Puregon - instructions for use, dose, side effects, contraindications

Active substanceFoliotropin betaFoliotropin beta

Similar drugsTo uncover

Puregon®

solution w / m PC

Organon, N.V. Netherlands

Puregon®

solution PC

Organon, N.V. Netherlands

Puregon®

solution PC

Organon, N.V. Netherlands

Dosage form: & nbsphypodermic solution

Composition:

Dosage 300ME / 0.36ml

-Active substance: follitropin beta recombinant 350 IU *

Excipients: sucrose 21.0 mg, sodium citrate dihydrate 6.17 mg, polysorbate 20 0.105 mg, benzyl alcohol 4.2 mg, methionine 0.21 mg, hydrochloric acid 0.1 N or sodium hydroxide 0.1 N to pH 7, water for injection up to 0.420 ml.

Dosage 600 ME / 0.72ml

Active substance: follitropin beta recombinant 650 IU *

Excipients: sucrose 39.0 mg, sodium citrate dihydrate 11.5 mg * polysorbate 20 0.177 mg, gasoline alcohol 7.8 mg, methionine 0.39 mg, hydrochloric acid 0.1 N or sodium hydroxide 0.1 N to pH 7, water for injection up to 0.780 ml.

Note:

* The concentration of follitropin beta is 833 IU / ml. , This corresponds to 83.3 μg protein / ml (the specific biological activity in vivo is approximately 10,000 IU FSH / mg protein).

The total dose is calculated for a maximum of 6 injections. With a greater number of injections, the total dose may be lower, because Before each injection, the air is expelled.

Description:clear, colorless solution

Pharmacotherapeutic group:Follicle stimulating agent

ATX: & nbsp

G.03.G.A Gonadotropins

G.03.G.A.06 Foliotropin beta

Pharmacodynamics:

Puregon® contains recombinant follicle-stimulating hormone (FSH), which is obtained by recombinant DNA technology, using the Chinese hamster ovary cell culture into which the genes of human FSH subunits are inserted. The primary amino acid sequence of recombinant DNA is identical to that of natural human FSH. There are small differences in the structure of the hydrocarbon chain. FSH provides normal growth and maturation of follicles and the synthesis of sex steroid hormones. The level of FSH in women is a factor determining the onset and duration of follicle development, as well as their number and maturation time. Thus, Puregon® can be used to stimulate the development of follicles and the synthesis of estrogens in certain disorders of the ovaries. In addition, Puregon® is used to induce multiple development of follicles during artificial insemination (for example, in in vitro fertilization / embryo transplantation (IVF / PE) procedures, intrauterine insemination (IMI), and intracytoplasmic sperm injection (ICSI)).After treatment with Puregon®, human chorionic gonadotropin (hCG) is usually introduced to induce the final stage of follicular maturation, resumption of meiosis and ovulation.

Pharmacokinetics:

After intramuscular or subcutaneous administration of Puregon®, the maximum concentration of FSH in the blood plasma is reached within 12 hours.

In men, after an intramuscular injection of Puregon, "the maximum concentration of FSH is reached faster than in women." Due to the gradual release of the drug from the injection site and a prolonged half-life (12 to 70 hours, an average of 40 hours), the FSH content remains elevated for 24-48 hours, in connection with which the repeated administration of the same dose of FSH leads to a further increase in the concentration of FSH by 1.5-2 times compared with a single administration.This allows the therapeutic concentration of FSH in the blood to be achieved.

Pharmacokinetic parameters after intramuscular and subcutaneous administration of Puregon® are not significantly different. In both ways, the bioavailability of the drug is approximately 77%. Recombinant FSH is biochemically similar to FSH isolated from human urine, and is similarly distributed, metabolized and excreted from the body.

Indications:

Treatment of infertility in women in the following cases:

anovulation (including polycystic ovary syndrome (PCOS) of female genitalia, insensitive to clomiphene);
induction of superovulation for the induction of multiple development of follicles during artificial insemination (for example, in IVF / PE, VMI and IRIS techniques).

Treatment of infertility in men in case of insufficiency of spermatogenesis in hypogonadotropic hypogonadism

Contraindications:

For men and women

hypersensitivity to any of the components of the drug;

- Tumors of the ovaries, breast, uterus, testicles, pituitary gland of the hypothalamus;

primary hypogonadism;

- diseases of the thyroid gland, adrenal glands or pituitary gland of the decompensation;

marked violation of the liver and kidneys.

Optional for women

- vaginal and uterine bleeding of unknown etiology;

ovarian cysts or ovarian enlargement not associated with PCOS;

malformations of the reproductive organs incompatible with pregnancy;

- myoma of the uterus, incompatible with pregnancy;

pregnancy, lactation;

Pregnancy and lactation:

The use of Puregon® during pregnancy is contraindicated.Due to the fact that the clinical data on the use of the drug in pregnancy is not enough, then in the case of unintentional administration during pregnancy, the teratogenic effect of recombinant FSH can not be ruled out.

Lactation

According to the results obtained from clinical studies or animal tests, at present there is insufficient information about the penetration of foliotropin beta into breast milk. It is unlikely that foliotropin beta is excreted in breast milk because of its high molecular weight. When foliotropin beta enters the breast milk, it will break down in the child's gastrointestinal tract.

Foliotropin beta can affect the secretion of milk.

Dosing and Administration:

The treatment with Puregon® should be initiated under the supervision of a physician with experience in the treatment of infertility. The first administration of Puregon® should be performed under the direct supervision of a physician.

Application in Women

The dose should be selected individually depending on the response of the ovaries, under the control of ultrasound and the concentration of estradiol in the plasma.

Puregon® is effective at a lower total dose and shorter treatment time than necessary for maturation,in comparison with FSH obtained from urine, which minimizes the risk of ovarian hyperstimulation. The total experience in the treatment of infertility by extracorporeal fertilization indicates that success is most likely during the first 4 courses of therapy and subsequently gradually decreases.

Anovulation

A consistent treatment regimen is recommended, starting with the daily administration of 50 IU of Puregon for at least 7 days. In the absence of ovarian response, the daily dose is gradually increased until the follicles grow and / or the plasma concentration of estradiol increases, indicating an optimal pharmacodynamic response. Optimum is considered the daily increase in the concentration of estradiol in plasma by 40-100%.

The daily dose thus obtained is then maintained until the predovulation state is reached. The state of predovulation is determined by the presence of a dominant follicle with a diameter of at least 18 mm (according to ultrasound) and / or estradiol concentration in the blood plasma of 300-900 pg / ml (1000-3000 pmol / l). As a rule, 7-14 days of treatment are required to achieve this condition.After this, the administration of the drug is stopped and induces ovulation by the administration of hCG. If the number of follicles is too large or the concentration of estradiol increases too rapidly, i.e. more than 2 times a day for 2-3 consecutive days, then the daily dose should be reduced. Since each follicle with a diameter of more than 14 mm is pre-causative, the presence of several follicles with a diameter of more than 14 mm carries the risk of multiple pregnancies. In this case, hCG is not injected and measures are taken to protect against possible pregnancy to prevent multiple pregnancies.

Induction of superovulation during artificial insemination

Various stimulation schemes are used. For at least the first 4 days, 100-225 IU of the drug is recommended. After that, the dose can be selected individually, based on the response of the ovaries. In clinical studies, it has been shown that there usually is a sufficient maintenance dose of 75-375 IU for 6-12 days, but in some cases longer treatment may be required. Puregon® can be used either alone or in combination with a gonadotropin-releasing hormone (GnRH) agonist or antagonist to prevent premature ovulation peak.When using EnE agonists, higher total doses of Puregon® may be required. The ovarian reaction is controlled by ultrasound and the determination of the concentration of estradiol in plasma. In the presence of at least 3 follicles with a diameter of 16-20 mm (according to US data) and a good ovarian response (estradiol concentration in blood plasma of 300-400 pg / ml (1000-1300 pmol / l) per follicle with a diameter of more than 18 mm) , induce the final phase of maturation of the follicle by the administration of hCG. After 34-35 hours, aspirate the eggs.

Use in men Puregon® should be used in men at a dose of 450 IU per week, preferably dividing the dose into three injections per week of 150 IU. Treatment should be carried out in combination with hCG. The combined use of Puregon ™ and hCG should last at least 3-4 months before the improvement of spermatogenesis. To assess the effectiveness of treatment, it is necessary to perform a sperm analysis 4-6 months after the start of treatment. If there is no improvement, the combination therapy can be continued. The current clinical experience of using the drug shows that to improve the indices of spermatogenesis it is necessary to carry out treatment for up to 18 months or more.

Side effects:

Side effect

The use of Puregon® can be accompanied by the development of local reactions, which were observed in 3 out of 100 patients treated with Puregon®. Most of these local reactions are mild and quick-passing. Genitalized hypersensitivity reactions occurred in 2 of 1,000 patients treated with Puregon®.

Women

The table lists the side effects of Puregon®, described in clinical trials involving women, according to the class of organ systems and frequency: frequent (> 1/100 to <1/10), infrequent (> 1/1000 to <1 /100)

System-Organ Class	Frequency	Unwanted reaction
Disturbances from the nervous system	Often	Headache
Disorders from the gastrointestinal tract	often	Feeling abdominal distension, abdominal pain
Disorders from the gastrointestinal tract	infrequently	Discomfort in the abdomen, constipation, diarrhea, nausea
Disorders from reproduction systems and dairy glands	often	CHF *, pain in small pelvis
Disorders from reproduction systems and dairy glands	infrequently	Soreness, pain in the nipple dairy gland and / or roughing dairy glands, metrorrhagia, ovarian cyst, ovarian enlargement, torsion of ovarian cysts, uterine enlargement, vaginal bleeding
General disorders and reactions at the site of administration	often	Hematoma, pain, redness, swelling, itching.
	infrequently	Erythema, urticaria, rash, itching

* - Ovarian hyperstimulation occurs in about 4 out of 100 women receiving treatment with the drug. Clinical symptoms of mild hyperstimulation of the ovaries are nausea, diarrhea, bloating and abdominal pain due to impaired venous circulation and irritation of the peritoneum, as well as an increase in the ovaries due to cysts. In rare cases, there was a pronounced ovarian hyperstimulation syndrome (OSS) that threatened the patient's life and was characterized by the presence of large, inclined ovarian cysts, ascites, hydrothorax and weight gain due to fluid retention in the body. In rare cases, when treated with Puregon® in combination with hCG, as well as when used with other gonadotropic hormones, SHH may be accompanied by the development of venous or arterial thromboembolism.

In addition, spontaneous abortion, an increased likelihood of multiple pregnancy and an increased likelihood of ectopic pregnancy are described.It is believed that they are associated with assistive technology or pregnancy.

Men's

The table lists the side effects of Puregon®, described in clinical trials (30 men), according to the organ system class and frequency: frequent (> 1/100 to <1/10). Adverse reactions, recorded only once, are indicated as frequent, since the single case corresponds to a frequency above 1%.

Systematically organ grade	Frequency	Unwanted reaction
Disturbances from the nervous system	Often	Headache
Disturbances from the skin and subcutaneous fat	Often	Acne, rash
Disorders from reproduction systems and dairy glands	often	Epididymal cyst, gynecomastia
Are common disorders and reactions at the site of administration	often	Local reaction, including compaction and soreness

Overdose:

There is no evidence of an acute overdose of Puregon®. High doses of FSH can lead to ovarian hyperstimulation. Symptoms: see the "Side effect" section.

Treatment: when symptoms of unwanted hyperstimulation (not associated with the induction of superovulation during in vitro fertilization) appear, Puregon® should be discontinued.In this case, measures should be taken to protect against the development of pregnancy and to abandon the administration of HG, which can exacerbate undesirable phenomena. It is necessary to carry out treatment aimed at eliminating the symptoms of ovarian hyperstimulation.

Interaction:

The simultaneous use of Puregon®, and clomiphene, can enhance the response of the ovaries. After desensitizing the pituitary gland with GnRH agonists, a higher dose of Puregon® may be required to achieve sufficient ovarian response. Pharmaceutically incompatible with other medicines.

Special instructions:

Puregon® may contain traces of streptomycin and / or neonomycin. These antibiotics can cause the development of the hypersensitivity reaction.

- Before the treatment, a couple with infertility should be properly examined. Namely, it is necessary to exclude hypothyroidism, insufficiency of the adrenal cortex, hyperprolactinemia, tumors of the pituitary gland or hypothalamus. If necessary, to treat these diseases.

Among women

- OHSS is an iatrogenic condition based on the ovarian response to the exogenous administration of ovulation induction drugs exceeding the physiological framework.Clinical manifestations and symptoms of HSH of mild and moderate severity: abdominal pain, nausea, diarrhea, mild / moderate ovarian enlargement, ovarian cysts. Clinical manifestations and symptoms of severe SWC: large ovarian cysts, acute abdominal pain, ascites, pleural exudate, hydrothorax, dyspnoea, oliguria, hematologic disorders, weight gain. OCS of severe degree can be complicated by vascular and arterial thrombosis and thromboembolism. Against the backdrop of SHH, there were cases of transient disorders of functional liver samples, indicating organ dysfunction as in combination with morphological changes from the biopsy data, and without them.

OCS can be caused by the use of hCG and pregnancy (endogenous hCG). Usually, early manifestations of CHD are noted within 10 days after the application of HCG. These phenomena are associated with an overly expressed ovarian response to gadotrophin stimulation. Late manifestations of HHV are noted after more than 10 days after the use of hCG and occur as a result of changes in the hormonal balance during pregnancy. Given the risk of developing CHD for at least 2 weeks after the administration of HCG, monitoring is required.

Women with known risk factors for an increased response are especially susceptible to ovarian hyperstimulation in the development of ovarian hyperstimulation in the background or after the use of Puregon. Against the background of the first cycle of ovarian stimulation, when the risk factors are known only in part, careful monitoring of the early symptomatology of the OHS is required.

In order to reduce the risk of HNS, it is advisable to perform an ultrasound to assess the size of the follicles before the course of therapy and then regularly throughout the course of therapy. It is also necessary to determine the concentration of estradiol in serum in parallel.

For assisted reproductive technologies (ART), there is an increased risk of OHSS in the presence of 18 or more follicles with a diameter of 11 mm or more. In the presence of 30 follicles and more it is recommended to abstain from using hCG.

Measures to reduce the risk of developing CHD depending on the severity of the response ovaries

- Termination of further stimulation by gonadotropin with a maximum period of up to 3 days.

- Abolition of hCG and termination of the therapeutic cycle.

- In order to activate the final maturation of the oocyte, the use of hCG (human chorionic gonadotropin isolated from urine) in a 10,000 IU dosage, for example 5000 IU hCG,isolated from urine, or 250 μg of chorio gadadotropin alfa obtained by recombinant technology, equivalent to approximately 6500 IU of HCG isolated from urine.

Abolition of embryo transfer with subsequent cryopreservation.

Abolition of hCG to support the luteal phase.

In the case of development of OHR, standard therapeutic measures are recommended.

After therapy with gonadotropins, including Puregon®, cases of ovarian torsion were reported. Torsion of the ovaries may be associated with other risk factors, for example, with HSH, pregnancy, the presence in the anamnesis of surgical interventions in the abdominal cavity and torsion of the ovary, the presence of ovarian / polycystic cysts at present or in the anamnesis.

Ovarian damage associated with decreased blood supply can be minimized provided early diagnosis and immediate medical intervention.

After the use of gonadotropins, including Puregon, thromboembolic events were reported, both connected and not associated with the CGD. Vascular thrombosis, both venous and arterial, can lead to a decrease in blood supply to vital organs or extremities.In women with known risk factors for thromboembolic events (personal or family history, pronounced obesity, thrombophilia), the use of gonadotropins, including Puregon®, may further increase the risk of developing CHD. In such cases, the risk and benefits of using gonadotropins, including Puregon, should be carefully evaluated. It should be noted that pregnancy also increases the risk of thrombosis.

- Against the background of the use of gonadotropins, including Puregon®, cases of multiple pregnancies with subsequent childbirth have been reported. In many cases, with multiple pregnancies, there was an increased risk of developing adverse events for the mother (complications of pregnancy and childbirth), as well as a newborn (low birth weight). To minimize the risk of multiple pregnancy in patients with anovulation when ovulation is induced, transvaginal ultrasound control of follicular development is advisable. It is also advisable to determine the concentration of estradiol in the blood serum. Patients should be informed about the risk of developing a multiple pregnancy before starting therapy.

Against the background of ART, the risk of multiple pregnancy is mainly related to the number of transplanted embryos. When ovulation is induced, correction of FSH dose prevents multiple growth of follicles.

Women who undergo ART procedures often have abnormalities of the fallopian tubes, which increases the risk of developing ectopic pregnancy. For such patients, it is important to conduct an ultrasound study early to confirm the intrauterine location of the fetal egg.

The frequency of congenital malformations with ART can be slightly higher than with natural fertilization. Perhaps this is due to the characteristics of the parents, for example, the age of the mother or the characteristics of the father's sperm, as well as the higher frequency of multiple pregnancy with ART. Indications that an increase in the risk of congenital malformation is associated with the use of gonadotropins has not been identified.

- There were reports of cases of development of neoplasms of ovaries and other organs of the reproductive system, both benign and malignant, in women who underwent various kinds of therapy in connection with infertility.At the moment, there is no relationship between the use of gonadotropins in the treatment of infertility and the increased risk of developing neoplasms in women.

- Before starting the use of Puregan drug, medical conditions should be excluded, in which pregnancy is contraindicated.

In men

- Increased concentrations of endogenous FSH in men indicate primary testicular failure. In such patients, combination therapy with Puregon and hCG is ineffective

Form release / dosage:

The solution for subcutaneous administration was 300 IU / 0.36 ml, 600 IU / 0.72 ml.

Packaging:

0.36 ml and 0.72 ml in a 1.5 ml colorless glass I (EF) cartridge, sealed on one side with a rubber stopper (bromobutyl / isoprene) with a stopper and a crimping cap and a rubber piston on the other side.

1 cartridge in plastic packaging, instructions for use and 2 cardboard packs with sterile needles, each of which contains 3 needles in individual plastic containers covered with a membrane of foil paper, placed in a cardboard box. '

Storage conditions:

At a temperature of 2-8 ° C, in a place protected from light, do not freeze. Keep out of the reach of children.

Shelf life:

3 years.

After inserting the needle into the cartridge, the solution can be stored for 28 days as much as possible. Do not use after the expiry date shown on the package,

Terms of leave from pharmacies:On prescription

Registration number:LS-001648

Date of registration:23.09.2011

The owner of the registration certificate:Organon, N.V.Organon, N.V. Netherlands

Manufacturer: & nbsp

ORGANON, N.V. Netherlands

Representation: & nbspMSD Pharmaceuticals Ltd.MSD Pharmaceuticals Ltd.

Information update date: & nbsp27.10.2015

Illustrated instructions

Instructions

Puregon® (Puregon)