Androgel 1% 5g 30s gel (topical application)

The instruction

for medical use





of Androgel Torgovoye medicine the name Androgel



Mezhdunarodnoye the unlicensed







name Testosterone Dosage Form Gel for external use of 10 mg/g



Structure

of 5 g of gel is contained:

active agent testosterone - 50 mg

excipients: isopropyl myristate, alcohol of 96%, karbopol 980, sodium hydroxide, water purified.



The description

Transparent or poorly opalescent colourless gel with an alcohol smell.



Pharmacotherapeutic group

Sex hormones and modulators of a reproductive system.

Derivative 3 oxoandrostenums. Testosterone.

The ATX G03BA03 code







varies the Pharmacological Pharmacokinetics Degree properties of absorption of testosterone when drawing Androgel's on skin within 9-14% of the put dose.

After dermal absorption testosterone comes to a system blood stream in rather constant concentration during a 24-hour cycle.

Concentration of testosterone increase in serum from the first hour after drug 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. Thus, at transdermalny use of Androgel it is possible to avoid the distribution peaks in blood arising at an injection route of administration. When comparing with testosterone drugs for intake, Androgel's use 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).

After the treatment termination the concentration of testosterone begins to decrease approximately in 24 hours after the last use. Concentration is restored to initial level in 72-96 hours after use of the last dose.

The main active metabolites of testosterone are dihydrotestosterone and oestradiol. Testosterone is removed, generally with urine, and in a small amount with a stake, in the form of the conjugated testosterone metabolites.

A pharmacodynamics

Endogenous androgens, generally testosterone, are developed in testicles and their main metabolite dihydrotestosterone (DGT), promote

- to forming of genitals

- ment of secondary sexual characteristics (stimulation of growth of hair, posterization of a voice, development of a libido) in men

- influence anabolism of proteins, development of skeletal muscles and distribution of hypodermic fatty tissue, reduce excretion with urine of nitrogen, sodium, potassium, chlorides, phosphates and waters.

Testosterone does not contribute to the development of testicles: it reduces hypophysial secretion of gonadotrophins.

Impact of testosterone on some target organs is shown after peripheral transformation of testosterone to oestradiol which contacts estrogen receptors in kernels of cells of target organs subsequently (such as hypophysis, fatty tissue, a brain, bones and testicular cells of Leydiga).



Indications

- replacement therapy by testosterone at a men's hypogonadism when the deficiency of testosterone is confirmed with clinical symptoms and the biochemical



Route of administration tests and doses

Adult and elderly men

the Recommended dose makes 5 g of gel (50 mg of testosterone) which is applied once a day approximately at the same time, it is preferable in the morning. The individual day dose can be adjusted by the doctor depending on clinical and laboratory indicators at patients, but should not exceed 10 g of gel a day.

Correction of the mode of dosing has to be carried out gradually, adding or diminishing 2.5 g of gel a day.

The patient independently applies gel to the clean, dry, uninjured skin of shoulders, forearms and/or a stomach.

After opening of a bag it is necessary to apply immediately to skin all its contents and to distribute a thin layer. It is not obligatory to rub it in skin. Let's it dry within 3-5 minutes before clothing.

After putting gel wash up hands with soap. Gel is not applied on area of genitalias as the high content of alcohol in gel can become the reason of irritation of skin.

Stable concentration of testosterone is reached approximately for the 2nd day of treatment by Androgel. For correction of a dose of testosterone 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 dosage can be reduced if testosterone content in plasma exceeds target value. If concentration low, the dose can be increased, but no more than 10 g a day.





Children:

Androgel do not apply at children and men 18 years



Side effects

Data of clinical trials

Very often

- local reactions are younger: an erythema, an acne, xeroderma

Often

- a polycythemia, increase in level of lipids

- change of a condition of a prostate

- a gynecomastia, a mastodynia

- a headache, dizziness

- paresthesia, amnesia, a hyperesthesia

- change of mood

- increase in arterial blood pressure

- diarrhea

- an alopecia, a small tortoiseshell

- aggression, irritability

Other undesirable effects of testosterone at intake or parenteral administration (according to literature):

- increase in body weight, change of electrolytic balance (delay of ions of sodium, chlorine, potassium, calcium, inorganic phosphate and water) at reception of high doses or long treatment

- muscular spasms

- nervousness, a depression, irritability

- an apnoea in a dream

- change of values of functional tests of a liver, sometimes followed by jaundice

- various skin reactions, including an acne, seborrhea and baldness

- decrease in a libido, increase of an erection, the reversible termination or decrease in a spermatogenesis at therapy in high doses, reduction of the size of testicles, a priapism, changes from a prostate, obstruction of urinary tract, a prostate cancer

- tumors of a liver is (very rare)

- a water delay in an organism, hypostases

- reactions of hypersensitivity



of the Contraindication

- hypersensitivity to testosterone or to other components of drug

- the confirmed or suspected prostate cancer or a breast cancer

is not applied at persons of a female.





Androgel it is necessary to appoint medicinal interactions with care with oral anticoagulants as strengthening of effect of oral anticoagulants by modification of synthesis of a hepatic factor of coagulation and competitive inhibition of linking with proteins of plasma is possible. It is recommended to control a prothrombin time. The patients receiving oral anticoagulants demand frequent control, especially at the beginning and/or at the end of a course of treatment androgens.

Joint prescribing of testosterone and adrenocorticotropic hormone or corticosteroids can increase risk of appearance of hypostases. These medicines have to be appointed together carefully, especially at the patients having diseases of heart, kidneys or a liver.

Impact on laboratory tests: 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.





Special instructions

Androgel apply, only if a hypogonadism (hyper - or hypogonadotropic) is confirmed and other etiology of clinical symptoms is excluded prior to treatment. Insufficiency of testosterone has to be accurately confirmed with clinical symptoms (regression of secondary sexual characteristics, change of the structure of a body, an asthenia, decrease in a libido, erectile dysfunction and others) and two blood tests on testosterone content. However it is necessary to take into account that physiologically the level of serumal testosterone decreases with age.

Because of variability of laboratory indications, definition of concentration of testosterone should be carried out in the same laboratory.

Androgel is not used for treatment of male infertility or erectile dysfunction which cause is not connected with insufficiency of testosterone.

Prior to treatment by testosterone all patients have to undergo inspection for an exception of a prostate cancer. The patients receiving therapy by testosterone need careful and regular observation of a condition of a prostate which is made according to the accepted recommendations (a manual rectal research, definition of prostatospetsifichesky antigen in serum) and a mammary gland, at least, once a year, and patients of advanced age and with risk factors (clinical or family) - two times a year.

Androgens can accelerate a progression of a subclinical prostate cancer and benign hyperplasia of a prostate. Androgel apply with care at patients with malignant new growths in the presence of metastases in a bone because of risk of a hypercalcemia (and the accompanying hypercalcuria). Periodic control of level of calcium in blood is recommended to these patients.

At the patients having a heavy heart, liver or renal failure, treatment by Androgel can lead to serious complications, including hypostases owing to heart failure. In such cases the treatment has to be immediately stopped. Besides, therapy by diuretics can be required. Androgel it is necessary to appoint with care the patient with coronary heart disease and arterial hypertension.

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

With care apply Androgel at patients with epilepsy and migraine as these states can be aggravated.

There are messages about increase in risk of an apnoea during sleep at the patients with a hypogonadism receiving treatment by testosterone ethers, especially with risk factors, such as obesity and chronic diseases of respiratory organs.

At the patients receiving replacement therapy by androgens at achievement of normal concentration of testosterone in blood plasma the increase in sensitivity to insulin can be observed.

Certain clinical symptoms, such as irritability, nervousness, increase in body weight, long or frequent erections can indicate the excess maintenance of an androgen that demands dose adjustment.

If at the patient the 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 that this drug contains active agent (testosterone) which can give positive reaction in anti-doping tests.

Women should not apply Androgel because of the possible virilizing effect.

Possibility of transfer of testosterone. If not to undertake precautionary measures, the gel containing testosterone can be transferred to other persons by means of close skin contact. It, in turn, can lead to increase in level of testosterone and possible undesirable effects (for example, growth of hair in the face and a body, decrease in a voice, to disturbance of a menstrual cycle) at the repeating contacts (inadvertent androgenization). The attending physician has to inform the patient on risk of transfer of testosterone and security measures carefully. Androgel should not appoint patients who will not be able to observe precautionary measures at drug use (for example, a heavy alcoholism, toxicomania, heavy mental disorders). Transfer of testosterone can be prevented if to cover the field of putting gel with clothes or previously to take a shower before contact. Also it is recommended to follow the following rules.

To patients:

- after putting gel to wash up carefully hands water with soap

- to put on clothes after gel drying

- to take a shower before possible skin contact with other person.

For persons who do not receive Androgel:

- in case of skin contact with the field of putting gel which is not covered with clothes or not washed with water carefully to wash out area of skin which could be in contact with the field of putting testosterone, with soap and water.

- to report about development of signs of the increased influence of androgens, such as acne or changes of growth of hair.

On the basis of results of a research of absorption of testosterone at Androgel's use, it is recommended not to take a shower or a bath within 6 hours after putting gel. But accidental acceptance of a shower or bathtub in an interval from 1 to 6 hours after putting gel will not influence considerably the treatment outcome.

To guarantee safety of the partner, the patient needs to advise to observe a time break between Androgel's drawing and sexual contact, to put on the clothes (for example, a t-shirt) covering the field of putting gel during contact or to take a shower before contact.

Also it is recommended to put on the clothes covering the field of putting gel (for example, a t-shirt), at communication with children to avoid risk of hit of testosterone on the child's skin.

Pregnancy and the period of a lactation

Drug is not used at pregnant women and the nursing mothers. Pregnant women have to avoid any contact with the field of putting gel. In case of contact by drug it is necessary to wash as soon as possible the kontaktirovanny place with water with soap. In case of approach of pregnancy at the wife, the patient is obliged to strengthen the precautionary measures described above. This drug can have the undesirable virilizing action on a fruit.

Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms

of the Research on studying influence of Androgel on ability to drive the car and the equipment, were not carried out. It is necessary to consider a possibility of side effect of Androgel during the driving of the car and work with potentially dangerous mechanisms.



Overdose

of Cases of overdose at Androgel's use it is noted. In literature one case of acute overdose of testosterone after an injection is described. It the patient had a case of disturbance of cerebral circulation with high concentration of testosterone in blood plasma of 114 ng/ml (395th nmol/l). It is a little probable that at a transdermalny way of introduction the same high concentration of testosterone was reached.



The form of release and packing

On 5 g of gel place in packages one-dose of polyethylene and the aluminum foil laminated.

On 10 or 30 packages together with the instruction for medical use in the state and Russian languages put in a pack from cardboard.



Storage conditions

At a temperature not higher than 25C.

To store out of children's reach!





3 years

not to apply a period of storage after the expiration date specified on packing!



Prescription status

According to the prescription





of Proizvoditel Bezen Manyufekchuring Beldzhium SA, Belgium

Groot, Biygaardenstraat of 128, 1620 Drogenbos, Belgium

the Name and the country of the owner of the registration certificate

of Bezen Helscare SA,

Belgium 287 Avenue Louise, 1050 Brussels, Belgium

the Name and the country

of the Enestia Beldzhium organization packer of NV, Belgium