Instructions for use Utrozhestan capsules 200 mg 14 pcs

Compound

It consists of female sex hormones, and its main active ingredient is progesterone. It also consists of peanut butter, soy lecithin, gelatin, glycerin and titanium dioxide (E171). This is a thyroid hormone that is involved in a woman's ovarian cycle. It also ensures that the uterus is in perfect condition to receive a fertilized egg.

This hormone can also regulate irregular or heavy bleeding cycles.

These drugs come in several forms:

• Pack of 15 capsules of 200 mg active ingredient: Utrozhestan 200 mg
• Pack of 30 capsules progesterone 100 mg: Utrogestan 100 mg

Interactions of the drug Utrozhestan

When treating the threat of premature birth, Utrozhestan is combined with β-adrenergic agonists, the dosage of the latter can be reduced. When used simultaneously with liver enzyme inducers (barbiturates, phenytoin, rifampicin, phenylbutazone, spironolactone, griseofulvin) or antibiotics (ampicillins, tetracyclines), an increase or decrease in the concentration of progesterone in the blood plasma is possible. Progestins reduce glucose tolerance, and it may be necessary to increase the daily dose of insulin and other antidiabetic agents in patients with diabetes.

Instructions for use

Any treatment with Utrozhestan must be monitored very carefully, trying to individualize the dose and duration of treatment for each patient as much as possible. The recommended dose depends on the level of hormones in the blood. Utrozhestan is usually prescribed for a period of 12 to 14 days.

When porgesterone treatment is started, some bleeding may occur. It is important not to confuse this bleeding with bleeding during your period because it is lighter, shorter and less painful. If Utrogestan is administered orally, the average recommended dose is 200 to 300 milligrams (mg) per day, usually 200 mg at bedtime or 100 mg in the morning and 200 mg at bedtime.

It is recommended to take each day at the same time on an empty stomach, since eating increases the absorption of the drug. For vaginal administration, the average recommended dose is 100 to 600 mg per day. The capsules, also called eggs, must be inserted into the vagina and pushed with your fingers.

If you forget to take Utrozhestan once during treatment, it is important not to take a double dose to make up for the missed dose.

O.A. Pustotina Scientific Center for Obstetrics, Gynecology and Perinatology, Russian Academy of Medical Sciences, Moscow

Utrozhestan is a preparation of natural progesterone in micronized form for oral and vaginal use [6, 20]. It has all the properties of natural progesterone and does not have side effects on metabolic processes, blood pressure and the hemostasis system, which are present to varying degrees in synthetic analogues. Utrozhestan is prescribed for the purpose of maintaining pregnancy in case of threat of termination, recurrent miscarriages, and in vitro fertilization programs [4, 6, 8]. Literature data on the use of utrogestan are very contradictory. Some authors consider it advisable to prescribe it in case of threat of miscarriage only in the first trimester of pregnancy [12, 15], others recommend using it at a later date [6-8]. The lack of consensus on this issue was the basis for our study. It is known that progesterone is the main hormone of pregnancy. It is necessary for the transformation of the endometrium into decidual tissue and preparation for embryo implantation [2, 12, 21], promotes the growth and vascularization of the myometrium, reduces its tone and excitability [6, 15, 16]. Progesterone-induced blocking factor ensures immunological tolerance of the mother’s body to the developing embryo and local hemostasis in the endometrium [16, 21]. In addition, progesterone exhibits high antiestrogenic activity, moderate antiandrogenic and quite pronounced antimineralocorticoid effects, and also improves vascular mobility. Until the 12th week of pregnancy, its synthesis occurs in the corpus luteum of the ovaries, later in the placenta and progressively increases in the dynamics of pregnancy [1, 11, 12]. The main part, 90% of the hormone, enters the mother’s bloodstream, the remaining 10% into the fetus’s body, where it is a precursor for the synthesis of fetal steroids. Estrogens are directly involved in the regulation of progesterone biosynthesis [13]. They are also of key importance in the formation and development of pregnancy [11, 18]. The production of estrogen in a pregnant woman is significantly higher than in a non-pregnant woman, with 80-90% occupied by the estriol fraction. The synthesis of estriol begins in the adrenal glands and liver of the fetus, where pregnenolone is formed from cholesterol supplied with the mother’s blood and then 16a-dehydroepiandrosterone sulfate. This compound is delivered to the placenta and, in the presence of placental enzymes, produces estriol, which is secreted into the maternal bloodstream. Estriol secretion gradually increases in accordance with increasing gestational age and fetal growth [1, 11, 17]. Most often, the level of estriol in maternal blood is used as a marker of the intrauterine condition of the fetus and is used in mass screening programs for pregnant women to exclude malformations and chromosomal abnormalities [22]. In addition, disruption of estriol synthesis occurs during intrauterine growth retardation (IUGR) of the fetus and placental insufficiency (PI) [9, 14, 17]. According to Gerhard I. et al. [10], with a significant decrease in estriol levels before birth, children are born with a low Apgar score twice as often as in the general population and their morbidity rate is the same times higher during the first year of life. Estrogens and progesterone are the main regulators of morphological changes in the functional layer of the endometrium during the menstrual cycle and in the peri-implantation period. Violation of the secretory transformation of the endometrium leads to inadequate development of the fertilized egg and termination of pregnancy [2, 4, 13]. Most often, dyschronization of the development of the endometrium and termination of pregnancy are caused by insufficient production of progesterone by the corpus luteum of the ovaries, which occurs in women with diseases such as hyperprolactinemia, hyperandrogenism, hyper- and hypothyroidism, chronic inflammatory diseases of the pelvic organs, endometriosis, etc. [4, 5 ]. At the same time, the mechanism of early pregnancy termination may be due not only to insufficient progesterone production, but also to a decrease in the number and disruption of the synthesis of receptors for steroid hormones in the endometrium [2]. Insufficiency of the receptor apparatus occurs against the background of chronic inflammatory processes, changes in the uterus after intrauterine manipulation, severe somatic diseases, and anatomical changes in the internal genital organs [3, 4, 5]. The development of pregnancy in these patients initially occurs against an unfavorable background and is often accompanied by impaired formation of the placenta and the development of PN. In the absence of timely treatment, the progression of PN leads to a persistent and in some cases irreversible decrease in progesterone concentration, which, according to some researchers, is the main reason for termination of pregnancy in the second half [3, 7, 8]. We conducted 248 studies of the concentration of progesterone and estriol in the blood serum of women with a singleton pregnancy and a burdened somatic and obstetric-gynecological history using the enzyme immunoassay method. Of these, 190 studies were carried out at 38-40 weeks and 58 at 27-33 weeks of pregnancy. All pregnancies ended in the birth of live, full-term children. After delivery, a morphological study of the placenta was carried out. Of the examined women with full-term pregnancies, 125 noted symptoms of threatened miscarriage at various stages, in 138, a morphological examination of the placenta revealed histological signs of PN, in 95 PN was combined with a threatened miscarriage, and in 32 these complications were absent (control group, Table 1). Literature data on the concentration of steroid hormones in maternal serum during full-term pregnancy vary [1, 8]. In our study, the concentration of progesterone was in the range of 458-2232 nmol/l, estriol - 10-110 or more nmol/l. In uncomplicated pregnancy (control group), the average progesterone level was 1246 ± 467 nmol/l, with 72% of values ​​being above 1100 nmol/l. The average estriol concentration was 89 ± 35 nmol/l with the main (78%) number of values ​​above 80 nmol/l. In the presence of morphological signs of PN, the average level of progesterone is significant (p Long-term PN leads to impairment of the condition and IUGR of the fetus [3, 14]. A morphological study of the placenta in 20 children with IUGR revealed signs of sub- and decompensated PN. In this group, we noted the maximum number low concentrations of placental steroids: 90% for progesterone (p In the group of women with the threat of miscarriage at various stages of pregnancy, most concentrations of the studied hormones were also reduced (p Thus, despite significant fluctuations in the concentration of steroid hormones in the maternal blood serum during full-term pregnancy, their significant reduction in PN and the threat of miscarriage, most pronounced when these complications are combined with each other and with IUGR of the fetus. As is known, the foundations for the further course of pregnancy are laid in the first trimester. Impaired development and invasion of the ovum leads to the threat of miscarriage, PN , gestosis [3, 9, 24]. Of the 190 women who underwent hormonal testing during full-term pregnancy, 115 suffered a threatened miscarriage in the first trimester. In 62% of them it persisted in the second half, in 78% PN developed, in 45% these complications were combined with each other, in 46% preeclampsia of varying degrees of severity developed. Sixty-five percent of women threatened with miscarriage in the first trimester of pregnancy had endocrine disorders (hyperandrogenism of adrenal and/or ovarian origin, hyperprolactinemia, thyroid disease), accompanied by insufficient synthesis of progesterone in the ovaries. As is known, progesterone deficiency is one of the main causes of miscarriage and, in some cases, infertility [4, 5]. 55% of women in this group had a history of recurrent miscarriage, primary or secondary infertility. In addition, 64% of pregnant women suffered from chronic inflammatory diseases of the genital organs, 17% had malformations and 11% multiple uterine fibroids, 27% had a uterine scar after cesarean section or conservative myomectomy. More than a third (37%) of pregnancies occurred after stimulation of ovulation, or in vitro fertilization and embryo transfer, or after replacement therapy with gestagens in the second phase of the cycle. Signs of threatened miscarriage (pulling pain in the lower abdomen and lumbar region, blood discharge from the genital tract) were identified at 4-7 weeks of pregnancy, of which 53% were found to have partial chorionic detachment during ultrasound examination. All pregnant women received complex therapy, including antispasmodics (mainly no-spa, Magne B6, suppositories with papaverine, baralgin), metabolic (actovegin, ascorbic acid, folic acid, cocarboxylase), hemostatic (dicinone, vikasol) and other agents. For 60 of them, we included a natural progesterone drug, Utrozhestan, 100-200 mg two to three times a day orally or vaginally in the treatment complex. Forty-five women included in the comparison group stopped taking Utrozhestan at 12-16 weeks of pregnancy, while gradually reducing the dose of the drug over 7-10 days. In the main group, consisting of 15 women, Utrozhestan was prescribed after this period, 200-300 mg (one tablet two or three times) per day until 35-36 weeks of pregnancy (gradually reducing the dosage in the last week). Fifteen pregnant women in the control group received complex maintenance therapy without progesterone medications. In almost all (87%) of them, the threat of interruption persisted at a later date (Table 2). In 80% of patients, infusion therapy with b-mimetics was carried out, followed by long-term oral administration in tablet form. About half (47%) of pregnancies were complicated by gestosis of varying severity. In all afterbirths, histological examination revealed signs of PN, in 27% combined with IUGR of the fetus. The inclusion of progesterone preparations in the complex treatment of threatened miscarriage led to an improvement in these indicators: significantly (p) It is generally accepted that insufficient synthesis of progesterone by the ovaries is a common cause of threatened miscarriage at up to 12 weeks [3, 15]. But not everyone shares the opinion about that the threat of miscarriage at a later date may also be due to insufficient synthesis of progesterone, but only in the placenta. We conducted a comparative analysis of the concentration of progesterone in the blood serum of 40 patients admitted to hospital treatment due to a pronounced threat of miscarriage at 28-33 weeks pregnancy, and 18 pregnant women at the same time with an uncomplicated course of the gestational process (Table 1). The concentration of progesterone in both groups was in the range of 327-1209 nmol/l. Its average level against the background of the threat of miscarriage was significant (p It is known that progesterone has a pronounced tocolytic effect, the mechanism of which is associated with the activation of the b-adrenergic reaction of the myometrium. Insufficient synthesis of it in the placenta leads to incomplete blocking of a-adrenergic receptors and the oxytocin effect of prostaglandin F2a, as a result of which the contractile activity of the uterus increases [6, 8, 19]. A double-blind, placebo-controlled experiment conducted by R. Erny et al. [8], showed that oral administration of 400 mg of Utrozhestan in all cases of threatened miscarriage at 30-36 weeks initiated an increase in the concentration of progesterone in the myometrium by 50% within an hour. This increase in 80% of pregnant women led to a decrease in uterine contractions, although not as strong and rapid as with intravenous administration of b-mimetics. Noblot et al. [19] showed that 100% results can be achieved by the combined use of utrozhestan and b-mimetics, since their actions complement each other. This combination makes it possible to reduce the dose and duration of administration of b-mimetics, reducing the risk of cardiovascular complications and shortening the length of hospitalization [7]. We conducted a comparative assessment of the effectiveness of treatment of threatened miscarriage at 27-33 weeks of pregnancy with intravenous infusions of b-mimetics and in combination with progesterone preparations. In one group, consisting of 25 pregnant women, to relieve uterine contractions, intravenous drip administration of 5 mg of ginipral in 400 ml of 6% sodium chloride solution was carried out for 6-8 hours, followed by a transition to tablet administration of the drug. Five (20%) pregnant women required repeated infusion of the solution in the next 1-2 days due to incomplete relaxation of the uterus. Subsequently, ginipral was taken one tablet (0.5 mg) six times a day, with a gradual reduction in the dose to 0.5-1 tablet four times a day. The drug was prescribed for a long time - up to 36-37 weeks of pregnancy. In 12% of women, two to three weeks after hospital treatment, the threat of termination resumed. They again underwent infusion therapy with b-mimetics with a positive effect. Fifteen pregnant women of the second group were prescribed 400 mg of Utrozhestan orally or vaginally once along with the infusion of b-mimetics. From the next day, the dose was reduced to 300 mg (one tablet three times a day) and combined with antispasmodics (no-spa - orally or intramuscularly, Magne B6). After 5-10 days, taking Utrozhestan continued at 100 mg twice a day until 35-36 weeks of pregnancy (with a gradual decrease in the last week), antispasmodics were prescribed as needed. A positive effect from the therapy on the first day was achieved in 93% of cases, and only in one case a repeated infusion of b-mimetics was required. Subsequently, there were no signs of a pronounced threat of termination of pregnancy. In both groups, live, full-term children were born; morphological examination of the placenta revealed signs of PN. Thus, the results obtained showed that the use of Utrozhestan was justified for the treatment of threatened miscarriage in the second half of pregnancy. Its combination with intravenous administration of b-mimetics led to a more rapid achievement of the antispasmodic effect and reduced the need for their repeated infusions by 5.7 times. In addition, the administration of a maintenance dose of Utrozhestan at 200-300 mg/day in combination with antispasmodics (no-spa, Magne B6) contributed to a further favorable course of pregnancy without b-mimetics therapy.

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Contraindications

Utrozhestan should not be taken in any of the following cases:

• Allergy to progesterone.
• Suffering from thromboembolism.
• Prolonged vaginal bleeding.
• Suffering from liver problems.

Because this drug may cause drowsiness, special attention should be taken when driving or using heavy machinery. For this reason, it is recommended to take the dose at night, that is, before going to bed.

Progesterone passes through breast milk. For this reason, it is not recommended to take during breastfeeding. Regarding pregnancy, since progesterone is a hormone that increases during pregnancy, taking it during pregnancy may not have side effects.

Side effects of the drug Utrozhestan

When administered orally, the following side effects are observed:

Drowsiness and/or dizziness are observed in case of concomitant hypoestrogenism. Reducing the dose of the drug or increasing the dose of estrogen eliminates these phenomena without reducing the therapeutic effect. If the course of treatment begins at the beginning of the monthly cycle, before the 15th day, a shortening of the cycle or occasional bleeding occurs. In general, changes in menstruation, amenorrhea, or mid-cycle bleeding occur when taking progestins. For intravaginal use: no side effects.

Overdose of the drug Utrozhestan, symptoms and treatment

The side effects symptoms described above usually appear as a result of an overdose. They disappear spontaneously when the dose is reduced. In some individuals, the usual dose may be too high due to the existing or secondary appearance of unstable endogenous secretion of progesterone, increased sensitivity to the drug, or a very low concomitant level of estradiol in the blood; in such cases, it is enough to: reduce the dose of progesterone or prescribe progesterone in the evening before bed for 10 days of the cycle in case of drowsiness or dizziness; postpone the start of treatment to a later period of the cycle (for example, the 19th day instead of the 17th) in case of its contraction or bleeding; It is necessary to check whether the level of estradiol is sufficient in a patient who is receiving premenopausal hormone replacement therapy.