Side effects of utrogestan when taken orally. Utrozhestan - instructions for use

Registration number No. JIC-000186

TradeName: Utrozhestan ®

international generic name: progesterone

Dosage form: capsules

Compound for 1 capsule:

Active substance: progesterone micronized 100 or 200 mg.

Excipients: sunflower oil 149 mg/298 mg, soy lecithin 1 mg/2 mg; capsule - gelatin 76.88 mg / 153.76 mg, glycerin 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 yellowish gelatin capsules containing an oily whitish homogeneous suspension (no visible phase separation).

Pharmacotherapeutic group: gestagen

The codeATX: G03 DA04

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

The active substance of the drug Utrozhestan ® is progesterone, which is identical to the natural hormone corpus luteum ovary. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where, by activating DNA, it stimulates RNA synthesis. Promotes the transition of the uterine mucosa from the proliferation phase caused by the follicular hormone estradiol to the secretory phase, and after fertilization to the state necessary for the development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes. Promotes the formation of normal endometrium. Stimulates the development of the terminal elements of the mammary gland and induces lactation.

By stimulating protein lipase, it increases fat reserves; 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 gonadotropic hormones of the pituitary gland; reduces azotemia, increases the excretion of nitrogen by the kidneys.

Pharmacokinetics

When taken orally

Suction

Micronized progesterone is well absorbed from the gastrointestinal tract (GIT). The concentration of progesterone in the blood plasma gradually increases during the first hour, the maximum concentration in the blood plasma (Cmax) is observed 1-3 hours after ingestion. 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 6 hours later and 1.64 ng/ml 8 hours after ingestion.

Metabolism

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

breeding

It is excreted by the kidneys in the form of metabolites, 95% of which are glucuronconjugated metabolites, mainly 3-alpha, 5-beta-pregnandiol (pregnandione). These metabolites, which are determined in blood plasma and urine, are similar to substances formed during the physiological secretion of the corpus luteum.

When administered vaginally

Suction and distribution

Absorption occurs quickly, a high concentration of progesterone in the blood plasma is observed 1 hour after administration. With m ah progesterone in blood plasma is achieved 2-6 hours after administration. With the introduction of 100 mg 2 times a day, the average concentration in blood plasma remains at the level of 9.7 ng / ml for 24 hours. When administered in doses of more than 200 mg / day, the concentration of progesterone corresponds to the first trimester of pregnancy. Communication with plasma proteins - 90%. Progesterone accumulates in the uterus.

Metabolism

It is metabolized with the formation of predominantly 3-alpha, 5-beta-pregnandiol. The concentration of 5-beta-pregnanolone in blood plasma does not increase.

breeding

https://website/autoload/itoc.html

It is excreted by the kidneys in the form of metabolites, the main part is 3-alpha, 5-beta-pregnandiol (pregnandione). This is confirmed by a constant increase in its concentration (Cmax 142 ng/ml after 6 hours).

INDICATIONS FOR USE

Progesterone deficiency in women:

For oral administration:

■ threatened abortion or prevention of habitual abortion due to

insufficiency of progesterone;

■ infertility due to luteal insufficiency;

§ premenstrual syndrome;

§ violations of the menstrual cycle due to violations of ovulation or anovulation;

§ fibrocystic mastopathy;

§ period of menopausal transition;

§ menopausal (replacement) hormone therapy(MHT) in peri- and postmenopause (in combination with estrogen-containing drugs).

For intravaginal use:

§ MHT in case of progesterone deficiency with non-functioning (absent) ovaries (egg donation);

§ prevention (prevention) of preterm birth in women at risk (with shortening of the cervix and / or the presence of anamnestic data of preterm 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 spontaneous or induced menstrual cycle;

§ premature menopause;

§ MHT (in combination with estrogen-containing drugs);

§ infertility due to luteal insufficiency;

§ threatened abortion or prevention of habitual abortion due to lack of progesterone.

CONTRAINDICATIONS

Hypersensitivity to progesterone or any of the excipients of the drug; deep vein thrombosis, thrombophlebitis; thromboembolic disorders (thromboembolism pulmonary artery myocardial infarction, stroke) intracranial hemorrhage or the presence of these conditions / diseases in history; bleeding from the vagina of unknown origin; incomplete abortion; porphyria; identified or suspected malignant neoplasms mammary gland and genitals; serious illnesses liver (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor, malignant tumors liver) at present or in history; childhood up to 18 years (efficacy and safety have not been established); period breastfeeding.

CAREFULLY

Diseases of cardio-vascular system, arterial hypertension, chronic kidney failure, diabetes, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, impaired liver function, mild and medium degree gravity; photosensitivity.

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

USE IN PREGNANCY AND DURING BREASTFEEDING

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

Progesterone enters breast milk therefore, the use of the drug is contraindicated during breastfeeding.

METHOD OF APPLICATION AND DOSES

oral

The drug is taken orally in the evening before bedtime, washed down with water.

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

§ In threatened abortion or to prevent recurrent abortion due to progesterone deficiency : 200-600 mg per day daily in the I and II trimesters of pregnancy. Further use of the drug Utrozhestan ® is possible as prescribed by the attending physician, based on an assessment of the clinical data of the pregnant woman.

§ With luteal phase deficiency (premenstrual syndrome,

fibrocystic mastopathy, dysmenorrhea, menopausal transition period) the daily dose is 200 or 400 mg taken for 10 days (usually from the 17th to the 26th day of the cycle).

§ At MHT in perimenopause against the background of taking estrogens, the drug Utrozhestan ®

applied at 200 mg per day for 12 days.

§ At MHT in postmenopausal women in continuous mode, the drug Utrozhestan ®

is used at a dose of 100-200 mg from the first day of taking estrogen-containing drugs. Dose selection is carried out individually.

intravaginally

The capsules are inserted deep into the vagina.

§ Prevention (prevention) of preterm birth in women

from the group risk (with short cervix and/or history of preterm labor and/or preterm rupture of membranes): The usual dose is 200 mg at bedtime, from 22 to 34 weeks of gestation.

§ Complete absence of progesterone in women with non-functioning

(absent ) ovaries (egg donation): against the background of estrogen therapy, 100 mg per day on the 13th and 14th days of the cycle, then 100 mg 2 times a day from the 15th to the 25th day of the cycle, from the 26th day, and on if pregnancy is determined, the dose is increased by 100 mg per day every week, reaching a maximum of 600 mg per day, divided into 3 doses. The specified dose can be used for 60 days.

§ Support of the luteal phase during the cycle of extracorporeal

§ Support of the luteal phase in spontaneous or induced menstruation

cycle in infertility associated with dysfunction of the corpus luteum : it is recommended to use 200-300 mg per day, starting from the 17th day of the cycle for 10 days, in case of delayed menstruation and diagnosis of pregnancy, treatment should be continued.

§ In cases of threatened abortion or to prevent habitual abortion ,

arising against the background of progesterone deficiency: 200-400 mg per day in 2 doses daily in the I and II trimesters of pregnancy.

SIDE EFFECT

The following adverse events noted at oral route applications drug, distributed by frequency of occurrence in accordance with the following gradation: often: > 1/100,< 1/10; нечасто: > 1/1000, < 1/100; редко: > 1/10000, < 1/1000; очень редко: < 1/10000.

These adverse reactions are usually the first signs of an overdose. Drowsiness, transient dizziness are possible, as a rule, 1-3 hours after oral administration of the drug. These adverse reactions can be reduced by reducing the dose, using the drug at bedtime, or switching to the vaginal route of administration.

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

If the course of treatment is started too early (in the first half of the menstrual cycle, especially before the 15th day), shortening of the menstrual cycle or acyclic bleeding is possible.

Recorded changes in the menstrual cycle, amenorrhea or acyclic bleeding are characteristic of all gestagens.

Application in clinical practice

When used in clinical practice, the following adverse events were noted at oral administration progesterone: insomnia; premenstrual syndrome; tension in the mammary glands; vaginal discharge; pain in the joints; hyperthermia; increased sweating at night; fluid retention; change in body weight; acute pancreatitis; alopecia, hirsutism; libido changes; thrombosis and thromboembolic complications (during MHT in combination with estrogen-containing drugs); promotion blood pressure.

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

When used vaginally

It was reported about individual cases of the development of reactions of local intolerance to the components of the drug (in particular, soy lecithin) in the form of hyperemia of the vaginal mucosa, burning, itching, oily discharge.

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

OVERDOSE

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

In some patients, the average therapeutic dose may be excessive due to existing or emerging unstable endogenous secretion of progesterone, special sensitivity to the drug, or too low a concentration of estradiol.

Treatment:

In case of drowsiness or dizziness, it is necessary to reduce the daily dose or prescribe the drug at bedtime for 10 days of the menstrual cycle;

In case of shortening of the menstrual cycle or "spotting" spotting it is recommended to postpone the start of treatment to a later day of the cycle (for example, on the 19th instead of the 17th);

In perimenopause and with MHT in postmenopause, it is necessary to make sure that the concentration of estradiol is optimal.

In case of overdose, if necessary, symptomatic treatment is carried out.

INTERACTION WITH OTHER DRUGS

When administered orally

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

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

The severity of these interactions may vary in different patients, so the prognosis clinical effects these interactions is difficult.

Ketoconazole may increase the bioavailability of progesterone.

Progesterone can increase the concentration of ketoconazole and cyclosporine.

Progesterone may reduce the effectiveness of bromocriptine.

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

The bioavailability of progesterone can be reduced in patients who smoke and with excessive alcohol consumption.

For intravaginal use

The interaction of progesterone with other drugs for intravaginal use has not been evaluated. The simultaneous use of other drugs used intravaginally should be avoided in order to avoid impaired release and absorption of progesterone.

SPECIAL INSTRUCTIONS

The drug Utrozhestan ® can not be used for contraception.

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

The drug Utrozhestan ® should be taken with caution in patients with diseases and conditions that may be aggravated by fluid retention (arterial hypertension, cardiovascular diseases, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes; impaired liver function of mild and moderate severity; photosensitivity.

Patients with a history of depression should be observed, and if severe depression develops, the drug should be discontinued.

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

Patients with concomitant cardiovascular diseases or their history should also be periodically observed by a doctor.

The use of the drug Utrozhestan ® after the first trimester of pregnancy can cause the development of cholestasis.

At long-term treatment progesterone should be taken regularly medical examinations(including the study of liver function); treatment should be discontinued in case of deviations from normal indicators functional tests 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 event of amenorrhea during treatment, it is necessary to exclude the presence of pregnancy.

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

Patients with a history of chloasma or a tendency to develop it are advised to avoid UV exposure.

Over 50% of spontaneous abortions early dates pregnancy is due to genetic disorders. In addition, the cause of spontaneous abortions in early pregnancy can be infectious processes and mechanical damage. The use of the drug Utrozhestan ® in these cases can only lead to a delay in rejection and evacuation of a non-viable fetal egg. The use of the drug Utrozhestan ® to prevent threatened abortion is justified only in cases of progesterone deficiency.

When conducting MHT with estrogens during the perimenopausal period, it is recommended to use the drug Utrozhestan ® for at least 12 days of the menstrual cycle.

With a continuous regimen of MHT in postmenopausal women, it is recommended to use the drug from the first day of taking estrogens.

When conducting MHT, the risk of developing venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of ischemic stroke, coronary disease hearts.

Due to the risk of developing thromboembolic complications, the use of the drug should be discontinued in the event 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 closely monitored.

When using the drug Utrozhestan ® with estrogen-containing drugs, it is necessary to refer to the instructions for their use regarding the risks of venous thromboembolism.

results clinical trial The Women Health Initiative Study (WHI) shows a small increase in the risk of breast cancer with long-term, more than 5 years, the combined use of estrogen-containing drugs with synthetic progestogens. It is not known whether there is an increased risk of breast cancer in postmenopausal women during MHT with estrogen-containing drugs in combination with progesterone.

The results of the WHI study also found an increased risk of dementia when starting MHT at age 65 or older.

Before starting MHT and regularly during it, a woman should be examined to identify contraindications to its implementation. In the presence of clinical indications, a breast examination and gynecological examination should be carried out.

The use of progesterone may interfere with the results of some laboratory tests, including liver function tests, thyroid gland; coagulation parameters; concentration of pregnandiol.

Influence on the ability to control vehicles and mechanisms

When using the drug orally, care must be taken when driving vehicles and engaging in other potentially dangerous species activities that require increased concentration of attention and speed of psychomotor reactions.

RELEASE FORM

Capsules 100 mg

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

Capsules 200 mg

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

Gestagen

Active substance

Release form, composition and packaging

Capsules soft gelatinous, round, shiny, yellowish; the contents of the capsules are an oily whitish homogeneous suspension (without visible phase separation).

Excipients: sunflower oil - 298 mg, soy lecithin - 2 mg.

The composition of the capsule shell: gelatin - 153.76 mg, glycerin - 62.9 mg, titanium dioxide - 3.34 mg.

7 pcs. - blisters (2) - packs of cardboard.

pharmachologic effect

The active substance of the drug Utrozhestan is progesterone, which is identical to the natural hormone of the corpus luteum of the ovary. By binding to receptors on the surface of cells of target organs, it penetrates into the nucleus, where it activates DNA and stimulates RNA synthesis.

Promotes the transition of the uterine mucosa from the proliferation phase, caused by the follicular hormone estradiol, to the secretory phase. After fertilization, it contributes to the transition to the state necessary for the development of a fertilized egg. Reduces the excitability and contractility of the muscles of the uterus and fallopian tubes. Promotes the formation of normal endometrium. Stimulates the development of the terminal elements of the mammary gland, induces lactation.

By stimulating protein lipase, it increases fat reserves, increases utilization. By increasing the concentration of basal and stimulated insulin, it contributes to the accumulation of glycogen in the liver, increases the production of gonadotropic hormones of the pituitary gland; reduces azotemia, increases the excretion of nitrogen in the urine.

Pharmacokinetics

When taken orally

Suction

Micronized progesterone is well absorbed from the gastrointestinal tract. The concentration of progesterone in the blood gradually increases during the first hour, C max in the blood plasma is observed 1-3 hours after ingestion. The concentration of progesterone in the blood plasma increases from 0.13 ng / ml to 4.25 ng / ml after 1 hour, up 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.

breeding

It is excreted in the urine as metabolites, 95% of which are glucuron-conjugated metabolites, mainly 3-alpha, 5-beta-pregnanediol (pregnandione). These metabolites, which are determined in blood plasma and urine, are similar to substances formed during the physiological secretion of the corpus luteum.

When administered intravaginally

Suction and distribution

Absorption occurs quickly, a high concentration of progesterone is observed 1 hour after administration. Cmax of progesterone in plasma is reached 2-6 hours after administration. With the introduction of the drug at 100 mg 2 times / day, the average concentration remains at the level of 9.7 ng / ml for 24 hours. When administered in doses of more than 200 mg / day, the concentration of progesterone corresponds to the first trimester of pregnancy.

Plasma protein binding is 90%. Progesterone accumulates in the uterus.

Metabolism

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

breeding

It is excreted in the urine as metabolites, the main part is 3-alpha, 5-beta-pregnanediol (pregnandione). This is confirmed by a constant increase in its concentration (C max 142 ng/ml after 6 hours).

Indications

Progesterone deficiency in women:

oral route of administration:

• threatening abortion or prevention of habitual abortion due to progesterone deficiency;
• premenstrual syndrome;
• menstrual disorders due to ovulation or anovulation disorders;
• fibrocystic mastopathy;
• period of menopausal transition;
• menopausal (replacement) hormone therapy (MHT) in peri- and postmenopause (in combination with estrogen-containing drugs).

vaginal route of administration:

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

Contraindications

• deep vein thrombosis, thrombophlebitis;
• thromboembolic disorders (pulmonary embolism, myocardial infarction, stroke), intracranial hemorrhage or a history of these conditions / diseases;
• bleeding from the vagina of unknown origin;
• incomplete abortion;
• porphyria;
• established or suspected malignant neoplasms of the mammary glands and genital organs;
• severe liver disease (including cholestatic jaundice, hepatitis, Dubin-Johnson syndrome, Rotor, malignant liver tumors) at present or in history;
• age up to 18 years (efficacy and safety have not been established);
• breastfeeding period;
• hypersensitivity to progesterone or any of the auxiliary components of the drug.

Carefully: diseases of the cardiovascular system, arterial hypertension, chronic renal failure, diabetes mellitus, bronchial asthma, epilepsy, migraine, depression, hyperlipoproteinemia, mild to moderate liver dysfunction, photosensitivity; II and III trimesters of pregnancy.

Dosage

Oral route of administration

The drug is taken orally, in the evening before bedtime, with water.

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

At threatened abortion or to prevent recurrent abortion due to progesterone deficiency appoint 200-600 mg / day daily in the I and II trimesters of pregnancy. Further use of the drug Utrozhestan is possible as prescribed by the attending physician, based on an assessment of the clinical data of the pregnant woman.

At luteal phase insufficiency(premenstrual syndrome, fibrocystic mastopathy, dysmenorrhea, menopausal transition period) the daily dose of the drug is 200 or 400 mg for 10 days (usually from the 17th to the 26th day of the cycle).

At MHT in perimenopause against the background of taking estrogens, the drug Utrozhestan is prescribed at 200 mg / day for 12 days.

At MHT in postmenopausal women in continuous mode, the drug Utrozhestan is used at a dose of 100-200 mg from the first day of taking estrogens. Dose selection is carried out individually.

Vaginal route of administration

The capsules are inserted deep into the vagina.

Prevention (prevention) of preterm birth in women at risk(with short cervix and/or history of preterm labor and/or preterm rupture of membranes): The usual dose is 200 mg at bedtime, from 22 to 34 weeks of gestation.

Complete lack of progesterone in women with non-functioning (missing) ovaries (egg donation): against the background of estrogen therapy, 100 mg / day on the 13th and 14th days of the cycle, then - 100 mg 2 times / day from the 15th to the 25th day of the cycle, from the 26th day and in case of pregnancy the dose is increased by 100 mg/day every week, reaching a maximum of 600 mg/day divided into 3 divided doses. The indicated dose is usually applied for 60 days.

Support of the luteal phase during the in vitro fertilization cycle: it is recommended to use from 200 to 600 mg / day, starting from the day of injection during the I and II trimesters of pregnancy.

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

AT cases of threatened abortion or for habitual warnings abortion, arising against the background of progesterone deficiency: 200-400 mg / day in 2 doses daily in the I and II trimesters of pregnancy.

Side effects

The following adverse events noted when administered orally drug, distributed by frequency of occurrence in accordance with the following gradation: often (> 1/100,<1/10); нечасто (>1/1000, <1/100); редко (>1/10 000, <1/1000); очень редко (<1/10 000).

Drowsiness, transient dizziness are possible, as a rule, 1-3 hours after taking the drug. These adverse reactions can be reduced by reducing the dose, using the drug at bedtime, or switching to the vaginal route of administration.

These side effects are usually the first signs of an overdose.

Drowsiness and / or transient dizziness are observed, in particular, in the case of concomitant hypoestrogenism. Reducing the dose or restoring higher estrogen levels immediately reverses these effects without reducing the therapeutic effect of progesterone.

If the course of treatment is started too early (in the first half of the menstrual cycle, especially before the 15th day), shortening of the menstrual cycle or acyclic bleeding is possible.

Recorded changes in the menstrual cycle, amenorrhea or acyclic bleeding are characteristic of all progestogens.

Application in clinical practice

When used in clinical practice, the following adverse events have been noted with oral progesterone: insomnia, premenstrual syndrome, tension in the mammary glands, vaginal discharge, joint pain, hyperthermia, increased sweating at night, fluid retention, changes in body weight, acute pancreatitis, alopecia, hirsutism, changes in libido, thrombosis and thromboembolic complications (during MHT in combination with estrogen-containing drugs), increased blood pressure.

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

When used vaginally

It was reported about individual cases of the development of reactions of local intolerance to the components of the drug (in particular, soy lecithin) in the form of hyperemia of the vaginal mucosa, burning, itching, oily discharge.

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

Overdose

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

In some patients, the average therapeutic dose may be excessive due to existing or emerging unstable endogenous secretion of progesterone, special sensitivity to the drug, or too low a concentration of estradiol.

Treatment:

• in case of drowsiness or dizziness, it is necessary to reduce the daily dose or prescribe the drug at bedtime for 10 days of the menstrual cycle;
• in case of shortening of the menstrual cycle or spotting, it is recommended to postpone the start of treatment to a later day of the cycle (for example, on the 19th instead of the 17th);
• in perimenopause and with MHT in postmenopause, it is necessary to make sure that the concentration of estradiol is optimal.

In case of overdose, if necessary, symptomatic treatment is carried out.

drug interaction

When administered orally

Progesterone enhances the effect of diuretics, antihypertensive drugs, immunosuppressants, anticoagulants.

Reduces the lactogenic effect of oxytocin.

Simultaneous use with drugs-inducers of microsomal liver enzymes CYP3A4, such as barbiturates, (phenytoin), rifampicin, phenylbutazone, spironolactone, griseofulvin, is accompanied by an acceleration of progesterone metabolism in the liver.

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

The severity of these interactions may vary in different patients, so the prediction of the 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 reduce the effectiveness of bromocriptine.

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

The bioavailability of progesterone can be reduced in patients who smoke and with excessive alcohol consumption.

For intravaginal use

The interaction of progesterone with other drugs for intravaginal use has not been evaluated. The simultaneous use of other drugs used intravaginally should be avoided in order to avoid impaired release and absorption of progesterone.

special instructions

The drug Utrozhestan can not be used for contraception.

The drug should not be taken with food, because. food intake increases the bioavailability of progesterone.

The drug Utrozhestan should be taken with caution in patients with diseases and conditions that may be aggravated by fluid retention (arterial hypertension, cardiovascular disease, chronic renal failure, epilepsy, migraine, bronchial asthma); in patients with diabetes; impaired liver function of mild and moderate severity; photosensitivity.

Patients with a history of depression should be observed, and if severe depression develops, the drug should be discontinued.

Patients with concomitant cardiovascular diseases or their history should also be periodically observed by a doctor.

The use of the drug Utrozhestan after the first trimester of pregnancy can cause the development of cholestasis.

With long-term treatment with progesterone, regular medical examinations (including a study of liver function) should be carried out; treatment should be discontinued in the event of abnormal liver function tests 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.

If amenorrhea occurs during treatment, pregnancy should be excluded.

If the course of treatment is started too early at the beginning of the menstrual cycle, especially before the 15th day of the cycle, shortening of the cycle and / or acyclic bleeding is possible. In the case of acyclic bleeding, the drug should not be used until their cause is clarified, including a histological examination of the endometrium.

Patients with a history of chloasma or a tendency to develop it are advised to avoid UV exposure.

More than 50% of cases of spontaneous abortions in early pregnancy are due to genetic disorders. In addition, the cause of spontaneous abortions in early pregnancy can be infectious processes and mechanical damage. The use of the drug Utrozhestan in these cases can only lead to a delay in rejection and evacuation of a non-viable fetal egg.

The use of the drug Utrozhestan in order to prevent a threatened abortion is justified only in cases of progesterone deficiency.

When conducting MHT with estrogens during the perimenopausal period, it is recommended to use the drug Utrozhestan for at least 12 days of the menstrual cycle.

With a continuous regimen of MHT in postmenopausal women, it is recommended to use the drug from the first day of taking estrogens.

When conducting MHT, the risk of developing venous thromboembolism (deep vein thrombosis or pulmonary embolism), the risk of ischemic stroke, and coronary artery disease increases.

Due to the risk of developing thromboembolic complications, the use of the drug should be discontinued in the event 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 closely monitored.

When using the drug Utrozhestan with estrogen-containing drugs, it is necessary to refer to the instructions for their use regarding the risks of venous thromboembolism.

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

The results of the WHI study also found an increased risk of dementia when starting MHT at age 65 or older.

Before starting MHT and regularly during it, a woman should be examined to identify contraindications to its implementation. In the presence of clinical indications, a breast examination and gynecological examination should be carried out.

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

Influence on the ability to drive a car Ansport and mechanism control

When using the drug orally, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Pregnancy and lactation

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

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

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 25 ° C. Shelf life - 3 years. Do not use after the expiration date.

With difficulties with conception and the threat of termination of pregnancy, doctors prescribe hormonal drugs. Utrozhestan is a drug with progesterone. Its main task is to help a woman bear a healthy baby.

Compound

The active substance is progesterone. In structure, it is an absolute analogue of the natural hormone of the corpus luteum of the ovary. The metabolism of substances is identical. The medication also contains excipients: peanut or sunflower oil, gelatin, soy lecithin, glycerol and titanium dioxide.

Forms of release of Utrozhestan

The drug is sold in the form of capsules 100 (round) or 200 mg (oval). They are soft to the touch. Inside contains a liquid, and on top - a gelatinous shell. This is a generic dosage form.

The capsules are taken orally or inserted into the vagina.

Mechanism of action

The natural active substance is well absorbed in the intestines, vagina. Through the blood, progesterone enters the tissues. It prepares the uterine mucosa for the introduction of the egg, relaxes its muscles, and promotes the development of the mammary glands.

These processes are necessary for the onset and maintenance of pregnancy.

When taken orally

The concentration of progesterone in the blood rises within an hour after ingestion. After 60-180 minutes, it reaches its maximum performance. Utrozhestan during pregnancy contributes to the fertilization of the egg. Up to 60% of the dose taken orally (metabolic products) is excreted by the kidneys.

For vaginal use

With the introduction of capsules into the vagina, the concentration in the blood is maximum after 2-6 hours. Vaginal use of Utrozhestan during pregnancy reduces the risk of miscarriage. Progesterone stimulates the growth of the endometrium. Up to 95% of the dose is excreted in the urine as metabolic products.

Why is Utrozhestan prescribed for pregnant women

Progesterone, after entering the blood, penetrates to the ovaries and uterus. The hormone promotes the fertilization of the egg, its introduction into the uterine mucosa and further growth. The uterus stops contracting, which helps the embryo to attach firmly. Progesterone helps the body of the expectant mother to accumulate fat for the safe bearing of the child. The hormone suppresses ovulation, prepares the mammary glands for lactation.

In the early stages

Assign to drink Utrozhestan with the threat of miscarriage in the early stages. It eliminates progesterone deficiency in the first weeks of pregnancy.

The drug is indicated for the treatment of such conditions:

• uterine hypertonicity;
• deficiency of progesterone by analysis;
• the threat of spontaneous abortion;
• cervical insufficiency;
• bloody issues;
• prevention of myoma or cyst;
• infertility earlier, IVF.

In the last trimesters

The appointment of Utrozhestan during late pregnancy is less common. After 16 weeks, the placenta provides the fetus with progesterone.

Conditions in which Utrozhestan is indicated for pregnant women:

• The placenta produces little progesterone.
• Shortening or early softening of the cervix.
• The patient has a history of miscarriage, premature birth, uterine surgery.
• The presence of thrombosis.
• Low position of the fetus.
• Liver disorder.

How best to take the drug

Only a gynecologist determines the scheme and method of taking Utrogestan by pregnant women. The course of treatment is also selected individually. Sometimes the doctor prescribes a combined use of the drug (vaginally and orally). It is contraindicated for a pregnant woman to drink medication on her own.

Do not spontaneously cancel the medication or reduce / increase the dosage.

Instructions for use

For oral administration, 200-300 mg (1-3 pcs.) Are prescribed per day. As a rule, the capsules are taken at bedtime. At high doses, add the morning dose.

For intravaginal use, the capsules are inserted deep into the vagina. On average, 1 capsule (200 mg) is prescribed, which is inserted into the vagina at night. The maximum dose for pregnant women is 600 mg / day. For proper insertion, you need to lie on your back, put a roller or pillow under your buttocks. After spreading your legs, insert a pill deep into the vagina.

For complete absorption, it is necessary to lie down for at least 15 minutes.

Cancellation of the drug during pregnancy

It is necessary to stop taking the hormone gradually. Especially important is the slow cancellation of Utrozhestan during pregnancy after the threat of interruption. Rapid cancellation can provoke rejection of the fetal egg.

If the patient drank capsules for the first trimester, the gradual withdrawal of the drug begins at 12-13 weeks. Some women take progesterone until the 20th week, when the hormone is not provided by the formed placenta. If the drug was prescribed in the second trimester, its cancellation begins at 30 weeks.

Completely refuse the use of Utrozhestan in 3-4 weeks.

Possible side effects of Utrozhestan

The influence of Utrozhestan on the fetus has not been revealed by studies.

The drug has the following undesirable effects on a woman:

• drowsiness, distraction;
• vomit;
• dizziness;
• bleeding from the vagina;
• urticaria, pruritus;
• swelling, weight gain;
• depression.

Contraindications

• systemic lupus erythematosus;
• diabetes;
• venous insufficiency, thrombosis, embolism earlier;
• neoplasms and suspicion of them;
• visual impairment;
• bronchial asthma.

Analogues

Other drugs are available not only in the form of capsules, but also in the form of a vaginal gel. Analogues are selected by the attending physician, taking into account individual characteristics and diseases.

Effective analogues of Utrozhestan:

• Prajisan.
• Iprozhin.
• Duphaston.
• Crinon.
• Progestogel.

Price

The cost of Utrozhestan in different cities of Russia differs little. The average price for 100 mg capsules is 370-450 rubles for 28 pieces. Tablets for intravaginal administration of 200 mg will cost more in pharmacies: within 400-470 rubles for 14 pieces.

Video

The most common cause of infertility and miscarriage is a deviation from the norm of the hormonal background, namely, progesterone deficiency. Utrozhestan during pregnancy is prescribed to make up for this shortage. The drug contains micronized progesterone, which has a high bioavailability and acts in the same way as a natural hormone. Positive dynamics in patients is observed already on the second day of using Utrozhestan.

What is the drug Utrozhestan

Progesterone is one of the most important female hormones. It is he who regulates the menstrual cycle, even before the onset of pregnancy prepares the endometrium for it, then ensures the process of implantation of the embryo into the uterus, supports the pregnancy, relaxes the uterus. In early pregnancy, progesterone has an anti-abortion effect: it suppresses the immune response to the embryo.

Progesterone deficiency at the beginning of pregnancy increases the risk of spontaneous abortion, therefore, with a threatened miscarriage, treatment is primarily aimed at filling the lack of this hormone.

Progesterone was first synthesized in 1934, but its use during pregnancy has been limited due to its low bioavailability. In addition, when taken, it quickly collapsed in the liver and simply did not have time to act. The use of progesterone in miscarriage became possible only after the invention of the micronized form, which was registered in Russia under the trademark Utrozhestan. The molecule of the active substance Utrozhestan completely coincides with progesterone, which is formed in the female body. Due to the small particle size (up to 10 microns), Utrozhestan can be quickly and completely absorbed into the bloodstream from both the gastrointestinal tract and the vaginal mucosa.

The rights to Utrozhestan belong to the Bezek Healthcare group of companies from Belgium. The drug itself is produced in Spain and Thailand, and a Russian drug under the same brand is expected to be released soon.

Why is Utrozhestan prescribed during pregnancy

The only indication for treatment with Utrozhestan is progesterone deficiency. The scope of the drug is wide:

1. With repeated miscarriages at the beginning of pregnancy, the drug can be prescribed prophylactically - even before the onset of any symptoms. It has been established that endocrine dysfunction, leading to a lack of progesterone, is found in 10-17% of patients with this problem.
2. If the first child was born prematurely, or the cervix of a woman is less than 2.5 cm long, the administration of Utrozhestan capsules to pregnant women reduces the likelihood of preterm birth by 35%.
3. With a high risk of miscarriage at a period of 7-20 weeks of pregnancy. Its signs are pain in the lower back and abdomen, increased uterine tone, uterine hematoma, spotting.
4. For women undergoing an IVF program, Utrozhestan is prescribed after ovulation stimulation, then to prevent miscarriage.
5. For the treatment of infertility, if luteal insufficiency is established in the presence of ovulation. This disorder is a malfunction of the corpus luteum, resulting in a deficiency of progesterone, and the uterus cannot accept and store the developing embryo. Insufficiency of the corpus luteum occurs in 4% of women with infertility.
6. Together with estrogens, Utrozhestan is prescribed for menopause. According to the instructions, replacement therapy is indicated for women with early menopause, at a high risk of osteoporosis, heart disease, Alzheimer's.

Forms of release and dosage

Utrozhestan comes in the form of thin gelatin capsules containing progesterone. Vegetable oil and lecithin obtained from soybean oil are used as excipients. Capsules are universal: they can be drunk like tablets, injected into the vagina like suppositories. The most rational method of treatment is chosen by the doctor, taking into account the clinical situation and the wishes of the woman:

1. The vaginal route of administration of Utrozhestan is the only possible one for toxicosis. Many doctors prefer it with a high probability of miscarriage and IVF. Progesterone is effectively absorbed into the vaginal mucosa and reaches the uterus faster, even before its concentration in the blood rises.
2. The oral route of administration is possible when Utrozhestan is used as part of hormone replacement therapy. If you drink the drug as tablets, Utrozhestan will have a more pronounced sedative effect. The effectiveness of oral treatment with Utrozhestan is slightly lower than when administered vaginally.

When choosing whether it is better to drink or insert vaginally Utrozhestan, vaginal administration should be preferred if the drug is taken when planning a pregnancy or to maintain it.

The drug has 2 dosage options - 100, 200 mg. From 100 to 600 mg of progesterone are prescribed per day. The daily dose depends on the type and severity of the hormonal disorder. The maximum dose is recommended in the complete absence of own progesterone or to prevent miscarriage. To improve the effectiveness of treatment, the instructions for use recommend dividing the daily dose of Utrozhestan into 2 or 3 doses.

How to take Utrozhestan during pregnancy

Information from the instructions on the rules for taking and the recommended dose of Utrozhestan:

What efficiency can be expected from Utrozhestan? According to one study, the pain syndrome decreases the next day, disappears by about the 3rd day of treatment, the bleeding decreases on the 2nd day, stops by the 6th day. The tone of the uterus in more than 80% of women normalizes after a week, hematomas decrease by the 10th day.

If the cause of miscarriage was not progesterone deficiency, but genetic disorders, infectious processes, injuries, Utrozhestan suppositories can slow down the miscarriage, but are unable to prevent it. A non-viable fetus will in any case be rejected.

How to insert Utrozhestan candles correctly

In order for progesterone to accumulate in the uterus, Utrozhestan should be inserted as close as possible to her neck. For this you need:

1. Wash the hands.
2. It is good to wipe them off, as the gelatin capsule of Utrozhestan can stick to wet skin.
3. Lie on the bed, placing a pillow under your hips, bend your legs at the knees, spread them wide.
4. Insert the Utrozhestan suppository into the vagina and immediately push it with your index finger as deep as possible. The candle should slide along the back wall of the vagina. If a pessary is installed in a woman with a short cervix, they try to insert a candle up to its ring.
5. If you have to administer Utrozhestan candles at work, it is more convenient to do this while standing in a similar position, that is, squat down and spread your knees.
6. In order for the drug to be absorbed into the mucous membrane, activity is limited in the first hour after administration. It is best to lie down, in extreme cases - to sit quietly.
7. Instructions for use indicate that at a dose above 300 mg, the most effective administration of Utrozhestan is with an 8-hour interval. In this case, a uniform concentration of progesterone is maintained in the blood and uterus around the clock.

Allocations after Utrozhestan during pregnancy- a common phenomenon associated with a change in the hormonal background, the reaction of the genital organs to it, increased activity of the vaginal mucosa. Usually they are watery or cheesy, quite plentiful, so you will have to use a daily pad. It is also possible to change the smell of urine.

The remnants of the candle Utrozhestan come out in the form of yellow discharge. This is the oil from the suspension that is inside the capsule. If it comes out later than an hour after the injection, you don’t have to worry: the drug has had time to act. If the yellow liquid begins to flow out earlier, it is worth finding the time and organizing an hour-long bed rest after each administration of the drug.

Course duration

How long to take the drug, is determined by the attending physician, based on the data of analyzes and ultrasound. Theoretically, it can be taken from pregnancy planning to 34 weeks. With prolonged use of Utrozhestan, additional monitoring of the woman's health is necessary. The instruction recommends regular medical examinations by a therapist, monitoring of liver functions. If abnormalities in the level of liver enzymes were detected, or jaundice appeared, the drug will have to be canceled.

How long to take Utrozhestan, depends on the level of its own progesterone. With habitual miscarriage, Utrozhestan can be used throughout the first trimester and the beginning of the second. As a rule, they try to cancel the drug by the end of the 1st trimester. If the cancellation of Utrozhestan has led to a deterioration in the condition, treatment is resumed. If problems arose after the middle of pregnancy, the drug is prescribed until 34 weeks.

Side effects

The risk of undesirable actions when taking Utrozhestan is low. Even if the doctor played it safe and prescribed the drug just in case, there will be no particular harm. The introduction of progesterone does not interfere with the synthesis of its own hormone, therefore, after discontinuation of the drug, the hormonal background will not suffer.

Vaginal administration of Utrozhestan is characterized by a lower frequency of side effects, undesirable consequences are only local in nature.

Side effects are usually the result of exceeding the dosage of Utrozhestan. You can eliminate them by reducing the dose of the drug, switching to the vaginal route of administration. With a small daily dose, the medication can be transferred to the evening.

How to cancel the drug

During a normal pregnancy, the level of hormones changes smoothly, without significant bursts. Therefore, the main requirement for how to cancel Utrozhestan during pregnancy is to gradually reduce the dose. Every week we remove 100 mg, starting with the evening intake. At this time, you need to visit a doctor more often and closely monitor your well-being. If your own progesterone is still not enough, the consequences of withdrawal may be blood smearing, a pulling feeling in the lower abdomen. If such symptoms appear, Utrozhestan should be resumed and an urgent visit to the doctor should be made.

Duphaston or Utrozhestan - which is better during pregnancy

Both drugs are progesterone preparations, they can be prescribed for difficulties with carrying a pregnancy. Duphaston is a tablet, they are drunk as usual, vaginal administration is not provided. The active substance of the drug is dydrogesterone, an analogue of progesterone. It is produced synthetically, the action of the hormone is close to natural, but does not completely repeat it. Due to its artificial origin, dydrogesterone has a high bioavailability, it lasts more than 8 hours. Like Utrozhestan, it is prescribed up to 3 times a day.

None of the ongoing studies have proven that any of these drugs is more effective, so the choice of Utrozhestan or Duphaston depends only on the preferences of the attending physician. Dufaston is more often used for IVF, Utrozhestan suppositories are preferred at the beginning of pregnancy in the presence of toxicosis or liver disease.