Utrozhestan - instructions for use, doses, side effects, contraindications

Excipients: sunflower oil 149 mg / 298 mg, soy lecithin 1 mg / 2 mg; capsule - gelatin 76.88 mg / 153.76 mg, glycerol 31.45 mg / 62.9 mg, titanium dioxide 1.67 mg / 3.34 mg.

Description:Capsules 100 mg - round, capsules 200 mg - oval, soft shiny gelatinous capsules of yellowish color, containing an oily whitish homogeneous suspension (without visible separation of phases).

Pharmacotherapeutic group:Gestagen

ATX: & nbsp

G.03.D.A Derivative derivatives

G.03.D.A.04 Progesterone

Pharmacodynamics:

The active substance of the drug is Utrozestan^® is an progesterone, identical to the natural hormone of the ovarian's yellow body. By binding to receptors on the surface cells of target organs, penetrates into the nucleus, where, by activating DNA, stimulates the synthesis of RNA. Promotes the transition of the mucous membrane of the uterus from the proliferation phase caused by follicular hormone estradiol, into the secretory phase, and after fertilization - into a state necessary for the development of a fertilized egg. Reduces excitability and contractility of the musculature of the uterus and fallopian tubes. Promotes the formation of normal endometrium. Stimulates the development of the end elements of the breast and induces lactation.

Stimulating proteinolipase, increases fat stores; increases the utilization of glucose; increasing the concentration of basal and stimulated insulin, promotes the accumulation of glycogen in the liver; increases the production of gonadotrophic pituitary hormones; reduces azotemia, increases excretion of nitrogen by the kidneys.

Pharmacokinetics:Ingestion

Suction

Micronized progesterone well absorbed in gastrointestinal tract (GIT). The concentration of progesterone in the blood plasma gradually rises during the first hour, the maximum concentration in plasma blood (C_max) is noted 1-3 hours after administration.The concentration of progesterone in the blood plasma increases from 0.13 ng / ml to 4.25 ng / ml after 1 hour, to 11.75 ng / ml after 2 hours and is 8.37 ng / ml after 3 hours, 2 ng / ml after 6 hours and 1.64 ng / ml 8 hours after administration.

Metabolism

The main metabolites that are determined in the blood plasma are 20-alpha-hydroxy-delta-4-alpha-pregnanolone and 5-alpha-dihydroprogesterone.

Excretion

Displayed kidneys in the form of metabolites, 95% of them are glucuron-conjugated metabolites, mainly 3-alpha, 5-beta-pregnanediol (pregnannione). These metabolites, which are determined in the blood plasma and in urine, are similar to substances formed during the physiological secretion of the yellow body.

With vaginal administration

Suction and distribution

Absorption occurs rapidly, a high concentration of progesterone in the blood plasma is observed 1 hour after injection. FROM_m_Oh Progesterone in the blood plasma is achieved 2-6 hours after administration. With the administration of 100 mg twice a day, the average concentration in the blood plasma remains at the level of 9.7 ng / ml for 24 hours. When administered at doses of more than 200 mg / day, the concentration of progesterone corresponds to the I trimester of pregnancy.The connection with plasma proteins is 90%. Progesterone accumulates in the uterus.

Metabolism

Metabolized with the formation of predominantly 3-alpha, 5-beta-pregnanediol. The concentration of 5-beta-pregnanolone in plasma blood does not increase.

Excretion

Displayed kidneys in the form of metabolites, the main part is 3-alpha, 5-beta-pregnanodiol (pregnannione). This is confirmed by a constant increase in its concentration (C_max 142 ng / ml after 6 hours).

Indications:

Progesterone deficiency in women:

For oral administration:

■ Threatening abortion or the prevention of habitual abortion due to Progesterone deficiency;

■ infertility due to luteal insufficiency;

premenstrual syndrome;
disorders of the menstrual cycle due to a violation of ovulation or anovulation;
fibrocystic mastopathy;
period of menopausal transition;
menopausal (replacement) hormone therapy (MGT) in peri- and postmenopausal (in combination with estrogen-containing drugs).

For intravaginal application:

MGT in the case of a deficiency of progesterone with non-functioning (absent) ovaries (donation of eggs);
prevention (prevention) of preterm delivery in women at risk (with shortening of the cervix and / or the presence of anamnestic data of premature birth and / or premature rupture of the membranes);
support of the luteal phase during preparation for in vitro fertilization;
support of the luteal phase in the spontaneous or induced menstrual cycle;
premature menopause;
MGT (in combination with estrogen-containing drugs);
infertility due to luteal insufficiency;
threatening abortion or prevention of habitual abortion due to insufficient progesterone.

Contraindications:

Hypersensitivity to progesterone or any of the excipients of the drug; deep vein thrombosis, thrombophlebitis; thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or the presence of these conditions / diseases in the anamnesis; bleeding from the vagina of unknown origin; incomplete abortion; porphyria; established or suspected malignant neoplasms mammary gland and genital organs; severe liver disease (including cholestatic jaundice, hepatitis, Dubin-Johnson syndromes, rotor, malignant liver tumors) at present or in the anamnesis; children under 18 years of age (efficacy and safety not established); Breastfeeding period.

Carefully:

Diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, violations of liver function of mild and moderate severity; photosensitivity.

The drug should be used with caution in the II and III trimesters of pregnancy.

Pregnancy and lactation:

The drug should be used with caution in the II and III trimesters of pregnancy because of the risk of developing cholestasis.

Progesterone penetrates into breast milk, so the use of the drug is contraindicated during breastfeeding.

Dosing and Administration:

Orally

The drug is taken internally in the evening before bedtime, washing down with water.

In most cases, with progesterone deficiency, the daily dose of the drug Utrozhestan^® is 200-300 mg divided into 2 doses (200 mg in the evening before bedtime and 100 mg in the morning, if necessary).

When threatening abortion or to prevent habitual abortion due to insufficient progesterone: 200-600 mg daily in I and II trimesters of pregnancy. Further use of the drug Utrozhestan^® possibly on the prescription of the attending physician based on the evaluation of the clinical data of the pregnant woman.

If the luteal phase is insufficient (premenstrual syndrome, fibro-cystic mastopathy, dysmenorrhea, period of menopausal transition) daily dose is 200 or 400 mg, taken within 10 days (usually from the 17th to the 26th day of the cycle).

When MGT in perimenopause against the background of taking estrogens, the drug is Utrozhestan^® is used for 200 mg in day within 12 days.

When MGT in postmenopausal women in continuous mode, the preparation of Utrozestan^® is applied in a dose of 100-200 mg from the first day of admission estrogen-containing drugs. The dose is selected individually.

Intravaginally

Capsules are injected deep into the vagina.

Prevention (prevention) of preterm labor in women from the group risk (with shortening of the cervix and / or the presence of anamnestic data of premature birth and / or premature rupture of the membranes): the usual dose is 200 mg at bedtime, from the 22nd to the 34th week of pregnancy.

Complete absence of progesterone in women with dysfunctional (absent) ovaries (egg donation): against estrogen therapy 100 mg per day on the 13th and 14th days of the cycle, then 100 mg twice a day from the 15th to the 25th day of the cycle, from the 26th day, and in In case of pregnancy, the dose increases by 100 mg per day every week, reaching a maximum of 600 mg per day, divided into 3 doses. This dose can be applied for 60 days.

Support of the luteal phase during the extracorporeal cycle impregnation: it is recommended to use 200 to 600 mg per day, starting from the day of injection of the chorionic gonadotropin during the first and second trimester of pregnancy.

Support of the luteal phase in spontaneous or induced menstrual cycle in infertility associated with a violation of the function of the yellow body: it is recommended to use 200-300 mg per day, starting from the 17th day of the cycle for 10 days, in case of delay in menstruation and pregnancy diagnosis treatment should be continued.

In cases of threatening abortion or in order to prevent a habitual abortion, occurring against a background of progesterone deficiency: 200-400 mg per day in 2 divided doses daily in the first and second trimesters of pregnancy.

Side effects:

The following undesirable phenomena marked for oral administration of the drug are distributed according to the frequency of occurrence in accordance with the following gradation: often:> 1/100, <1/10; infrequently:> 1/1000, <1/100; rarely:> 1/10000, <1/1000; very rarely: <1/10000.

System	Adverse events
bodies	often	infrequently	rarely	rarely
Violations of the genitals and mammary gland	Violations menstrual cycle Amenorrhea Acyclic bleeding	Mammalgia
Disorders from the psyche				Depression
Disturbances from the nervous system	Headache	Drowsiness Transient dizziness
Disorders from the gastrointestinal tract	Bloating	Vomiting Diarrhea Constipation	Nausea
Disturbances from the liver and bile ducts		Cholestatic jaundice
Immune system disorders				Hives
Disturbances from the skin and subcutaneous tissues		Itching Acne		Chloasma

Drowsiness, transient dizziness are possible, as a rule, 1-3 h after oral drug administration. Data undesirable reactions can be reduced by reducing the dose, applying the drug before bed or switching to the vaginal route of administration.

These undesirable reactions are usually the first signs of an overdose.

Drowsiness and / or transient dizziness are observed, in particular, in the case of concomitant hypoestrogenia. Reducing the dose or restoring a higher estrogenation immediately eliminates these phenomena without reducing the therapeutic effect of progesterone.

If the treatment starts too early (in the first half of the menstrual cycle, especially before the 15th day), there may be a shortening of the menstrual cycle or acyclic bleeding.

Recorded changes in the menstrual cycle, amenorrhea, or acyclic bleeding are common to all gestagens.

Application in clinical practice

When applying in clinical practice the following undesirable phenomena are noted when administered orally progesterone: insomnia; premenstrual syndrome; tension in the mammary glands; highlightingfrom the vagina; pain in the joints; hyperthermia; increased sweating at night; fluid retention; change in body weight; acute pancreatitis; alopecia, hirsutism; changes in libido; thrombosis and thromboembolic complications MGT in combination with estrogen-containing drugs); increase in blood pressure.

The composition of the drug includes soy lecithin, which can cause hypersensitivity reactions (hives and anaphylactic shock).

With vaginal application

Individual cases of development of local intolerance reactions of the drug components (in particular, soy lecithin) have been reported as hyperemia of the vaginal mucosa, burning, itching, oily discharge.

Systemic side effects with intravaginal administration of the drug at recommended doses, in particular, drowsiness or dizziness (observed with oral administration of the drug), were not noted.

Overdose:Symptoms: drowsiness, transient dizziness, euphoria, shortening of the menstrual cycle, dysmenorrhea.

In some patients, the average therapeutic dose may be excessive because of the available or unstableendogenous secretion of progesterone, a particular sensitivity to the drug or a too low concentration of estradiol.

Treatment:

in case of occurrence of drowsiness or dizziness it is necessary to reduce the daily dose or prescribe the drug before bedtime for 10 days of the menstrual cycle;
in the case of a shortening of the menstrual cycle or "smearing" bloody discharge, it is recommended that the treatment be started on a later day of the cycle (for example, on the 19th day instead of the 17th);
in perimenopause and with MGT in postmenopause, you need to make sure that the concentration of estradiol is optimal.

In case of an overdose, if necessary, symptomatic treatment is performed.

Interaction:

When administered orally

Progesterone enhances the action of diuretics, hypotensive drugs, immunosuppressants, anticoagulants. Reduces the lactogenic effect of oxytocin. Simultaneous application with induction drugs of microsomal liver enzymes CYP3A4, such as barbiturates, antiepileptic drugs (phenytoin, carbamazepine), rifampicin, phenylbutazone, spironolactone, griseofulvin, is accompanied by an acceleration of the metabolism of progesterone in the liver.

Simultaneous intake of progesterone with certain antibiotics (penicillins, tetracyclines) can lead to a decrease in its effectiveness due to the violation of intestinal hepatic recirculation of sex hormones due to changes in the intestinal microflora.

The degree of expression of these interactions can vary in different patients, so the prognosis of clinical effects of these interactions is difficult.

Ketoconazole may increase the bioavailability of progesterone.

Progesterone can increase the concentration of ketoconazole and cyclosporine.

Progesterone may decrease the effectiveness of bromocriptine.

Progesterone can cause a decrease in glucose tolerance, thereby increasing the need for insulin or other hypoglycemic drugs in patients with diabetes mellitus.

Bioavailability of progesterone can be reduced in smoking patients and with excessive consumption of alcohol.

With intravaginal application

The interaction of progesterone with other drugs for intravaginal application was not evaluated.It should avoid the simultaneous use of other drugs used intravaginally, to prevent disruption of the release and absorption of progesterone.

Special instructions:

The drug is Utrozestan^® can not be used for contraception.

The drug should not be taken with food, as eating increases the bioavailability of progesterone.

The drug is Utrozestan^® should be taken with caution in patients with diseases and conditions that can worsen with fluid retention (arterial hypertension, cardiovascular disease, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes mellitus; violations of liver function of mild and moderate severity; photosensitivity.

It is necessary to observe patients with a history of depression, and in case of severe depression it is necessary to cancel the drug.

The composition of the drug Utrozestan^®enters soy lecithin, which can cause hypersensitivity reactions (hives and anaphylactic shock).

Patients with concomitant cardiovascular diseases or their presence in anamnesis should also be observed periodicallydoctor.

Application of the drug Utrozhestan^® after the first trimester of pregnancy can cause the development of cholestasis.

Prolonged treatment with progesterone requires regular physical examinations (including liver function tests); treatment should be canceled in case of deviations from normal indicators of functional liver or cholestatic jaundice.

When using progesterone, it is possible to reduce glucose tolerance and increase the need for insulin and other hypoglycemic drugs in patients with diabetes mellitus.

In the case of amenorrhea in the process of treatment, it is necessary to exclude the presence of pregnancy.

If the treatment starts too early at the beginning of the menstrual cycle, especially before the 15th day of the cycle, cycle shortening and / or acyclic bleeding may occur. In the case of acyclic bleeding, the drug should not be used until the cause is determined, including the histological examination of the endometrium.

If there is a history of chloasma or a tendency to develop it, patients are advised to avoid UV irradiation.

More than 50% of cases of spontaneous abortions in the early stages of pregnancy are due to genetic disorders. In addition, the cause of spontaneous abortions in the early stages of pregnancy can be infectious processes and mechanical damage. Application of the drug Utrozhestan^® in these cases can only lead to a delay in the rejection and evacuation of a non-viable fetal egg. Application of the drug Utrozhestan^® with the aim of preventing threatening abortion is justified only in cases of insufficient progesterone.

In carrying out MGT Estrogen during the period of perimenopause recommended the use of the drug Utrozhestan^®for no less than 12 days of the menstrual cycle.

In continuous mode MGT In postmenopause, the use of the drug is recommended from the first day of taking estrogens.

In carrying out MGT increased risk of venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of ischemic stroke, ischemic heart disease.

Because of the risk of developing thromboembolic complications, the drug should be discontinued in case of: visual disturbances such as loss of vision, exophthalmos, double vision,vascular lesions of the retina; migraine; venous thromboembolism or thrombotic complications, regardless of their location.

If there is a history of thrombophlebitis, the patient should be carefully monitored.

With the use of the drug Utrozhestan^® with estrogen-containing drugs should refer to instructions for their use regarding the risks of venous thromboembolism.

Clinical trial results Women Health Initiative Study (WHI) indicate a slight increase in the risk of breast cancer in long-term, more than 5 years, the combined use of estrogen-containing drugs with synthetic gestagens. It is not known whether there is an increased risk of breast cancer in postmenopausal women MGT estrogen-containing drugs in combination with progesterone.

Results of the study WHI increased risk of dementia at the onset of MGT age over 65 years.

Before the beginning MGT and regularly during her conduct, a woman should be examined to identify contraindications to its conduct. If there is a clinical indication, a breast examination and gynecological examination should be performed.

The use of progesterone may affect the results of some laboratory tests, including indicators of liver function, thyroid function; coagulation parameters; concentration of pregnanediol.

Effect on the ability to drive transp. cf. and fur:When using the drug orally, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Capsules 100 mg, 200 mg.

Packaging:

Capsules 100 mg

For 14 capsules in a blister of PVC / aluminum foil or PVC / PVDC / aluminum foil. 2 blisters with instructions for use in a cardboard package (28 capsules in a consumer package).

Capsules 200 mg

For 7 capsules in a PVC / aluminum foil blister or PVC / PVDC / aluminum foil. 2 blisters with instructions for use in a cardboard package (14 capsules in a consumer package).

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000186

Date of registration:13.10.2009 / 19.09.2017

Expiration Date:Unlimited

The owner of the registration certificate:Bezen Helskea SABezen Helskea SA Belgium

Manufacturer: & nbsp

OLIC (THAILAND) LIMITED Thailand

CYNDEA PHARMA SL Spain

DOBROLEK, LLC Russia

Representation: & nbspBEZEN HELSKEA ENG LLCBEZEN HELSKEA ENG LLCRussia

Information update date: & nbsp30.10.2017

Illustrated instructions

Instructions

Utrozestan® (Utrogectan®)