Элонва®

General characteristics. Structure:

Active ingredient: 100 mkg or 150 mkg of a korifollitropin an alpha in 0,5 ml of solution.

Excipients: citrate sodium a dihydrate, sucrose, L-methionine, polysorbate 20, Acidum hydrochloricum 0.1M or sodium hydroxide 0.1M - to pH 7.0, water for injections.

Pharmacological properties:

Pharmacodynamics. Follicle-stimulating drug. Korifollitropin an alpha is a glycoprotein which is produced by cells of ovaries of the Chinese hamsters by means of recombinant DNA of technology.

Korifollitropin an alpha is a growth-promoting factor of follicles of the prolonged action which on pharmakodinamichesky properties is comparable to recombinant follicle-stimulating hormone (RFSG), but possesses much longer action. Drug causes and supports growth of follicles within a week therefore one п / to an injection of the recommended dose of the drug Elonva® can replace the first 7 daily injections of any drugs RFSG when carrying out controlled stimulation of ovaries. Increase in duration of follicle-stimulating activity was reached due to accession of carboxyterminal peptide of beta subunit of the chorionic gonadotrophin of the person (CGP) to a beta chain of human FSG. Korifollitropin an alpha has no activity of HGCh and LG.

Pharmacokinetics. Indicators of pharmacokinetics of a korifollitropin an alpha did not depend on a dose with the broad range of doses (7.5-240 mkg). Distribution, metabolism and removal of a korifollitropin an alpha are similar to those of other gonadotrophins, such as FSG, HGCh and LG.

Absorption. After a single p / to introduction of a korifollitropin Cmax alpha in plasma was reached in 44 h (34-57 ch1). Absolute bioavailability made 58% (48-70%1).

Exposure of a korifollitropin an alpha depends on body weight. In clinical trials of concentration of a korifollitropin an alpha in plasma were similar after introduction of a korifollitropin an alpha in doses of 100 mkg and 150 mkg to women with the body weight of ≤60 kg and> 60 kg respectively.

Distribution. After absorption in blood корифоллитропин the alpha is distributed generally in ovaries and kidneys.

In an equilibrium state Vd and clearance make 9.2 l (6.5-13.1 l1) and 0.13 l/h (0.10-0.18 l / ч1) respectively.

Metabolism. Kidneys participate in metabolism of a korifollitropin an alpha, preferential. As a result of metabolism an inactive alpha and a beta of subunit (including carboxy - terminal peptide) which, preferential, are removed by kidneys are formed pharmacological.

Removal. T1/2 of a korifollitropin the alpha makes 69 h (59-79 ch1).

Korifollitropin an alpha is brought, preferential, by kidneys.

Pharmacokinetics in special clinical cases. Removal can be reduced at patients with a renal failure.

Microsomal enzymes of a liver slightly participate in metabolism and removal of a korifollitropin an alpha. Though data on use of a korifollitropin an alpha patients with a liver failure are absent, influence of a liver failure on a pharmacokinetic profile of a korifollitropin an alpha is improbable.

1 - Estimated range at 90% of patients.

Indications to use:

— controlled stimulation of ovaries in a combination with antagonists of GNRG for the purpose of formation of multiple follicles at the women participating in the program of an auxiliary reproduction.

Route of administration and doses:

Use of the drug Elonva® should be carried out under control of the doctor having experience of treatment of infertility. Drug can be used, only if solution in the syringe transparent.

To women with body weight <60 kg once enter 100 mkg.

To women with body weight> 60 kg once enter 150 mkg.

The recommended doses were established only at the combined use with the antagonist of GNRG.

In the 1st day of stimulation the drug Elonva® is administered once п / to (preferably under stomach skin) in an early follicular phase of a menstrual cycle.

For the 5th or 6th day of stimulation, depending on quantity and the size of the growing follicles and/or concentration of oestradiol in blood, use of the antagonist of GNRG for prevention of premature increase in concentration of LG has to be begun.

For the 8th day of stimulation (in 7 days after a drug Elonva® injection) treatment can be continued by daily introduction of RFSG until the sizes of follicles do not correspond to criteria for introduction of a trigger dose of HGCh (3 follicles of ≥17 mm). The daily dose of RFSG depends on the answer of ovaries which monitorirutsya regularly at ultrasonography, since 5th or 6th day of stimulation. If the answer normal, then the recommended daily dose makes 150 ME RFSG.

Reception of RFSG in day of introduction of HGCh can be missed depending on the answer of ovaries. Usually sufficient maturing of follicles is reached for the 9th day of treatment (range of duration of treatment makes from 6 to 18 days).

When maturing 3 follicles to the size of ≥17 mm, single introduction from 5000 ME to 10 000 MEHGCh in the same or next day is made for induction of final maturing of oocytes. In case of the excessive answer of ovaries it is necessary to use recommendations about minimization of risk of development of SGYa.

Clinical trials of drug at patients with a renal failure were not conducted. Since removal of a korifollitropin an alpha at such patients can be reduced, use of the drug Elonva® for women with a renal failure is not recommended.

Though data on use of drug for patients with a liver failure are absent, influence of a liver failure on removal of a korifollitropin an alpha is improbable.

Use of the drug Elonva® for children does not correspond to the indication.

Rules of administration of drug. П / to an injection of drug it can be made by the woman or other person if the doctor provided the corresponding recommendations.

Recommendations for patients about preparation and performance п / to an injection. Syringe components with a needle:

1. Piston

2. Syringe

3. Solution

4. Syringe cap

5. Needle cap

6. Needle

7. Needle case

8. Perforation

Preparation for an injection:

1. To process leather in the place of an estimated injection disinfectant.

2. To break a needle cap through perforation, to take the case containing a needle. Not to remove a case from a needle. To put the case containing a needle on a dry pure surface.

3. To hold the syringe a cap up (vertically). It is careful to knock with a finger on the syringe that vials of air rose up.

4. To hold the syringe vertically. To turn off a syringe cap counterclockwise.

5. To hold the syringe vertically. To fasten to it the needle case containing a needle, clockwise.

6. To hold the syringe vertically. To remove a case from a needle and to throw out it. It is necessary to be careful at the address with a needle.

Performance of an injection:

1. To clamp the syringe between index and average fingers and to hold it vertically. To place a thumb on the piston. To carefully press the piston that on a tip of a needle the solution droplet appeared.

2. Big and index fingers to make a skin fold. To enter a needle at an angle 90 ° pleated skin. To press carefully on the piston against the stop. To count to 5 to enter all solution.

3. To take away a thumb from the piston. The needle will automatically clean up in the syringe and will be blocked.

Features of use:

Use at pregnancy and feeding by a breast. Use of the drug Elonva® at pregnancy is contraindicated.

After controlled stimulation of ovaries by gonadotrophins in clinical practice of teratogenic effect it is not revealed. Clinical data do not allow to exclude teratogenic effect of a korifollitropin an alpha, in case of its inadvertent introduction to pregnancy time. In preclinical trials of the teratogenic effect connected with use of medicine did not observe.

Use of the drug Elonva® in the period of a lactation is contraindicated.

Use at abnormal liver functions. Though data on use of drug for patients with a liver failure are absent, influence of a liver failure on removal of a korifollitropin an alpha is improbable.

Use at renal failures. Clinical trials of drug at patients with a renal failure were not conducted. Since removal of a korifollitropin an alpha at such patients can be insufficiency, use of drug is not recommended.

Use for children. At children it is not applied.

Special instructions. Before an initiation of treatment, couple has to be inspected properly, the diagnosis of infertility is made and possible contraindications are considered. In particular, it is necessary to inspect the patient on existence of a hypothyroidism, adrenal insufficiency, a giperprolaktinemiya and tumors of a hypophysis or a hypothalamus, in case of identification to appoint the corresponding treatment.

The drug Elonva® is intended only for a single p / to introduction. During the same cycle it is not necessary to appoint additional injections of the drug Elonva®.

During the first 7 days after administration of the drug Elonva® it is not necessary to enter RFSG.

At patients with a renal failure disturbance of removal of a korifollitropin an alpha is possible. Use of drug for such patients is not recommended.

Experience of use of the drug Elonva® in a combination with an agonist of GNRG is limited. Results of a small uncontrollable research testified to more expressed answer of ovaries in comparison with that at introduction of a combination of drug with the antagonist of GNRG. In this regard, it is not recommended to use the drug Elonva® in combination with GNRG agonist.

The drug Elonva® was not studied at women with a syndrome of a polycystosis of ovaries. Use of drug for such patients is not recommended.

After administration of drug the answer of ovaries was more expressed, than after daily injections of RFSG. Therefore, patients with the estimated excess answer of ovaries can be especially predisposed to development with SGYa in time or after administration of drug. Careful control of possible hyper stimulation of ovaries in the first cycle of stimulation at patients with not specified risk factors of SGYa is recommended.

Syndrome of Hyper Stimulation of Ovaries (SHSO). SGYa differs from uncomplicated increase in ovaries. Clinical manifestations of SGYa easy or moderate severity: abdominal pains, nausea, diarrhea, small or moderate increase in ovaries and cyst of ovaries. At heavy degree of SGYa the threat of life is possible. Clinical manifestations: big cysts of ovaries (inclined to a gap), an acute pain in a stomach, ascites, a pleural exudate, a hydrothorax, an asthma, an oliguria, changes from blood and increase in body weight. In rare instances venous or arterial thromboembolisms can develop.

Signs of SGYa arise under the influence of reception of HGCh or pregnancy (endogenous HGCh). Early SGYa usually develops within 10 days after introduction of HGCh and can be followed by the excess response of ovaries to stimulation gonadotrophins. Usually early SGYa passes independently after the beginning of periods. Late SGYa develops more than in 10 days after introduction of HGCh as a result of pregnancy. Considering risk of development of SGYa, patients should be observed within, at least, 2 weeks after introduction of HGCh.

To reduce risk of development of SGYa, to treatment and regularly during treatment it is necessary to carry out ultrasonic monitoring of the growing follicles and/or to define concentration of oestradiol in plasma. In programs of an auxiliary reproduction the risk of development of SGYa is increased in the presence 18 and more follicles with a diameter of ≥11 mm. If total number of follicles makes ≥30, it is not necessary to enter HGCh.

Depending on the answer of ovaries it is possible to take the following measures for prevention of SGYa:

— to postpone further stimulation by a gonadotrophin at most for 3 days;

— to postpone induction of final maturing of an oocyte under the influence of HGCh until stabilization or decrease in concentration of oestradiol;

— for induction of final maturing of an oocyte to use HGCh in a dose less than 10 000 ME, for example, of 5000 MEHGCh or 250 mkg of rHGCh (about 6500 ME are equivalent);

— to kriokonservirovat all embryos for transfer in the following cycle;

— not to enter HGCh and to stop a medical cycle.

For support of a lyuteinovy phase it is necessary to avoid introduction of HGCh.

To minimize risk of development of SGYa, it is necessary to use the recommended doses and schemes of use of the drug Elonva® and to carefully control the answer of ovaries.

At use of all drugs of gonadotrophins cases of approach of polycarpous pregnancy and twinning were observed. Before an initiation of treatment it is necessary to inform the woman and her partner on possible risk for mother (a complication of pregnancy and childbirth) and newborns (low body weight). At treatment by methods of auxiliary reproductive technologies the risk of polycarpous pregnancy, generally depends on number of the postponed embryos.

Pathology of uterine tubes often occurs at women with infertility which treatment by methods of auxiliary reproductive technologies, especially, extracorporal fertilization (EKO) is offered that can lead to increase in risk of ectopic pregnancy. In this regard, on early durations of gestation it is necessary to conduct ultrasonography to confirm existence of a uterine or extrauterine pregnancy.

Frequency of inborn malformations after auxiliary reproductive technologies is slightly higher, than after natural fertilization. It is connected with specific features of parents (for example, age of the woman, sperm indicators) and the increased frequency of polycarpous pregnancy.

At the women receiving various schemes of treatment concerning infertility cases of development of tumors of ovaries and other bodies of reproductive system are described. It is not established that treatment by gonadotrophins can lead to increase in risk of development of these tumors in women with infertility.

At women with risk factors of tromboembolic episodes (a thromboembolism in the anamnesis, the burdened family anamnesis, obesity (a body weight index> of 30 kg/sq.m) or a thrombophilia) treatment by gonadotrophins can promote further increase in this risk. In such cases it is necessary to estimate risk and advantage of use of gonadotrophins. It should be noted that pregnancy increases risk of development of thrombosis.

Influence on ability to driving of motor transport and to control of mechanisms. Reactions to control of vehicles and use of a difficult technique were not studied.

Элонва® can cause dizziness. Patients should be warned that at dizziness it is not necessary to be engaged in driving of vehicles or to use a difficult technique.

Side effects:

SGYa (5.2%), pain and discomfort in the bottom of a stomach (4.1% and 5.5% respectively), a headache (3.2%), nausea (1.7%), fatigue (1.4%) and complaints from mammary glands (painful feelings, pain, discomfort, a nagrubaniye of mammary glands, increase in a breast) (1.2%) were the main side reactions in clinical trials at treatment ^{by the drug Elonva®}.

Often (≥ 1%, <10%), infrequently (≥0.1%, <1%).

Disturbances from a nervous system. Often - a headache; infrequently - dizziness.

Disturbances from digestive tract. Often - nausea; infrequently - an abdominal pain, vomiting, diarrhea, a lock, abdominal distention.

Disturbances from urinogenital system and mammary glands. Often - SGYa, pain and discomfort in a small pelvis, the complaint from mammary glands; infrequently - ovary torsion.

General and local reactions. Often - fatigue.

Besides, ectopic pregnancy, not incubation of pregnancy and polycarpous pregnancy which are considered as a complication of methods of an auxiliary reproduction are described.

Interaction with other medicines:

Interaction with other drugs was not studied.

Korifollitropin an alpha is not substrate for P450 cytochrome isoenzymes therefore interaction with other drugs is not expected.

Contraindications:

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

— bleedings and bloody allocations from a genital tract (not connected with periods) the unspecified reason;

— primary insufficiency of ovaries;

— cysts of ovaries or increase in ovaries;

— the syndrome of hyper stimulation of ovaries (SHSO) in the anamnesis;

— if the previous cycle of controlled stimulation of ovaries led to growth of more than 30 follicles to the size not less than 11 mm revealed at ultrasonography;

— quantity of the basal antral follicles more than 20 revealed at ultrasonography;

— fibroidny tumors of a uterus at which approach and further incubation of pregnancy is complicated;

— malformations of reproductive organs at which pregnancy is impossible;

— pregnancy;

— breastfeeding;

— hypersensitivity to drug components.

Overdose:

Introduction of more than one of the controlled stimulation of ovaries recommended a drug Elonva® dose during one cycle and/or use of RFSG in too high doses can lead to increase in risk of development of SGYa.

Storage conditions:

Drug should be stored in the unavailable to children, protected from light place, at a temperature from 2 °C to 8 °C. Not to freeze. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

0.5 ml - syringes one-time of 1 ml of colourless glass (1) with automatic system of blocking of a needle in a set with a sterile needle (1) - containers plastic (1) - packs cardboard.