Puregon

Puregon – drug with follicle-stimulating action.

Form of release and structure

Dosage forms of release of Puregon:

• Solution for intramuscular and hypodermic introduction: colourless, transparent (in colourless glass bottles on 0,5 ml, on 1, 5 or 10 bottles in a cardboard pack);
• Solution for hypodermic introduction: colourless, transparent (in colourless glass cartridges on 0,36, 0,72 or 1,08 ml (300/600/900 ME), on 1 cartridge in a cardboard pack complete with needles – 6 pieces (300/600 ME) or 9 pieces (900 ME)).

Is a part of 1 bottle (0,5 ml):

• Active agent: recombinant follitropin a beta – 100, 150 or 200 IU (international units);
• Auxiliary components: polysorbate of 20 - 0,1 mg, sucrose – 25 mg, a sodium citrate dihydrate – 7,35 mg, methionine – 0,25 mg, sodium hydroxide of 0,1 N or Acidum hydrochloricum of 0,1 N – to pH 7, water for injections – to 0,5 ml.

Is a part of 1 cartridge:

• Active agent (0,36/0,72/1,08 ml): recombinant follitropin a beta – 300, 600 or 900 ME;
• Auxiliary components (0,36/0,72/1,08 ml): polysorbate 20 – 0,105/0,177/0,234 mg, sucrose – 21/39/58,5 mg, a sodium citrate dihydrate – 6,17/11,5/17,2 mg, methionine – 0,21/0,39/0,59 mg, sodium hydroxide of 0,1 N or Acidum hydrochloricum of 0,1 N – to pH 7, benzyl alcohol – 4,2/7,8/11,7 mg, water for injections – to 0,42/0,78/1,17 ml.

Indications to use

Puregon appoint at treatment of female infertility in the presence of the following indications:

• Induction of a superovulation – for induction of multiple development of follicles when carrying out artificial fertilization (for example, in techniques of extracorporal fertilization / transfer of an embryo (EKO/PE), intrauterine insemination (VMI) and introduction of a spermatozoon to cytoplasm (IKSI));
• Anovulation, including a syndrome of a polycystosis of ovaries (SPKYa) at nonsensitivity to clomifene.

Contraindications

• Anatomic disturbances of generative organs which are incompatible with pregnancy;
• The expressed functional disturbances of livers/kidneys;
• Bleedings (vaginal/uterine) unspecified genesis;
• Tumors of a uterus, mammary gland, ovaries, hypothalamus, hypophysis;
• Cyst/increase in ovaries, not connected with a syndrome of a polycystosis of ovaries;
• Hysteromyoma, incompatible with pregnancy;
• Primary insufficiency of ovaries;
• Dekompensirovanny diseases of endocrine system (for example, disturbances of a thyroid gland, hypophysis or adrenal glands);
• Pregnancy and period of chest feeding;
• Hypersensitivity to the components which are a part of drug.

Route of administration and dosage

The doctor having experience of treatment of infertility has to appoint therapy by Puregon.

The dose needs to be selected individually, based on the answer of ovaries, under control of concentration of oestradiol and ultrasonography.

Puregon has effect at the smaller total dose and a course of therapy, smaller on duration, necessary for maturing, in comparison with the follicle-stimulating hormone (FSG) received from urine that minimizes probability of emergence of hyper stimulation of ovaries.

Success of treatment is most probable during the first 4 courses, further it gradually decreases.

At anovulation use of the consecutive scheme of the therapy beginning with daily introduction of Puregon in a dose 50 ME for, at least, 7 days is recommended. In case of lack of the answer of ovaries gradual increase in a daily dose up to achievement of growth of follicles and/or increases in concentration of oestradiol in plasma which demonstrate achievement of the optimum pharmakodinamichesky answer – daily significant (for 40-100%) of increase in concentration of oestradiol in plasma is shown.

Then the daily dose is supported before achievement of a condition of a preovulyation which is determined by existence of a dominant follicle with a diameter, at least, 0,18 cm (according to ultrasonography) and/or concentration of oestradiol in a blood plasma of 1000-3000 pmol/L (300-900 pg/ml).

In most cases achievement of this state requires carrying out a medical course lasting 1-2 weeks.

After achievement of the necessary state Puregon's introduction is stopped and induce an ovulation introduction of the chorionic gonadotrophin (CG). If concentration of oestradiol increases too quickly (within several consecutive days more than twice daily) or the quantity of follicles is too high, the daily dose is reduced. As each follicle with a diameter from 0,14 cm is preovulyatorny, in the presence of several such follicles the probability of development of polycarpous pregnancy increases. In this case it is not necessary to enter a gonadotrophin. Also for prevention of polycarpous pregnancy it is necessary to take measures for protection from pregnancy approach.

For the purpose of induction of a superovulation during artificial fertilization use of various schemes of stimulation is possible. Within, at least, 4 first days introduction 150-225 ME drugs is recommended. Further the dose is selected individually, proceeding from reaction of ovaries. As a rule, within 6-12 days it is enough to apply maintenance doses in 75-375 ME, however more long medical courses sometimes are required.

Puregon apply as monotherapy or in combination with other drugs (an agonist or the antagonist of a gonadoliberin (GNRG)) for the purpose of prevention of premature peak of an ovulation. In cases of use of analogs of GNRG higher total doses of Puregon can be appointed.

Control of reaction of ovaries is exercised by means of ultrasonography and definition of concentration of oestradiol in plasma. In the presence of, at least, 3 follicles having diameter of 0,16-0,20 cm according to ultrasonography and good reaction of ovaries (at concentration of oestradiol in a blood plasma of 1000-1300 pmol/L (300-400 »¿¬«úÓá¼¼/ml) on each follicle with a diameter more than 0,18 cm) introduction of HG induce a final phase of maturing of a follicle. Aspiration of ova is carried out in 34-35 hours.

For the purpose of prevention of painful feelings at administration of solution and minimizing of its leak from the place of an injection Puregon it is necessary to enter slowly intramusculary or subcutaneously. Because of the existing risk of development of a fatty atrophy sites for hypodermic introduction should be alternated. Unused solution is destroyed.

It is possible to enter Puregon subcutaneously independently after obtaining detailed instructions from the doctor.

The solution produced in cartridges is intended for hypodermic introduction by means of the Puregong Pan handle injector, in bottles – for introduction by means of the syringe.

The area of a stomach around a navel is the most suitable place for hypodermic administration of drug. It is necessary to change an injection site at each injection. Administration of solution in other body parts is possible.

At administration of drug the needle is entered under the surface of skin at an angle 90 °. Before use it is necessary to be convinced that the needle did not pierce an artery or a vein.

Careful massage of an injection site of Puregon (at invariable pressing) promotes hypodispersion of solution and promotes decrease in risk of development of unpleasant feelings.

Side effects

During Puregon's use development of local reactions in the form of a hematoma, pain, a hyperemia, hypostasis, an itch is possible (were observed at 3% of patients). In most cases these disturbances have short-term and moderate character.

In 1% of cases development of system allergic reactions – an erythema, a small tortoiseshell, rash and an itch was observed.

Also during therapy development of such diseases / states was noted:

• Syndrome of hyper stimulation of ovaries (about 4% of cases). The main clinical symptoms of this disturbance (at a moderate current): diarrhea, nausea, swelling and an abdominal pain (it is connected with disturbance of venous blood circulation and irritation of a peritoneum), increase in ovaries at the expense of cysts. In some cases the life-threatening expressed syndrome of hyper stimulation of ovaries develops. It is characterized by ascites, existence of cysts of ovaries, big, inclined to a gap, a hydrothorax and increase in weight (because of a liquid delay in an organism). Against the background of a syndrome of hyper stimulation of ovaries development of a thromboembolism was in rare instances noted (venous or arterial);
• Misbirth;
• Morbidity, nagrubaniye and/or pain of mammary glands;
• Increase in probability of development of a polycarpous and extrauterine pregnancy.

In rare instances when carrying out a combination therapy in combination with HG or other gonadotropic hormones development of a thromboembolism is possible.

Special instructions

Prior to Puregon's use it is necessary to exclude existence of endocrine diseases.

When carrying out induction of an ovulation by means of gonadotropic drugs the risk of development of polycarpous pregnancy increases. Development of multiple follicles is prevented by the corresponding dose adjustment of FSG. At polycarpous pregnancy higher risk of emergence of complications is noted during pregnancy and during the perinatal period. Prior to therapy of women it is necessary to warn about a possibility of development of polycarpous pregnancy.

The first introduction of Puregon needs to be carried out under direct observation of the specialist.

At artificial fertilization the risk of early abortion, and also frequency of development of inborn malformations is higher (in comparison with natural conception).

When carrying out artificial fertilization (in particular EKO) often anomalies of uterine tubes are available that increases probability of development of an extrauterine pregnancy. Therefore receiving early ultrasonic confirmation of an intrauterine attitude of fetus is important.

Prior to Puregon's use and regularly during therapy it is necessary to carry out ultrasonography for the purpose of control of development of follicles and to define concentration of oestradiol in plasma. The diagnosis of hyper stimulation of ovaries can be confirmed by means of ultrasonography. Tranzitorny deviations of results of hepatic functional trials can indicate functional disturbances of a liver which can be followed by morphological changes on a liver biopsy (there are data on communication of this disturbance with a syndrome of hyper stimulation of ovaries).

At women from the conventional risk groups concerning thromboses (at the corresponding personal or family anamnesis, a gross obesity with a body weight index> 30 ^kg/sq.m or the diagnosed thrombophilia) the risk of emergence of arterial or venous thromboembolisms is higher (even without the accompanying syndrome of hyper stimulation of ovaries against the background of therapy). In this regard before Puregon's appointment such patients need to compare probability of successful carrying out induction of an ovulation with possible risk of emergence of complications. At the same time it is necessary to consider that pregnancy in itself is followed by increase in risk of development of thrombosis.

Puregon may contain traces of Neomycinum and/or streptomycin that can be a hypersensitivity reaction origin.

Medicinal interaction

Puregon pharmaceutical is incompatible with other medicines.

At the combined use with clomifene reaction of ovaries can amplify.

For achievement of sufficient reaction of ovaries after carrying out a desensitization of a hypophysis by means of GNRG agonists the doctor can appoint higher doses of Puregon.

Terms and storage conditions

To store in protected from light, the place, unavailable to children, at a temperature of 2-8 °C, without freezing.

Period of validity – 3 years.

The maximum period of storage of solution after introduction of a needle to a cartridge – 28 days.