GONAL-F (The solution for the p / to the introduction)

Active material: Follitropin alfa
When ATH: G03GA05
CCF: Recombinant human follicle-stimulating hormone
ICD-10 codes (testimony): E23.0, N97, Z31.1
When CSF: 15.06.05.01
Manufacturer: MERCK SERONO S.p.A. (Italy)

Pharmaceutical form, composition and packaging

The solution for the p / to the introduction clear, colorless, Slight opalescence.

Excipients: poloxamer 188, sucrose, methionine, sodium dïgïdrofosfata monohydrate, sodium dihydrogen phosphate dihydrate, m-cresol, phosphoric acid, Sodium hydroxide, water d / and.

0.5 ml – pen (1) complete with disposable needles (5 PC.) – Plastic containers (1) – cardboard boxes.

The solution for the p / to the introduction clear, colorless, Slight opalescence.

Excipients: poloxamer 188, sucrose, methionine, sodium dïgïdrofosfata monohydrate, sodium dihydrogen phosphate dihydrate, m-cresol, phosphoric acid, Sodium hydroxide, water d / and.

0.75 ml – pen (1) complete with disposable needles (7 PC.) – Plastic containers (1) – cardboard boxes.

The solution for the p / to the introduction clear, colorless, Slight opalescence.

Excipients: poloxamer 188, sucrose, methionine, sodium dïgïdrofosfata monohydrate, sodium dihydrogen phosphate dihydrate, m-cresol, phosphoric acid, Sodium hydroxide, water d / and.

1.5 ml – pen (1) complete with disposable needles (14 PC.) – Plastic containers (1) – cardboard boxes.

Pharmacological action

The recombinant human follicle stimulating hormone. The drug is produced by genetic engineering, cell culture, Chinese hamster ovary. It has gonadotropic action: It stimulates the growth and maturation of the follicle / follicles, It contributes to the development of multiple follicles during controlled ovarian hyperstimulation for assisted reproductive technology programs.

Pharmacokinetics

Absorption

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

It has been shown, that women with suppressed secretion of endogenous gonadotropins, follitropin alfa effectively stimulate follicular development and steroidogenesis, despite inaccessible to measure small levels of LH.

Distribution and excretion

After repeated injections Gonal-F^® observed triple drug accumulation in the blood as compared to a single injection. C_ss Blood achieved within 3-4 days. V_d is 10 l.

After the on / in the follitropin alpha is determined in the extracellular fluid. Initial T_1/2 the body is about 2 no, final T_1/2 – about 24 no.

1/8 follitropin alfa administered dose excreted in urine. Total clearance – 0.6 l /.

Testimony

Women

- Ovarian stimulation in the absence of growth and maturation of follicles (incl. the polycystic ovary syndrome) and in case of failure of treatment with clomiphene citrate;

- Controlled ovarian hyperstimulation in assisted reproductive technologies;

- Ovarian stimulation when conditions hypogonadotropic women (in combination with a preparation of N).

Men

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

Dosage regimen

The drug is administered s / c.

Women

At anovulatory infertility with preserved menstrual cycle or the breach of periodicity Treatment starts on the first 7 days cycle. Stimulation is performed under ultrasound guidance (measure the size of the follicles) and / or estrogen levels. Stimulation begins with a daily dose 75-150 ME, increasing it on 37.5 ME-75 ME через 7-14 days until the desired effect. The maximum dose for one injection – 225 ME. In the absence of positive dynamics after 4 weeks, treatment should be stopped. In the next cycle, the stimulation should be started with a higher dose of.

After reaching the optimal size of follicles through 24-48 hours after the last injection Gonal-F^® administered once recombinant human chorionic gonadotropin (hCG) dose 250 ug dose of hCG or 5000-10 000 ME. On the day of the hCG injection and the next day the patient is recommended sex.

In the case of an excessive ovarian response to stimulation should be discontinued administration of human chorionic gonadotropin. In the next cycle prescribed lower, compared with the previous, dose.

At controlled ovarian hyperstimulation conduct for assisted reproductive technologies Gonal-F^® administered daily at a dose 150-225 ME, starting from 2-3 day cycle. The daily dose may vary, but generally does not exceed 450 ME. Treatment continued until a follicle of adequate size by ultrasound (average 5-20 days). Through 24-48 hours after the last injection Gonal-F^® administered once in a dose of recombinant hCG 250 ug dose of hCG or 5000-10 000 ME to induce final follicular maturation.

To suppress endogenous LH surge and maintaining it at a low level using GnRH analogues.

At anovulatory infertility with the absence of the menstrual cycle as a result of deficiency of FSH and LH dose regimen and doctor sets individually. Typically, Gonal-F^® administered daily for up to 5 weeks simultaneously with LH. Treatment with Gonal-F^® start with a dose 75-150 ME along with a dose of alpha lutropinom 75 ME. If necessary, the dose Gonal-F^® can be increased by 37.5-75 ME every 7-14 days. In the absence of an adequate response to stimulation during 5 weeks of therapy should be stopped and resume in the new cycle at a higher dose.

After reaching the optimal size of the follicle / follicles through 24-48 hours after the last injection Gonal-F^® and lutropina alpha administered once at a dose of recombinant hCG 250 ug dose of hCG or 5000-10 000 ME. On the day of the hCG injection and the next day the patient is recommended sex. Alternatively, it may be carried out intrauterine insemination.

In the case of an excessive ovarian response to stimulation treatment should be discontinued, and to revoke the appointment of hCG. The stimulation was repeated in the next cycle, starting from lower compared to the previous cycle dose.

Men

Gonal-F^® appointed, usually, dose 150 ME 3 times a week for at least 4 months in combination with hCG. If there is no positive effect during this time the treatment may be continued until 18 months.

Rules of administration

With self-use of the drug, patients should carefully read the instructions.

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

1. The injection should be performed under aseptic and antiseptic.

2. For the injection must decompose on the clean surface 2 propitannыh spirtom swab, prefilled pen syringe and needle for injection.

Preparation of pre-filled pen preparation Gonal-F^® for first use: remove the cap handles, put the needle as described in claim 3. Then fill the pen, setting the dose arrow pointer opposite point 37.5 black disk for the dose. Push the button to inject until it stops, remove the outer needle cap, then – the inner needle cap, holding the pen syringe with a needle vertically (the needle should be directed upwards). Gently tap on the location of the cartridge, that possible air bubbles gather at the base of the needle. Directing the needle straight up, fully release the injection. At the tip of the needle can appear a drop. It means, that the pre-filled syringe pen is ready for injection. A minor amount of fluid loss, located at the tip of the needle, irrelevant, tk. syringe pen specially filled with some excess. If the liquid on the tip of the needle does not appear, you should repeat the process of preparation. Then follows the set dose, as described in claim 4.

For the next injection should attach the needle and set the dose, as described in subclauses. 3 and 4 respectively.

3. Attaching the needle. Take a new needle. If the package is broken needles, it should be thrown away and take a new needle. Remove the protective tab from the outer needle cap, Remove the protective tab from the inner needle cap. Firmly holding the needle for the inner cap to insert the needle pen tip with thread, turn it clockwise until it engages audibly. Only use needles, attached to the handle or handle set for this separate.

4. Installation dose. Set the desired dose by rotating the dose setting disc until, until the dose will not rise at the arrow. Dial lets you set the dose to dose interval 37.5 ME. The minimum dose and maximum dose is in the range from 37.5 ME до 300 ME. After the establishment of the required dose should dial it, pressing the injection until it stops. It is necessary to closely monitor the set dose to disk, tk. after clicking on the button to change the injection it will no longer be. If you press the button to set the injection dose and turns, the dose dialed incorrectly, injections should not be done. Remove mistakenly dialed dose and repeat the set again. You should check the red disk monitoring for dose, To make sure, typed the correct dosage: when the button is released for injection, figure on a red disk monitoring, reflecting dialed dose, It is against dose, mounted on a black disk against a set dose arrow. If the dialed dose less, than the desired, the dosing is not finished. In this case it is necessary to act in accordance with paragraph 2.

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

5. Selected on the recommendation of a doctor injection site should be treated with an alcohol swab. Inserting a needle into the skin and press for injection. Leave the needle into the skin of at least 10 sec. Hold the button down until, while the needle remains in the skin. This ensures, that the required dose has been fully.

6. Removing the needle. After each injection, the needle should be discarded. Firmly holding the pen over the reservoir for the drug, carefully put on the outer cap on the needle. Tighten the outer needle cap and unscrew the needle by turning anticlockwise. Discard the used needle. Place the protective cap on the pen.

7. Storage prefilled pen. After injection, the needle used to remove as described in claim 6. To put on the pen cap. Keep the pen should be in a safe place, preferably in its original packaging. After, syringe pen is empty, it should be discarded.

Note: scale, which can be seen through the container for drug, an indicator of the volume of the drug, remaining in the reservoir. It can not be used for dose setting. Red disc control dose injection button is used to control the, It is fully was recruited last dose. It changes its position, indicating the amount of drug in reservoir. If the dialed dose insufficient, to complete injection, There are two possibilities: and) enter dose, which remained in the injection pen, and then take a new insulin pen, set on it the rest of the required dose and type it; to) Dispose of the old pen syringe, take a new and enter the required dose.

Patients should be warned of the need to see a doctor, if a large dose has been introduced, than is required, or in the case of missing the next dose; should not be administered twice daily dose.

Side effect

Determining the frequency of side effects: Often (>1/10, <1/100), often (>1/100, < 1/1000), rarely (>1/10 000, <1/1000), rarely (< 1/10 000).

Women

On the part of the endocrine system: Often – ovarian cysts; often – ovarian hyperstimulation syndrome (SGYA) mild or moderate severity; rarely – severe form of ovarian hyperstimulation syndrome, torsion of ovarian cyst (as a complication of OHSS), ovarian apoplexy, ectopic pregnancy (when specifying a history of tubal disease), polycyesis. Mild OHSS is accompanied by pain in the abdomen, toshnotoy, vomiting, weight gain, an increase in ovarian, incl. due to the formation of cysts. When moderate to severe form of ovarian hyperstimulation syndrome, Besides, marked shortness of breath, oligurija, ascites, gidrotoraks, pleural effusion, accumulation of fluid in the pericardial cavity; possible acute pulmonary insufficiency, thromboembolism.

CNS: often – headache.

From the digestive system: often – stomach ache, nausea, vomiting, diarrhea, what, belching.

Cardio-vascular system: rarely – increased blood clotting (thromboembolism), pulmonary embolism, ischemic stroke, myocardial infarction.

The respiratory system: rarely – in patients with asthma worsening or exacerbation of the disease.

Allergic reactions: rarely – Mild systemic allergic reactions (erythema, rash, swelling of the face, hives, labored breathing), severe allergic reactions (incl. anaphylaxis).

Other: fever, arthralgia.

Local reactions: Often – mild to moderate pain, redness, bruising, swelling at the injection site.

Men

On the part of the endocrine system: often – gynecomastia, varicocele.

Dermatological reactions: often – acne (acne).

Other: often – weight gain.

Local reactions: Often – mild to moderate pain, redness, bruising, swelling at the injection site.

Contraindications

- Hypothalamic-pituitary tumors;

- Hypersensitivity to the drug.

Women

- Pregnancy;

- Bulky tumors or ovarian cysts (not due to polycystic ovary syndrome);

- Uterine bleeding of unknown etiology;

- Carcinoma âičnika;

- Uterine cancer;

- Breast cancer;

- Anomalies of the genital and uterine fibroids, not compatible with pregnancy;

- Primary ovarian insufficiency;

- Prezhdevremennaya menopause.

Men

- Primary testicular failure.

Pregnancy and lactation

The drug is not indicated during pregnancy and lactation.

Cautions

Unnecessarily. Gonal-F^® It can cause serious adverse reactions, it should appoint a doctor-specialist, directly dealing with the problems of infertility. Starting therapy should be preceded by a survey infertile couple, in particular, We should be investigated to rule out hypothyroidism, adrenal insufficiency, hyperprolactinemia, hypothalamic-pituitary tumors, if necessary – prescribe appropriate therapy.

It is necessary to assess the patency of the fallopian tubes in order to select the method of assisted reproductive technology. There should be no 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 the presence of porphyria relatives, during therapy with Gonal-F^® It requires careful monitoring. With the deterioration of the condition or the first signs of the disease may require discontinuation of therapy. In drug treatment requires assessment of the ovaries using ultrasound as a separate, and in conjunction with the determination of estradiol in blood plasma. The preparation should be applied in the minimum effective dose in females, and men.

In the appointment of hCG increases the risk of OHSS and multiple superovulation. Therefore, when an excessive ovarian response to stimulation of hCG is not indicated, and the patient to refrain from coitus for at least 4 days or to use barrier methods of contraception. The likelihood of extreme weather events in patients, undergoing controlled ovarian hyperstimulation in assisted reproductive technologies, reduce by aspiration of follicles.

The risk of multiple pregnancy in assisted reproductive technologies depends on the number of embryos transferred, more common pregnancy with twins. After ovulation induction frequency of multiple pregnancies and births is increased compared with natural conception.

The frequency of termination of pregnancy after ovulation induction and assisted reproductive technology programs is slightly higher, than in the population, but comparable with that of women, suffering from other forms of infertility.

The probability of ectopic pregnancy after using assisted reproductive technology programs range from 2% to 5%, compared with 1-1.5% in the general population.

High levels of FSH in the blood serum of men may indicate primary testicular failure. In this case, treatment with Gonal-F^® inefficiently.

To assess the response to stimulation with Gonal-F^® control of semen analysis is recommended by 4-6 months after initiation of therapy.

It is necessary to obtain information on all types of allergic reactions, patients who have, as well as all medications, Patients who have received prior treatment with Gonal-F^®.

Patients should be warned of the need to inform the doctor and the appearance of serious side effects, or effects, not described above.

It is necessary to mark on the handle with the preparation date of the first day of use. Do not use solution after preparation 28 days from the date of first use. Can be stored in preparation for 28 days at room temperature not exceeding 25 ° C. The drug should be destroyed, if during this period is not utilized.

Effects on ability to drive vehicles and management mechanisms

Gonal-F^® It does not affect the ability to drive vehicles and operate machinery.

Overdose

Currently, cases of drug overdose Gonal-F^® not reported. In applying the drug in excessive doses, apparently, we should expect the development of ovarian hyperstimulation syndrome.

Drug Interactions

With the combination of the drug Gonal-F^® other stimulant drugs (hCG, klomyfena citrate) Ovarian response is enhanced; against the backdrop of the desensitization of pituitary GnRH analogues – decreases (It requires an increase in dose).

About compatibility preparation Gonal-F^® with other drugs, no data available.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, protected from light, in its original packaging at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.