GONAL-f - instructions for use, dose, side effects, contraindications

Active substanceFoliotropin alfaFoliotropin alfa

Similar drugsTo uncover

GONAL-f®

solution PC

Merck Serono Juorope Limited United Kingdom

GONAL-f®

lyophilizate PC

Merk Serono SA, Oborn Branch Switzerland

Foliotrop®

lyophilizate w / m PC

Al Gee Life Senses Ltd The Republic of Korea

Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration

Composition:

1 bottle contains:

active substance: follitropin alpha (p-hFSH) 5.5 μg (75 IU); Excipients: sucrose 30 mg, sodium hydrogen phosphate dihydrate 1.11 mg, sodium dihydrogen phosphate monohydrate 0.45 mg, methionine 0.1 mg, polysorbate 20 0.05 mg, phosphoric acid q.s., sodium hydroxide q.s.

Description:

White lyophilized powder or white lyophilized mass (lyophilizate).

Pharmacotherapeutic group:Follicle stimulating agent

ATX: & nbsp

G.03.G.A Gonadotropins

G.03.G.A.05 Foliotropin alfa

Pharmacodynamics:

GONAL-f® - recombinant human follicle-stimulating hormone (r-hFSH) - is a drug that stimulates the growth and development of follicles. The preparation is obtained by genetic engineering on the culture of Chinese hamster ovary cells. Has a gonadotropic effect: stimulates the growth and maturation of the follicle / follicles, promotes the development of several follicles during controlled ovarian hyperstimulation, including for assistive reproductive technologies (ART) programs.

Comparative clinical trials of r-hFSH (follitropin alfa) and y-FSH (urinary follicle-stimulating hormone) for ART and induction of ovulation demonstrated greater efficacy of GONAL-f® for the initiation of follicular maturation in terms of both the reduction in the cumulative dose and the duration of treatment, as compared to y-FSH and, thus, a reduction in the risk of unwanted ovarian hyperstimulation. For ART, the administration of GONAL-f® at a lower total dose with a shorter duration of treatment results in a greater number of oocytes recovered than y-FSH.

It has also been shown that in women with depressed secretion of endogenous gonadotropins, follitropin alfa effectively stimulates the development of follicles and steroidogenesis, despite the inaccessible for measuring a small concentration of luteinizing hormone (LH).

Pharmacokinetics:

When administered subcutaneously, the absolute bioavailability is approximately 70%. After repeated injections of GONAL-f®, a three-fold cumulation of the drug in the blood is observed compared with a single injection. The steady-state equilibrium concentration in the blood is reached within 3-4 days.It has also been shown that in women with depressed secretion of endogenous gonadotropins, follitropin alfa effectively stimulates the development of follicles and steroidogenesis, despite the inaccessible to measure a small level of luteinizing hormone (LH).

After intravenous administration follitropin alfa is defined in extracellular fluids, with an initial half-life of approximately 2 hours from the body, whereas the final half-life is approximately 24 hours. The magnitude of the equilibrium volume of distribution is 10 liters, ground clearance - 0,6 l / hour. One eighth of the administered dose of follitropin alfa is excreted in the urine.

Indications:

- Anovulation (including polycystic ovary syndrome) in women in case of ineffective clomiphene therapy.

- Controlled ovarian hyperstimulation in ART programs.

- Ovarian stimulation in women with a marked deficiency of FSK and LH (in combination with drugs LH).

- Stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with chorionic gonadotropin (hGH)).

Contraindications:

Hypersensitivity to the drug or excipients, hypothalamic-pituitary tumors.

In women: pregnancy, volumetric neoplasms or ovarian cysts (not caused by polycystic ovary syndrome), uterine bleeding of unclear etiology, ovarian carcinoma, uterine cancer, breast cancer.

The drug should not be prescribed:

in women: with anomalies in the development of genital organs and uterine fibroids that are not compatible with pregnancy, primary ovarian failure, premature menopause.
in men: with primary testicular failure.

Pregnancy and lactation:During pregnancy and breastfeeding, GONAL-f® is not prescribed.

Dosing and Administration:

Treatment with GONAL-f® should be started under the supervision of a specialist doctor who has experience of infertility treatment.

The drug GONAL-f® is intended for subcutaneous administration.

The first injection of GONAL-f® is carried out under the supervision of the attending physician or qualified medical personnel. Self-administration of GONAL-f® can only be carried out by patients who are well-motivated, trained and having the opportunity to get expert advice.

It is recommended to change the injection site daily.

The dry substance is dissolved in the applied solvent immediately before use. In 1 ml of solvent dissolve the contents of up to three vials of the preparation, which allows to reduce the injected volume of injection.

Women Anovulation (including polycystic ovary syndrome in women with clomiphene ineffective therapy GONAL-f® should be given as daily injections. Treatment begins in the first 7 days of the cycle. The stimulation is carried out under the control of the ovary ultrasound (measure the size of the follicles) and / or the concentration of estradiol in the blood plasma. Stimulation begins with a daily dose of 75-150 ME, increasing by 37.5 -75 ME 7-14 days before receiving an adequate, but not excessive, response. The maximum dose of a daily injection should not exceed 225 ME. If there is no positive dynamics after 4 weeks, treatment is stopped. In the next cycle, stimulation can begin with a higher dose than in the previous cycle. After the optimal size of the follicles is reached, after 24-48 hours after the last injection of GONAL-f®, 250 μg of recombinant human chorionic gonadotropin (r-hGH) or 5000-10,000 ME human chorionic gonadotropin (hGH). On the day of injection of hCG and the next day, the patient is recommended to have sexual intercourse. As an alternative, intrauterine insemination can be performed.

In case of excessive ovarian response to stimulation, treatment with follicotropin alfa should be discontinued and hGH administration should be discontinued. Stimulation is repeated in the next cycle, starting with a lower dose of GONAL-f® than in the previous cycle.

Controlled ovarian hyperstimulation in ART programs GONAL-f® is prescribed daily for 150-225 ME, starting from 2-3 days of the cycle. Correction of the dose of GONAL-f® should be performed no more than once in 3-5 days, a single dose can be increased by 75-150 ME. The daily dose may vary, but usually does not exceed 450 ME. Treatment is continued until the follicles reach adequate size according to ultrasound (5-20 days, on average, on the 10th day of treatment).

After 24-48 hours after the last injection of GONAL-f®, 250 μg p-HG or 5000-10 000 ME hGH to induce the final maturation of follicles.

To suppress the endogenous release of LH and maintain it at a low level, an agonist or gonadotropin-releasing hormone antagonist (GnRH) is used.In a conventional protocol, the administration of GONAL-f® commences approximately two weeks after initiation of treatment with the GnRH agonist, and then the administration of both drugs is continued until the follicles are adequately sized. For example, after two weeks of treatment with a GnRH agonist, 150-225 ME GONAL-f® for 7 days. In the future, the dose is adjusted depending on the development of follicles and the concentration of estradiol in the blood plasma. The experience with ART shows that in the main the probability of successful treatment persists during the first 4 attempts and then gradually decreases.

Ovarian stimulation in women with a marked deficiency of FSH and LH (in combination with drugs LH)

The dose and scheme of treatment is selected by the doctor individually.

Normally, GONAL-f® is administered daily subcutaneously for up to 5 weeks at the same time as LH. Treatment with GONAL-f® starts at a dose of 75-150 ME simultaneously with lutropin alfa in a dose of 75 ME. If necessary, the dose of GONAL-f® can be increased by 37.5 - 75 ME every 7-14 daysher. In the absence of an adequate response to stimulation for 5 weeks, therapy should be discontinued and restarted in a new cycle at a higher dose.

After the optimum size of the follicle / follicles 24-48 hours after the last injection and Gonal-f® lutropina alpha singly administered 250 ug p-5000-10 or chGH 000 ME hGH. On the day of injection of hCG and the next day, the patient is recommended to have sexual intercourse. As an alternative, intrauterine insemination can be performed.

In case of excessive ovarian response to stimulation, treatment should be discontinued and the administration of hCG should be canceled. Stimulation is repeated in the next cycle, starting with a lower dose of GONAL-f® than in the previous cycle.

Men's

Stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with hGH).

Men are usually prescribed GONAL-f® in a dose of 150 ME three times a week for at least 4 months in combination with hGH. In the absence of a positive effect during this time, treatment can be continued up to 18 months.

Side effects:

In applying the drug Gonal-f® may develop side effects which, depending on the frequency of appearance are regarded as very frequent (≥1 / 10), frequent (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100), rare (≥1 / 10,000 to <1/1000), very rare (<1/10000, including single messages).The frequency of side effects in each group is listed in descending order.

Application in Women

Immune system disorders: very rarely - from mild to moderate severity of systemic allergic reactions (for example, reddening of the skin, rashes, swelling of the face, urticaria, shortness of breath), the development of severe allergic reactions, including anaphylactic reactions and shock.

Disturbances from the nervous system: often - a headache.

Vascular disorders: very rarely - thromboembolism, usually associated with a severe form of HSH.

Disturbances from the respiratory system: very rarely - in patients with bronchial asthma, worsening of the course or exacerbation of the disease.

Disorders from the gastrointestinal tract: often - abdominal pain, heaviness, discomfort in the abdomen, nausea, vomiting, diarrhea, colic, eructation.

Disorders from the reproductive system and the mammary gland: very often - ovarian cysts; often - a syndrome of hyperstimulation of ovaries (SWS) of mild or moderate severity (including concomitant symptomatology); infrequently - severe form of SWN (including concomitant symptomatology); rarely complication of acute hypoglycemia.section "Special instructions").

General disorders and disorders at the site of administration: very often - mild to moderate degree of severity at the injection site (pain, redness, bruising, swelling).

Application the men

Immune system disorders: very rarely - from mild to moderate severity systemic allergic reactions (eg, redness of the skin, rash, swelling of the face, hives, shortness of breath), development of severe allergic reactions, in including anaphylactic reactions and shock.

Disturbances from the respiratory system: very rarely - in patients with bronchial asthma, worsening of the course or exacerbation disease.

Disturbances from the skin and subcutaneous cellulose: often - the appearance of acne (acne).

Violations of the genitals or of the breast: often - gynecomastia, varicocele.

General disorders and disorders at the site of administration: very often a mild to moderate reaction at the injection site (eg, pain, redness, bruising, swelling). often - an increase in body weight.

If serious side effects or effects not described above occur, you should inform your doctor.

Overdose:

At present, no cases of overdose of GONAL-f® have been reported. Apparently, one should expect the development of the syndrome of ovarian hyperstimulation (see section "Special instructions").

Interaction:

With the combination of GONAL-f® with other stimulant drugs (hGH, clomiphene), the response of the ovaries is enhanced; against the background of desensitization of the pituitary gland by an agonist or GnRH antagonist - decreases (an increase in the dose of the drug is required). Data on the interaction of GONAL-f® with other drugs are not available.

Special instructions:

Since the drug can cause various adverse reactions, GONAL-f® should only be prescribed by a specialist doctor directly dealing with infertility problems.

The initiation of therapy should be preceded by examination of the infertile couple, in particular, examinations should be conducted to exclude hypothyroidism, adrenocortical insufficiency, hyperprolactinaemia, hypothalamic-pituitary tumors and, if necessary, appropriate therapy.

It is necessary to evaluate the patency of the fallopian tubes in order to select the ART method.It is necessary to exclude obstruction of the fallopian tubes if the patient does not participate in the program of in vitro fertilization.

In patients with porphyria, as well as in the presence of porphyria from relatives, careful monitoring is required during therapy with GONAL-f®. If the condition worsens or the first signs of this disease appear, it may be necessary discontinuation of therapy.

When treating with GONAL-f®, evaluation of the ovarian condition by ultrasound (ultrasound) is required both separately and in combination with the determination of estradiol in blood plasma. The response to FSH administration may differ in different patients, so the minimum effective doses should be used in both women and men.

The drug GONAL-f® contains less than 1 mmol (23 mg) of sodium in 1 dose, that is, it is not a significant source of sodium.

Ovarian hyperstimulation syndrome (OSS)

OCS must be differentiated from uncomplicated ovarian enlargement. Unlike uncomplicated enlargement of the ovaries, the HNS is a medical case, the severity of which can vary.

The mild form of HSH is accompanied by pains in the lower abdomen, an increase in its size, an increase in the size of the ovaries.With moderate OHSS may additionally marked nausea, vomiting, ovarian enlargement, including through the formation of cysts. If severe OHSS marked dyspnea, oliguria, a marked increase of ovarian size, weight gain, disorders of the gastrointestinal tract, high concentrations of sex hormones, increased vascular permeability, leading to an accumulation of fluid in the peritoneal, pleural cavities and, rarely, pericardium .. In severe OHSS can occur hypovolemia, hemoconcentration, electrolyte imbalance, ascites, hemoperitoneum, hydrothorax, acute respiratory distress syndrome. In very rare cases, severe OHSS may be complicated by torsion of an ovarian cyst or thromboembolic disorders, such as pulmonary embolism, ischemic stroke or myocardial infarction.

There is reason to believe that hGH plays a key role in the emergence of HHV. Therefore, when an excessive ovarian response to stimulation chGH not prescribe, and patients to refrain from coitus or use barrier methods

contraception for at least 4 days.SHH can quickly progress (from days to several days) to a serious condition, so after the administration of hCG, patients should be monitored for a minimum of two weeks.

HSH of mild or moderate severity is usually resolved spontaneously. In the case of severe HSH, therapy with GONAL-f®, if it continues, should be discontinued. The patient should be hospitalized and prescribed appropriate treatment.

To minimize the risk of CHD and multiple pregnancy, ultrasound and estrogen concentrations in the blood plasma are used regularly. The risk factors for the development of CHD are polycystic ovary syndrome, concentration Estradiol> 900 pg / ml (3300 pmol / l) and presence of more than 3 follicles of diameter not less than 14 mm. With ART, the risk of developing CHD increases with an estradiol concentration> 3000 pg / ml (1100 pmol / l) or the presence of 20 or more follicles with a diameter of 12 mm or more. When the concentration of estradiol> 5500 pg / ml (20200 pmol / l) or when 40 or more follicles are present, hCG should be avoided.

Strict adherence to the recommended dosage of GONAL-f®, as well as careful monitoring of therapy, minimize the risk of developing CHD and multiple pregnancies.

The probability of occurrence of OHSS in patients undergoing controlled ovarian hyperstimulation for ART is reduced by aspiration of all follicles.

At the onset of pregnancy, the severity of CHD may worsen, and its duration may increase. Most often, CHD occurs after the cessation of hormonal therapy and reaches its maximum after 7-10 days. As a rule, CHD spontaneously disappears with the onset of menstruation.

In patients with polycystic ovary syndrome, the risk of developing CHD is higher.

Multiple pregnancy

The frequency of multiple pregnancy and childbirth with induction of ovulation is higher, compared with natural conception, the most frequent option when Multiparty is twins.

Multiple pregnancy, especially in the case of a large number of embryos, increases the risk of an adverse outcome for the mother and fetus. To minimize the risk of multiple pregnancies, careful monitoring of the ovarian response is recommended. In ART, the risk of multiple pregnancies is mainly related to the number of transferred embryos, their viability and age of the patient.

Unintention of pregnancy

The frequency of miscarriage after ovulation induction and ART programs is higher than in the general population.

Ectopic pregnancy

Patients with tubal diseases have a history of increased risk of ectopic pregnancy, regardless of whether the pregnancy has occurred in the usual way or in the treatment of infertility. Probability ectopic pregnancy after application of subsidiary reproductive technologies are higher than in the general population.

Neoplasms of the organs of the reproductive system

There are reports of benign and malignant neoplasms of the ovary and other reproductive organs in women after repeated induction of courses of infertility treatment by various medicinal preparations. At present The time of communication between gonadotropin therapy and an increased risk of neoplasm with infertility is not established.

Congenital malformations of development

The frequency of congenital anomalies after the application of ART programs can be slightly higher than with natural pregnancy and childbirth. Nevertheless, it is not known whether this is due to the peculiarity of the parents (for example, the mother's age, the quality of the sperm) and the multiple pregnancy or directly with the ART procedures.

Thromboembolic complications

In patients with recent or current thromboembolic disease, as well as a possible risk of their occurrence, in the presence of a history of disease or with relatives, the use of GONAL-f® may increase the risk or complicate the course of these diseases. For patients in this group, the benefits of therapy should be correlated with the possible risk. It should be noted that pregnancy in itself, like the OHSS, carries an increased risk of thromboembolic disorders.

Treatment of men

An increased concentration of FSH in the blood plasma of men may indicate primary testicular failure. In this case, treatment with r-hFSH / hGH is ineffective and GONAL-f® should not be prescribed. After 4-6 months after the start of the course of therapy, it is recommended that spermogram monitoring be performed.

Patients should be aware of the above risks before starting therapy.

It is necessary to inform the doctor about all types of allergic reactions that are present in the patient, as well as about all drugs used before starting treatment with the drug GONAL-f®.

In the case of the appointment of GONAL-f® together with lutropine alpha, they can be mixed in one syringe.

RECOMMENDATIONS ON THE INDEPENDENT ADMINISTRATION OF THE PREPARATION

1. Wash your hands. It is very important that your hands and all the items you use are as clean as possible.

2. Collect all that you need. Find a clean surface and decompose everything that you will use:

- Vial with preparation

- pre-filled syringe with solvent

- 2 alcohol impregnated swabs

- one needle for solution preparation and a hypodermic needle

- container for recycling.

3. Prepare the solution for injection. Remove the snap-in lid from the vial and the protective cap from the syringe needle. Insert the needle of the syringe with the solvent into the vial, piercing the rubber cap of the vial. Slowly inject the entire contents of the syringe into the vial. Rotate the vial for better dissolution. Do not shake it.

4. After dissolving the lyophilizate, check whether the solution is clear, whether it contains any particles. Turn the bottle upside down and draw the solution back into the syringe. Remove the syringe from the vial.

(If you are given a dose contained in several vials, slowly inject the contents of the syringe into the next vial. Repeat the procedure as described above until you get the correct dose. lutropin alfa You can mix the two drugs in one syringe. Prepare a solution of lutropin alfa, put it in a syringe, inject the solution into the bottle with GONAL-f®, dissolve the drug and put the solution back into the syringe. In 1 ml of solvent can dissolve up to 3 bottles.

5.Change the needle on the needle for subcutaneous injection. If you see air bubbles in the syringe, rotate it with the needle up and tap gently on the syringe so that all the bubbles gather at the top of the syringe. Push the plunger until they all disappear.

6. Enter the solution slowly. Your doctor or nurse should have already advised you where to inject. It can be a stomach or a hip. Squeeze the skin and insert the needle sharply at an angle of 45 or 90 °. Do the injection under the skin as you were taught. Do not enter into a vein. When injecting, push the piston gently until you enter the entire dose. After this, immediately remove the needle and in a circular motion, wipe the injection site with an alcohol swab.

7. Immediately after the end of the injection, discard the used syringes (preferably in a separate container) and the remnants of the drug solution.

Form release / dosage:Lyophilizate for the preparation of a solution for subcutaneous administration, 5.5 μg (75 ME).

Packaging:In a transparent, colorless glass vial, with a capacity of 3 ml, sealed with a rubber stopper and an aluminum ring with a protective removable lid. Solvent: water for injection of 1 ml in a pre-filled syringe of colorless glass.

1, 5 or 10 vials with lyophilizate, the same number of pre-filled syringes with a solvent and 2,

10 or 20 sterile needles, respectively, are placed in a plastic container and then in a cardboard pack together with the Instruction for use.

Storage conditions:

At a temperature of no higher than 25 ° C in the place protected from light.

Keep out of the reach of children.

Shelf life:

2 years for lyophilizate.

3 years for solvent.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000200

Date of registration:15.03.2010 / 08.02.2017