Nebido

Active material: Testosterone
When ATH: G03BA03
CCF: Androgenic – depot form
ICD-10 codes (testimony): E23.0, E29.1
When CSF: 15.11.02.01
Manufacturer: BAYER SCHERING PHARMA AG (Germany)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

The solution for the / m clear, yellowish, oil.

Excipients: benzyl, castor oil refined (for parenteral administration).

4 ml – vials of dark glass (1) – packs cardboard.

Pharmacological action

Androgen. Testosterone undecanoate is an ester of the natural androgen, Testosterone. The active form, Testosterone, formed by cleavage of the side chain.

Testosterone – the male sex hormone, has all the spectrum of biological activity, necessary for the formation and maintenance functions androgenic. Synthesized, mainly, in the testes and, less, adrenal cortex. It provides the formation of internal and external genitalia of male type during fetal development, early childhood; puberty – the formation of the genital organs and the development of secondary sexual characteristics. Subsequently, testosterone maintains the male phenotype and function androgenozavisimyh (eg, spermatogenesis, gonads). It also regulates the performance of certain functions, eg, in the skin, muscle, skeletal, kidney, liver, bone marrow and central nervous system.

Insufficient secretion of testosterone results in male hypogonadism, which is characterized by low serum testosterone concentrations. Symptoms, associated with male hypogonadism, inter alia, include impotence, decreased sex drive, fatiguability, depressed mood, absence, underdevelopment or regression of secondary sexual characteristics, and increased risk of osteoporosis. Exogenous androgens are appointed to improve the insufficient levels of endogenous testosterone and reduce the symptoms of hypogonadism.

Depending on the target organ is the nature of the action of testosterone, mainly, androgenic (eg, prostate, seminal vesicles, parorchis) or protein-anabolic (muscle, bones, hematopoietic system, kidneys, liver).

The action of testosterone in some organs shown after peripheral conversion of testosterone to estradiol, which then binds to the estrogen receptor in the nuclei of target cells (eg, pituitary, fat tissue, brain, bone and testicular Leydig cells).

Men, hypogonadal, androgens application reduces body fat mass, increasing lean body mass, and prevents bone loss. Androgens may improve sexual function, as well as have a positive impact psychotropic, improving mood.

Pharmacokinetics

Absorption

After the / m injection of testosterone undecanoate oil solution is gradually released from the depot and is almost completely cleaved by serum esterases for testosterone and undecanoic acid. Increased serum concentrations of testosterone relative to baseline can be determined on the next day after injection.

Distribution

In two separate studies, the mean C_max Testosterone, constituents of 24 nmol / l 45 nmoli /, determined, respectively, by 14 and 7 days after a single i / m testosterone undecanoate injected at a dose 1 g men with hypogonadism. The male serum protein binding (SHBG and albumin) is about 98%. Biologically Active considered only the free fraction of testosterone. After i / v infusion of testosterone to elderly men V_d was about 1 l / kg.

After repeated / m injectable testosterone undecanoate in the dosage 1 g men with hypogonadism when the interval between injections 10 C Weeks_ss It reached between 3 and 5 inaektsiyami. The mean values ​​of C max_ss and minimum C_ss testosterone were about 42 and 17 nmol / l, respectively. T_1/2 testosterone is approximately 90 days, which corresponds to a release rate of the substance depot.

Metabolism

Testosterone, produced from testosterone undecanoate as a result of the splitting of the ester bond, metabolized and excreted by the same pathways, the endogenous testosterone. Undecanoic acid is metabolized by p-oxidation as well, as well as other aliphatic carboxylic acids.

Deduction

Testosterone undergoes significant hepatic metabolism and outside. After administration of the labeled testosterone around 90% Radioactivity is determined in the urine as glucuronide and sulfate conjugates acid, and 6% after passing the enterohepatic circulation is found in feces. Defined in the urine products include androsterone and etioholanolon.

Testimony

- Lack of testosterone during the primary and secondary hypogonadism in men.

Dosage regimen

The injection at a dose of Nebido 1 g (1 ampoule) made 1 once every 10-14 weeks. At this frequency of injections provided to maintain sufficient levels of testosterone, and there is no accumulation of substances.

Injections should be made slowly. Nebido can be administered only in strict / m. It is necessary to carefully monitor the, that the drug did not get into the blood vessel.

Before treatment should determine the amount of testosterone in serum. The first interval between injections may be reduced, but should be at least 6 weeks. C_ss at this dose is achieved quickly.

At the end of the interval between the injections it is recommended to measure the content of testosterone in serum. If the level below normal levels, that fact may indicate the need to reduce the interval between injections. At high concentrations, should consider whether to extend the interval. The interval between injections should be within the recommended range in 10-14 weeks.

Side effect

Because of the small sample of research participants, the frequency of occurrence of each of the registered side effect, appearance is presumably due to the use of the drug, falls, at least, in category “often” (≥1%).

From the digestive system: ≥1% – diarrhea.

On the part of the musculoskeletal system: ≥1% – pain in the legs, arthralgia.

CNS: ≥1% – dizziness, headache.

The respiratory system: ≥ 1% – respiratory failure.

Dermatological reactions: ≥1% – acne, itch, skin disorders.

On the part of the endocrine system: ≥1% – breast pain, gynecomastia.

On the part of the reproductive system: ≥1% – pain in the testicles (prostate disease). Registered one case seals the middle of the small size of the prostate gland.

Local reactions: ≥1% – pain at the injection site, subcutaneous hematoma at the injection site.

Other: ≥1% – increased perspiration.

The literature describes the following adverse reactions to preparations, containing testosterone:

Contraindications

- Androgenozavisimaya prostate carcinoma;

- Androgenozavisimaya breast carcinoma in males;

- Hypercalcemia, related malignancies;

- Liver tumors at present or in history;

- Hypersensitivity to the drug.

Nebido is not used in women.

FROM caution should use the drug in patients with sleep apnea syndrome.

Pregnancy and lactation

Nebido is not used in women.

Cautions

When applied for the treatment of androgen elderly patients may increase the risk of developing prostate hyperplasia. Despite the lack of evidence, Androgens may cause prostate carcinoma, they can promote the growth of existing carcinomas. Therefore, before starting treatment with, containing testosterone, should be deleted prostate cancer.

As a precaution it is recommended to carry out regular examinations of the prostate gland in men.

Patients, are on long-term androgen therapy, it is recommended to periodically monitor hemoglobin and hematocrit to detect cases of polycythemia.

Against the background of sex steroids, which include testosterone, rarely observed benign and, even rarer, hepatoblastoma, which may lead to intra-abdominal haemorrhage. If the background of treatment with Nebido developed severe pain in the upper abdomen, enlarged liver, or there are signs of intra-abdominal bleeding, the differential diagnosis should take into account the likelihood of having a liver tumor.

Caution should be exercised in patients, prone to edema.

The existing sleep apnea may increase.

Androgens are not used to enhance muscle development in healthy subjects, as well as to improve physical ability.

Like all oily solutions, Nebido injected i / m. Experience shows, that the extremely slow introduction of the solution can avoid short-term reactions, in rare cases during or immediately after the injection of an oil solution (the urge to cough, coughing, respiratory insufficiency).

Use in Pediatrics

Clinical trials involving Nebido children or adolescents under the age of 18 years so far not held.

The use of testosterone to treat the children, along with masculinization can cause accelerated growth and maturation of bone tissue, and the premature closure of the growth zone of epiphysis, that will result in final reduction of growth. Perhaps the appearance of acne vulgaris.

Effects on ability to drive vehicles and management mechanisms

Nebido not affect the ability to drive the vehicle and operate machinery.

Overdose

In case of overdose special therapeutic measures not required, except for temporary discontinuation or dose reduction.

Drug Interactions

Under the influence of androgens may increase hypoglycemic effects of insulin. You may need to decrease the dose of hypoglycemic medication.

Possible interactions with drugs, inducing microsomal enzymes (eg, barbiturates), which may lead to an increase in clearance of testosterone.

Androgens may affect the metabolism of other drugs. In accordance with this, drug concentrations in plasma and tissues may vary: eg, there may be an increase in the concentration of serum oxyphenbutazone. Besides, Testosterone and its derivatives can increase the activity of oral anticoagulants, which may necessitate dose adjustment. Regardless of the fact dannogo, As a general rule you should always observe restrictions, on a / m injections to patients with acquired or inherited bleeding disorders.

Since the compatibility studies was conducted, not be mixed with other active drug drugs.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.