Merional

General characteristics. Structure:

Deystvuyushche substance: 75 ME or 150 ME follicle-stimulating hormones, 75 ME or 150 ME luteinizing hormones.

Excipients: lactoses monohydrate of 10 mg.

Solvent: sodium chloride (depyrogenized for and) 9 mg, water for and (to 1 ml).

Pharmacological properties:

Pharmacodynamics. Drug of a human menopauzny gonadotrophin (chMG) of high extent of cleaning. Treats group of menotropin. The ratio of biological activity of follicle-stimulating hormone (FSG) and luteinizing hormone (LH) makes 1:1. Drug is received from urine of women in a postmenopause.

Specific receptors to gonadotrophins are present only at fabrics of generative organs. In ovaries of LG contacts receptors on a surface of teka-cells and a yellow body, and also granulosa cells of big follicles. FSG contacts receptors on a surface of granulosa cells of small follicles in ovaries and Sertoli's cells in testicles.

Receptors to LG and FSG are tied with adenylatecyclase by means of guanine - a nucleotide - the connecting regulatory protein (Gs-protein). Increase in intracellular tsAMF causes increase in quantity of a mitochondrial euzymatic complex which by oxidation splits side chains of cholesterol; this reaction is the limiting stage in the course of transformation of cholesterol in прегненалон. Though the mechanism of stimulation of a gametogenesis gonadotrophins is unknown, it is also carried out with participation of cyclic AMF.

Pharmacokinetics. Absorption. After a single p / to and introductions in oil in a dose 225 ME time of achievement of Cmax of drug in plasma makes 17.9 and 27.5 h, respectively. After repeated use (150 ME daily within 7 days) time of achievement of Cmax of drug in plasma makes 8.0 h for п / to and 9.0 h for introduction in oil.

At a single p / to and introduction in oil Cmax averages 8.5 and 7.8 MME/ml, respectively. At a repeated p / to and introduction in oil Cmax averages 15.0 MME/ml and 12.5 MME/ml, respectively.

AUC at a single p / to and introduction in oil averages 726.2 мМЕ×ч/мл and 656.1 мМЕ×ч/мл, respectively. At a repeated p / to and introduction in oil AUC averages 622.7 мМЕ×ч/мл and 546.2 мМЕ×ч/мл, respectively.

Bioavailability of drug at п / to introduction above, than at introduction in oil.

Removal. T1/2 FSG at repeated introduction makes about 11-13 h.

Indications to use:

At women:

— anovulation at inefficiency of therapy by clomifene;

— controlled hyper stimulation of ovaries for the purpose of induction of growth of multiple follicles when carrying out auxiliary reproductive technologies, such as fertilization of in vitro, intra fallopian transfer of a gamete, intra fallopian transfer of zygotes.

At men:

— stimulation of a spermatogenesis at the inborn or acquired hypogonadotropic hypogonadism in a combination with drug of a human chorionic gonadotrophin (chHG).

Route of administration and doses:

Treatment by drug Merional should be carried out only under control of the doctor having the corresponding specialization and experience of treatment of infertility.

It is applied in oil or п / to. Solution prepares just before an injection with use of the enclosed solvent. In 1 ml of solvent it is possible to dissolve contents of 5 bottles.

Doses are given on FSG. To women at anovulation the drug is administered daily in a dose of 75-150 ME/days during the first 7 days of a cycle at the menstruating women. Injections proceed before achievement of the adequate answer who can be judged approach according to daily analyses of concentration of estrogen and size discriminations of follicles by means of ultrasonography.

Maturing of follicles occurs usually during a medical cycle lasting 7-12 days. In the absence of reaction of ovaries to introduction the daily dose of drug can be gradually increased. The maximum daily dose usually does not exceed 225 ME.

After performing treatment and in the presence of adequate, but not the overreaction of ovaries determined by data of clinical and biochemical trials in 24-48 h after the last administration of drug, for the purpose of induction of an ovulation once enter 5000-10 000 ME chHG, the LG increasing contents and stimulating emission of a mature ovum. Day of an injection of chHG and the next day are optimum for conception.

In the presence of an ovulation and lack of approach of pregnancy treatment can be repeated during 2 cycles. In the absence of the adequate response to therapy within 4 weeks from its beginning drug it is necessary to cancel and begin a new course with higher initial dose.

At stimulation of "superovulation" (when carrying out auxiliary reproductive technologies) drug is used daily in a dose of 150-225 ME/days, since 2 or 3 days of a cycle. Injections proceed before achievement of the adequate answer who can be judged approach according to daily analyses of concentration of estrogen and size discriminations of follicles by means of ultrasonography. The dose is selected according to reaction of the patient. The maximum daily dose usually does not exceed 450 ME. Adequate maturing of follicles usually occurs for the 10th day of treatment (in the range from 5 up to 25 days).

Later 24-48 h after the last injection of Merional it is necessary to make an injection of 5000-10 000 ME chHG for stimulation of maturing of follicles. At the patients applying GNRG agonist to suppression of gonadotropic activity of a hypophysis, Merional's use is begun approximately in two weeks after an initiation of treatment with an agonist of GNRG and continue use of both drugs before achievement of adequate development of follicles. For example, after two weeks of use of an agonist of GNRG enter Merional in a dose 150-225 ME within 7 days. Then the dose is adjusted according to reaction of ovaries of the patient. Correction of a dose has to be carried out not more often than 1 time in 2 days and no more than on 150 ME.

Experience of use of auxiliary reproductive technologies shows that degree of success of treatment remains stable during the first four attempts and then gradually decreases.

At the anovulation caused by heavy insufficiency of LG and FSG, treatment can be begun at any time as at such patients the amenorrhea and very low endogenous concentration of estrogen is observed.

The drug is administered daily in a dose of 75-150 ME/days before achievement of the adequate answer who can be judged approach according to daily analyses of concentration of estrogen and size discriminations of follicles by means of ultrasonography.

If the dose is necessary to be increased, selection of a dose should be carried out preferably in 7-14 days and it is desirable about increase on 150 ME. Stimulation duration in one cycle can reach 5 weeks.

After performing treatment and in the presence of adequate, but not the overreaction of ovaries determined by data of clinical and biochemical trials in 24-48 h after the last administration of drug, for the purpose of induction of an ovulation 5000-10 000 ME chHG are once entered. Day of an injection of chHG and the next day are optimum for conception.

In this case lyuteinovy support as the lack of substances with luteotropic activity (LG/chHG) after an ovulation can lead to premature degradation of a yellow body can be necessary.

To men for the purpose of stimulation of a spermatogenesis enter 1-2 thousand ME chHG 2-3 times a week before normalization of concentration of testosterone into blood. Then enter Merional 75-150 ME 2-3 times a week, at least, within 3 months before emergence of any improvements of a spermatogenesis. The available clinical experience shows that for achievement of a spermatogenesis treatment can continue within 18 months.

Features of use:

Use at pregnancy and feeding by a breast. Drug is contraindicated at pregnancy and during feeding by a breast.

Use for children. It is contraindicated at children's age.

Special instructions. Before an initiation of treatment carrying out careful gynecologic and endocrinological inspection, including basin anatomy is necessary. At patients with obstruction of uterine tubes Merional can be applied only in case of carrying out auxiliary reproductive technologies. It is necessary to exclude primary ovarian insufficiency. It is necessary to conduct careful examination for an exception of early pregnancy. Patients at late reproductive age have the increased predisposition to an endometrial carcinoma, and also big frequency of anovulatory disturbances.

At patients with pathological uterine bleedings or other symptoms of endometrial pathologies carrying out careful diagnostic inspection is necessary. It is also necessary to carry out assessment of fertility of the partner.

Before purpose of drug it is necessary to carry out the corresponding treatment at dysfunctions of a thyroid gland or bark of adrenal glands, giperprolaktinemiya of various etiology, a tumor of gipotalamo-pituitary area.

Approach of polycarpous pregnancy can be result of treatment. In case of signs of hyper stimulation of ovaries (an abdominal pain and the educations palpated by the doctor or determined by ultrasonography, increased in a stomach bottom) treatment is stopped (develops at women with a syndrome of polycystic ovaries more often).

During therapy daily hormonal control and ultrasonography of the developing follicles is obligatory (reaction of ovaries can be estimated on a cervical index).

If concentration of estrogen in urine reaches the 540th nmol (150 mkg) of/24 h or concentration 17β-эстрадиола in plasma reaches 3000 pmol/L (800 pg/ml) or excessive increase in these values is observed, then there is an increased risk of hyper stimulation of ovaries, and treatment by Merional needs to be stopped immediately, and to cancel use of chHG.

In case of a syndrome of hyper stimulation of ovaries it is contraindicated to enter an ovulatory dose of HGCh!

In case of pregnancy approach symptoms of excessive hyper stimulation can amplify and be observed for a long time, being threat for the patient's life.

Development of tromboembolic episodes is probable. The intravascular fibrinferments and embolisms developing in arteries and veins can lead to reduction of inflow of blood to vitals and extremities.

Venous thrombophlebitis, pulmonary embolism, lung heart attack, stroke, and the thrombosis of arteries leading to loss of an extremity can be a complication of it.

During treatment at men with high concentration in FSG blood of a menotropina are inefficient.

Side effects:

Adverse side reactions classified as follows: very frequent (> 1/10); frequent (from ≥ 1/100 to ≤ 1/10); infrequent (from ≥1/1000 to ≤1/100); rare (from ≥1/10 000 to ≤ 1/1000); very rare (<1/10 000).

From the alimentary system: often - an abdominal pain, a gastrointestinal syndrome, including nausea, vomiting, diarrhea, abdominal spasms and swelling.

From a nervous system: very often — a headache.

From a reproductive system: very often - cysts of ovaries; often - an easy and moderate syndrome of hyper stimulation of ovaries; infrequently - a heavy syndrome of hyper stimulation of ovaries; seldom - torsion of ovaries, a complication of a syndrome of hyper stimulation of ovaries.

Allergic reactions: very seldom - an easy erythema, rash or puffiness of the person.

From an organism in general: very seldom - the clotting disease which is usually associated with a heavy syndrome of hyper stimulation of ovaries.

Local reactions: very often - heavy and easy reactions in the place of an injection (pain, reddening, bruises, a swelling and/or irritation).

Besides, there can be following side reactions: a mastalgiya, significant increase in removal of estrogen with urine, pains in a stomach bottom, increase in ovaries in a size, a hypovolemia, a pachemia, water and electrolytic disturbances, ascites, a hydrothorax, fever, an arthralgia, an oliguria, decrease in the ABP, increase in body weight, a hemoperitoneum, polycarpous pregnancy.

At the men using Merional's combination with drug chHG it is reported about such side effects as swelling of chest glands, an acne and increase in body weight. These effects mostly are caused by chHG.

Occasionally at reception of similar drugs an abdominal blood coagulation (blood is turned in vessels) was observed that can also arise at Merional's reception.

Interaction with other medicines:

Pharmakodinamicheskoye. Combined use of Merional with other drugs used for stimulation of an ovulation (for example, chHG, clomifene) can strengthen reaction of follicles.

At combined use with agonists of GNRG increase in a dose of a menotropin can be required.

Pharmaceutical. Merional it is not necessary to mix with other medicines in one syringe.

Contraindications:

— tumors of gipotalamo-pituitary area;

— giperprolaktinemiya;

— diseases of adrenal glands and thyroid gland;

— organic lesions of TsNS, for example, hypophysis tumors;

— children's age;

— hypersensitivity to drug.

For women:

— primary yaichnikoy insufficiency;

— the persistent increase in ovaries, a cyst of ovaries (which are not caused by existence of a syndrome of polycystic ovaries);

— syndrome of polycystic ovaries;

— anomalies of development of generative organs (pregnancy, incompatible with normal course);

— hysteromyoma;

— metrorrhagia (obscure etiology);

— estrogenzavisimy tumors (ovarian cancer, uterus cancer, breast cancer);

— primary insufficiency of ovaries;

— pregnancy;

— lactation period.

For men:

— prostate cancer;

— tumor of testicles;

— androgenzavisimy tumors.

With care it is necessary to appoint drug with risk factors of a thromboembolism, such as individual or family predisposition, heavy degree of obesity (body weight index> of 30 kg/sq.m) or at a thrombophilia as in this case there is an increased risk of a venous or arterial thromboembolism in process or after treatment by gonadotrophins. In this case the advantage of treatment has to surpass by gonadotrophins risk from their use.

Overdose:

Symptoms: a syndrome of hyper stimulation of ovaries (increase in ovaries, pains in a stomach bottom, nausea, vomiting, diarrhea, increase in body weight, an oliguria, ascites, a hydrothorax, a hemoperitoneum, haemo concentration, an asthma), polycarpous pregnancy, tromboembolic episodes.

Treatment consists of 3 stages: the first stage is directed to decrease in concentration of hormones in blood and preventions of development of tromboembolic episodes (pneumonia, an acute renal failure), it consists in in introduction of small amounts of albumine (with constant control of concentration of electrolytes in blood and a hematocrit). The second stage begins after stabilization of a condition of the patient and has to lead to decrease in content of liquid in organism cavities for what in/in enter small amounts of hypertonic salt solution of sodium of chloride and albumine. The third stage aims to warn edematization of lungs, the organism connected with massive intake of liquid from cavities in a vascular bed, and includes use of diuretics (at constant control of a hematocrit and concentration of electrolytes in plasma).

Storage conditions:

Drug should be stored in protected from light, the place, unavailable to children, at a temperature not above 25 °C. A lyophilisate period of validity - 2 years, solvent - 5 years. The period of validity of a set is established on a component with the smallest period of validity.

Issue conditions:

According to the recipe

Packaging:

Bottles glass (1) complete with solvent (amp. 1 pieces) - packs cardboard. Bottles glass (1) complete with solvent (amp. 1 pieces) - packs cardboard (10) - packs the cardboard general.