Progestogel Patient Information Leaflet - Besins Healthcare

INSTRUCTION
on medical use of medicinal product
Progestogel
П N013765/01-091008
Registration number:
Trade name: Progestogel
International nonproprietary name: progesterone
Pharmaceutical form: gel for cutaneous application
COMPOSITION per 100 g
Active ingredient:
natural micronized progesterone - 1 g
Excipients:
octyldodecanol, carbomer 980, macrogol glyceryl hydroxystearate (polyoxyl
hydrogenated castor oil), trolamine (triethanolamine), ethanol calculated with
reference to absolute ethanol 96% (v/v), purified water.
Appearance:
a colorless, semitransparent, slightly opalescent gel with odor of alcohol without
visible particles.
PHARMACOTHERAPEUTIC GROUP:
gestagen
ATC code: G03DA04
PHARMACOLOGICAL PROPERTIES
Pharmacodynamics. The action of progesterone, on the one hand, is based on
blockade of estrogen receptors resulting in an improvement of absorption of fluid
from tissues, a decrease of compression of the milk ducts; on the other hand - on
blockade of prolactin receptors in the breast tissue that leads to a reduction of
lactopoesis. Thus, the local application of the product, by creating a high
concentration of progesterone in the area of application does not exert the systemic
action and makes it possible to avoid adverse side effects.
The mechanism of action of Progestogel is based on an increase of
progesterone concentration in the breast tissues. The active ingredient of the
product is progesterone. Progesterone decreases expression of estrogen receptors in
the breast tissues and also lowers the local level of active estrogens by stimulating
production of enzymes (17-beta-hydroxysteroid dehydrogenase and estrone
sulfotransferase) which oxidize estradiol into less active estrone and then by
binding the latter transform it into inactive estrone sulfate. Thus, progesterone
limits the proliferative action of estrogens on the breast tissues. Also, progesterone
possesses the greatest natriuretic effect due to suppression of tubular reabsorption
and increase of cellular filtration, thereby preventing retention of fluid at secretory
transformations of the glandular component of the breasts and as a consequence,
the development of pain syndrome (mastalgia or mastodynia). Along with that,
Approved 09.20.2008 by RUS HA P. 1

transdermal method of gestagen administration allows also to provide an impact on
the condition of the glandular epithelium and vascular network that results in a
decrease of capillary permeability and consequently a reduction of severity of
edema of the breast tissues and disappearance of symptoms of mastalgia.
Pharmacokinetics. At transdermal administration Progestogel reaches tissues of the
breasts without being destroyed in the liver and does not exert the systemic effects
on the body. A study of serum concentration of prolactin, estradiol and
progesterone during treatment with Progestogel has showed that one hour after the
product application, when its maximum absorption in tissues of the breasts is
observed, the level of hormones virtually does not change. Progesterone absorption
at cutaneous application is about 10% of the dose. Cutaneous applications on the
area of the breasts permit, on the one hand, to decrease the used dose of the
product, and on the other hand, to create a high concentration in the area of action
(as much as 10 times of that in the systemic blood flow). The product undergoes
secondary metabolization in the liver with formation of conjugates with glucuronic
and sulphuric acid. Isoenzyme CYP2C19 is also involved in metabolism.
Eliminated by kidneys - 50-60%, in the bile - more than 10%. The amount of
metabolites eliminated by kidneys varies depending on the phase of corpus luteum.
INDICATIONS
Indications
Mastodynia
Difuse Fibrocystic Mastopathy
CONTRAINDICATIONS
Nodal forms of fibrocystic mastopathy
Tumors (tumor-like formations) of the breasts of unclear etiology
Individual intolerance of any of the components of the product
Cancer of breast and genitals (as monotherapy)
Pregnancy (trimesters II and III)
WITH CAUTION
Hepatic insufficiency; renal insufficiency; bronchial asthma; epilepsy; migraine;
depression; hyperlipoproteinemia, extrauterine pregnancy; incipient abortion;
predisposition to thromboses, acute forms of phlebitis or of thromboembolic
diseases; bleeding from the vagina of unclear etiology; porphyria; arterial
hypertension; diabetes mellitus.
Approved 09.20.2008 by RUS HA P. 2

PREGNANCY AND BREAST FEEDING
There is no sufficient experience of using Progestogel during pregnancy. The use
of the product during pregnancy and in the period of lactation is possible only if
the expected benefit for the mother overweighs the potential risk for the fetus and
child.
ADMINISTRATION AND DOSAGE
1 application (2.5 g of gel) containing 0.025 g of progesterone is applied on the
skin of the breasts with an applicator-dispenser until complete absorption 1-2 times
daily or in the 2nd phase (from the 16th through the 25th day) of the menstrual
cycle. The course of treatment - for up to 3 cycles.
The repeated course of treatment may be prescribed only after a consultation with
the doctor.
SIDE EFFECTS
Extremely rarely: tenderness of the breasts, hot flushes, metrorrhagia, decreased
libido. In increased sensitivity to the product components - erythema at the site of
gel application, edema of the lips and neck, fever, headache, nausea.
OVERDOSE
Overdose is unlikely due to a low systemic absorption.
INTERACTION WITH OTHER DRUG PRODUCTS
The action of Progestogel can increase against the background of contraception
with combined hormone drugs.
SPECIAL WARNINGS AND PRECAUTIONS
Progestogel may be prescribed in mastodynia related to the use of oral
contraceptives, pubertal period, premenopause, premenstrual syndrome.
The product should be applied on the skin of the breast with an applicatordispenser
without rubbing in it and massaging the breasts.
Avoid exposure to direct sun rays after application of the cream.
EFFECT OF THE PRODUCT ON THE ABILITY TO DRIVE A VEHICLE
AND WORK WITH MECHANISMS
There were no studies to reveal a possible effect of the product on the ability to
drive a vehicle or to work with mechanisms.
HOW SUPPLIED
Gel for cutaneous application 1%.
Approved 09.20.2008 by RUS HA P. 3

80 g of the product in AN aluminum tube closed with a screw cap. One tube in a
carton together with a dosing applicator and the instruction on use
Shelf life 3 years
Do not use after the expiry date printed on the pack.
STORAGE
At a temperature not exceeding 25C
Keep out of the reach of children!
DISPENSING FROM PHARMACIES
Prescription medicine.
Name and address of the manufacturer:
Laboratoires BESINS INTERNATIONAL
13, rue Périer, 92120 Montrouge,
France
Besins Manufacturing Belgium
128, Groot Bijgaardenstraat,
1620 Drogenbos,
Belgium
Approved 09.20.2008 by RUS HA P. 4