Femigel Patient Information Leaflet (Russia) - Besins Healthcare

П N013773/01-291209
INSTRUCTION
on medical use of
OESTROGEL
Registration number:
Trade name: Oestrogel
International nonproprietary name: estradiol
Pharmaceutical form: transdermal gel
Composition per 100 g of gel
Active ingredient:
Estradiol hemihydrate [calculated with reference to estradiol] 60 mg
Excipients:
Carbomer (carbopol 980), trolamine (triethanolamine), ethanol, purified water.
Pharmacotherapeutic group
Estrogen
Appearance
A colorless transparent gel with an odor of ethanol.
ATC code [G03CA03]
Pharmacological action
The pharmacological action is conditioned by the presence of estradiol which is an
estrogen. During treatment with Oestrogel the degree of climacteric syndrome
(including flushes, increased sweating, dry vaginal mucosa, depressed mood)
significantly decreases. The clinical efficacy of Oestrogel during treatment of
symptoms of the postmenopause period is comparable with that during oral
administration of estrogens.
The use of the product contributes to a decrease of concentration of total
cholesterol without a change of cholesterol/HDLP ratio. The use of the product
inhibits a decrease of bone tissue density in the period of menopause.
It exerts the anticoagulant action, increases synthesis in the liver of vitamin K-
dependent factors of blood coagulation (II, VII, IX, X), decreases antithrombin III
concentration.
Pharmacokinetics
Absorption and distribution
At the gel application alcohol quickly evaporates, and estradiol penetrates the skin,
with its greater part entering the systemic blood flow immediately and some
amount of estradiol remaining in the subcutaneous fat and releasing gradually into
the systemic blood flow.
Approved 29.12.2009 by RUS HA P. 1

The maximum concentration in the blood is reached after 3-4 hours, bioavailability
is 82%.
Metabolism and elimination
At external application estradiol is not subject to the effect of the "first pass"
through the liver that provides a higher estradiol concentration in blood plasma
comparing to oral forms.
Metabolism and elimination of estradiol during the use of Oestrogel corresponds to
biotransformation and elimination of natural estrogens.
Indications
- relief of symptoms of the climacteric syndrome including those during artificial
menopause;
- prevention and treatment of posmenopause osteoporosis.
Contraindications
Stroke (hemorrhagic or ischemic);
Thromboembolisms or acute thrombophlebitis;
Uterine bleedings of unclear etiology;
Estrogen- dependent malignant neoplasms or suspicion of them;
Malignant and benign tumors of the pituitary body;
Severe diseases of the liver, tumors of the liver; jaundice;
Hepatic insufficiency;
Dubin-Johnson syndrome;
Rotor's syndrome;
Pregnancy, period of breast feeding;
Hypersensitivity to the components of the product.
With caution
Should be prescribed to patients with coronary artery disease, circulatory
insufficiency; diabetes mellitus, migraine, bronchial asthma, inflammatory diseases
of the female genitals, epilepsy, severe form of arterial hypertension; liver
dysfunction, history of thrombophlebites, thromboses or thromboembolisms during
administration of estrogens; familial hyperlipoproteinemia, pancreatitis,
endometriosis, history of diseases of the gallbladder (especially cholelithiasis),
history of jaundice (including during previous pregnancy), hepatic porphyria,
leiomyoma, hypercalcemia associated with bone metastases of breast cancer
Pregnancy and period of breast feeding
The product is contraindicated for use during pregnancy and in the period of breast
feeding.
Approved 29.12.2009 by RUS HA P. 2

Administration and dosage
Oestrogel is administered externally, continuously or in cycles. Doses and duration
of therapy are determined individually.
1 dose of the applicator corresponds to 2.5 g of gel and contains 1.5 mg of
estradiol.
1 dose of the applicator or 2.5 g of gel is applied in a thin layer on the skin of the
abdomen, lumbar region, shoulders or arms until complete absorption once daily.
The area of application should be not less than the area of two palms.
Application is considered to be correct if the gel is absorbed completely within 2-3
minutes.
If sticky consistency persists over 5 min after application, it implies that the gel
covers too small surface of the skin.
Side effects
Central nervous system: headache, migraine, changes in mood, dizziness.
Genital system: tenderness, sensitivity and enlargement of the breasts, amenorrhea,
"breakthrough" bleedings, menorrhagia, intermenstrual spottings, a tumor of the
breasts, increased libido.
Gastrointestinal tract-related side effects are seen extremely rarely as there is no
effect of the "first pass" through the liver: dyspeptic disturbances, spasms of
smooth musculature of GIT (including intestinal or biliary colic), pain in the
epigastrium, cholestatic jaundice, cholelithiasis, flatulence, anorexia, nausea,
vomiting (mainly of the central genesis, mostly at the use of large doses), diarrhea,
obstruction of the gallbladder, hepatitis, pancreatitis. Local reactions: irritation and
hyperemia of the skin.
Others: peripheral edemas, a change of body mass, an increase of blood pressure,
allergic skin reactions (urticaria, pruritis), thromboembolism, contact dermatitis,
intolerance of contact lenses. Side effects, as a rule, are weakly pronounced, are
noted mainly in the first months of therapy and very rarely cause discontinuation of
the product.
Overdose
Symptoms: nausea, vomiting, in some cases - metrorrhagia.
Treatment: discontinuation of the product, symptomatic therapy.
Interaction with other drug products
Estrogens can decrease the effect of indirect anticoagulants, hypotensive and
hypoglycemic agents (adjustment of dosage may be required).
Increases efficacy of other hypolipidemic agents. At concomitant use of estrogens
and the medicines inducing microsomal enzymes of the liver (barbiturates,
carbamazepine, griseofulvin and rifampicin), a decrease of the plasma
concentration of estradiol is possible.
Weakens effects of male sex hormones, diuretic agents.
Anxiolytic agents (tranquilizers), narcotic analgetics, agents for general anesthesia
accelarate metabolism of estradiol.
Approved 29.12.2009 by RUS HA P. 3

The plasma concentration decreases at concomitant use of phenylbutazone and
some antibiotics (ampicilline, rifampicin) that is related to a change of microflora
in the intestine.
Folic acid and agents of thyroid gland hormones enhance the action of estradiol.
Special warnings and precautions
A gynecological examination should be conducted before the treatment, and it
should be conducted not less than once a year during prolonged therapy. It is
advisable to combine estradiol treatment with gestagens according to the doctor's
recommendation.
Avoid contact of the gel with the breasts, mucosa of the vulva and vagina.
A prolonged treatment with estradiol increases the risk of developing breast and
endometrium cancer (depends on the duration of treatment and the dose of
estrogen).
Hyperplasia (atypical or glandular) frequently precedes endometrium cancer. The
combination of estrogens with gestagen exerts the protective action on the
endometrium. The treatment should be discontinued 4-6 weeks before the planned
surgical treatment.
The product is not a contraceptive and does not protect against pregnancy.
If irregular menstrual discharges appear during treatment (in women with intact
uterus), diagnostic curettage is needed to exclude a malignant neoplasm of the
uterus. The use of estradiol should be immediately discontinued in case of
thrombosis of deep veins, thromboembolism of other localization, occurrence of
jaundice, increase or occurrence of not existing previously migraine-like pains, a
sudden disorder of vision, a significant increase of blood pressure.
It is necessary to monitor systematically the liver function and blood pressure,
blood concentration of glucose diabetes mellitus.
OESTROGEL should be applied:
by a woman herself,
in the morning or in the evening, preferably on the clean skin.
OESTROGEL does not stain.
How supplied
Transdermal gel 0.6 mg/g
80 g o in each aluminum tube, varnished inside with the protective membrane
closed with a screw cap made from high density polyethylene. One tube together
with the instruction on use and an applicator per carton.
Shelf life
3 years
Do not use after the expiry date printed on the pack.
Storage
List B.
Approved 29.12.2009 by RUS HA P. 4

At a temperature not exceeding 25C.
Keep out of the reach of children.
Dispensing
Prescription medicine.
Name and address of manufacturer:
Laboratoires Besins International
13, rue Périer, 92122 Montrouge,
France
Besins Manufacturing Belgium
128, Groot Bijgaardenstraat,
1620 Drogenbos, Belgium
Approved 29.12.2009 by RUS HA P. 5