Instruction

for medical use of

Utrogestan

Registration number:
Trade name: UTROGESTAN
International nonproprietary name: progesterone
Pharmaceutical form: capsules
Composition (per capsule)
Active ingredient: natural micronized progesterone 100 or 200 mg.
Excipients: peanut oil, soya lecithin, gelatin, glycerol, titanium dioxide.
Appearance: capsules 100 mg - round, capsules 200 mg - oval, soft shiny gelatin capsules
yellowish in color, containing oil whitish homogenous suspension (without a visible division of
phases).
Pharmacotherapeutic group: gestagen
ATC code: G03DA04

PHARMACOLOGICAL PROPERTIES
Gestagen, a hormone of the corpus luteum. Binding to receptors on the surface of cells of target
organs, penetrates into the nucleus, where, by activating DNA, stimulates RNA synthesis.
Contributes to transition of the uterine mucous membrane from the phase of proliferation caused by
the follicular hormone into the secretory phase, and after fertilization - into the condition necessary
for the development of the fertilized oocyte. Decreases excitability and contractility of the
musculature of the uterus and uterine tubes, stimulates the development of terminal end buds of the
mammary gland.
By stimulating protein lipase, increases reserves of fat; increases utilization of glucose; by
increasing the concentration of basal and stimulated insulin, contributes to accumulation of
glycogen in the liver; increases production of gonadotropic hormones of the hypophysis; decreases
azotemia, increases excretion of nitrogen in the urine. Activates the growth of the secretory
department of acini of the mammary glands and induces lactation. Contributes to the formation of
normal endometrium.

PHARMACOKINETICS
Oral administration
Absorption
Micronized progesterone is absorbed from the gastrointestinal tract. The progesterone concentration
in blood plasma increases gradually within the first hour, the maximum concentration in blood
(C max ) is noted 1-3 hours after administration.
The progesterone concentration in blood plasma increases from 0.13 ng/mg to 4.25 ng/mg in 1 hour,
to 11.75 ng/ml in 2 hours and is 8.37 ng/ml in 3 hours, 2 ng/ml in 6 hours and 1.64 ng/ml in 8 hours
after administration.
Metabolism
The main metabolites which are determined in blood plasma are 20-alpha-hydroxy-delta-4-alpha-
pregnanolon and 5-alpha-dihydroprogesterone.
Elimination
Eliminated in the urine in the form of metabolites 95% of which are glucuron conjugated
metabolites, mainly 3-alpha, 5-beta-pregnandiol (pregnandion). The above metabolites determined

Approved 20.12.2010 by BEL HA C.1

in the blood plasma and urine are similar to the substances formed during physiological secretion of
the corpus luteum.
Vaginal administration
Absorption
Absorption proceeds quickly, progesterone accumulates in the uterus, a high level of progesterone
in blood plasma is observed 1 hour after administration. Cmax of progesterone in blood plasma is
reached 2-6 hours after administration. At the administration of the product in a dose of 100 mg
twice a day the average concentration persists at the level of 9.7 ng/ml for 24 hours.
At the administration in doses over 200 mg/day the progesterone concentration corresponds to the
first trimester of pregnancy.
Metabolism
Metabolized with formation of predominantly 3-alpha, 5-beta-pregnandiol. The level of 5-beta-
pregnanolon in plasma does not increase.
Elimination
Eliminated in the urine in the form of metabolites, the main part is 3-alpha, 5-beta-pregnandiol
(pregnandion). This is confirmed by a constant increase of its concentration (Cmax 142 ng/ml after
6 hours).

INDICATIONS
Progesterone-deficiency conditions in women.

Oral route:
menace of spontaneous abortion or prevention of habitual miscarriage due to the established
luteal insufficiency
menace of preterm delivery
infertility due to luteal insufficiency
premenstrual syndrome
menstrual irregularities due to ovulation disorders or anovulation
fibrous-cystic mastopathy
premenopause
hormone replacement therapy of peri- and postmenopause (in combination with estrogen agents)

Vaginal route:
hormone replacement therapy in deficiency of progesterone in non-functioning (absent) ovaries
(oocyte donation)
luteal phase support during preparation to extracorporeal fertilization
luteal phase support in spontaneous or induced menstrual cycle
preterm menopause
hormone replacement therapy (in combination with estrogen agents)
infertility due to luteal insufficiency
prevention of habitual or threatening abortion due to progestin insufficiency
prevention of uterus myoma
prevention of endometriosis

CONTRAINDICATIONS
Hypersensitivity, including hypersensitivity to peanut oil, soya, predisposition to thromboses, acute
forms of phlebitis or thromboembolic diseases; bleedings from the genital tracts of unclear genesis;
incomplete abortion, porphyria.
The established or suspected malignant neoplasms of the mammary glands and genital organs.
Oral route of administration - in marked hepatic impairment.

Approved 20.12.2010 by BEL HA C.2

WITH CAUTION
Diseases of the cardiovascular system, arterial hypertension, chronic renal insufficiency, diabetes
mellitus, bronchial asthma, epilepsy, migraine, depression; hyperlipoproteinemia, period of
lactation.

ADMINISTRATION AND DOSAGE

Duration of treatment is determined by the character and specifics of the disease.
Oral route
The medicinal product is taken orally with water. In most cases in progesterone deficiency the daily
dose of Utrogestan is 200-300 mg divided into 2 doses (to take in the morning and in the evening).
In threatening spontaneous abortion or for prevention of habitual miscarriage: 200-600 mg daily.
In threatening preterm delivery: 400 mg progesterone every 6-8 hours depending on the clinical
results during the acute phase, then in the supporting dose of 600 mg/day divided into 3 doses till
the 36th week of pregnancy. In luteal phase insufficiency (premenstrual syndrome, fibrous-cystic
mastopathy, dysmenorrhea, premenopause) the daily dose is 200 or 400 mg taken for 10 days
(usually from the 17th through the 26th day of the cycle). During hormone replacement therapy in
peri-and postmenopause against the background of administration of estrogens Utrogestan is used is
a dose of 200 mg a day for 10-12 days.
Vaginal route
The complete absence of progesterone in women with non-functioning (absent) ovaries (oocyte
donation): concomitantly with estrogen therapy in a dose of 200 mg/day on the 13th and 14th days
of the cycle, then in a dose of 100 mg twice a day from the 15th through the 25th day of the cycle,
from the 26th day and if pregnancy is established the dose increases by 100 mg a day every week,
reaching the maximum of 600 mg/day divided into 3 doses. Such dosage may be used within 60
days. The support of the luteal phase during the cycle of extracorporeal fertilization: it is
recommended to take from 200 to 600 mg a day, beginning from the day of the injection of
chorionic gonadotropin during trimesters I and II of pregnancy. The support of the luteal phase
during the spontaneous or induced menstrual cycle, in infertility related to impairment of the
corpus luteum function, it is recommended to take 200-300 mg a day, beginning from the 17th day
of the cycle for 10 days, in case of menstruation delay and diagnosis of pregnancy the treatment
should be continued. In cases of the threat of abortion or for prevention of habitual abortions
occurring against the background of progesteron deficiency: 200-400 mg daily in 2 divided doses
during trimesters I and II of pregnancy. Capsules are inserted deep into the vagina.

SIDE EFFECTS
Allergic reactions.
During oral administration - drowsiness, transient dizziness (1-3 hours after the intake of the
product), extremely rarely - intermenstrual bleeding.

OVERDOSE
Adverse effects, enumerated above, indicate most often about overdose. They disappear
spontaneously at a decrease of the dose.

INTERACTION WITH OTHER MEDICINAL PRODUCTS

Increases the action of diuretics, hypotensive medicinal products, immunodepressants,
anticoagulants. Decreases the lactogenic effect of oxytocin.
The concomitant administration Utrogestan with barbiturates, phenytoin, rifampicin,
phenylbutazone, spironolactone, griseofulvin, ampicillin, tetracycline can lead to a change of the
action of the medicinal product.
Utrogestan and other progestagens can cause a reduction of glucose tolerance and increase the
demand of insulin or other hypoglycemic agents in patients with diabetes mellitus.

Approved 20.12.2010 by BEL HA C.3

WARNINGS AND PRECAUTIONS
The product should not be used with the purpose of contraception.
It should be used with caution orally in pregnancy in patients with hepatic impairment.
At oral administration caution should be exercised while driving and engaging in other potentially
hazardous kinds of the activities requiring increased concentration of attention and quickness of
psychomotor reactions.

HOW SUPPLIED
Capsules 100 mg, 15 capsules in each blister, 2 blisters in each cardboard pack together with the
instruction on use.
Capsules 200 mg, 7 capsules in each blister, 2 blisters in each cardboard pack together with the
instruction on use.

SHELF LIFE
3 years. Do not use after the expiry date designated on the pack.

STORAGE
List B.
At a temperature not exceeding 25C out of the reach of children.

HOW DISPENSED
Prescription medicine.

NAME AND ADDRESSES OF MANUFACTURER:

"Besins Manufacturing Belgium"

128, Groot Bijgaardenstraat,
1620 Drogenbos, Belgium

Claims of consumers to be sent at the address of

the Moscow Representative Office:
28, Sredny Tishinsky per., 123557 Moscow
tel. (495) 980 10 67, fax (495) 980 10 68

Approved 20.12.2010 by BEL HA C.4