Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):ONLS
VED
АТХ:L.02.A.E.01 Buserelin
Pharmacodynamics:
The drug is a synthetic analogue of natural gonadotropin-releasing hormone. Competitively binds to the receptors of the anterior pituitary cells, causing a short-term increase in the level of sex hormones in the blood plasma. Further use of therapeutic doses of the drug leads (on average 12-14 days) to complete blockade of the gonadotropic function of the pituitary gland, thus inhibiting the release of lutein stimulating hormone and follicle-stimulating hormone. As a result, the synthesis of sex hormones in the ovaries is suppressed and the concentration of estradiol (E2) in the blood plasma is reduced to post-menopausal values or to the level corresponding to ovariectomy. It causes a transient increase in testosterone concentration in men. With daily use (an average of 12-14 days) leads to a complete blockade of the gonadotropic function of the pituitary gland, suppressing the secretion of lutropin and follicle-stimulating hormone and reducingtestosterone concentration in men with prostate cancer (within 2-3 weeks decreases to the index characteristic for the state after orchiectomy - chemical castration).
Pharmacokinetics:
Bioavailability after intramuscular injection is high. Well absorbed from the subcutaneous tissue and through the mucous membrane of the nose. The half-life is 3 hours. Time to reach the maximum concentration in the blood plasma after intramuscular injection - 2-3 hours. It accumulates in the liver and kidneys, in the anterior pituitary gland. Metabolized by peptidase tissue. Inhibition of gonadotropin synthesis by the pituitary gland is maintained for 4 weeks or more after a single intramuscular injection. Eliminated by the kidneys and with feces (in the form of unchanged substance and metabolites). In small amounts excreted in breast milk.
Indications:
Hormone-dependent prostate cancer; hormone-dependent pathology of the reproductive system due to absolute or relative hyperestrogenism; endometriosis (pre- and postoperative periods); uterine myoma; hyperplastic processes of the endometrium; treatment of infertility (when carrying out the program of in vitro fertilization).
II.D10-D36.D25 Leiomyoma of the uterus
II.D10-D36.D26 Other benign neoplasms of the uterus
IV.E20-E35.E28.0 Excess estrogens
XIV.N80-N98.N80 Endometriosis
XIV.N80-N98.N85.1 Adenomatous hyperplasia of the endometrium
XIV.N80-N98.N85.0 Glandular endometrial hyperplasia
XIV.N80-N98.N97 Female infertility
XXI.Z30-Z39.Z31.1 Artificial insemination
Contraindications:
Hypersensitivity. State after orchidectomy (further decrease in testosterone concentration when using depot form is impossible). Pregnancy, breast-feeding.
Carefully:
Arterial hypertension, diabetes mellitus, depression. Patients with any form of depression during treatment with buserelin should be under close supervision of the doctor. The ovulation induction should be performed under strict medical supervision. Patients who use contact lenses may have signs of eye irritation. Considering intranasal method of application, possibly irritation of the nasal mucosa, sometimes nasal bleeding. The drug can be used in rhinitis, but before using it, the nasal passages should be cleared. The effect on the ability to drive and othermechanisms: during the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Pregnancy and lactation:
The category of recommendations Food and Drug Administration (US Food and Drug Administration) is not defined. The use of other analogues of lutropin releasing factor is contraindicated in pregnancy (the recommendations of the Food and Drug Administration of category D for the treatment of breast cancer and X for the treatment of benign processes). In view of the potential threat to the fetus for women of childbearing age, it is recommended to use contraceptives during treatment with buserelin. There is no information on the penetration into breast milk. Other analogs of the lutropin releasing factor are excreted by breast milk. In view of the potential risk of undesirable effects on the baby during treatment with Buserelin, breast-feeding is recommended to be discontinued.
Dosing and Administration:
A single dose of the drug with a full pressure pump is 150 mcg. Prostate cancer (stage D, as a palliative therapy,alternative to orchiectomy and the use of estrogens; response to treatment - within 4-6 weeks). Initial treatment: subcutaneously at a dose of 500 μg (0.5 mg) of the base every 8 hours for 7 days. Supportive treatment: subcutaneously at a dose of 200 mcg (0.2 mg) of the base once a day daily. Supportive treatment: intranasally at a dose of 400 μg (0.4 mg) of the base (200 μg per each nasal passage) every 8 hours (with one click, 100 μg of the drug is released). Supportive treatment: intranasally at a dose of 100 μg (0.1 mg) of the base in each nasal passage 6 times a day (before and after meals). Intramuscularly at a dose of 4.2 mg once every 4 weeks. The hormone dependent pathology of the reproductive system, caused by absolute or relative hyperestrogenism: endometriosis (pre- and postoperative periods), uterine myoma, endometrial hyperplasia. Endometriosis, hyperplastic processes in the endometrium are intramuscularly at a dose of 4.2 mg once every 4 weeks. Treatment begins in the first 5 days of the menstrual cycle; duration - 4-6 months. Endometriosis - intranasal in a dose of 150 mcg in each nasal passage 3 times a day. Duration of treatment is 4-6 months (with longer therapy, the risk of developing osteoporosis is increased). Uterine myoma - intramuscularly at a dose of 4.2 mg once every 4 weeks.Treatment begins in the first 5 days of the menstrual cycle. Duration of therapy: before the operation - 3 months, in the remaining cases - 6 months. The drug is administered intranasally, after cleansing the nasal passages, at a dose of 900 mcg per day (150 mcg is given in one push). The daily dose is administered in equal portions, one dose in each nasal passage 3 times a day at regular intervals (6-8 hours), in the morning, in the afternoon and in the evening. Treatment begins on the 1st or the 2nd day of the menstrual cycle. Bespladia (induction of ovulation during in vitro fertilization or ineffectiveness of clomiphene). Intramuscularly once in a dose of 4.2 mg, on the 2nd day of the menstrual cycle. Intranasal at 600 mcg per day (in a dose of 150 mcg in the nasal passage 4 times a day at regular intervals). The drug is used from the middle of the luteal phase of the menstrual cycle (from 21-24 days of the cycle) to the day of administration of the ovulatory dose of the chorionic gonadotropin. Against this background, upon reaching the blockade of the synthesis of estradiol from 2 to 5 days of menstrual bleeding, stimulation with gonadotropin preparations is carried out according to standard schemes. With severe blockade of the reproductive system and a weak response of the ovaries to stimulation of ovulation with preparations of gonadotropins, the daily dose of the drug should be reduced.Subcutaneously at 200-500 mcg per day before oppression of the pituitary gland (usually 1-3 weeks). It is possible to increase the dose of buserelin up to 300 mcg 4 times a day (with intranasal application) and 500 mcg 2 times a day (with subcutaneous application). Porphyria Intranasal in a dose of 300 μg in the evening, 1-21 days of the menstrual cycle in combination with medroxyprogesterone (10 mg per day at 12-21 days of the menstrual cycle). Central premature puberty In premature puberty buserelin (1800 mg per day in the form of a nasal spray every 4 weeks) significantly reduces the concentration of follicle-stimulating hormone, inappropriately reduces the content of estradiol in blood plasma after 2 months of treatment and exceeds tryptorelin in the rate of decrease in the concentration of lutropin, but inferior to it, not providing a decrease in the volume of pelvic organs. Implant: subcutaneously the content of the applicator (6.3 mg) is injected into the lateral surface of the stomach 1 every 2 months.
Side effects:
From the side of the central nervous system: headache, dizziness, nervousness, fatigue, sleep disturbance, drowsiness, decreased memory and ability to concentrate, emotional lability,the development of depression or worsening of its course. On the part of the senses: tinnitus, hearing and vision impairment (an unclear vision), a feeling of pressure on the eyeball. On the part of the endocrine system: flushes of blood to the skin of the face and upper chest, increased sweating, vaginal dryness, decreased libido, abdominal pain, demineralization of bones, rarely menstrual bleeding (usually during the first weeks of treatment). From the cardiovascular system: palpitation, increased blood pressure (in patients with arterial hypertension). Allergic reactions: urticaria, skin itching, skin hyperemia, very rarely bronchospasm, anaphylactic and / or anaphylactoid shock, angioedema. From the gastrointestinal tract: nausea, vomiting, thirst, diarrhea, constipation, impaired appetite, increase or decrease in body weight. Laboratory indicators: a decrease in glucose tolerance, hyperglycemia; changes in the lipid spectrum; an increase in the activity of serum transaminases, hyperbilirubinemia; thrombocytopenia or leukopenia. Other: nasal bleeding; pulmonary embolism; edema in the ankles and feet; weakening or amplificationgrowth of hair on the head and on the body; pain in the back, joints. Locally: irritation of the nasal mucosa, dryness and pain in the nose.
Overdose:
At present, no cases of buserelin overdose have been reported.
Interaction:Oral hypoglycemic agents: reducing their effect.
Medicines containing sex hormones (for example, in the induction of ovulation): contribute to the development of the ovarian hyperstimulation syndrome.
Special instructions:
The use of buserelin in combination with surgical treatment for endometriosis reduces the size of pathological foci and their blood supply, inflammatory manifestations and, consequently, shortens the operation time, and postoperative therapy improves results, reducing the frequency of postoperative relapses and reducing the formation of adhesions. Before starting treatment with the drug, it is recommended to exclude pregnancy and stop taking hormonal contraceptives, but during the first two months of using the drug, you need to use other (neg Ormonal) methods of contraception. In the initial stage of drug treatment, it is possibledevelopment of ovarian cysts. Repeated treatment should be started only after a thorough assessment of the relationship between the expected benefit and the potential risk of osteoporosis. In metastatic prostate cancer buserelin (400 μg 3 times a day) is comparable in effectiveness to orchiectomy; its combination with cyproterone (50 mg per day for 2 weeks or for a long time) does not improve the results of treatment. In metastatic prostate cancer buserelin (p <0.05) and orchiectomy, diethylstilbestrol, and methotrexate (p <0.0001). In the endometriosis of stage I-II, it is inferior (or comparable in effectiveness) to the relapse-free survival of the combination of orchiectomy and diethylstilbestrol buserelin (intranasal at 1200 mg per day for 6 months) provides a significant reduction in dysmenorrhea, pelvic pain and dyspareunia both during treatment and within 12 months after its completion. In 19% of patients, spontaneous spontaneous regression of the disease is possible. Buserelin (900-1200 mg per day) is comparable in effectiveness with danazol (400-800 mg per day) in relieving symptoms of endometriosis with a higher incidence of a menopausal-like clinical picture and headache and a lower frequency of weight gain, myalgia and acne.After discontinuation of treatment, relapse of pain syndrome is noted in 50% of patients. In the treatment of infertility due to endometriosis, the probability of pregnancy for 18 months is 43-48% (OR 1.3; 95% CI 0,97-1,76) that does not justify the risk of side effects when using analogues releasing factor lutropina and does not allow to recommend them for treatment. Comparable in efficiency with gestrinone and provides therapy success rate of 33-36% at worst subjective tolerance (p <0.001) .If uterine leiomyoma buserelin (900 mg per day for 3 months) provides a decrease in tumor volume by 47.2% (p <0.05) and an increase in the concentration of hemoglobin from 102 ± 5 g / l to 134 ± 6 g / l (p <0, 05), exceeding danazol (at a dose of 400 mg per day) in the frequency of tumor size reduction (76.1 vs. 56.7%). In general, the use of analogues of releasing factors lutropina for 3-4 months before the expected hysterectomy for uterine fibroids leads to a marked reduction in uterine volume and fibroid size of the hearth, the correction of hemoglobin, some reduction in intraoperative blood loss and time of the operation, and in some cases - it is possible to replace the medial laparotomy access with a transverse (Pfannenstil) or perform a vaginal myomectomy instead of a laparotomy.There is not enough information to recommend them for routine use to all women. At the same time, these drugs can be used to treat patients with very large uterine sizes requiring mid laparotomy and preoperative anemia. In metastatic breast cancer, a combination of Buserelin and chemotherapy in CAF regimenscyclophosphamide, doxorubicin, adriamycin, fluorouracil) and CMF (cyclophosphamide, methotrexate, fluorouracil) provides a more reliable suppression of ovarian function, while the depot form is more effective than nasal. In a widespread receptor-positive breast cancer in premenopausal women, the combination of buserelin and tamoxifen is superior to buserelin and tamoxifen in monotherapy. In the latter case buserelin is comparable in effectiveness to tamoxifen and provides a response rate of 28-48%, a median relapse-free survival rate of 9.7 months (vs. 6.3 and 5.6 months, respectively, p = 0.03), a median overall survival rate of 3.7 years (vs. 2 , 5 and 2.9 years, respectively, p = 0.01) and an actuational five-year survival rate of 34.2% (95% CI 20.4-48.0%) vs. 14.9% (CI 3.9-25.9 % and 18.4%,95% CI, 7.0-29.8%, respectively). Induction of ovulation with recombinant human follicle stimulating hormone, the addition of buserelin (0.5 mg once) increases the number of oocytes in metaphase II (p <0.02) and decreases the concentration of follicle-stimulating hormone, lutropine, progesterone and estradiol (p <0.001), which prevents premature ripening of oocyte (compared with the use of chorionic gonadotropin in a dose of 10 thousand IU), reduces the likelihood of pregnancy (6 vs. 36%, p = 0.002) and increases frequency of early miscarriages (79 and 4%, p = 0.005). Induction of folliculogenesis before in vitro fertilization, the combination of buserelin and menopausal gonadotropin is comparable in effectiveness to that of clomiphene and menopausal gonadotropin, providing a fertility rate of 75.8-76.5%. In endometriosis and infertility due to endometriosis , buserelin in the form of an implant (6.6 mg) is superior to intranasal application (1200 mg per day) in reducing the size of the focus of endometriosis. When stimulating ovulation during extracorporeal fertilization, depot form analogs of lutropin releasing factor are comparable in effectiveness with daily (subcutaneous or intranasal) application in the probability of pregnancy (OR 0.94, 95% CI 0.65-1.37),but with the use of depot forms, the consumption of drugs and the duration of the stimulation period increase, which increases the cost of treatment. In porphyria, the use of buserelin in the above dosing regimen has made it possible to eliminate cyclic and premenstrual exacerbations in two patients (complete remission within 11 months of treatment).