindications

Nebido cannot be used in the presence of androgen-dependent carcinoma of the prostate or breast in men; hypercalcemia accompanying malignant tumors; with liver tumors at this time or in history; as well as with increased sensitivity to the active substance or to any auxiliary component of the drug.

Nebido is contraindicated in women.

Side effects

During clinical trials, the following side effects were recorded, probably associated with the use of nebido:

* Due to the small sample of study participants, the frequency of each recorded side effect, the appearance of which is probably associated with the use of the drug, falls into the category of “frequent” (≥1 / 100).

** One case of compaction of the middle part of a small prostate.

The following adverse reactions to drugs containing testosterone were noted in the literature:

special instructions

When using androgens to treat elderly patients, the risk of developing prostate hyperplasia may be increased. although there is no clear evidence that androgens can actually cause prostate carcinoma, they can help grow an existing prostate carcinoma. In this regard, before starting treatment with drugs containing testosterone, a diagnosis of prostate carcinoma should be excluded.

For preventive purposes, it is recommended to conduct regular examinations of the prostate in men.

In patients who are on long-term androgen therapy, it is recommended to periodically check hemoglobin and hematocrit levels in order to detect cases of polycythemia (see ADVERSE EFFECTS).

During the use of hormonal substances, for example, testosterone compounds, benign and very rarely malignant tumors of the liver were rarely noted. In some cases, these tumors led to life-threatening bleeding in the abdominal cavity. If a patient receiving Nebido has severe pain in the upper abdomen, an increase in liver size is noted, or there are signs of intra-abdominal bleeding, the differential diagnosis should take into account the likelihood of a liver tumor.

Caution should be exercised in patients predisposed to swelling.

Clinical trials of Nebido with the participation of children or adolescents under the age of 18 years have not been conducted.

The use of testosterone for the treatment of children along with masculinization can cause accelerated growth and maturation of bone tissue, as well as premature closure of the growth zone of the pineal gland, which will result in a decrease in final growth. The appearance of ordinary eels is possible.

Existing sleep apnea can be aggravated.

Like all oil solutions, Nebido is introduced in oil. Experience shows that with an extremely slow administration of a solution, short-term reactions that are sometimes observed during or immediately after an injection of an oil solution can be avoided (urging to cough, coughing, respiratory depression).

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