Gonal-f injection solution syringe pen 22mkg/0.5ml +8 needles

Active substance

Follitropin alfa - 22 mcg (300 IU).

Indications for use

Among women:

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

Controlled ovarian hyperstimulation in assisted reproductive technology programs.

Ovarian stimulation in women with severe deficiency of FSH and LH (in combination with LH).

In men:

Stimulation of spermatogenesis in hypogonadotropic hypogonadism (in combination with human chorionic gonadotropin).

Pharmacokinetics

Suction

When s / to the introduction of the absolute value of bioavailability of approximately 70%.

Distribution

Following IV injection, follitropin alpha is distributed in extracellular fluids. V _ss makes 10 l.

After repeated injections of Gonal-f there is a threefold cumulation of the drug in the blood compared to a single injection. C _ss in blood is reached within 3-4 days.

Removal

After i / v administration of follitropin alpha, its initial T _1/2 from the body is approximately 2 h, the final T _1/2 approximately 24 hours. 1/8 of the dose of follitropin alpha is excreted in the urine. Overall clearance - 0.6 l / h.

Clinical Pharmacology

Recombinant human follicle-stimulating hormone (r-hFSH), stimulating the growth and development of follicles. The drug is obtained by genetic engineering on the culture of Chinese hamster ovary cells. It has gonadotropic action: stimulates the growth and maturation of the follicle / follicles, contributes to the development of several follicles when conducting controlled ovarian hyperstimulation for assisted reproductive technology programs (ART).

Comparative clinical studies of r-hFSH (follitropin alpha) and y-FSH (urinary follicle-stimulating hormone) for ART and induction of ovulation have demonstrated greater efficiency of Gonal-f to initiate follicle maturation in terms of both a reduction in the cumulative dose and the duration of treatment compared to y-FSH. For ART, the administration of Gonal-f in a smaller total dose with a shorter duration of treatment results in a larger number of oocytes extracted compared to y-FSH.

It was also shown that in women with suppressed secretion of endogenous gonadotropins, follitropin alfa effectively stimulates follicular development and steroidogenesis, despite the low level of luteinizing hormone (LH) that is inaccessible to measure.

Use during pregnancy and lactation

The drug is not prescribed during pregnancy and lactation (breastfeeding).

Contraindications

Hypothalamic-pituitary tumors.

Hypersensitivity to the drug.

Among women:

Pregnancy.

Volumetric neoplasms or ovarian cysts (not caused by polycystic ovarian syndrome).

Uterine bleeding of unknown etiology.

Ovarian cancer.

Uterine cancer.

Mammary cancer.

The drug should not be prescribed in cases where a positive effect can not be obtained:

Among women:

Abnormalities of genital organs and uterine fibroids, incompatible with pregnancy.

Primary ovarian failure.

Premature menopause.

In men:

Primary testicular failure.

Side effect

Determination of the frequency of side effects:

Very often> 1/10.

Often> 1/100, <1/10.

Infrequently> 1/1000, <1/100.

Seldom> 1/10 000, <1/1000.

Very rarely <1/10 000, including single messages.

Among women

From the endocrine system

Very often - ovarian cysts.

Often - ovarian hyperstimulation syndrome (OHSS) mild or moderate severity.

Rarely - a severe form of OHSS, torsion of ovarian cysts (as a complication of OHSS), ovarian apoplexy, ectopic pregnancy (given a history of diseases of the fallopian tubes), multiple pregnancy. The mild form of OHSS is accompanied by lower abdominal pain, nausea, vomiting, weight gain, ovarian enlargement, including due to the formation of cysts. In moderate and severe form of OHSS, in addition, shortness of breath, oliguria, ascites, hydrothorax, pleural effusion, fluid accumulation in the pericardial cavity are noted.

Possible acute pulmonary disease, thromboembolism.

From the side of the central nervous system

Often - a headache.

From the digestive system

Often - abdominal pain, nausea, vomiting, diarrhea, colic, belching.

Since the cardiovascular system

Very rarely - increased blood clotting (thromboembolism), pulmonary embolism, ischemic stroke, myocardial infarction.

On the part of the respiratory system

Very rarely - in patients with bronchial asthma, the deterioration of the course or exacerbation of the disease.

Allergic reactions

Very rarely, mild systemic allergic reactions (redness of the skin, rash, swelling of the face, urticaria, difficulty breathing), severe allergic reactions (including anaphylaxis).

Other

Fever,

Local reactions

Very often - light or moderate pain, redness, bruising, swelling at the injection site.

In men

From the endocrine system

Often - gynecomastia, varicocele.

Dermatological reactions

Often - the appearance of acne.

Other

Often - an increase in body weight.

Very often - light or moderate pain, redness, bruising, swelling at the injection site.

Interaction

With simultaneous use of the drug Gonal-F along with other means to stimulate ovulation, an increase in the growth of follicles is possible, whereas simultaneous desensitization of the pituitary by the GnRH agonist can lead to a decrease in the reaction of follicle formation and the need to increase the dose of Gonal-F.

On the incompatibility of the drug Gonal-F with other drugs were not reported.

Overdosage

Currently, no cases of overdose of the drug Gonal-F have been reported.

Symptoms: ovarian hyperstimulation syndrome may develop.

Treatment: symptomatic.

Dosage and administration

The drug is injected s / c. Treatment with Gonal-f should be started under the supervision of a specialist physician with experience in infertility treatment.

Women

With anovulation (including polycystic ovary syndrome) in case of ineffective therapy with clomiphene Gonal-f

The drug should be prescribed a course in the form of daily injections. Treatment begins in the first 7 days of the cycle. Stimulation is carried out under the control of ultrasound (measure the size of the follicles) and / or level of estrogen. Stimulation begins with a daily dose of 75-150 ME, increasing it to 37.5 ME-75 ME in 7-14 days to obtain the desired effect. The maximum dose of a daily injection should not exceed 225 ME. In the absence of positive dynamics after 4 weeks, treatment is stopped. In the next cycle, stimulation should start with a higher dose.

After reaching the optimal size of the follicles, 24-48 hours after the last injection of Gonal-f, a single recombinant human choriogonadotropin (p-hCG) is administered at a dose of 250 mcg or human chorionic gonadotropin (hCG) at a dose of 5000-10 000 ME. On the day of hCG injection and the next day, the patient is recommended to have sexual contact.Alternatively, intrauterine insemination may be performed.

In case of excessive ovarian response to stimulation, the introduction of human chorionic gonadotropin should be abolished. In the next cycle, a lower dose is prescribed compared to the previous one.

When conducting controlled ovarian hyperstimulation in assisted reproductive technology programs

Gonal-f is prescribed daily in a dose of 150-225 IU, starting from 2-3 days of the cycle. The daily dose may vary, but usually does not exceed 450 IU. The treatment is continued until the follicles are of adequate size according to the ultrasound data (on average 5-20 days). 24-48 hours after the last injection of the drug Gonal-f, r-hCG is administered once at a dose of 250 mcg or hCG at a dose of 5000-10 000 ME to induce the final maturation of the follicles.

To suppress the endogenous release of LH and maintain it at a low level, an analogue or antagonist of GnRH is used.

When conducting ovarian stimulation in women with severe deficiency of FSH and LH (in combination with LH drugs)

The dose and treatment regimen is selected individually by the doctor.

Gonal-f is usually prescribed daily for up to 5 weeks at the same time as PH. Treatment with Gonal-f is started with a dose of 75-150 ME at the same time as lutropin alpha at a dose of 75 ME. If necessary, the dose of Gonal-f can be increased by 37.5-75 IU every 7-14 days.

In the absence of an adequate response to stimulation within 5 weeks, therapy should be stopped and resumed in a new cycle at a higher dose.

After reaching the optimal size of the follicle / follicles, 24-48 hours after the last injection of the drug Gonal-f and lutropin alpha, r-hCG is administered once at a dose of 250 μg or hCG at 5000-10 000 ME. On the day of hCG injection and the next day, the patient is recommended to have sexual contact. Alternatively, intrauterine insemination may be performed.

In case of an excessive ovarian response to stimulation, treatment should be discontinued and hCG should be discontinued. Stimulation is repeated in the next cycle, starting with a lower dose compared with the previous cycle.

Men

To stimulate spermatogenesis in hypogonadotropic hypogonadism in men (in combination with human chorionic gonadotropin) Gonal-f

Gonal-f is usually prescribed at a dose of 150 ME 3 times a week for at least 4 months in combination with hCG.In the absence of a positive effect during this time, treatment can be continued up to 18 months.

Rules of drug administration

With self-medication, patients should carefully study the instructions.

The first injection is recommended under the supervision of the attending physician or qualified medical personnel.

Packaging of the drug is intended for individual use. After the first injection, the next injection should be done the next day at the same time.

Injection should be carried out in compliance with the rules of asepsis and antisepsis.

To carry out the injection, it is necessary to place on the clean surface 2 tampons impregnated with alcohol, a pre-filled syringe-pen and a needle for injection.

Preparation of a pre-filled syringe pen for Gonal-f for first use:

Remove the cap cap.

Put on the needle.

Then fill the pen with the dose arrow pointing 37.5 on the black scale to set the dose.

Pull out the button for injection until it stops, remove the outer needle cap, then the inner needle cap, while holding the syringe handle with the needle vertically (the needle should be pointing up).

Gently tap on the location of the cartridge so that possible air bubbles gather at the base of the needle.

Directing the needle straight up, release the injection button completely. A drop may appear on the tip of the needle. This means that the pre-filled pen is ready for injection. The loss of a small amount of fluid at the needle tip is irrelevant, because the pen is specially filled with some excess. If the liquid at the tip of the needle does not appear, then the preparation process should be repeated.

Then you should set the dose, as described in section 4.

For the next injection, reattach the needle and set the dose.

Attaching a needle:

Take a new needle. If the needle packaging is broken, then the needle should be discarded and a new one should be taken.

Remove the protective membrane from the outer needle cap, remove the protective membrane from the inner needle cap.

Holding the needle firmly by the inner cap, insert the handle on the threaded end into the needle, turn it clockwise until the locking click.Only use needles attached to the handle or supplied for this handle separately.

Dose setting:

Set the required dose by turning the dose setting dial until the dose reaches the arrow. The dose setting disc allows you to set the dose at intervals of 37.5 ME. The minimum dose and maximum dose are in the range from 37.5 ME to 300 ME.

After establishing the required dose, you should dial it, pulling the button for injection until it stops. The button should be raised straight and not rotated, because this may change the set dose.

It is necessary to carefully monitor the installed dose on the disk, because after pressing the button for the injection, it will no longer be possible to change it. If, after pressing the button for an injection and the dose is set, it turns out that the dose was incorrectly taken, then the injection should not be given. It is necessary to remove the erroneously administered dose and repeat the set again.

The red dial of the dose control disc should be checked to ensure that the correct dose is dialed: when the injection button is released, the number on the red control disc reflecting the dialed dose is against the dose set on the black dial of the dose dial counter-arrow. If the dialed dose is less than the required dose, the dosing is not complete. In this case, you must act in accordance with paragraph 2.

If the same dose is required each time, the dose indicator should remain in the same position.

Drug administration:

Selected on the recommendation of a physician injection site should be treated with an alcohol swab. The patient should use the technique of s / c administration according to the recommendation of a doctor or nurse.

Introduce the needle into the skin and press the button for injection.

You must ensure that the gray indicator for the full dose is invisible. This indicator position indicates delivery of the full dose.

Hold the needle in the skin and keep the button pressed for at least 10 seconds.

When removing the needle from the skin, keep the button pressed.

Needle removal.

After each injection, the needle should be thrown away.

While holding the syringe firmly behind the drug reservoir, carefully push the outer cap onto the needle.

Tighten the outer cap of the needle and twist the needle counterclockwise.

Throw away the used needle.

Put the protective cap on the pen.

Storage of a pre-filled pen:

After the injection, remove the used needles as described in section 6.

Put the protective cap on the pen.

The pen should be stored in a safe place, preferably in its original packaging. After the pen becomes empty, discard it.

Note: The scale, which can be seen through the reservoir for the drug, serves as an indicator of the volume of the drug remaining in the reservoir. It cannot be used to set the dose. Gonal-f

A dose control dial with a red scale on the injection button serves to control whether the last dose was fully collected. He changes his position, indicating the amount of drug in the tank. If the dose is insufficient to complete the injection, there are two possibilities:

Introduce the dose that remained in the pen and then take a new pen, install the remaining portion of the required dose on it and inject it.

Throw away the old pen, take a new one and inject the required dose.

Patients should be warned about the need to consult a doctor if a large dose has been injected, what is required, or if another dose is missed; Do not enter a double dose of the drug.

Precautionary measures

Since Gonal-f can cause serious adverse reactions, it should only be prescribed by a specialist who is directly involved in infertility problems. The beginning of therapy should be preceded by an examination of the infertile couple, in particular, studies should be conducted to rule out hypothyroidism, adrenal insufficiency, hyperprolactinemia, hypothalamic-pituitary tumors, if necessary, appropriate therapy should be given.

It is necessary to assess the patency of the fallopian tubes in order to select the method of assisted reproductive technology. Obstruction of the fallopian tubes should be excluded if the patient does not participate in the in vitro fertilization program.

Patients with porphyria, as well as with the presence of porphyria in relatives, should be carefully monitored during therapy with Gonal-f. When the condition worsens or the first signs of this disease appear, it may be necessary to discontinue therapy.

When treating the drug requires an assessment of the state of the ovaries using ultrasound, both separately and in combination with the definition of estradiol in the blood plasma.

The response to the introduction of follicle-stimulating hormone can be different in different patients, so you should use the drug in the minimum effective doses 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 (OHSS)

EHH must be differentiated from uncomplicated enlargement of the ovaries. Clinical symptoms of OHSS can manifest with increasing severity. Characterized by a significant increase in the size of the ovaries, a high level of sex hormones, an increase in vascular permeability, leading to accumulation of fluid in the abdominal, pleural, and, rarely, pericardial cavities.

The following symptoms are most characteristic of severe OHSS: pain and a feeling of fullness in the abdomen, marked increase in the size of the ovaries, increased body weight, shortness of breath, oliguria, gastrointestinal symptoms (nausea, vomiting, diarrhea); hypovolemia, hemoconcentration, electrolyte imbalance, ascites, hemoperitonium, pleural effusion, hydrothorax, acute respiratory distress syndrome, thromboembolic disorders may occur. In very rare cases, severe OHS can be complicated by ovarian torsion, pulmonary embolism, ischemic stroke, or myocardial infarction.

When hCG is prescribed, the likelihood of OHS and multiple superovulation increases. Therefore, in case of excessive ovarian response to hCG stimulation, they are not prescribed, and patients are recommended to refrain from coitus for at least 4 days or use barrier methods of contraception. EHH can rapidly progress (from a day to several days) to a serious condition, therefore, after the introduction of hCG, observation for at least 2 weeks is necessary.

To minimize the risk of OHS and multiple pregnancies, ultrasound and an estimate of the serum estradiol concentration are regularly used. With anovulation, the risk of developing OHSS increases with an estradiol concentration of> 900 pg / ml (3300 pmol / l) and the presence of more than 3 follicles with a diameter of at least 14 mm. With ART, the risk of developing OHSS increases with an estradiol concentration of> 3000 pg / ml (1100 pmol / l) or if there are 20 or more follicles with a diameter of 12 mm or more. When estradiol levels are> 5500 pg / ml (20200 pmol / l) or when 40 or more follicles are available, one should refrain from using hCG.

Strict adherence to the recommended dosage of the drug Gonal-f, as well as careful monitoring of therapy, minimizes the risk of developing OHSS and multiple pregnancies.

The likelihood of OHS in patients undergoing controlled ovarian hyperstimulation in assisted reproductive technology programs is reduced by aspirating all follicles.

With the onset of pregnancy, the severity of OHS may worsen, and its duration will increase. Most often, OHSS occurs after the termination of hormone therapy and reaches its maximum after 7-10 days. As a rule, OHS spontaneously disappears with the onset of menstruation.

With the development of severe OHSS therapy with gonadotropins, if it continues, should be discontinued. The patient should be hospitalized and prescribed specific therapy for OHSS.

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

Multiple pregnancy

The frequency of multiple pregnancies and deliveries during the induction of ovulation is higher compared to natural conception, the most frequent option for multiple babies is twins. Multiple pregnancy, especially in the case of a large number of embryos, increases the risk of adverse outcome for the mother and fetus. To minimize the risk of multiple pregnancies, careful monitoring of the ovarian response is necessary. With ART, the risk of multiple pregnancies is mainly related to the number of transferred embryos, their viability and the patient's age.

Miscarriage of pregnancy

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

Ectopic pregnancy

In patients with diseases of the fallopian tubes in a history of increased risk of ectopic pregnancy. The probability of ectopic pregnancy after the use of assisted reproductive technologies ranges from 2 to 5%, compared with 1-1,5% in the general population.

Neoplasms of the reproductive organs

There are reports of benign and malignant neoplasms of the ovary and other reproductive organs in women after repeated courses of infertility treatment with various drugs.Currently, the link between gonadotropin therapy and an increased risk of neoplasm in infertility has not been established.

Congenital malformations

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

Thromboembolic complications

In patients with recent or ongoing thromboembolic diseases, as well as at the likely risk of their occurrence, the use of gonadotropins may increase this 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 itself carries an increased risk of thromboembolic disorders.

Men treatment

An increased concentration of follicle-stimulating hormone in the serum of men may indicate primary testicular failure. In this case, treatment of r-hFSH / hCG is ineffective and Gonal-f should not be prescribed. After 4-6 months after the start of therapy, it is recommended to check the spermogram.

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 a patient has, as well as about all the drugs used before starting treatment with Gonal-f.

It is necessary to mark the date of first use on the pen with the preparation.

Within the shelf life of the drug can be stored at a temperature not higher than 25 ° C up to 3 months. The drug should be destroyed if after 3 months it has not been used. Re-placement in the refrigerator is not allowed.

Influence on ability to drive motor transport and control mechanisms

Gonal-f does not affect the ability to drive vehicles and work with mechanisms.

Storage conditions

Store in a dark place in the original packaging at a temperature of from 2 ° to 8 ° C. Do not freeze. After the first use, the drug can be stored at a temperature not higher than 25 ° C.