Treatment of hormone-dependent prostate cancer, progressive.
active substance: leuprorelin acetate;
1 implant contains 5 mg of leuprorelin (in the form of leuprorelin acetate);
excipient: polylactic acid.
Main physical and chemical properties: implant from white to slightly yellowish color with a homogeneous surface.
Gonadotropin-releasing hormone analogues.
The active substance is leuprorelin acetate, is a synthetic analogue of the natural hypothalamic gonadotropin-releasing hormone (LHRH), which controls the secretion of gonadotropin-releasing hormones LH (luteinizing hormone) before FSH (and lustipole). These hormones stimulate the synthesis of steroids by the gonads.
In contrast to physiological LHRH, which is secreted by the hypothalamus in a pulse-like manner, leuprorelin acetate (also called LHRH agonist) provides a permanent blockade of pituitary LHRG receptors throughout the treatment period, resulting in the pituitary gland stops receiving and responding to the response. Due to the reverse suppression of gonadotropin secretion by the pituitary gland, there is a decrease in testosterone levels, which affects the growth of prostate cancer tissue. Under normal circumstances, this tissue is stimulated by dihydrotestosterone, which is released in response to a decrease in testosterone levels in prostate cells.
Constant intake of leuprorelin acetate provides a decrease in the number and sensitivity (so-called down-regulation) of pituitary receptors and, as a consequence, a decrease in levels of LH, FSH and DHT. This, in turn, leads to a decrease in testosterone levels to the castrate range. Animal studies have shown an antiandrogenic effect and inhibition of prostate cancer growth. According to experimental and clinical studies, a three-month course of treatment with leuprorelin acetate after initial stimulation provides a decrease in gonadotropin secretion. In men, subcutaneous administration of leuprorelin acetate initially causes an increase in LH and FSH levels, accompanied by a temporary increase in testosterone and dihydrotestosterone levels. Due to the short-term deterioration of the clinical picture in the first 3 weeks of treatment, which was observed in isolated cases, men with prostate cancer at the initial stage of treatment can be prescribed additional antiandrogens. Prolonged use of leuprorelin acetate, in contrast, causes a decrease in LH and FSH levels. Androgen levels in men are reduced to values that are fixed after surgical removal of both testicles. These changes usually occur 2-3 weeks after the start of therapy and persist throughout subsequent treatment. However, when considering treatment with leuprorelin acetate, it is necessary to assess the hormonal sensitivity of prostate cancer tissue and the potential therapeutic benefits of orchiectomy. If necessary, orchiectomy can be replaced by 3-month doses of leuprorelin acetate. According to the obtained data, constant intake of leuprorelin acetate can maintain castrated testosterone levels for more than 5 years.
After injection of the implant, a constant release of leuprorelin acetate (the active substance of the drug) from the lactic acid polymer begins, which lasts up to 182 days (26 weeks). Over time, the polymer is absorbed in the same way as it is with surgical suture material.
Within 2 hours after a single dose, the level of leuprorelin reaches the highest level of 5216 pg / ml (5.2 ng / ml). The area under the pharmacokinetic curve during three months of treatment with the drug is 32.4 ng / ml * d. Serum levels are maintained for up to 182 days (26 weeks) after administration. Serum levels are maintained for up to 182 days (26 weeks) after administration. The volume of distribution of leuprorelin in men is 36 liters; the total clearance is 139.6 ml / min
Repeated administration results in a permanent decrease in testosterone levels to the level of castration (sterility), in the absence of a temporary increase in testosterone levels that occurs after the first injection.
In patients with impaired renal or hepatic function, leuprorelin levels were determined at the same level as in patients with healthy kidneys and liver. Serum leuprorelin levels were higher in some patients with chronic renal failure. However, this observation is unlikely to be clinically relevant.
Treatment of progressive hormone-dependent prostate cancer.
Hypersensitivity to leuprorelin or other analogues of gonadotropin-releasing hormone or polylactic acids.
It should not be used in women or children.