Пурегон®

General characteristics. Structure:

Active ingredient: 100 ME, 150 ME, 200 ME, 300 ME, 600 ME or 900 ME follitropins a beta recombinant * in 1 cartridge.

Excipients: sucrose, citrate sodium a dihydrate, polysorbate 20, benzyl alcohol, methionine, Acidum hydrochloricum of 0.1 N or sodium hydroxide of 0.1 N - to pH 7, water for injections.

* - specific biological activity of in vivo is equal to about 10 000 ME FSG/ml of a protein.

Pharmacological properties:

Pharmacodynamics. Recombinant follicle-stimulating hormone (FSG) which is received by means of technology of recombinant DNA, using culture of cells of ovaries of the Chinese hamster in which genes of subunits of human FSG are implemented. Primary amino-acid sequence of recombinant DNA is identical that of natural human FSG. At the same time there are small distinctions in structure of a hydrocarbon chain.

FSG provides the normal growth and maturing of follicles and synthesis of sex steroid hormones. The FSG level at women is the factor defining the beginning and duration of development of follicles, and also time of their maturing. Thus, the drug Puregon® can be used for stimulation of development of follicles and synthesis of estrogen at some disturbances of functions of ovaries. Besides, the drug Puregon® is used for induction of multiple development of follicles when carrying out artificial fertilization (for example, in techniques of extracorporal fertilization / change of an embryo (EKO/PE), at intrauterine insemination (VMI) and an intracytoplasmic injection of spermatozoa (IKSI). After treatment by the drug Puregon® usually enter the chorionic gonadotrophin (CG) for induction of a final stage of maturing of a follicle, resuming of meiosis and an ovulation.

Pharmacokinetics. After in oil or п / to administration of the drug Puregon® Cmax FSG in a blood plasma it is reached during 12 h. Thanks to gradual release of drug from area of an injection and to long T1/2 (from 12 to 70 h, on average 40 h) the maintenance of FSG remains raised during 24-48 h in this connection repeated introduction of the same dose of FSG leads to further increase in concentration of FSG by 1.5-2 times in comparison with single introduction. It allows to reach therapeutic concentration of FSG in blood.

Pharmacokinetic indicators after in oil and п / to administration of the drug Puregon® significantly do not differ. At both ways of introduction bioavailability of drug makes about 77%. Recombinant FSG is biochemical similar to FSG allocated from urine of the person and is similar to it is distributed, metabolized and brought out of an organism.

Indications to use:

Treatment of female infertility in the following cases:

— anovulation (including a polycystosis syndrome of ovaries/SPKYa/) at women, insensitive to treatment by clomifene);

— induction of a superovulation, for induction of multiple development of follicles when carrying out artificial fertilization (for example, in techniques of EKO/PE, VMI and IKSI).

Route of administration and doses:

It is necessary to begin treatment with the drug Puregon® under observation of the doctor having experience in treatment of infertility. The dose has to be selected individually depending on the answer of ovaries, under control of ultrasonography and concentration of oestradiol.

The drug Puregon® is effective at the smaller total dose and smaller time of treatment necessary for maturing, in comparison with FSG received from urine that minimizes risk of development of hyper stimulation of ovaries.

Total experience in treatment of infertility by extracorporal fertilization demonstrates that success is most probable during the first 4 courses of therapy and further gradually decreases.

At anovulation the consecutive scheme of treatment beginning with daily introduction 50 ME drugs Puregon® during, at least, 7 days is recommended. In the absence of the answer of ovaries the daily dose is gradually increased before achievement of growth of follicles and/or increase in concentration of oestradiol in plasma, testimonial of achievement of the optimum pharmakodinamichesky answer. Daily increase in concentration of oestradiol in plasma for 40-100% is considered optimum.

The daily dose received thus then is supported before achievement of a condition of a preovulyation. The condition of a preovulyation is determined by existence of a dominant follicle by diameter, at least, of 18 mm (according to ultrasonography) and/or concentration of an ekstradiol in a blood plasma 300-900 »¿¬«úÓá¼¼/ml (1000-3000 pmol/L).

As a rule, achievement of this state requires 7-14 days of treatment.

After that administration of drug is stopped and induce an ovulation introduction of HG. If the quantity of follicles is too high or concentration of oestradiol increases too quickly, i.e. more than twice per day within 2-3 consecutive days, then the daily dose should be reduced. As each follicle with a diameter more than 14 mm is preovulyatorny, existence of several follicles with a diameter more than 14 mm bears risk of polycarpous pregnancy. In this case HG do not enter and take measures to protection from possible pregnancy for prevention of polycarpous pregnancy.

When carrying out artificial fertilization apply various schemes of stimulation to induction of a superovulation. During, at least, 4 first days it is recommended to enter 150-225 ME drugs. After that the dose can be selected individually, proceeding from reaction of ovaries. In clinical trials it was shown that usually there is enough use of a maintenance dose in 75-375 ME within 6-12 days, however also more prolonged treatment in certain cases can be required.

The drug Puregon® can be used or separately, or in a combination with an agonist or the antagonist of GNRG for prevention of premature peak of an ovulation. When using analogs of GNRG higher total doses of the drug Puregon® can be required.

Reaction of ovaries is controlled by ultrasonography and definition of concentration of oestradiol in plasma. In the presence of, at least, 3 follicles with a diameter of 16-20 mm (according to ultrasonography) and existence of good reaction of ovaries (concentration of oestradiol in a blood plasma 300-400 »¿¬«úÓá¼¼/ml (1000-1300 pmol/L) on each follicle with a diameter more than 18 mm), induce a final phase of maturing of a follicle by introduction of HG. In 34-35 h carry out aspiration of ova.

Rules of use of drug. For prevention of painful feelings at an injection and for minimizing of leak of drug from the place of an injection, solution should be entered slowly in oil and п / to. It is necessary to alternate sites п / to introduction to avoid development of a fatty atrophy. Unused solution should be destroyed.

П / to an injection of the drug Puregon® the woman or her partner who received detailed instructions from the doctor can see off. Independent administration of drug is admissible only for the patients having good skills and a constant possibility of consultation with the specialist.

The drug produced in cartridges is intended for introduction by means of the Puregong Pan handle injector. In this case the drug is administered п / to.

When using the Puregong Pan handle injector it is necessary to consider that the handle is the exact device releasing the dose established on it. It is shown that when using the handle injector 18% more FSG is entered, than when using the syringe. It can be essential, in particular, when changing the handle injector with the ordinary syringe and vice versa, in one cycle of treatment. Some dose adjustment is especially necessary upon transition from the syringe to the handle to avoid inadmissible increase in the entered dose.

The drug produced in bottles is intended for introduction by means of the syringe.

Stage 1 - Preparation of the syringe. It is necessary to use one-time sterile syringes and needles to administration of drug. The volume of the syringe has to be rather small to enter the appointed dose rather precisely. If solution is opaque or contains mechanical inclusions, it cannot be used. Contents of a bottle have to be used right after piercing of a rubber bung. The solution which remained after single use is thrown out. At first delete the bottle cover valve. Put on a needle the syringe and puncture with a needle a rubber bung of a bottle. Gather solution in the syringe and replace a needle with an injection cannula. Holding the syringe a needle up, carefully tap it sideways for replacement of vials of air in an upper part of the syringe, then press on the piston before full removal of air while in the syringe there is no drug Puregon® solution. If necessary install by additional pressing the volume of the solution intended for introduction on the piston.

Stage 2 - Injection site. The most suitable place for п / to introduction - area of a stomach around a navel with mobile skin and a layer of a fatty tissue. At each injection it is necessary to change an injection site a little. It is possible to administer the drug in other body parts.

Stage 3 — Preparation of the site of introduction. For reduction of unpleasant feelings at introduction of a needle it is possible to make several cottons in the place of an estimated injection. Hands should be washed up, and to wipe an injection site of an injection with disinfecting solution (for example, a 0.5% hlorgeksidin) for removal of superficial bacteria. Process about 6 cm around a point where the needle will enter, and wait about a minute that disinfecting solution dried.

Stage 4 - Introduction of a needle. Delay skin a little. Other hand enter a needle at an angle 90 ° under the surface of skin.

Stage 5 — Check of correctness of provision of a needle. At the correct provision of a needle it is quite difficult to return back the piston.

The blood getting into the syringe demonstrates that the needle pierced a vein or an artery. In this case take out the syringe, cover the place of an injection with a tampon with disinfecting liquid and press, at the same time bleeding will stop in 1-2 minutes. Do not use solution and remove it from the syringe. Begin with the 1st stage again, using a new needle and the syringe, and a new bottle of drug.

Stage 6 - Administration of solution. Lower the piston slowly and gradually correctly to enter solution and not to damage skin tissue.

Stage 7 - Removal of the syringe. Quickly remove the syringe, cover an injection site with a tampon with disinfecting liquid and press. Careful massage of this place (at invariable pressing) promotes distribution of solution of the drug Puregon® and will help to avoid unpleasant feelings.

Features of use:

Use at pregnancy and feeding by a breast. Use of the drug Puregon® at pregnancy and during feeding by a breast contraindicated. Because clinical data on use of drug at pregnancy are not enough, in case of inadvertent reception at pregnancy it is impossible to exclude teratogenic effect of recombinant FSG.

Use at abnormal liver functions. Contraindication: the expressed abnormal liver function.

Use at renal failures. Contraindication: the expressed renal failure.

Special instructions. Before an initiation of treatment it is necessary to exclude existence of endocrine diseases (for example, diseases of a thyroid gland, adrenal glands or a hypophysis).

Induction of an ovulation by means of gonadotropic drugs increases risk of development of polycarpous pregnancy. The corresponding dose adjustment of FSG prevents development of multiple follicles. At polycarpous pregnancy higher risk of development of complications is noted during pregnancy and in the perinatal period. Before an initiation of treatment patients have to be warned about a possibility of development of polycarpous pregnancy.

The first administration of the drug Puregon® has to be carried out under direct observation of the doctor.

Women to whom carry out artificial fertilization (especially EKO) often have anomalies of uterine tubes, in this regard the risk of development of an extrauterine pregnancy increases. Therefore it is important to receive early ultrasonic confirmation of an intrauterine attitude of fetus.

At women to whom carry out artificial fertilization the risk of early abortion is higher, than at natural conception.

Frequency of inborn malformations at use of the auxiliary reproductive technologies (ART) can be a little higher, than at natural fertilization. Perhaps, it is connected with features of parents (for example, their age or characteristics of sperm), and also with higher frequency of development of polycarpous pregnancy when using VRT. Instructions on the fact that increase in risk of development of inborn defects is connected using gonadotrophins is not revealed.

Prior to treatment and regularly in the course of treatment it is necessary to carry out ultrasonography for control of development of follicles and to define concentration of oestradiol in plasma. In addition to development of too large number of follicles, concentration of oestradiol can grow in plasma very quickly (i.e. more than twice per day within 2-3 consecutive days), reaching excessively high values. The diagnosis of hyper stimulation of ovaries can be confirmed to ultrasonography. Tranzitorny deviations of results of hepatic functional trials can indicate an abnormal liver function which can be followed by morphological changes on a liver biopsy, about what there are messages in connection with a syndrome of hyper stimulation of ovaries.

Women from the conventional risk groups concerning thromboses, for example, with the corresponding personal or family anamnesis, a gross obesity (a body weight index> of 30 kg/sq.m) or the diagnosed thrombophilia, can be exposed to the increased risk of venous or arterial thromboembolisms at treatment by gonadotrophins even without the accompanying syndrome of hyper stimulation of ovaries. At treatment of such women it is necessary to compare probability of successful carrying out induction of an ovulation and possible risk of development of complications. However it should be noted that pregnancy in itself is followed by increase in risk of development of thrombosis.

Пурегон® may contain traces of streptomycin and/or Neomycinum. These antibiotics can become the hypersensitivity reaction development reason.

Influence on ability to driving of motor transport and to control of mechanisms. It is not revealed.

Side effects:

Local reactions: a hematoma, pain, a hyperemia, hypostasis, an itch (were observed at 3 of 100 patients receiving treatment by the drug Puregon®). The majority of these reactions are moderate and fast-passing.

System allergic reactions: an erythema, urticaria, rash and an itch (were observed at 1 of 1000 patients receiving treatment by the drug Puregon®).

Also can be noted:

— a syndrome of hyper stimulation of ovaries (approximately at 4 of 100 women receiving treatment by drug).

Clinical symptoms of moderate hyper stimulation of ovaries are nausea, diarrhea, swelling and an abdominal pain owing to disturbance of venous blood circulation and irritation of a peritoneum, and also increase in ovaries at the expense of cysts. The expressed syndrome of hyper stimulation of ovaries threatening life of the patient and characterized by existence of cysts of ovaries, big, inclined to a gap, ascites, a hydrothorax and increase in body weight at the expense of a liquid delay in an organism was in rare instances observed. In rare instances the syndrome of hyper stimulation of ovaries can be followed by development of a venous or arterial thromboembolism.

— morbidity, pain and/or nagrubaniye of mammary glands;

— misbirth;

— increase in probability of development of polycarpous pregnancy;

— increase in probability of an extrauterine pregnancy.

At treatment by the drug Puregon® in a combination with HG, also as well as at use with other gonadotropic hormones, development of a thromboembolism is in rare instances possible.

Interaction with other medicines:

Simultaneous use of the drug Puregon® and clomifene can strengthen reaction of ovaries.

After carrying out a desensitization of a hypophysis by means of GNRG agonists for achievement of sufficient reaction of ovaries higher dose of the drug Puregon® can be required.

Pharmaceutical it is incompatible with other medicines.

Contraindications:

— tumors of ovaries, mammary gland, uterus, hypophysis and hypothalamus;

— vaginal and uterine bleedings of an unspecified etiology;

— primary insufficiency of ovaries;

— cysts of ovaries or the increase in ovaries which is not connected with SPKYa;

— disturbance of anatomy of generative organs incompatible with pregnancy;

— hysteromyoma incompatible with pregnancy;

— dekompensirovanny diseases of endocrine system (for example, diseases of a thyroid gland, adrenal glands or hypophysis);

— the expressed abnormal liver function and kidneys;

— pregnancy;

— lactation period;

— hypersensitivity to any of drug components.

Overdose:

Data on acute overdose of the drug Puregon® are absent. Use of FSG in high doses can lead to development of a syndrome of hyper stimulation of ovaries which symptoms are described above.

Treatment: at emergence of symptoms of the undesirable hyper stimulation (which is not connected with induction of a superovulation when carrying out extracorporal fertilization) administration of the drug Puregon® should be stopped. In this case it is necessary to take measures to protection from development of pregnancy and to refuse introduction of HG that can aggravate the undesirable phenomena. It is necessary to carry out the treatment directed to elimination of symptoms of a syndrome of hyper stimulation of ovaries.

Storage conditions:

List B. Drug should be stored in protected from light, the place, unavailable to children, at a temperature from 2 °C to 8 °C; not to freeze. A period of validity - 3 years. After introduction of a needle to a cartridge, solution it can be stored within 28 days as much as possible.

Issue conditions:

According to the recipe

Packaging:

On 0:36 ml - cartridges of colourless glass of 1.5 ml (1) complete with needles (6 pieces) - packagings plastic (1) - packs cardboard.