Buy Buserelin-depot lyophilisate for the preparation of suspension intramuscularly 3.75 mg in pharmacies

Buy Buserelin-depot lyophilisate for the preparation of suspension intramuscularly 3.75 mg in pharmacies

Buserelin-depot Buy Buserelin-depot in pharmacies DOSAGE FORMS lyophilisate for preparing a suspension for intramuscular injection. entered prolong. active 3.75 mg lyophilized powder for the preparation of intramuscular solution 3.75 mg

MANUFACTURERS Deco Company (Russia) Pharm-Sintez (Russia)

GROUP Antiandrogens

COMPOSITION Active ingredient: buserelin acetate 3.75 mg in the form of a free peptide.

INTERNATIONAL NON-PROPENTED NAME Buserelin

SYNONYMS Buserelin, Buserelin FSintez, Buserelin-long FS, Buserelin acetate solution

PHARMACOLOGICAL ACTION Pharmacodynamics. A synthetic analogue of natural gonadotropin-releasing hormone (GnRH). Buserelin competitively binds to the receptors of the cells of the anterior pituitary gland, 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 after 12-14 days) to a complete blockade of the gonadotropic function of the pituitary gland, thus inhibiting the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). As a result, there is a suppression of the synthesis of sex hormones in the gonads, which is manifested by a decrease in the concentration of estradiol in the blood plasma to post-menopausal values ​​in women and a decrease in testosterone content to a post-castration level in men. The concentration of testosterone with continuous treatment for 2-3 weeks decreases to the level characteristic of the orchiectomy state, i.e. pharmacological castration is caused. Pharmacokinetics. Bioavailability is high. The maximum plasma concentration is reached approximately 2-3 hours after intramuscular administration and remains at a level sufficient to inhibit the synthesis of gonadotropins by the pituitary gland for at least 4 weeks.

INDICATIONS FOR USE Hormone -dependent prostate cancer, breast cancer, endometriosis (pre- and postoperative periods), uterine fibroids, endometrial hyperplastic processes, infertility treatment (during an in vitro fertilization (IVF) program.

CONTRAINDICATIONS Pregnancy, breastfeeding, hypersensitivity to the components of the drug.

SIDE EFFECTS Allergic reactions: urticaria, skin hyperemia, rarely - angioedema. In women, typical adverse reactions are a manifestation of the achieved hypoestrogenic state - “pharmacological menopause”: From the central nervous system: frequent mood swings, sleep disturbances, depression, headache. From the endocrinological status: hot flashes, increased sweating, vaginal dryness, decreased libido, pain in the lower abdomen, demineralization of bones, rarely - menstrual-like bleeding (usually during the first weeks of treatment). In men, during the treatment of prostate cancer - during the first 2-3 weeks after the first injection, it can cause exacerbation and progression of the underlying disease, which is associated with stimulation of the synthesis of gonadotropins and, accordingly, testosterone, gynecomastia, a transient increase in the concentration of androgens in the blood (rarely - ossalgia , urinary retention, renal edema, muscle weakness in the lower extremities, lymphostasis). Other: in isolated cases (the cause-and-effect relationship has not been clearly established) - pulmonary embolism, dyspeptic disorders.

INTERACTION The simultaneous use of Buserelin with drugs containing sex hormones (for example, in the mode of ovulation induction) may contribute to the occurrence of ovarian hyperstimulation syndrome. With simultaneous use, Buserelin may reduce the effectiveness of hypoglycemic agents.

DOSAGE AND ADMINISTRATION For hormone-dependent prostate cancer: 3.75 mg intramuscularly (IM) every 4 weeks; In the treatment of endometriosis, endometrial hyperplastic processes: 3.75 mg IM once every 4 weeks. Treatment begins in the first five days of the menstrual cycle. Duration of treatment - 4-6 months; For the treatment of uterine fibroids: 3.75 mg IM once every 4 weeks. Treatment begins in the first five days of the menstrual cycle. Duration of treatment - 3 months before surgery, in other cases - 6 months; When treating infertility using in vitro fertilization (IVF): 3.75 mg IM once on the 2nd day of the menstrual cycle.

OVERDOSE Currently, no cases of overdose with Buserelin have been reported.

SPECIAL INSTRUCTIONS For women. Patients with any form of depression during treatment with the drug should be under close medical supervision. Ovulation induction should be performed under strict medical supervision. In the initial stage of treatment with the drug, the development of ovarian cysts is possible. Before starting treatment with the drug, it is recommended to exclude pregnancy and stop taking hormonal contraceptives, however, during the first two months of using the drug, it is necessary to use other (non-hormonal) methods of contraception. In men. In order to effectively prevent possible side effects in the first phase of the drug’s action, it is necessary to use antiandrogens two weeks before the first injection of buserelin depot and for two weeks after the first injection. Influence on the ability to drive a car and other mechanisms. Caution should be exercised when prescribing the drug to patients engaged in potentially hazardous activities that require increased attention and speed of mental and motor reactions.

STORAGE CONDITIONS Store in a place protected from light and out of reach of children, at a temperature of 8 to 20

The role of buserelin in the treatment of common forms of prostate cancer (PCa).

The role of buserelin in the treatment of common forms of prostate cancer (PCa).

S.V. Mishugin, A.A. Drobyazko, A.A. Mordovin, A.A. Gritskevich, I.G. Rusakov.

Since 1941, following a study published by Huggins and Hodges demonstrating the dependence of prostatic cells on androgens, hormone therapy (HT) has been the mainstay of treatment for locally advanced and metastatic PCa [1]. The basis of any HT strategy is the principle of androgen blockade, which can be achieved by turning off the production of endogenous testosterone [2], as well as stopping the androgenic effect due to the competitive action of medicinal agents [3].

Currently, the main method of androgen deprivation is medical castration using LHRH agonists [4]. Today, preference is given to drug androgen deprivation rather than surgical castration. This is due to the psycho-emotional state of patients after surgery and many side effects, with an equal clinical effect, which is reflected in a number of studies. It is also possible to use intermittent hormone therapy regimens, which leads to regression of adverse reactions during temporary drug withdrawal [5,6].

One of the drugs of this group widely used in clinical practice is buserelin.

The drug buserelin is enclosed in microspheres with different resorption periods, the basis of which is a biosoluble copolymer of DL lactic and glycolic acids. Microspheres in the form of an aqueous suspension are injected deeply intramuscularly. After injection of the drug, a gradual release of the LHRH analogue from the surface of the microspheres begins, which during the first few days leads to stimulation of the synthesis of gonadotropins, and then to desensitization of the pituitary gland and blockade of the pituitary-gonadal axis. Subsequently, the microspheres, undergoing biodegradation in tissues, slowly release the LHRH analogue they contain, long-term maintaining the concentration of the drug in the blood necessary for desensitization of the pituitary gland [7,8,9].

From the beginning of December 2011 to December 2014, we observed 142 patients with prostate cancer aged 56 to 70 years who were treated with LHRH analogues. The average age of patients was 64.6 years.

Before the start of treatment, all patients underwent an examination, which included a survey, examination, and determination of PSA levels in the blood serum (at least 7-10 days after transrectal/transurethral manipulations). To assess the local extent of the tumor process, a digital rectal examination was performed in all cases. To determine the location, size and extent of the primary tumor, all patients underwent TRUS of the prostate. After receiving the measurement data, the prostate volume was calculated using software. In order to identify regional and distant metastases, transabdominal ultrasound of the abdominal organs, retroperitoneum and pelvis, chest radiography, and bone scanning were performed in all cases. To clarify the extent of the primary tumor and the condition of the pelvic lymph nodes, patients underwent CT or MRI of the pelvis. Also, all patients underwent clinical and laboratory tests (analyses of the general, biochemical composition of the blood, its coagulation system, general urine analysis and bacteriological examination of urine (as indicated), electrocardiography). To verify the diagnosis, all patients underwent transrectal biopsy of the prostate gland under ultrasound guidance.

75 had locally advanced PCa, 67 had generalized PCa (Table 1). The patients are divided into two groups.

In the first group (n=55), patients received therapy with the drug Buserelin-depot, in the second (n=87) - one of the other LHRH analogues (goserelin, leuprorelin, triptorelin). The period of drug treatment was at least 6 months.

Table 1. Distribution of patients by disease stage

At the time of inclusion in the study, 137 (96.5%) of 142 men had complaints. The main symptoms of the disease were urinary disorders (77.6% of cases in the group of patients receiving Buserelin and 66.7% in the group receiving other LHRH analogues), pain of various locations caused by the primary tumor (5.5% of cases in the first group and 13.8% in second), bone metastases (30.9% of patients from the first group and 35.6% from the second), as well as impaired outflow of urine from the collecting system (23.6% of patients from the first group and 17.2% from the second) (Table 2 ).

Table 2. Complaints of 142 patients with advanced prostate cancer.

The purpose of the study was to evaluate the effectiveness of the drug Buserelin-depot at a dose of 3.75 mg, with a dosage frequency of 1 time in 28 days, by studying the dynamics of testosterone, PSA levels, and prostate volume; to determine the effect of the drug on the activity status of patients and the level of pain and compare it with a group of patients treated with other LHRH analogues, and monitor side effects.

Patients of group 2 received one of the LHRH analogues also once every 28 days. In addition to hormone therapy, patients with bone metastases were treated with other specialized treatment methods: palliative distant therapy for bone metastases, treatment with zoledronic acid.

During histological verification of the diagnosis, moderately and poorly differentiated forms of prostate cancer predominated (Table 3).

Table 3. Histological types of tumors

For patients in both groups, before the start of treatment, PSA and testosterone levels were determined, activity status was assessed according to the Karnofsky scale, pain status according to the WHO scale, and prostate volume was measured using TRUS.

Subsequently, all patients underwent PSA and testosterone monitoring every 4 weeks; after 3 months, a control determination of prostate volume was performed; upon completion of treatment, the activity status and pain status of the patients were re-determined.

All patients had PSA above normal before treatment. The average PSA value in the first group was 107.3 ng/ml, in the second - 97.5 ng/ml. After the start of treatment, most patients had positive PSA dynamics, characterized by a sharp decrease in the first 2 months of treatment, after which gradual regression and stabilization of indicators occurred.

During therapy with Buserelin-depot in patients with prostate cancer, a consistent decrease in average PSA values ​​was revealed from 107.3 ng/ml to 37.8 ng/ml after 2 months, to 27.9 ng/ml after 4 months, to 3.3 ng /ml after 6 months. In the group of patients treated with other LHRH analogues, there was also a regression of the average PSA value: from 97.5 ng/ml to 24.05 ng/ml after 2 months, to 12.35 ng/ml after 4 months, to 3. 1 ng/ml after 6 months.

The dynamics of prostate volume correlated with a decrease in PSA levels. During therapy with Buserelin-depot in patients with prostate cancer, a decrease in the volume of the prostate gland was noted from 55.9 to 39.8 cm3 by 6 months of treatment (-28.8%). The average volume of the prostate gland in patients of group 2 was 63.9 cm3. After 6 months of treatment, the volume of the gland decreased by 33.2% (42.7 cm3). The registered change in the volume of the prostate gland during treatment became a prerequisite for reducing the symptoms of urinary disorders in the vast majority of patients in the study groups.

The average testosterone level in patients of the first group before treatment was 17.7 ng/ml, in the second group the average value was 14.21 ng/ml.

During the therapy, a decrease in testosterone levels to post-castration values ​​was achieved in patients of both groups within a month after the start of hormone therapy. In the first group: from initial 17.7 to 2.12 ng/ml after 2 months and 0.41 ng/ml after 4 months of treatment. In the second group, after 2 months there was a decrease in the average testosterone level from 14.21 to 1.53 ng/ml and to 0.39 ng/ml after 4 months of treatment. After 4 months of treatment, no further significant changes in testosterone levels were observed.

The treatment provided was intermittent. Considering the positive results of 6 months of therapy in the buserelin group and the other LHRH agonists group, further use of the drugs was discontinued with subsequent dynamic monitoring of PSA and testosterone levels.

The dynamics of testosterone levels were monitored in the first and second groups of patients after discontinuation of treatment with LHRH analogues. When analyzing the data obtained, it turned out that an increase in testosterone levels above castration values ​​when using buserelin occurs 1 month after completion of treatment, and in the second group of patients, where other LHRH analogues were used, this was noted after 1.8 months. Further observation showed that the time to restore initial testosterone levels occurred in the buserelin group after 2.4 months, and when using other LHRH analogues after 3.2 months.

In 822 patients before treatment, the activity status on the Karnofsky scale was 80-100%, in 35 – 60-70% and in 25 patients – 50-60% when assessing both groups. It should be noted that patients with generalized forms of prostate cancer had a lower status index. Upon completion of HT, a change in activity status in a positive direction occurred in 5 (9%) patients of group 1 and in 8 (9.2%) in the group of patients receiving therapy with LHRH agonists (Table 4).

Table 4. Activity status of patients in groups before and after treatment

Before the prescription of hormonal therapy, 66 patients (46.5%) had pain syndrome. 76 patients did not require pain relief. 22 (15.5%) patients took non-narcotic analgesics irregularly, 16 (11.3%) patients required inconsistent use of narcotic analgesics to reduce pain, and 28 (19.7%) patients constantly took non-narcotic analgesics. After 6 months of drug use, the number of patients who did not require analgesics in both groups increased by 5.8%. At the same time, none of the patients was able to completely abandon the use of analgesic drugs (Table 5).

Table 5. Dynamics of pain status of patients in groups according to the WHO scale.

When using Buserelin-depot, the vast majority of patients complained of hot flashes and sweating, which was also noted by patients treated with other LHRH agonists. There were no cases of urinary retention, muscle weakness in the lower extremities, edema or lymphostasis. It should be noted that most side effects are completely reversible after discontinuation of the drugs.

Experience with the use of Beserelin Depot has shown that it is highly effective for the treatment of hormone-dependent prostate cancer. The use of Buserelin-depot leads to a decrease in PSA levels, ensures a stable decrease in serum testosterone levels to the post-castration level, a decrease in the volume of the prostate gland and a decrease in symptoms of urinary disorders in the absence of serious side problems. A number of patients showed an increase in activity status, as well as a decrease in the need and dose of analgesics.

An earlier restoration of the initial testosterone level was noted after completion of the course of Buserelin-depot compared to other LHRH analogues, which reduces the severity of side effects of HT and improves the quality of life of patients.

Buserelin depot can be recommended for use as independent therapy or in combination with other hormonal drugs in patients with prostate cancer.

Bibliography

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2. Oefelein MG, Feng A, Scolieri MJ, et al. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology 2000;56:1021-4.
3. Evans CP, Fleshner N, Fitzpatrick JM, et al. An evidence-base approach to understanding the pharmacological class effect in the management of prostatic diseases. BJU Int 2005;95:742-9.
4. Seidenfeld J., Samson DJ, Hasselblad V. et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Annals of Internal Medicine, 2000, v. 132, issue 7, p. 566-577.
5. Anderson J, Abrahamsson PA, Crawford D, et al. Management of advanced prostate cancer: can we improve on androgen deprivation therapy. BJU Int 2008;101:1497-1501.
6. Heidenreich A, Pfister D, Ohlamann CH, et al. Androgen deprivation for advanced prostate cancer. Urologe 2008;47:270-83.
7. Klioze SS, Miller MF, Spiro TP. A randomized, comparative study of buserelin with DES/ orchiectomy in the treatment of stage D2 prostatic cancer patients. Am J Clin Oncol 1988;11(Suppl 2):S17-S182
8. Huben RP, Murphy GP. A comparison of diethylstilbestrol or orchiectomy with buserelin and with methotrexate plus diethylbestrol or orchiectomy in newly diagnosed patients with clinical stage D2 cancer of the prostate. Cancer 1988; 62:1881-7.
9. Bruun E, Frimodt-Moller C. The effect of buserelin versus conventional antiandrogenic treatment in patients with T2-4NXM1 prostatic cancer. A prospective, randomized multicentre phase III trial. The “Danish Buserelin Study Group”. Scand J Urol Nephrol 1996;30:291-7.