ANDROGEL


Androgel - the official instruction for use


INSTRUCTIONS

on medical use of the drug


Registration number:

LS-000869-151012

Trade name of the preparation:

Androgel®

International non-proprietary name or group name:

testosterone

Dosage form:

gel for external use

Composition:

In 1 g of gel contains:

Active substance:

Testosterone 10 mg

Excipients: isopropyl myristate 5 mg, carbomer 980 9 mg, sodium hydroxide 47.2 mg, ethanol 96% 0.714 g, water purified to 1 g

In 1 packet containing 2.5 g of gel:

Active substance:

Testosterone 25 mg

Excipients: isopropyl myristate 12.5 mg, carbomer 980 22.5 mg, sodium hydroxide 118 mg, ethanol 96% 1.785 g, water purified to 2.5 g


In 1 packet containing 5.0 g of gel:

Active substance:

Testosterone 50 mg

Excipients: isopropyl myristate 25 mg, carbomer 980 45 mg, sodium hydroxide 236 mg, ethanol 96% 3.570 g, water purified to 5 g


In 1 extractable dose of a vial containing 1.25 g of gel:

Active substance:

Testosterone 12.5 mg

Excipients: isopropyl myristate 6.25 mg, carbomer 980 11.25 mg, sodium hydroxide 59 mg, ethanol 96% 0.892 g, water purified to 1.25 g.


Description


Transparent or slightly opalescent colorless gel with the smell of alcohol.


Pharmacotherapeutic group:

androgen.


ATX: G03BA03


Pharmacological properties

Pharmacodynamics

Endogenous androgens, mainly testosterone, secreted by the testes, and their basic metabolite dihydrotestosterone are responsible for the development of external and internal genital organs and for the development and preservation of secondary sexual characteristics (stimulation of hair growth, coarsening of the voice), libido; for the general effect on the anabolism of proteins; for the development of skeletal muscles and the distribution of subcutaneous fat; for a decrease in urinary excretion of nitrogen, sodium, potassium, chlorides, phosphates and water. Testosterone does not cause development of testicles: it reduces the pituitary secretion of gonadotropins.

The effects of testosterone on certain target organs are manifested after the peripheral conversion of testosterone to estradiol, which then binds to estrogen receptors in the target cell nuclei (such as the pituitary gland, adipose tissue, brain, bones, etc.).

Pharmacokinetics

The degree of absorption of testosterone through the skin varies between approximately 9% and 14% of the applied dose.

After absorption through the skin, testosterone enters the systemic circulation at relatively constant concentrations within 24 hours.

The concentration of testosterone in the serum increases from the first hour after the application of Androgel®, reaching a constant value from the second day of treatment. Daily fluctuations in testosterone concentrations have the same amplitude as the changes in endogenous testosterone content observed in circadian rhythms. With the external route of administration of the preparation, there are no supraphysiological peaks of testosterone concentration in the blood arising from the injection method of administration.

In contrast to oral androgen therapy, external use of the drug does not cause an increase in the concentrations of steroids in the liver above physiological norms.
The use of 5 g of Androgel causes an average increase in plasma testosterone 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 dose. Concentration returns to the baseline level approximately 72-96 hours after the last dose.
The main active metabolites of testosterone are dihydrotestosterone and estradiol.
Androgel® is excreted mainly with urine and with feces in the form of conjugated testosterone metabolites.

Indications for use
Replacement therapy for endogenous testosterone deficiency.

Contraindications

Androgens are contraindicated:
- in the presence of breast carcinoma, prostate cancer or suspected of their presence;
- if there is a hypersensitivity to testosterone or to other components of the drug.
The experience of using Androgel in women and children is absent.

Carefully

Malignant neoplasms (due to the danger of hypercalcemia and hypercalciuria); severe cardiac, hepatic or renal insufficiency; cardiac ischemia; arterial hypertension; epilepsy; migraine.

Dosing and Administration

The recommended dose is 5 g of gel (ie 50 mg of testosterone), applied once a day at about the same time, preferably in the morning. Individual daily dose can be adjusted by the doctor depending on clinical and laboratory parameters in patients, but should not exceed 10 g of gel per day. Correction of the dosing regimen should be performed in steps of 2.5 g of gel per day. The gel is applied to clean, dry, undamaged skin of the shoulders, shoulders and / or abdomen.
The gel should be removed from the vial or from the package directly to the palm, and then applied to the required application areas.
After opening the package, it is necessary to immediately apply to the skin all its contents and distribute it in a thin layer.
Do not rub Androgel® into the skin. Allow the gel to dry for at least 3-5 minutes before dressing. Wash hands with soap after application.
Do not apply gel to the genital area, since a high content of ethyl alcohol in the preparation can cause local irritation.
The constant concentration of testosterone in the plasma is reached approximately on the second day of treatment with Androgel®. To adjust the dose of testosterone, it is necessary to determine the concentration of testosterone in the serum in the morning, before the drug, from the third day after the start of treatment (within one week).
Dosage can be reduced if the testosterone content in the plasma is increased. If the concentrations are low, the dose can be increased, but not more than 10 g of gel per day.

Side effects

The most frequent undesirable effects (about 10%) with the recommended dose were 5 g of gel per day; skin reactions at the site of application, erythema, acne, dry skin.
In the course of Androgel's clinical trials, the following undesirable effects were noted (> 1/100, <1/10):
From the blood and lymphatic system: changes in the results of laboratory tests (polycythemia, changes in lipid levels).
From the genitourinary system: changes in the prostate gland, gynecomastia, mastodynia.
From the nervous system: dizziness, paresthesia, amnesia, hyperesthesia, mood changes.
From the cardiovascular system: increased blood pressure.
From the gastrointestinal tract: diarrhea.
From the skin and its appendages: alopecia, urticaria.
General disorders: headache.
The drug contains alcohol, so when it is often applied to the skin may appear irritation and dryness.

Overdose

Cases of overdose in the application of Androgel is not fixed. Only one case of an overdose has been described after the injection of testosterone. This was a stroke in a patient with a high plasma testosterone concentration of 114 ng / ml (395 nmol / L). However, it is unlikely that such concentrations of testosterone in the plasma can be achieved by applying the drug to the skin.

Application during pregnancy and lactation

Pregnant women should avoid any contact with the drug because of its possible virilizing effect on the fetus. In case of contact with the drug, it is necessary, as soon as possible, to wash the place of contact with soap.

Interaction with other medicinal products


Androgel® should be given with caution with oral anticoagulants, since it is possible to enhance the effect of oral anticoagulants by modifying the synthesis of the hepatic coagulation factor and competitive inhibition of binding to plasma proteins. It is recommended to monitor prothrombin time. Patients receiving oral anticoagulants require frequent monitoring, especially at the beginning and / or end of the course of treatment with androgens.
Co-administration of testosterone and ACTH or corticosteroids may increase the risk of edema. These medications should be administered together cautiously, especially in patients suffering from heart, kidney or liver disease.
Impact on laboratory tests: androgens may reduce levels of thyroxine-binding globulin, leading to a decrease in serum T4 concentrations and an increase in sensitivity to T3 and T4. Levels of free thyroid hormones, however, remain unchanged, and there are no clinical manifestations of hypothyroidism.
special instructions
Androgel® should be used only if testosterone deficiency is present, accompanied by such clinical manifestations as: underdevelopment or regression of secondary sexual characteristics, changes in body structure, violation of carbohydrate and lipid metabolism, obesity, asthenia, sexual dysfunction (decreased libido, erectile dysfunction, etc.) , decreased bone mineral density, mood swings, depression, hot flashes, etc. Before starting treatment, other possible causes underlying the above symptoms should be excluded.
At present, there are no clear age standards for testosterone values. However, it should be taken into account that the physiological levels of serum testosterone begin to decline from 30-40 years, and the level of globulin binding sex steroids increases. This, accordingly, leads to a decrease in the level of biologically active testosterone.
Due to variability in laboratory values, testosterone concentrations should be determined in the same laboratory.
Androgel® is not used to treat male infertility or erectile dysfunction, the cause of which is not related to testosterone deficiency.
Prior to the appointment of testosterone, all patients should be screened to rule out the risk of prostate cancer, since androgens can accelerate the progression of subclinical prostate cancer and benign prostatic hyperplasia. Careful and regular monitoring of the prostate gland (digital rectal examination, determination of prostate-specific antigen (PSA) in the serum) and breast can be performed at least once a year, and in elderly patients and at-risk patients (with clinical or family factors) - twice a year.
Testosterone preparations should be used with caution in patients with malignant neoplasms because of the risk of hypercalcemia (and concomitant hypercalciuria) due to metastases in the bone. In these patients, it is recommended that the concentration of calcium in the serum be monitored.
In patients with severe cardiac, hepatic or renal insufficiency, treatment with testosterone preparations can cause complications characterized by edema with or without congestive heart failure. In this case, treatment should be stopped immediately. In addition, diuretic therapy may be required.
In patients taking androgens for a long period of time, in addition to laboratory measurements of testosterone concentration, it is periodically necessary to check the following laboratory parameters: hemoglobin, hematocrit (for detection of polycythemia), functional liver samples and lipid profile.
Data have been published on the increased risk of sleep apnea in patients with hypogonadism receiving treatment with esters of testosterone, especially in those who have risk factors such as obesity and chronic respiratory diseases.
In patients with diabetes, receiving androgens, when the normal concentration of testosterone in the blood plasma can be increased sensitivity to insulin.
Some clinical symptoms: irritability, nervousness, weight gain, prolonged or frequent erections may indicate excessive androgen exposure, requiring dosage adjustment.
If a patient develops a severe local reaction, treatment should be reviewed and, if necessary, discontinued.
When using Androgel, athletes should take into account the fact that this drug contains an active substance (testosterone), which can give a positive reaction in the anti-doping tests.

Potential transfer of testosterone


When appointing Androgel, it is necessary to inform the patient about safety measures. To ensure the safety of the partner, the patient needs, for example, to advise to have sexual intercourse before using the drug or to observe the interval between Androgel's application and sexual intercourse. If the sexual intercourse is performed within 6 hours after application of Androgel®, during the contact period it is recommended to wear a T-shirt covering the place of application of the gel or take a shower before the sexual intercourse.
It is preferable to observe an interval of not less than 6 hours between applying the gel and taking a bath or shower. However, occasional showering from 1 to 6 hours after the application of the gel does not have a significant effect on the treatment.
The following precautions are recommended:
• for the patient:
- Wash hands with soap after applying the gel;
- Cover the area of ​​application of the gel with clothing after the gel has dried;
- Take a shower before contacting a partner.
• for people who do not take Androgel®:
- in case of contact with the application area of ​​the gel, previously not washed with water, it is necessary to rinse as soon as possible with water and soap a skin area on which testosterone could be ingested;
- It is necessary to inform the doctor about the appearance and development of such signs of hyperandrogenization, as acne or a change in normal hair growth.
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 the drug with the skin. In case of contact with the drug, a woman should wash the contact area with soap and water as soon as possible.
When contacting children, it is recommended to wear a T-shirt covering the place of application of the gel in order to avoid the risk of skin contact of children with the drug.
Androgel® should not be given to patients who can not follow safety instructions (for example, severe chronic alcoholism, substance abuse, severe mental disorders).

Impact on the ability to drive and other mechanisms

At present, there is no data on the influence of Androgel on the ability to drive a car and the control of machinery and mechanisms.

Form of issue
Gel for external use 10 mg / g:
By 2.5 or 5.0 g of gel in single-dose packages of polyethylene and laminated aluminum foil.
For 10 or 30 packs together with instructions for use in a cardboard box. 75 g of gel (60 doses of 1.25 g of gel) in a plastic vial with a metering pump equipped with a protective cap.
For 1 bottle or 2 bottles together with instructions for use in a cardboard pack.

Storage conditions
At a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life
3 years.
Do not use after the expiration date.

Conditions of leave from pharmacies
On prescription.