Androgel

General characteristics. Structure:

Active ingredient: 25 mg or 50 mg of testosterone.

Excipients: isopropyl myristate, ethanol of 96%, carbomer, sodium hydroxide, the water purified.

Pharmacological properties:

Pharmacodynamics. Androgenic drug. The endogenous androgens (generally testosterone) cosecreted by testicles and their main metabolite dihydrotestosterone are responsible for development of outside and internal generative organs and for development and preservation of secondary sexual characteristics (stimulation of growth of hair, a voice posterization), a libido. Exert the general impact on anabolism of proteins, on development of skeletal muscles and distribution of a hypodermic fatty tissue, reduce excretion with urine of nitrogen, sodium, potassium, chlorides, phosphates and waters. Testosterone does not cause development of testicles: it reduces pituitary secretion of gonadotrophins.

Effects of testosterone on some target organs are shown after peripheral transformation of testosterone to oestradiol which then contacts estrogenic receptors in kernels of cells of target organs (such as hypophysis, fatty tissue, a brain, bones, etc.).

Pharmacokinetics. Absorption. Extent of absorption of testosterone through skin varies in limits approximately from 9% to 14% of the put dose.

Distribution. After absorption testosterone comes to a system blood stream in rather constant concentration during 24 h. Concentration of testosterone increases in serum from the first hour after drug Androgel® use, reaching constant value from the second day of treatment. Daily fluctuations of concentration of testosterone have the same amplitude, as well as the changes of content of endogenous testosterone observed in circadian rhythms.

At an outside way of administration of drug there are no suprafiziologichesky peaks of concentration of testosterone in the blood arising at an injection route of administration. Contrary to peroral therapy by androgens, external use of drug does not cause increase in concentration of steroids in a liver above physiological norms. Use of 5 g of Androgel causes average increase in concentration of testosterone in plasma approximately on 2.5 ng/ml (8.7 nmol/l).

Metabolism. The main active metabolites of testosterone are dihydrotestosterone and oestradiol.

Removal. After the treatment termination concentration of testosterone begins to decrease approximately in 24 h after the last drawing. Concentration is returned to initial level approximately in 72-96 h after use of the last dose. Drug is removed generally with urine and with a stake in the form of the conjugated testosterone metabolites.

Indications to use:

— replacement therapy at insufficiency of endogenous testosterone.

Route of administration and doses:

The recommended daily dose makes 5 g of gel (i.e. 50 mg of testosterone). Drug is used by 1 times/days approximately at the same time days, it is preferable in the morning. The daily dose can be adjusted depending on clinical and laboratory indicators, but should not exceed 10 g of gel. Correction of the mode of dosing has to be carried out in steps 2.5 g of gels/days.

For dose adjustment of drug it is necessary to define concentration of testosterone in serum in the morning, before drug use, with the day before yesterday after an initiation of treatment (within one week). The dose can be reduced if the content of testosterone in plasma is increased or to increase on the contrary if concentration of testosterone low.

Rules of use of drug. Gel is applied on the clean, dry, unimpaired skin of shoulders, forearms and/or a stomach. It is impossible to apply gel on area of genitalias since the high content of alcohol in drug can cause local irritation.

After opening of a bag it is necessary to apply immediately on skin all its contents and to distribute a thin layer. It is not obligatory to rub it in skin. It is possible to allow to it to dry within, at least, 3-5 min. before clothing. After drawing it is necessary to wash up hands with soap.

Features of use:

Андрогель® it is necessary to apply only at the insufficiency of testosterone which is followed by such clinical manifestations as an underdevelopment or regression of secondary sexual characteristics, change of a structure of a body, disturbance of carbohydrate and lipidic exchanges, obesity, an adynamy, disturbance of sexual function (including decrease in a libido, erectile dysfunction), decrease in mineral density of bones, differences of mood, a depression, inflows, etc. Before an initiation of treatment other possible reasons which are the cornerstone of the above described symptoms have to be excluded.

Now there are no accurate age norms of sizes of testosterone. However the fact that physiological levels of serumal testosterone begin to decrease from 30-40 years has to be taken into account, and the level of the globulin connecting sexual steroids increases. It, respectively, leads to decrease in level of biologically active testosterone.

Owing to variability of laboratory values, definition of concentration of testosterone should be carried out in the same laboratory.

Андрогель® do not apply to treatment of male infertility or erectile dysfunction which reason is not connected with insufficiency of testosterone.

Before purpose of testosterone all patients have to undergo inspection to exclude existence of a prostate cancer since androgens can accelerate a progression of a subclinical prostate cancer and benign hyperplasia of a prostate. It is necessary to make careful and regular observation of a condition of a prostate (a manual rectal research, definition of prostatspetsifichesky antigen (DOG) in serum) and chest glands, at least, once a year annually, and at elderly patients and patients from risk group (with clinical or family factors) - 2 times a year.

Андрогель® it is necessary to apply with care at patients with malignant new growths because of danger of a hypercalcemia (and the accompanying hypercalcuria), owing to metastasises in a bone. At these patients it is recommended to control concentration of calcium in serum.

At the patients having a heavy heart, liver or renal failure, treatment by Androgel can cause the complications which are characterized by hypostases with congestive heart failure or without it. In this case treatment has to be immediately stopped. Besides, therapy by diuretics can be required.

At the patients accepting androgens during the long period in addition to laboratory measurements of concentration of testosterone, it is periodically necessary to check the following laboratory indicators: hemoglobin, a hematocrit (for identification of a polycythemia) both functional trials of a liver and a lipidic profile.

Data on increase in risk of development of an apnoea in a dream at the patients with a hypogonadism receiving treatment by testosterone esters, especially at what had risk factors, such as obesity and chronic respiratory diseases were published.

At the patients with a diabetes mellitus receiving androgens at achievement of normal concentration of testosterone in a blood plasma increase in sensitivity to insulin can be observed.

Some clinical symptoms: irritability, nervousness, increase in body weight, long or frequent erections can indicate the excessive influence of an androgen demanding dose adjustment.

If at the patient heavy local reaction develops, treatment has to be reconsidered and, in case of need, is stopped.

When using Androgel's at athletes it is necessary to take into account the fact that drug contains testosterone which can give positive reaction in anti-doping tests.

Use of the drug ANDROGEL® at pregnancy and feeding by a breast. Drug is not used at women. In case of pregnancy of the sexual partner the patient needs to treat observance of precautionary measures more attentively. Pregnant women have to avoid any contact with drug owing to its possible virilizing effect on a fruit. In case of contact with drug it is necessary to wash up, as soon as possible, the place of contact by water with soap.

Use at abnormal liver functions. At the patients having a heavy liver failure, treatment by Androgel can cause the complications which are characterized by hypostases with congestive heart failure or without it. In this case treatment has to be immediately stopped.

Use at renal failures. At the patients having a heavy renal failure, treatment by Androgel can cause the complications which are characterized by hypostases with congestive heart failure or without it. In this case treatment has to be immediately stopped.

Use for children. Experience of use of Androgel for children is absent.

Potential transfer of testosterone. At Androgel's appointment it is necessary to inform the patient on security measures.

To guarantee safety of the partner, the patient needs, for example, to advise to carry out sexual intercourse before use of drug or to observe an interval between Androgel's use and sexual intercourse. If sexual intercourse is carried out in an interval to 6 h after putting the drug Androgel®, during the period of contact it is recommended to put on the t-shirt covering a site of application of gel or to take a shower before sexual intercourse.

Not less than 6 h between putting gel and acceptance of a bathtub or shower are preferable to observe an interval. However accidental acceptance of a shower during from 1 to 6 h after putting gel has no significant effect on treatment.

Patients are recommended to observe the following precautionary measures:
— to wash up hands with soap after putting gel;
— to close the field of putting gel clothes after gel dries;
— to take a shower before contact with the partner.

To the persons which are not applying Androgel®:
— in case of contact with the field of putting gel which is previously not washed up by water it is necessary to wash out as soon as possible water with soap the site of skin on which testosterone could get;
— it is necessary to report to the doctor about emergence and development of such signs of a giperandrogenization as an acne or change of usual growth of hair.

To the patients applying Androgel® at contact with children recommend to wear the t-shirt covering a gel site of application to avoid risk of contact of skin of children with drug.

Андрогель® should not appoint patients who will not be able to observe security guidelines (for example, a heavy alcoholism, toxicomania, heavy mental disorders).

Influence on ability to driving of motor transport and to control of mechanisms. There are no data on Androgel's influence on ability to driving of the car and control of cars and mechanisms now.

Side effects:

The most frequent undesirable effects (about 10%) at use of the recommended dose of 5 g of gel/days were: skin reactions on site drawings, erythema, acne, xeroderma. During clinical tests of Androgel the following undesirable effects were noted (> 1/100, <1/10):

From blood and lymphatic system: changes of results of laboratory tests (polycythemia, changes of level of lipids).

From urinogenital system: changes in a prostate, gynecomastia, mastodynia.

From a nervous system: headache, dizziness, paresthesia, amnesia, hyperesthesia, changes of mood.

From cardiovascular system: increase in the ABP.

From the alimentary system: diarrhea.

Dermatological reactions: alopecia, small tortoiseshell.

Drug contains alcohol therefore at its frequent drawing on skin the irritation and dryness can appear.

Interaction with other medicines:

At simultaneous use of Androgel and indirect anticoagulants strengthening of action of the last by modification of synthesis of a hepatic factor of coagulation and competitive inhibition of linkng with proteins of plasma is possible. The patients receiving peroral anticoagulants against the background of Androgel's use are recommended to control a prothrombin time, it is especially frequent at the beginning and/or at the end of a course of treatment androgens.

Combined use of Androgel with AKTG or corticosteroids can increase risk of emergence of hypostases. It is necessary to show care at combined use of these medicines, especially at patients with heart diseases, kidneys or a liver.

Androgens can reduce levels of tiroksinsvyazyvayushchy globulin, leading to reduction of serumal concentration of T4 and to increase in sensitivity to T3 and T4. Levels of free hormones of a thyroid gland, however, remain invariable, and at the same time there are no clinical manifestations of a hypothyroidism.

Contraindications:

— a carcinoma of chest gland or suspicion on its existence;
— a prostate cancer or suspicion on its existence;
— hypersensitivity to testosterone or other components of drug.
Experience of use of Androgel for women and children is absent.

With care it is necessary to appoint drug at malignant new growths (because of danger of a hypercalcemia and a hypercalcuria), at a heavy heart, liver or renal failure, at an ischemic heart disease, arterial hypertension, epilepsy, migraine.

Overdose:

Overdose cases at Androgel's use are not recorded. Only one case of overdose after use of testosterone entered injektsionno is described. It the patient had a stroke with high concentration of testosterone in plasma of 114 ng/ml (the 395th nmol/l). However it is improbable that similar concentration of testosterone in plasma can be reached when putting drug on skin.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 25 °C. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

In the laminated bags on 2,5 or 5 g; in a pack of cardboard 10 or 30 pieces of bags.