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

Active substanceUrophrolthyropinUrophrolthyropin

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Alterpur

solution w / m PC

IBSA Institute Biokimik S.A. Switzerland

Bravelle

solution w / m PC

Ferring Artsynmittel GmbH Germany

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

Composition:

1 bottle with lyophilizate contains:

active substance - urofolitropin 75 ME;
Excipients - lactose monohydrate 21 mg, sodium hydrogen phosphate heptahydrate 0.268 mg, polysorbate-20 0.005 mg, phosphoric acid 0.0001-0.0006 ml.

1 ampoule with a solvent (0.9% sodium chloride solution) contains:

sodium chloride 9,0 mg, hydrochloric acid 10% 0.007-0.02 mg, water for injection 995.4 mg.

Description:

lyophilizate: lyophilized mass from almost white to light yellow color; solvent: colorless clear solution.

Pharmacotherapeutic group:follicle stimulating agent

ATX: & nbsp

G.03.G.A.04 Urophrolthyropin

G.03.G.A Gonadotropins

G.03.G Gonadotropins and other stimulants of ovulation

Pharmacodynamics:

The composition of the drug includes highly purified follicle-stimulating hormone (FSH), obtained from the urine of postmenopausal women, with a slight admixture of luteinizing hormone (LH). Stimulates the growth and maturation of follicles, causes an increase in the concentration of estrogens and proliferation of the endometrium. Practically not has luteinizing action.FSH interacts with specific receptors on the surface of small granular cells of the ovaries. Treatment with BRAWELL is usually combined with the administration of human chorionic gonadotropin (hCG) to induce the final ripening of follicles and the onset of ovulation.

Pharmacokinetics:

The concentration of FSH depends on the route of administration of the drug:

	Single injection		Multiple administration for 7 days
	subcutaneously	within muscularly	subcutaneously	within muscularly
FROM_ta_X (mIU / ml)	6,0 ± 1,7	8,8 ±4,5	14,8 ±2,9	11,5 ±2,9
Ttah (hour)	20,5 ± 7,7	17,4 ± 12,2	9,6 ±2,1	11,3 ±8,4
AUC_abs (mIU-hr / ml)	379±111	331± 179	234,7 ±77	192,1 ±52,3
ti/2 (hour)	31,8	37	20,6	15,2
Ka (hour)^-1)	0,0500±0,0231	0,1408±0,1227	0,0905±0,0383	0,0358±0,0108

With intramuscular injection of BRAWELL, the maximum concentration of FSH in the blood plasma (C_max) and the area under the curve AUC (plasma concentration / time) were 84.5% and 82.4%, respectively, of the concentrations with subcutaneous administration of the drug. Bioavailability of FSH with repeated administration is 81.8% with subcutaneous administration and 77.7% with intramuscular injection.

suction: after a single subcutaneous or intramuscular injection of BRAWELL C_max FSH is observed after 20.5 and 17.4 hours (T_max). After the repeated administration of the drug C_max FSH is reached after about 10 hours (T_max) after injection, regardless of the route of administration.
distribution: not studied.
metabolism: not studied.
excretion: after a single subcutaneous or intramuscular injection of BRAWELL, the half-life (B / g) of FSH averaged 31.8 and 37 hours, respectively.

Indications:

Anovulation (including polycystic ovary syndrome with clomiphene therapy ineffective);
controlled ovarian hyperstimulation with the aim of inducing the growth of multiple follicles during assisted reproductive technologies (ART).

Contraindications:

hypersensitivity to urofollitropine or to any other component of the drug;
Infertility, not associated with impaired ovarian function;
primary failure of the ovaries;
persistent enlargement of ovaries, ovarian cyst (not caused by polycystic ovary syndrome);
anomalies in the development of genital organs, uterine fibroids (incompatible with pregnancy);
diseases of the thyroid gland or adrenal glands in the stage of decompensation;
organic lesions of the central nervous system (eg, pituitary and hypothalamic tumors);
bleeding from the vagina of an unclear etiology;
cancer of the ovaries, uterus and / or breast;
high concentration of FSH in primary ovarian failure;
pregnancy and the period of breastfeeding;
childhood.

Carefully:

Caution is required when using the drug in women with polycystic ovary syndrome (PCOS), in women with an increased risk of blood clots in the blood vessels (eg, deep vein thrombosis, pulmonary embolism) in a personal or family history, with a hereditary predisposition to thrombosis (resistance to activated protein C, antithrombin deficiency III, Protein C deficiency, protein deficiency S, hyperhomocysteinemia, antibodies to phospholipids) and obesity with a body mass index> 30kg / m².

Pregnancy and lactation:

BRAWELL is contraindicated in pregnant and lactating women.

Dosing and Administration:

BRAWELL can be administered intramuscularly or subcutaneously. The subcutaneous route of administration is preferable, since it provides the greatest absorption of the drug substance. Treatment with the drug should be carried out only under the supervision of a doctor who has the appropriate specialization and experience in treating infertility. Recommendations for the preparation of solution: the injection solution should be prepared immediately before administration with the supplied solvent. Avoid sudden shaking. The solution is not suitable for use if it contains undissolved particles or it is opaque.

The dose of the drug, described below, is the same for both the subcutaneous and intramuscular route introduction.

The dose should be selected individually depending on the response of the ovaries. To do this, monitoring of the ovarian response to ongoing therapy - ultrasound (ultrasound) of pelvic organs and the determination of the concentration of estradiol in the blood plasma in the dynamics. BRAWELL can be administered alone or in combination with gonadotropin-releasing hormone (GnRH) agonists or antagonists.

Anovulation (including polycystic ovary syndrome):

The goal of treatment with BRAWELL in such patients is the development of one mature follicle, from which the oocyte will be released after the introduction of human chorionic gonadotropin (hCG).

Therapy with BRAWELL should be started approximately 2 weeks after the start of treatment with GnRH agonists.The recommended initial daily dose of BRAWELL is 150 ME during the first 5 days of treatment. Based on clinical monitoring (ultrasound examination of the ovaries separately, and preferably in combination with an estradiol concentration estimate), the subsequent increase in the dose of the drug should correspond to the individual reaction of the patient. Increase the dose of the drug is not more often than once in 2 days and once it should not exceed 75-150 ME. The maximum daily dose should not exceed 450 ME. It is not recommended to administer the drug for more than 12 days.

If the treatment regimen does not presuppose the use of GnRH agonists, the BRAVELL drug should be started in the first 7 days of the menstrual cycle. The recommended initial dose of the drug is 75-150 IU / day, the duration of therapy is not less than 7 days. Based on clinical monitoring (ultrasound examination of the ovaries separately, and preferably in combination with an estradiol concentration estimate), subsequent doses of the drug should correspond to the individual response of the patient. Change in the dose of the drug is not more often than once in 5 days and should not exceed more than 75 ME for a single dose change. The maximum daily dose should not exceed 225 ME. If the patient does not have an adequate response to the therapy for 4 weeks, stop the cycle and start a new cycle from initially higher doses than in the discontinued treatment regimen. Partners are advised to use barrier methods of contraception before the next menstruation.

When the optimal response to the therapy is achieved, 24-48 hours after the last injection of BRAWELL, a single injection of 5000 - 10000 ME HECH. The patient is recommended to have sexual intercourse or an intrauterine insemination procedure on the day of HCH administration and the day after the introduction.

Careful observation of patients should be carried out within two weeks after the administration of hCG. If you overreact to treatment with BRAWELL (estradiol concentration above 2000 pg / ml, ovarian enlargement, pain in the lower abdomen), discontinue therapy and discontinue hCG.

With insufficient development of the follicle or the development of ovulation without the onset of pregnancy, you can repeat the cycle of therapy with BRAWELL.

- Controlled hyperstimulation of the ovaries during assisted reproductive technologies:

BRAWELL should be prescribed approximately 2 weeks after the start of treatment by EnRE agonists.The recommended initial daily dose of BRAWELL is 150-225 ME during the first 5 days of treatment. Based on clinical monitoring (ultrasound examination of the ovaries separately, and preferably in combination with an estradiol concentration estimate), subsequent doses of the drug should correspond to the individual response of the patient. Increase the dose of the drug is not more often than once in 2 days and once it should not exceed 75-150 ME. The maximum daily dose should not exceed 450 ME and in most cases should not be administered more than 12 days. If the treatment regimen does not presuppose the use of GnRH agonists, BRAWELL should be started on the 2nd or 3rd day of the menstrual cycle. The method of administration and the same doses of the preparation as described above are recommended.

When the optimal response to the therapy is achieved, 24-48 hours after the last injection of BRAWELL, a single injection of 5000

10000 ME HCG to induce the final maturation of the follicle and prepare the exit of a full-blown oocyte. Careful observation of patients should be carried out within two weeks after the administration of hCG.In case of excessive reaction to BRAWELL treatment, therapy should be discontinued, HCG should be discontinued and barrier methods of contraception should be used before the next menstruation.

Side effects:

	Very often> 1/10	Frequently from> 1/100 to <1/10	Rarely (> 1/10000 and <1/1000)	Very rarely (<1/10000)
Disorders from the nochek and urinary tract		urinary tract infections
Violations from the sexual bodies and dairy glands		bleeding from the vagina, a feeling of discomfort in the vagina, abdominal pain, ovarian hyperstimulation syndrome (OCS), pain and tightness in the mammary glands,
Disturbances from the nervous system	headache		mood changes, depression, dizziness, general weakness
Disorders from the gastrointestinal tract	stomach ache	nausea, vomiting, diarrhea, abdominal cramps, flatulence, constipation
Disorders from the endocrine system		an increase in the excretion of estrogen in the urine, an increase in body weight	hyperthyroidism
Disorders from the cardiovascular system		lowering of blood pressure	deep vein thrombosis, dyspnea
General disorders and disorders at the site of administration		pain in the muscles, skin rash, "hot flashes", pain, swelling and irritation at the injection site	fever, general weakness, urticaria, hypersensitivity reactions, dry skin, alopecia	with prolonged use of the drug, the formation of antibodies

The most serious side effect is ovarian hyperstimulation syndrome and associated complications: thromboembolic (stroke, myocardial infarction, thrombosis deep veins, thromboembolism of the pulmonary artery), torsion of ovarian cysts. Also, side effects include development of ectopic pregnancy, multiple pregnancies and spontaneous abortion (for more details, see section "Special instructions"). If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Cases of overdose are unknown, however, in such situations, development of HNS and thromboembolic complications should be expected. Symptoms of CHD are ovarian enlargement, abdominal pain, nausea, vomiting, diarrhea, weight gain, oliguria, ascites, hydrothorax, hemoperitoneum, hemoconcentration, dyspnea.Symptoms of HSH of mild or moderate severity usually do not require additional treatment and pass independently for 2-3 weeks. With severe complications, hospitalization in intensive care units of specialized gynecological hospitals is necessary for complex treatment. For more information on the SGN, see "Special instructions".

Interaction:

The drug should not be mixed with other drugs! It is assumed that the joint use of the drug BRAWELL and clomiphene can lead to increased follicular growth, although there is no clinical data on the combined use of these drugs. When the GnRH agonist is prescribed to lower the pituitary's own activity, BRAWELL should be administered at higher doses to achieve the desired follicular reaction.

Special instructions:

Before the start of treatment, it is necessary to conduct an appropriate examination of the patient and her partner to determine the cause of infertility; if necessary, to treat hypothyroidism, adrenocortical insufficiency, hyperprolactinaemia. Gynecological examination with an increase in the ovaries is carried out very carefully to avoid rupture of the ovarian cysts. After stimulation of maturation of follicles and ovulation, the possibility of multiple pregnancy during natural conception increases. When the possibility of a multiple pregnancy depends on the number of transplanted embryos. It should be borne in mind the risk of ectopic pregnancy, especially in diseases of the fallopian tubes in the anamnesis. The frequency of early and spontaneous abortions in pregnancy after treatment with urofollitropine is higher than in healthy patients, but comparable to that of infertility of another etiology.

Treatment with gonadotropin drugs can lead to ovarian hyperstimulation, which becomes clinically pronounced after the administration of HCG preparations and is manifested in the formation of large ovarian cysts. This is combined with the accumulation of fluid in the abdominal cavity (ascites), pleural cavity (hydrothorax), accompanied by a decrease in the volume of excreted urine (oliguria), a decrease in blood pressure, thromboembolic complications. Most often, CHD occurs on the 7-10th day after ovulation, stimulated by the introduction of hCG, less often - during ART.

СГЯ 1 degree treatment does not require, accompanied by a slight increase in the size of the ovaries (up to 5-7 cm), an increase in the concentration of sex hormones and abdominal pain. The patient should be informed about her condition and carefully monitored. СГЯ 2 degrees requires hospitalization and symptomatic treatment, including intravenous infusions of solutions to maintain the volume of circulating blood (in case of increased hemoglobin concentration). Ovarian cysts up to 8-10 cm in size are accompanied by abdominal symptoms, nausea and vomiting.

For СГЯ 3 degrees characterized by ovarian cysts measuring 10 cm or more, ascites, hydrothorax, an increase in abdominal pain, dyspnea, electrolyte imbalance, an increase in hemoglobin concentration in the blood, and an increase in its viscosity, accompanied by increased adhesion of platelets to the risk of thromboembolism. Hospitalization is compulsory.

At the first signs of SWC (abdominal pain, palpated by a doctor or diagnosed with ultrasound of the pelvic organs voluminous formations), treatment should be stopped immediately!

With the development of pregnancy, the severity of hypertension can worsen, and the duration may increase, which can threaten the patient's life.

In cases of hyperstimulation, it is not necessary to administer a hCG preparation for the purpose of ovulation. When carrying out ART, the risk of an OHR may be reduced if aspirates the contents of all follicles before ovulation.

Effect on the ability to drive transp. cf. and fur:

The use of the drug does not adversely affect the ability to drive vehicles and other mechanisms.

Form release / dosage:

Lyophilizate for solution for intramuscular and subcutaneous administration, 75 ME.

Packaging:

Vial with lyophilizate: 75 each ME lyophilizate in a vial of colorless glass type I, ukuporenny brombutilovoy stopper with aluminum obkatkoy and plastic cap type "flip-off."

Ampoule with solvent: 1 ml of solvent in an ampoule of colorless glass type I and possible color coding as a color point and / or one or more rings.

5 vials with lyophilizate and 5 ampoules with a solvent in a cell package.

For 1 or 2 packs of cells in a cardboard pack together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Do not freeze!

Keep out of the reach of children.

The prepared solution should not be stored for more than 2 hours at a temperature of no higher than 25 ° C. Unused solution must be disposed of.

Shelf life:

Lyophilizate: 2 years.

Solvent: 3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002273

Date of registration:11.10.2013

The owner of the registration certificate:Ferring Artsynmittel GmbHFerring Artsynmittel GmbH Germany

Manufacturer: & nbsp

FERRING, GmbH Germany

Representation: & nbspFERRING PHARMACEUTICALS LLCFERRING PHARMACEUTICALS LLCRussia

Information update date: & nbsp25.11.15

Illustrated instructions

Instructions

Bravelle (Bravell)