Gonal-F, syringe-pen, 450IU 33mcg

Composition

Active ingredient:

follitropin alfa;

Auxiliary substances:

poloxamer 188;

sucrose;

methionine;

sodium dihydrogen phosphate monohydrate;

sodium hydrophosphate dihydrate;

m-cresol;

phosphoric acid;

sodium hydroxide;

water for injection

Pharmacological action

of GONAL-f® — recombinant human FSH (r-hFSH) – it is a drug that stimulates the growth and development of follicles. The drug is obtained by genetic engineering on the culture of ovarian cells of a Chinese hamster. It has a gonadotropic effect: stimulates the growth and maturation of the follicle/follicles, promotes the development of several follicles during controlled ovarian hyperstimulation for assisted reproductive technology (ART) programs.

Comparative clinical studies of r-FSH (follitropin alfa) and urinal FSH (u-FSH) for ART and ovulation induction have demonstrated greater effectiveness of GONAL-f® for initiating follicle maturation in terms of reducing the cumulative dose and duration of treatment compared to u-FSH and, thus, reducing the risk of unwanted ovarian hyperstimulation.

For ART, the use of GONAL-f® in a lower total dose with a shorter duration of treatment leads to a larger number of extracted oocytes compared to y-FSH.

It has also been shown that in women with suppressed endogenous gonadotropin secretion, follitropin alpha effectively stimulates follicle development and steroidogenesis, despite the low LH level that is not available for measurement.

With subcutaneous use, the absolute bioavailability is approximately 70%. After repeated injections of GONAL-f®, there is a three-fold accumulation of follitropin alpha in the blood compared to a single injection. C_ss in the blood is reached within 3-4 days. After intravenous use, follitropin alpha is distributed into extracellular fluids, with an initial T_1/2from the body being approximately 2 hours, while the final T_1/2 is approximately 24 hours. The_{vss value} is 10 l, the total clearance is 0.6 l/h. 1/8 of the administered dose of follitropin alfa is excreted by the kidneys.

Indications

• anovulation (including polycystic ovary syndrome) in women in case of ineffectiveness of clomiphene therapy;
• controlled ovarian hyperstimulation in ART programs;
• ovarian stimulation in women with severe FSH and LH deficiency (in combination with ILG);
• stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with sHG).

Use during pregnancy and lactation

Gonal-F is contraindicated during pregnancy and lactation

Contraindications

• hypersensitivity to the drug or excipients, hypothalamic-pituitary tumors;
• in women-pregnancy, bulky neoplasms or ovarian cysts (not caused by polycystic ovary syndrome), uterine bleeding of unknown etiology, ovarian cancer, uterine cancer, breast cancer;
• the drug should not be prescribed in cases where a positive effect can not be obtained: in women-with genital abnormalities and uterine fibromyoma incompatible with pregnancy, primary ovarian insufficiency, premature menopause; in men – with primary testicular insufficiency.

Side effects

Use in women

From the immune system:  very rarely-mild to moderate systemic allergic reactions (for example, skin redness, rash, facial swelling, urticaria, difficulty breathing), the development of severe allergic reactions, including anaphylactic reactions and shock.

From the central nervous system:  very often — a headache.

From the vascular system:  very rare — thromboembolism, usually associated with severe OHSS.

Respiratory system disorders:  very rarely-in patients with bronchial asthma, the course of the disease worsens or worsens.

From the gastrointestinal tract:  often — abdominal pain, heaviness, abdominal discomfort, nausea, vomiting, diarrhea.

From the side of the reproductive system and mammary glands:  very often — ovarian cysts; often-mild or moderate OHSS (including appropriate symptoms); infrequently-severe OHSS (including appropriate symptoms); rarely — complication of OHSS (see “Special instructions”), ectopic pregnancy (in women with a history of fallopian tube diseases), multiple pregnancies.

Local reactions:  very often-mild/moderate reactions at the injection site (pain, redness, bruising, swelling).

Use in men

From the immune system:  very rarely-mild to moderate systemic allergic reactions (for example, skin redness, rash, facial swelling, urticaria, difficulty breathing), the development of severe allergic reactions, including anaphylactic reactions and shock.

Respiratory system disorders:  very rarely-in patients with bronchial asthma, the course of the disease worsens or worsens.

Local reactions:  very often — a mild/moderate reaction at the injection site (pain, redness, bruising, swelling).

Skin and subcutaneous tissue disorders:  often — the appearance of blackheads (acne).

From the side of the reproductive system and mammary glands:  often-gynecomastia, varicocele.

Other services:  often — an increase in body weight.

Interaction

When GONAL-f® is combined with other stimulant medications (hCG, clomiphene) the ovarian response is enhanced; against the background of pituitary desensitization with an agonist or antagonist of GnRH, it decreases (an increase in the dose of GONAL-f®is required). No data are available on the interaction of GONAL-f with other medicinal products.

How to take, course of use and dosage

Treatment with GONAL-f® should be initiated under the supervision of a specialist doctor with experience in the treatment of infertility.

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

The first injection of GONAL-f® should be performed under the supervision of the attending physician or qualified medical personnel. Self-use of GONAL-f® can only be carried out by patients who are well motivated, trained and have the opportunity to receive specialist advice.

It is recommended to change the injection site daily.

Women

Anovulation (including polycystic ovary syndrome) in women with ineffective clomiphene therapy. GONAL-f® should be administered as a course of daily injections. Treatment begins in the first 7 days of the cycle. Stimulation is carried out under control Ultrasound of the ovaries (measuring the size of follicles) and / or estrogen concentrations. Stimulation begins with a daily dose of 75-150 IU, increasing by 37.5-75 IU after 7-14 days until an adequate but not excessive response is received.

The maximum daily injection dose should not exceed 225 IU. If there is no positive dynamics after 4 weeks, treatment is discontinued. In the next cycle, the stimulation should be started with a higher dose than in the previous cycle.

After achieving an optimal response,250 mcg of p-hCG or 5000-10000 mcg is administered once 24-48 hours after the last injection of GONAL-f®.IU chHG. Sexual contact is recommended on the day of hCG injection and the next day. Alternatively, intrauterine insemination may be performed.

If the ovaries respond excessively to stimulation, follitropin alfa treatment should be discontinued and hCG should be discontinued. Stimulation is repeated in the next cycle, starting with a lower dose of GONAL-f®compared to the previous cycle.

Controlled ovarian hyperstimulation in ART programs. GONAL-f® is prescribed daily for 150-225 IU, starting from the 2-3 th day of the cycle. The daily dose may vary, but usually does not exceed 450 IU. Treatment is continued until the follicles reach adequate size according to ultrasound (5-20 days, on average by the 10th day of treatment).24-48 hours after the last injection of GONAL-f®,250 mcg of p-hCG or 5000-10000 is administered once hCG for the induction of final maturation of follicles.

An agonist or antagonist of GnRH is used to suppress endogenous LH release and maintain it at a low level. In the usual protocol, use of GONAL-f® begins approximately 2 weeks after the start of agonist treatment, then both drugs are continued until adequate follicles are obtained. For example, after 2 weeks of agonist treatment,150-225 IU of GONAL-f® is prescribed for 7 days. In the future, the dose is adjusted depending on the response of the ovaries. The available experience of ART shows that in general, the probability of successful treatment persists during the first 4 attempts and then gradually decreases.

Ovarian stimulation in women with severe FSH and LH deficiency (in combination with MILH). The dose and treatment regimen are selected individually by the doctor.

Usually, GONAL-f® is prescribed daily subcutaneous injection for up to 5 weeks simultaneously with LH. Treatment with GONAL-f® begins with a dose of 75-150 IU simultaneously with lutropin alfa at a dose of 75 IU. 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 discontinued 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 GONAL-f® and lutropin alfa,250 mcg of p-hCG or 5000-10000 is administered once ME chHG. Sexual contact is recommended on the day of hCG injection and the next day. Alternatively, intrauterine insemination may be performed.

If the ovaries respond excessively to stimulation, follitropin alfa treatment should be discontinued and hCG should be discontinued. Stimulation is repeated in the next cycle, starting with a lower dose of GONAL-f®compared to the previous cycle.

Men

Stimulation of spermatogenesis in hypogonadotropic hypogonadism in men (in combination with sHG). Men are usually prescribed GONAL-f® at a dose of 150 IU 3 times a week for at least 4 months in combination with hCG. If there is no positive effect during this time, treatment can be continued for up to 18 months.

Special instructions

Since the drug can cause various adverse reactions, GONAL-f® should only be prescribed by a specialist doctor directly involved in infertility problems. The beginning of therapy should be preceded by an examination of the infertile couple, in particular, examinations should be performed to exclude hypothyroidism, adrenal cortical insufficiency, hyperprolactinemia, hypothalamic – pituitary neoplasms, if necessary, appropriate therapy is prescribed.

It is necessary to assess the patency of the fallopian tubes in order to choose the ART method. Tubal obstruction should be excluded if the patient is not participating in an in vitro fertilization program.

In patients with porphyria, as well as in the presence of porphyria in the anamnesis, 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 to stop therapy.

During treatment with GONAL-f®, an assessment of the ovarian condition is required using ultrasound, either separately or in combination with the determination of estradiol in blood plasma.

The response to FSH use may vary from patient to patient, so the minimum effective dose should be used in both women and men.

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

OHSS should be differentiated from uncomplicated ovarian enlargement. The clinical symptoms of OHSS may appear with increasing severity. It is characterized by a significant increase in the size of the ovaries, a high level of sex hormones, an increase in vascular permeability, leading to fluid accumulation in the abdominal, pleural and, less often, pericardial cavities.

For severe OHSS, the following symptoms are most characteristic: pain and a feeling of bursting in the abdomen, a pronounced 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 may occur. In very rare cases, severe OHSS can be complicated by ovarian torsion and cases of thromboembolism, such as pulmonary embolism, ischemic stroke, or myocardial infarction.

In order to minimize the risk of OHSS and multiple pregnancies, it is recommended to regularly use ultrasound and evaluate the concentration of estradiol in blood plasma for early identification of risk factors.

Independent risk factors for OHSS are polycystic ovarian disease or high plasma estradiol concentrations. With anovulation, the risk of OHSS increases if the estradiol concentration is >900 pg / ml (3300 pmol/L) and there are more than 3 follicles with a diameter of 14 mm or more. In ART, the risk of OHSS increases if the estradiol concentration is >3000 pg / ml (11000 pmol / L) or if there are 20 or more follicles with a diameter of 12 mm or more.

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

There is reason to believe that hCG plays a key role in the occurrence of OHSS. With the onset of pregnancy, the severity of OHSS may worsen, and its duration may increase. When the estradiol level is >5,500 pg/ml (20,200 pmol/L) or when 40 or more follicles are present, hCG should be avoided. The patient is recommended to refrain from coitus or use barrier methods of contraception for 4 days.

OHSS can progress rapidly (from a day to several days) to a severe condition. Most often, OHSS occurs after discontinuation of hormone therapy and reaches its maximum in 7-10 days, so after the introduction of hCG, monitoring for at least two weeks is necessary.

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

OHSS of mild or moderate severity passes spontaneously. If severe OHSS develops, gonadotropin therapy should be discontinued if it is still ongoing. The patient should be hospitalized and prescribed OHSS-specific therapy.

Multiple pregnancies

The frequency of multiple pregnancies and deliveries during ovulation induction is higher compared to natural conception. The most common option for multiple pregnancies is twins. Multiple pregnancies, especially in the case of a large number of embryos, increase the risk of an unfavorable outcome for the mother and fetus. To minimize the risk of multiple pregnancies, careful monitoring of the ovarian response is necessary. In ART, the risk of multiple pregnancies is mainly related to the number of embryos transferred, their viability, and the patient’s age.

Miscarriage

The incidence of miscarriage or spontaneous abortions (miscarriages) after ovulation induction and ART programs is higher than in the general population.

Ectopic pregnancy

Patients with a history of fallopian tube diseases have an increased risk of ectopic pregnancy. The probability of ectopic pregnancy after the use of assisted reproductive technologies is higher than in the general population.

Neoplasms of the reproductive system

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 medications. Currently, the association between gonadotropin therapy and an increased risk of neoplasms in infertility has not been established.

Congenital malformations

The frequency of congenital malformations after the use of ART programs may be slightly higher than during natural pregnancy and childbirth. However, it is not known whether this is due to a specific feature of the parents (for example, the mother’s age, sperm quality) and multiple pregnancies, or directly to ART procedures.

Thromboembolic complications

In patients with recent or ongoing thromboembolic diseases, as well as with a probable 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.

Treatment of men

An increased concentration of FSH in the blood serum of men may indicate primary testicular insufficiency. In this case, treatment with p-hFSH/xXH is ineffective and GONAL-f® should not be prescribed.

In 4-6 months after the start of the course of therapy, it is recommended to monitor the spermogram. Patients should be aware of the above risks before starting therapy.

You should inform your doctor about all types of allergic reactions that the patient has, as well as about all medications used before starting treatment with GONAL-f®.

It is necessary to mark the date of the first application on the handle with the drug.

After the first application, the drug can be stored for no more than 28 days at a temperature of no more than 25 °C. Do not use the drug after this period. Within the shelf life, the drug can be stored at a temperature not exceeding 25 °C for up to 3 months. After 3 months, it should be destroyed if it has not been used. Re – placing in the refrigerator is not allowed.

The effect of the drug on driving a car and controlling other mechanisms. The drug GONAL-f® does not affect the ability to drive a car and control other mechanisms.

Recommendations for self-use of the drug

When using the drug independently, you must first carefully read the instructions. The doctor will prescribe IU doses to the patient. One package of the drug is intended for use by only one patient. The patient should prepare a pre-filled pen and administer the injection. The next injection should be given the next day at the same time.

1. Wash your hands. It is very important that the hands and all objects used by the patient are as clean as possible. Collect everything you need to perform the injection. On a clean surface, spread out everything that will be used: 2 alcohol-soaked swabs, a pre-filled pen and an injection needle.

2. Prepare a pre-filled GONAL-f ® pen for first use: Remove the pen cap and insert the needle as described in step 3. Then fill the pen by placing the dose indicator arrow opposite point 37.5 on the black scale of the dose adjustment dial.Pull the injection button all the way out, remove the outer needle cap, then the inner needle cap, while holding the handle with the needle vertically (the needle should point up). Tap gently on the cartridge location so that possible air bubbles collect at the base of the needle. While pointing the needle vertically upwards, press the injection button. A drop should appear on the tip of the needle. This means that the pre-filled pen is ready for injection. If the liquid does not appear on the tip of the needle, repeat the preparation process. Then set the dose as described in point 4. For the next injection, put on the needle and set the dose as described in points 3 and 4, respectively.

3. Needle attachment

Get a new needle. If the packaging of the needle is broken, do not use it, you must take a new one. Remove the protective membrane from the outer needle cap. Firmly holding the needle by the outer cap, insert the needle into the handle on the threaded tip, turn clockwise until it clicks into place.

Attention: use only the needles provided with the pen or supplied separately for this pen.

4. Setting the dose

Set the required dose by turning the dose dial with the black scale until the dose value is opposite the arrow (the dose dial allows you to set the dose at intervals of 37.5 IU. The minimum dose and maximum dose range from 37.5 to 300 IU). After setting the required dose, dial it by pulling the injection button all the way out. Try to raise the button straight instead of rotating it, as this may change the set dose.

Attention: you should carefully monitor the set dose on the disk, because after pulling out the injection button, you will no longer be able to change the dose, because it is already dialed. If an error is detected after pulling the injection button and setting the dose, do not inject. Remove the selected dose and repeat the set again.

Check the red scale of the dose control dial to make sure that the correct dose has been dialed: when the injection button is extended, the number on the red scale of the control dial that reflects the dialed dose is opposite the dose set on the black scale of the dose dial counterclockwise. If the selected dose is less than the required one, the dosage is not finished. In this case, you must follow the instructions given in paragraph 2.

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

5. Dose use

Choose the injection site according to your doctor’s recommendations. Wipe the injection site with an alcohol swab. Use the injection technique recommended by your doctor or nurse. Insert the needle into the skin and press the button for injection. Make sure that the gray full dose indicator is no longer visible. This position of the indicator indicates that the full dose has been delivered. You must hold the needle in the skin and hold the insertion button down for at least 10 seconds. When removing the needle from the skin, you must continue to hold down the button.

6. Removing the needle

Remove the needle after each injection and discard it. Hold the handle firmly by the drug reservoir. Carefully place the outer cap on the needle. Clamp the outer needle cap and unscrew the needle by turning it counterclockwise. Discard the used needle. Put the cap on the handle.

7. Storing a pre-filled pen

After the injection, remove the used needles as described in step 6. Put a protective cap on the handle. Keep the pen 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 drug tank, serves as an indicator of the amount of drug remaining in the tank. It cannot be used to set the dose.

8. The dose control dial with a red scale on the injection button is used to check whether the last dose was fully dialed or not. It changes its position, indicating the amount of drug in the tank. If the selected dose is not sufficient to complete the injection, there are two possibilities::

a. Enter the dose that remains in the pen, and then take a new pen, set the rest of the required dose on it, and enter it.

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

Form of production

Solution for subcutaneous use

Storage conditions

Store in a dark place at a temperature of 2-8 °C (do not freeze).

Shelf life

2 years

Active ingredient

Follitropin alfa

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults with a doctor’s prescription, For women planning pregnancy

Indications

Infertility Treatment