Index of drugs

Palliative treatment of patients with advanced, hormone-dependent prostate cancer.

1 implant contains 3.6 mg or 5 mg of leuprorelin in the form of acetate.

A synthetic analogue released from the hypothalamus of the LHRH factor, which controls the release of the luteinizing hormone LH and the follicle stimulating hormone FSH from the anterior lobe of the pituitary gonadotropin. These hormones stimulate the synthesis of gonadal steroids. In contrast to physiological LHRH, which is released from the hypothalamus in a pulsatile manner, leuprorelin acetate blocks long-term continuous LHRH receptors in the pituitary gland, thus causing their insensitivity after initial short-term stimulation. As a result, there is a transient suppression of gonadotropin release from the pituitary gland, after which testosterone levels decrease, affecting the growth of prostate tissue that has undergone neoplastic changes. This tissue is physiologically stimulated by dihydrotestosterone, produced by the reduction of testosterone in prostate cells. Continuous administration of leuprorelin acetate leads to a reduction in the number and / or sensitivity of the receptors in the pituitary gland and consequently to a reduction in LH, FSH and DHT, with testosterone levels reduced as a result of castration; without a transient increase in testosterone levels, as is the case after the first injection. After the implant is injected, leuprorelin acetate is continuously released from the polymer (consisting of: glycolic acid and lactic acid - 3.6 mg implant, polylactic acid - 5 mg implant) for 1 month. The polymer is absorbed in the same way as the material from which the surgical sutures are made. The measurable concentration of leuprorelin in the serum persists for over 1 month. After two injections of 3.6 mg implant, made 28 days apart, the measurable leuprorelin concentration is observed up to 67 days after the first injection. During 3 months of treatment with the 5 mg implant, the measurable serum concentration is maintained up to 26 weeks after administration. In some cases, higher concentrations of leuprorelin were observed in patients with impaired renal function. In contrast, leuprorelin concentrations were lower in patients with hepatic impairment. It seems that these observations have no significant clinical significance.

Hypersensitivity to leuprorelin, other GnRH analogues or to any of the excipients. Confirmed lack of cancer dependence on hormones. Women. Children.

In the initial phase of treatment, testosterone levels increase first (which may be associated with relapse or worsening of tumor growth and may include worsening of existing or new symptoms - appearance or worsening of bone pain, narrowing of urinary outflow pathways with its effects, spinal cord compression, weakness or leg tingling, lymphoedema), and then decreased over 2 weeks. After 2-4 weeks, testosterone levels are comparable to those observed after bilateral testicular removal and persist throughout the treatment period. To reduce the risk of relapse, treatment with androgen suppressant may be started 3 days before starting leuprorelin and continued for the first 2-3 weeks of treatment. Patients with spine or brain metastases and / or patients with urinary outflow obstruction should be closely monitored (ideally in the hospital), especially in the first weeks of treatment (in these patients spinal cord compression and renal dysfunction have been observed in these patients). The response to treatment with the implant can be monitored - determining the acid phosphatase activity and the concentration of PSA and total testosterone, which should be determined at the beginning and after 3 months of using the implant. Prostate cancer is susceptible to androgens if, after 3 months, testosterone levels are at the castration level (≤0.5 ng / ml) and the PSA value is reduced. An early significant reduction in PSA (approximately 80% of baseline) can be considered as a predictive indicator for a long-lasting response to inhibition of androgen secretion.In this situation, ablation therapy is indicated. If the levels of PSA remain unchanged or increased in patients with inhibited testosterone secretion, prostate cancer is insensitive to androgens. In such cases, the continuation of hormonal ablation therapy is not appropriate. However, if a patient develops a clinical response (eg, reduction of pain and dysentic symptoms, reduction in prostate size), false negative results should be considered. In these rare cases, the implant should be continued for another 3 months and PSA levels should be monitored and clinical signs monitored. The success of treatment should be monitored at regular intervals (especially in the case of signs of progressive disease despite appropriate treatment) by a clinical examination (a palpable examinationper rectum prostate gland, sonographic examination, bone densitometry, computed tomography) and control of phosphatase and / or PSA and serum testosterone. Patients may have metabolic changes (eg Glucose intolerance or worsening of existing diabetes) and cardiovascular disorders. Patients with a high risk of metabolic or cardiovascular disorders should be carefully examined before treatment and adequately controlled during anti-androgen therapy. In patients treated with GnRH agonists, there is an increased risk of depression (including severe) episodes; patients should be informed of this risk and appropriate treatment should symptoms occur.

Not applicable - the drug is contraindicated for use in women.

Very common: hot flashes with paroxysmal sweating, bone pain, decreased libido, impotence, increased sweating. Common: increased appetite, sleep disturbances, mood changes, depression, paresthesia, nocturia, painful urination, pollakiuria. Uncommon: decreased appetite, increased or decreased blood Glucose, weight gain or loss, headache, dizziness, hypertension or hypotension, difficulty in breathing, diarrhea, alopecia, dry skin and mucous membranes, night sweats, urinary retention , testicular size reduction, testicular pain, gynecomastia, increased LDH, ALP, AST, ALT, and GGT. Rare: thrombosis, pulmonary embolism. Very rare: generalized allergic reactions (fever, skin rash, pruritus, eosinophilia), anaphylactic reactions, transient disturbances of taste, hemorrhage to the pituitary gland (after initial administration of leuprorelin to patients with pituitary adenoma), nausea, vomiting, joint pain, back pain, pains Muscle, swelling, fatigue, local skin reactions (eg redness or induration at the injection site). Isolated cases: ulcer at the injection site; one case of central retinal artery thrombosis. Frequency unknown: QT interval prolongation. There have been reports of cases of interstitial pneumonia, mainly in Japan. Hypogonadism associated with long-term treatment with LHRH analogs and / or removal of testes may lead to osteoporosis with an increased risk of fractures.

Subcutaneously. Adult men: 3.6 mg every month or 5 mg every 3 months. Implant 3.6 mg: in exceptional cases, after the second administration, the Next dose may be delayed for up to 2 weeks, usually without reducing the therapeutic effectiveness in the majority of patients. Implant 5 mg: if in exceptional cases the deadline for the next dose is shifted by a maximum of 4 weeks, the therapeutic efficacy in most patients should not be reduced. It is recommended to implement supportive antiandrogen treatment for about 5 days before starting the use of leuprorelin. Treatment of advanced, hormone-dependent prostate cancer is generally long-term. At the beginning and after 3 months of using the implant, both PSA and total testosterone levels should be determined. Prostate cancer is susceptible to androgens if, after 3 months, testosterone levels are at the castration level (≤0.5 ng / ml) and the PSA value is reduced. An early significant reduction in PSA (approximately 80% of baseline) can be considered as a predictive indicator for a long-lasting response to inhibition of androgen secretion. In this situation, ablation therapy is indicated. If the levels of PSA remain unchanged or increased in patients with inhibited testosterone secretion, prostate cancer is insensitive to androgens.In such cases, the continuation of hormonal ablation therapy is not appropriate. However, if a patient develops a clinical response (e.g., pain reduction and dysentic symptoms, a reduction in prostate size), the possibility of false negative results should be taken into account. In these rare cases, the drug should be continued for another 3 months and the PSA level should be checked again and the clinical symptoms monitored very closely.Special groups of patients. No dosage adjustment is necessary in patients with renal or hepatic impairment as well as in elderly patients. The drug is contraindicated in children and adolescents.Method of administration. One implant is injected subcutaneously into the front wall of the abdominal cavity. Before injection you can use a local anesthetic.