Eligard 45 Mg 1 Piece Lyophilisate for the preparation of a solution for subcutaneous administration Astellas Pharma Europe Bv

Pharmacological properties of the drug Eligard

Leuprorelin acetate is a synthetic non-peptide analogue of natural gonadotropin-releasing hormone, which, with prolonged use, inhibits the secretion of pituitary gonadotropin and inhibits testicular steroidogenesis in men. It is more effective than the natural hormone and its effects are reversible after stopping treatment. The administration of leuprorelin acetate initially leads to an increase in circulating levels of LH and FSH, resulting in an increase in the levels of gonadal steroids, testosterone and dihydrotestosterone in men for some time. With prolonged use of leuprorelin acetate, the levels of LH and FSH decrease. In men, testosterone levels drop to castration levels (50 ng/dL). This occurs within 3–5 weeks after the start of treatment. The average testosterone level after 6 months of treatment is for leuprorelin acetate 7.5 mg - 6.1 (±0.4) ng/dl and leuprorelin acetate 22.5 mg - 10.1 (±0.7) ng/dl, respectively, which is comparable to its level after bilateral orchiectomy. In all patients participating in the clinical study, when using leuprorelin acetate 7.5 mg, the castration level was achieved after 6 weeks (in 94% of patients before the 28th day and in 98% before the 35th day); leuprorelin acetate 22.5 mg - in all patients the castration level was achieved after 5 weeks (in 99% of them - before the 28th day). Most patients had testosterone levels below 20 ng/dL. Prostate-specific antigen levels decreased by 94% with a dose of 7.5 mg for 6 months and by 98% with a dose of 22.5 mg, respectively. Research results have shown that with long-term treatment, testosterone levels remain below castration levels for up to 7 years and even until the end of life. Absorption : in patients with advanced prostate carcinoma, after the first injection of leuprorelin acetate 7.5 mg, the maximum concentration of leuprorelin in the blood serum increases sharply to 25.3 ng/dL 4-8 hours (Cmax) after injection; after administration of leuprorelin acetate 22.5 mg - Cmax increases to 127 ng/dl after 4.6 hours. After an initial increase after each injection (plateau phase from 2 to 28 days after administration of leuprorelin acetate 7.5 mg and from 3 to 84 days after administration of leuprorelin acetate 22.5 mg), serum levels remained relatively stable for leuprorelin acetate 7.5 mg 0.28-1.67 ng/ml and leuprorelin acetate 22.5 mg - 0.2-2.0 ng/ ml. There are no data on the accumulation of the substance with repeated injections. Distribution : The mean volume of distribution of leuprorelin after intravenous administration to healthy male volunteers was 27 L. Binding to human plasma proteins in vitro for leuprorelin acetate 7.5 mg was 43-49%, for leuprorelin acetate 22.5 mg - 47-49%, respectively. Elimination : When 1 mg of leuprorelin acetate was administered intravenously to healthy volunteers, the average clearance was 8.34 L/h with a final half-life of 3 hours. Elimination studies have not been conducted.

Prostate cancer is a national problemProstate cancer (PCa) in Russia is gradually acquiring the status of a national problem. In the structure of cancer incidence among men in the Russian Federation, this localization is in the 3rd place, and in terms of the magnitude of the increase, it is in the 1st ranking place. The introduction into clinical practice of determining the level of prostate-specific antigen (PSA), along with the improvement of diagnostic techniques, has led to a gradual migration of the stage of the disease towards a decrease in the frequency of detection of common tumors. However, 16% of patients at initial treatment already have distant metastases, and prostate cancer ranks 2nd in mortality among malignant neoplasms [1].

The role of hormone therapy in the treatment of prostate cancer In 1941, Huggins and Hodges discovered the stimulating effect of androgens on the growth of prostate cancer cells. Numerous studies following this event have demonstrated that prostate adenocarcinoma consists of three cell populations: hormone-sensitive, hormone-dependent, and hormone-insensitive. Due to the initial numerical predominance of cell pools, the viability of which is determined by male sex hormones, PCa is an androgen-dependent tumor, uniquely sensitive to the blockade of androgen stimulation through hormone therapy (HT).

HT is used for all stages of the tumor process with the exception of localized forms of the disease, the cure of which is possible through local eradication of the primary lesion through radical prostatectomy, radiation therapy or various types of ablation. The method of choice in the treatment of locally advanced prostate cancer is irradiation, the results of which can be significantly improved through long-term androgen deprivation. For common forms of the disease, the only effective type of treatment is HT. The transition of PCa into the hormone-resistant phase is an indication for taxane-based chemotherapy; at the same time, to suppress residual hormone-sensitive and hormone-dependent pools, continued androgen deprivation is indicated. The main methods of HT used for prostate cancer are surgical castration, therapy with agonists and antagonists of luteinizing hormone releasing hormone (LHRH), estrogens, antiandrogens, as well as some agents of other groups. Androgen blockade can be carried out by castration, maximum androgen blockade (MAB - a combination of castration and antiandrogens), monotherapy with antiandrogens, a combination of 5α-reductase inhibitors with antiandrogens, and also using trimodal therapy (a combination of castration, antiandrogens and 5α-reductase inhibitors) [2] .

Medical castration with LHRH agonists is an attractive alternative to bilateral orchiectomy. Surgical castration is still one of the most common hormonal treatments used for PCa. Bilateral orchiectomy has a number of serious disadvantages, which include the risk of developing surgical complications, the irreversible nature of hormonal effects and severe psychological discomfort, which significantly worsens the quality of life of patients.

An attractive alternative to surgical castration, which eliminates moral injury and is associated with reversible changes in endocrine levels, is the use of LHRH agonists. One of the most studied agents in this group is leuprorelin, a synthetic non-peptide analogue of human LHRH. Leuprorelin has a longer half-life compared to natural LHRH, which is due to its greater affinity for receptors and the presence of resistance to protein degradation [3].

Eligard: advantages of a progressive LHRH agonist delivery system The use of leuprorelin occurs through subcutaneous or intramuscular injections. Leuprorelin was initially developed at a dose of 1 mg for daily administration. Subsequently, a depot form appeared, based on the technology of biodegradable polymer microspheres, inside of which the active substance is located. After parenteral administration of the drug, the microspheres gradually disintegrate and leuprorelin is released, which determines the prolonged action of the agent. Consistently, 1-, 3- and 4-month depot forms of leuprorelin were developed, which made it possible to avoid daily injections. A technology for surgical implantation of implants containing leuprorelin, released over 12 months, has also been proposed. However, implantation of this form of the agent is associated with a higher incidence of complications than injections.

Currently, a new drug has appeared in Russia, the active substance of which is leuprorelin - Eligard (Astellas Pharma). Its peculiarity lies in the unique delivery system of the active substance Atrigel, which is a biodegradable polymer matrix. After administration of the drug, a spherical implant is formed, which slowly biodegrades, leading to the gradual release of leuprorelin. Eligard exists in several forms, differing in the composition of the polymer matrix, which provides different rates of release of the active substance. Compared to Eligard depot microspheres, due to the delivery system, Atrigel contains a double dose of the active substance [4].

Doses and frequency of administration of Eligard: the less often the better Eligard is produced in the form of a combination of two sterile pre-filled syringes, one of which contains lyophilisate of leuprorelin acetate (10.2 mg for a dosage of 7.5 mg; 28.2 mg for a dosage of 22. 5 mg; 58.2 mg for a dosage of 45 mg), in the other - a solvent (330 mg for a dosage of 7.5 mg; 440 mg for a dosage of 22.5 mg; 426 mg for a dosage of 45 mg). Excess leuprorelin acetate compensates for losses in the syringe and needle.

Eligard is prescribed as a subcutaneous injection once a month at a dosage of 7.5 mg, once every 3 months at a dosage of 22.5 mg and once every 6 months at a dosage of 45 mg. Eligard is the only drug in Russia that can be used once every 6 months. The use of a 6-month depot form of leuprorelin provides a number of advantages for the patient and the doctor, one of which is the provision of high-quality treatment with a visit to the clinic only 2 times a year. This is especially important for men whose lifestyle involves long trips, and patients with limited physical activity. A six-month depot of LHRH agonist is also convenient for neoadjuvant therapy for irradiation of patients with locally advanced forms of PCa. In addition, administering the drug twice a year reduces the risk of post-injection complications [5]. According to S. Schulman (2007), almost 3/4 of patients are convinced that the possibility of using the drug once every 6 months can significantly improve their quality of life [6]. In a survey of urologists, 77% of doctors indicated that they preferred a 6-month depot of leuprolide over forms with a shorter duration of action [7].

Pharmacokinetics of Eligard 4-8 hours after the first injection of Eligard, the average level of leuprorelin concentration (Cmax) determined in the blood serum increases to 25.3, 127 and 82 ng/dl when using leuprorelin at a dose of 7.5, 22.5 and 45 mg respectively. After the initial increase, serum leuprorelin levels remain relatively stable (0.2-2 ng/ml). The plateau phase ranges from 2 to 28, 3 to 84 and 3 to 168 days for dosages 7.5; 22.5 and 45 mg respectively. Bonding with plasma proteins is 43-49%. When 1 mg of leuprorelin acetate was administered intravenously to healthy male volunteers, the average clearance was 8.34 L/h with a terminal half-life of approximately 3 hours. Eligard elimination studies were not conducted. Pharmacokinetic data from clinical trials confirm the constant and controlled release of leuprorelin from the Atrigel matrix within the time stated by the manufacturer [8].

Mechanism of action of Eligard Eligard causes long-term constant stimulation of LHRH receptors in the pituitary gland, which leads to a temporary increase in the level of sex steroids. Then there is a paradoxical decrease in stimulation of the expression of LHRH receptors with a subsequent decrease in the production of LH, follicle-stimulating hormone and, as a consequence, testosterone, the level of which decreases to castration values, on average within 2-4 weeks after the start of treatment [8].

Castration testosterone levels: Eligard versus traditional forms of LHRH analogues The ability to optimally control androgen levels is one of the most important characteristics of LHRH analogues. For many years, testosterone concentration was considered castration

According to clinical studies, Eligard is the only drug that leads to a persistent decrease in testosterone concentration to a level comparable to surgical castration, both when using 1-[18] and 3-[19], and when using 6-month [5 ] depot forms. The median testosterone level after 6 months of treatment with Eligard is 6.1±0.4; 10.1±0.7 and 10.4±0.53 ng/dL for dosages 7.5; 22.5 and 45 mg respectively. One- and 3-month depot forms of the drug allow you to achieve testosterone concentration

Table 1. Reduction of testosterone concentration and its maintenance when using traditional LHRH agonists and Eligard

0	0	1
>20	13-38	2	6	12
>50 after the first injection	0-12,5	0	1	1
>50 during treatment	0-10	0	0	0

The effectiveness of Eligard in prostate cancer Leuprorelin acetate is a well-studied drug that appeared on the pharmaceutical market in 1984. A number of studies have demonstrated the high effectiveness of the use of leuprorelin in patients with advanced prostate cancer in the form of monotherapy [20-23], as part of a permanent MAB [20, 23] and intermittent [24] modes (Table 2).

Table 2. Efficacy of leuprorelin acetate in advanced prostate cancer [20-25]

Author, year	Number of patients	Mode	Objective response to treatment, %	Median overall survival, months
R. Sharifi, M. Soloway 1990 [23]	56	Monotherapy (7.5 mg once every 28 days)	81	—
W. Bischoff, 1990 [21]	190	Monotherapy (3.75 or 7.5 mg once every 28 days)	84,1	25,3
ED Crawford et al., 1990 [22]	300	Monotherapy (3.75 mg once every 28 days)	—	27,9
E. Kienle, G. Lubben, 1996 [20]	102	Monotherapy (3.75 mg once every 28 days)	94,1	42,5
ED Crawford et al., 1990 [22]	303	MAB, continuous regimen (leuprorelin 3.75 mg once every 28 days + flutamide 750 mg/day)	—	35
E. Kienle, G. Lubben, 1996 [20]	71	MAB, continuous regimen (leuprorelin 3.75 mg once every 28 days + flutamide 750 mg/day)	94,4	33

The effectiveness of 1-, 3- and 6-month depot forms of leuprorelin with the Atrigel (Eligard) delivery system has been proven in clinical trials. In an open multicenter study, R. Perez-Marreno et al. [18] included 120 patients with advanced prostate cancer who were prescribed subcutaneous injections of Eligard at a dose of 7.5 mg once every 28 days for 6 months. During the treatment, there was no increase in the frequency of clinical manifestations of the disease, as well as significant changes in somatic status. Over 6 months, the median PSA concentration in the group decreased from 32.9 (0.1-639.1) to 3.2 (0.2-93.2) ng/ml, the average acid phosphatase level as a percentage of the norm fell from 140 to 39%.

An open-label, non-comparative, multicenter study conducted by FM Chu et al. [19], included 117 patients with advanced prostate cancer who received subcutaneous injections of Eligard at a dose of 22.5 mg every 3 months for 6 months. During therapy, there was no increase in the incidence of bone pain, pain during urination, or difficulty urinating. The somatic status in the group did not change. After 6 months, median PSA decreased significantly compared to the baseline level from 86.4±48.8 to 1.7±0.5 ng/ml. The average concentration of acid phosphatase during treatment decreased by 15% (from 5.7±1.8 to 4.8±0.1 IU).

At the Russian Scientific Research Center named after. N.N. Blokhin RAMS Eligard at a dose of 22.5 mg once every 3 months was administered subcutaneously to 38 patients with disseminated prostate cancer. Not a single observation recorded an increase in the intensity of clinical manifestations of the disease or changes in somatic status during therapy. A decrease in PSA concentration after the first injection was noted in all cases; the marker level decreased by 96.7%.

An open-label, multicenter study by ED Crawford et al. [5] included 111 patients suffering from advanced prostate cancer. All patients were prescribed Eligard at a dose of 45 mg once every six months for 12 months. After a year of therapy, the median PSA concentration in the group decreased by 97% (from 39.8±21.5 to 1.2±0.3 ng/ml).

Leuprorelin acetate is not inferior to other types of therapy in terms of lowering testosterone levels. A number of studies have compared the immediate and long-term results of the use of leuprorelin acetate and other methods of castration therapy. The Leuprolide Study Group (1984) conducted a comparative analysis of the effectiveness and safety of leuprolide (n=98) and diethylstilbestrol (n=101) in patients with disseminated prostate cancer who had not received previous treatment. Objective response rates (86% and 85%, respectively) and 1-year survival (87% and 78%) were not significantly different between the groups. There was a significant increase in the incidence of complications among patients receiving estrogens [25].

Several protocols have now been completed comparing the efficacy of leuprorelin acetate and the LHRH antagonist abarelix. In a randomized study, D. McLeod et al. [26], which included 271 patients with advanced prostate cancer, conducted a comparative analysis of the results of medical castration with leuprorelin acetate (n=91) and abarelix (n=180). It has been established that abarelix naturally causes a faster decrease in the concentration of serum testosterone to the castration level due to the absence of the flash effect induced by initial hyperandrogenemia. Both drugs allow one to achieve and maintain castration testosterone concentrations in 90% of patients during an observation period of 12 weeks. J. Trachtenberg et al. [27], who compared the effectiveness of leuprorelin acetate and abarelix in 255 patients with prostate cancer, found no differences between the drugs in terms of reduction in PSA and serum testosterone concentrations, with a slower rate of reduction in androgen levels in the group receiving the LHRH agonist.

Multicenter randomized studies have proven the same effectiveness of medical castration performed using all LHRH analogues, including leuprorelin, and bilateral orchiectomy. The objective response rates in the groups were 82 and 77%, time to progression was 52 and 53 weeks, and median survival was 119 and 136 weeks, respectively [28].

A meta-analysis performed by J. Seidenfeld [29] and including data from 1908 patients with prostate cancer from 10 studies (including 1 series of observations in which leuprorelin acetate was used) revealed that differences in overall and progression-free survival rates when using surgical castration, medical There are no castrations with estrogens or LHRH agonists. When comparing the effectiveness of leuprorelin acetate and bilateral orchiectomy, the risk ratio was 1.0994 (confidence interval 0.207-5.835). There was also no difference in treatment results depending on the type of LHRH agonist used (leuprorelin, buserelin, goserelin).

Safety and Tolerability of Eligard In completed clinical trials, Eligard was not associated with serious side effects or death. No treatment refusals due to treatment complications were registered. The side effects observed with the use of Eligard were mainly due to the pharmacological action of the drug and are characteristic of the group of LHRH agonists. The most common complications were hot flashes and transient discomfort at the injection site. In addition, a number of patients experienced malaise and weakness, testicular atrophy and gynecomastia. Most side effects were mild or moderate and were well tolerated by patients (Table 3) [5, 18, 19].

Table 3. Side effects of Eligard

By-effect	Eligard, %
By-effect	7.5 mg	22.5 mg	45 mg
Tides:
weak degree	44,2	48,7	33,3
moderate degree	11,7	10,3	24,3
severe	0,8	0	0
Weakness/malaise:
weak degree	3,3	6	7,2
moderate degree	0	0	4,5
severe	0	0	0
Nausea, vomiting:
weak degree	0	2,6	0
moderate degree	0	0,9	0
severe	0	0	0
Dizziness:
weak degree	3,3	3,3	0
moderate degree	0	0	0
severe	0	0	0
Testicular atrophy:
weak degree	4,2	1,7	5,4
moderate degree	0,8	0	0
severe	0	0	0
Decreased libido:
weak degree	0	0,9	0
moderate degree	0	0	0
severe	0,8	0	0
Gynecomastia:
weak degree	0,8	0,9	3,6
moderate degree	0,8	0	0
severe	0	0	0

Conclusion Eligard (leuprorelin acetate, Atrigel delivery system) is a synthetic analogue of LHRH that causes a rapid decrease in testosterone levels to a concentration comparable to that after surgical castration.
Eligard demonstrated significant benefits in terms of the depth of androgen suppression, as well as the frequency of transient increases in testosterone levels at baseline and during treatment, compared with other LHRH analogues, including leuprorelin microsphere-delivered formulations. Eligard is available in 1-, 3- and 6-month depot forms, which provides the opportunity for a flexible approach to individual development of a treatment regimen; The prolonged 6-month form of the drug allows you to reduce the frequency of visits to the doctor to 2 times a year and reduce the risk of post-injection complications. The effectiveness of Eligard is at least as good as other methods of castration therapy. Treatment with Eligard is associated with a low incidence of side effects and is well tolerated by patients. Literature:

Davydov M.I., Aksel E.M. Statistics of malignant neoplasms in Russia and the CIS countries in 2007. M., 2009.
Heidenreich A., Aus G., Bolla M. et al. EAU guidelines on prostate cancer. Eur Urol 2008;53:68–80.
Chrisp P., Sorkin EM Leuprorelin: a review of its pharmacology and therapeutic use in prostatic disorders. Drugs Aging 1991;1:487–509.
Perez-Marrero R., Tyler RC A subcutaneous delivery system for the extended release of leuprolide acetate for the treatment of prostate cancer. Expert Opin Pharmacother 2004;5(2):447–57.
Crawford ED, Sartor O., Chu F. et al. A 12-month clinical study of LA-2585 (45.0 mg): a new 6-month subcutaneous delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2006;175:533–6.
Schulman C. Assessing the attitudes to prostate cancer treatment among European male patients. BJU Int 2007;100(Suppl. 1):6–11.
Painter MR Reimbursement issues with hormonal therapies for prostate cancer. Rev Urol 2005;7:44–7.
Berges R. Eligard: pharmacokinetics, effect on testosterone and PSA levels and tolerance. Eur Urol Suppl 2005;4:20–5.
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.
Lin BJ, Chen KK, Chen MT, Chang LS The time for serum testosterone to reach castrate level after bilateral orchidectomy or oral estrogen in the management of metastatic prostatic cancer. Urology 1994;43:834–7.
Oefelein MG, Cornum R. Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm. J Urol 2000;164:726–9.
McLeod D., Zinner N., Tomera K. et al. A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 2001;58:756–61.
Esquena S., Abascal JM, Trilla E., Morote J. Failure of luteinizing hormonal releasing hormonal agonist therapy to achieve castration. Does it exist? Eur Urol Suppl 2004;3:57;
Wechsel HW, Zerbib M., Pagano F., Coptcoat MJ Randomized open labeled comparative study of the efficacy, safety and tolerability of leuprorelin acetate 1M and 3M depot in patients with advanced prostatic cancer. Eur Urol 1996;30(suppl 1):7–14.
Kawakami J., Morales A. A comprehensive hormonal evaluation in patients with cancer of the prostate on androgen suppression with LHRH agonists. J Urol 2002;167(suppl 4):288.
Zinner NR, Bidair M., Centeno A., Tomera K. Similar frequency of testosterone surge after repeat injections of goserelin (Zoladex) 3.6 mg and 10.8 mg: results of a randomized open-label trial. Urology 2004;64:1177–81.
Sharifi R., Browneller R. Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly and 3-month depot formulations of leuprolide acetate for advanced prostate cancer. J Urol 2002;168:1001–4.
Perez-Marreno R., Chu F.M., Gleason D. et al. A six-month, open-label study assessing a new formulation of leuprolide 7.5 mg for suppression of testosterone in patients with prostate cancer. Clin Ther 2002;24:1902–14.
Chu FM, Jayson M, Dineen MK et al. A clinical study of 22.5 mg. La-2550: a new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. J Urol 2002;168:1199–203.
Kienle E., Lubben G. Efficacy and safety of leuprorein depot for prostate cancer. Urol Int 1996;56(Suppl 1):23–30.
Bischoff W., German Leuprorelin Study Group. 3.75 and 7.5 mg leuprorelin acetate depot in the treatment of advanced prostate cancer: preliminary report. J Int Med Res 1990;18(Suppl 1):103–13.
Crawford ED, Blumenstein BA, Goodman PJ et al. Leuprolide with and without flutamide in advanced prostate cancer. Cancer 1990;66(5 Suppl):1039–44.
Sharifi R., Soloway M. Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. J Urol 1990;143(1):68–71.
Sato K., Akakura S., Isaka H. et al. Intermittent androgen suppression for locally advanced and metastatic prostate cancer: Preliminary report of a prospective multicenter study. Urology 2004;64(2):341–5.
Heyns CF, Simonin MP, Grosgurin P. et al. For the South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int 2003;92(3):226–31.
McLeod D., Zinner N., Tomera K. et al. Aberalix Study Group. A phase 3, multicenter, open-label, randomized study of abarelix versus leuprolide acetate in men with prostate cancer. Urology 2001;58:756–61.
Trachtenberg J., Gittleman M., Steidle C. et al. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol 2002;167(4):1670–4.
Parmar H., Lightman SL, Allen L. et al. Randomized controlled study of orchidectomy vs. long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet 1985;2:1201–5.
Jerome S., David J. Samson DJ Hasselblad V. et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000;132:566–77.
Abbou CC, Lucas C., Leblanc V. Tolerance and clinical and biological responses during the first 6 months of treatment with 1-month sustained release LHRH agonists leuprolerin and triptolerin in patients with metastatic prostate cancer. Prog Urol 1997;7(6):984–95.

Authors: V.B.
Matveev, M.I. Volkova, D.Z. Kupchan, Ya.V. Gridneva, GU RONC im. N.N. Blokhin RAMS, Moscow Source: netoncology.ru

Use of the drug Eligard

Eligard 7.5 mg is prescribed as a subcutaneous injection once a month. The administered solution forms a drug depot, which ensures the constant release of leuprorelin acetate for 1 month. Eligard 22.5 mg is prescribed as a subcutaneous injection once every 3 months. The administered solution forms a drug depot, which ensures the constant release of leuprorelin acetate for 3 months. Treatment of hormone-dependent prostate cancer with Eligard is a long-term treatment and should not be interrupted after improvement or remission occurs. Introduction. The contents of two pre-filled sterile syringes should be mixed immediately before administering Eligard as a subcutaneous injection. Getting the drug into an artery or vein is unacceptable! As with other drugs prescribed subcutaneously, the site of Eligard administration must be periodically changed. The response to treatment with the drug should be monitored by observing the clinical manifestations of the disease and measuring the level of prostate-specific antigen in the blood serum. If the patient's response to treatment is insufficient, it is advisable to check whether testosterone levels have reached or remain at castration levels. The mixture is prepared according to the instructions. After mixing, the solution should be administered immediately. Unused solution should not be used. Clinical studies have not been conducted in patients with hepatic or renal impairment.

Description

Eligard is a hormonal drug prescribed for the treatment of hormone-dependent prostate tumors. The active substance is Leuprorelin - a non-peptide artificial analogue of natural gonadotropin-releasing factor.
Eligard is an injectable suspension that stimulates the production of certain hormones in the body, which ultimately reduces the amount of testosterone in men. Unlike the natural hormone, the drug is more effective. The effect of the drug on the body is reversible after cessation of therapy. The drug is contraindicated for use by women and children.

Side effects of the drug Eligard

They mainly arise in connection with the specific pharmacological action of leuprorelin acetate, namely: an increase and decrease in hormonal levels. From the cardiovascular system : hot flashes, blood pressure lability, loss of consciousness, peripheral edema, pulmonary embolism, palpitations, chills, shortness of breath. From the nervous system: hypoesthesia, dizziness, headache, insomnia, disorders of taste, vision, smell, voluntary movements, sleep disturbance, depression, amnesia, and hyperesthesia of the skin. From the gastrointestinal tract: nausea, dry mouth, constipation or diarrhea, flatulence. From the respiratory system : rhinorrhea. From the genitourinary system : dysuria, nocturia, oliguria, urinary tract infections, softness and hypertrophy of the mammary glands, testicular atrophy, testicular pain, infertility, hematuria, acute urinary retention, gynecomastia, impotence, soreness of the mammary glands, decreased libido. From the musculoskeletal system : arthralgia, back pain, muscle cramps, myalgia, muscle weakness. From the laboratory parameters : changes in the general blood test, increased levels of creatinine, phosphokinase, ALT, TG in the blood, prolongation of blood clotting time and prothrombin time, in some cases - thrombocytopenia and leukopenia. Common side effects are malaise and fatigue. Local side effects : very often - transient minor burning/tingling after injection; often - pain, erythema, bruising, itching; rarely - induration and ulceration. In general, these side effects are minor and quickly transient. There may also be a skin rash, alopecia, and increased sweating. Changes in glucose tolerance have been reported.

Special instructions for the use of Eligard

Studies regarding the effect of Eligard on the ability to drive vehicles and operate complex machinery have not been conducted. Due to a feeling of fatigue, dizziness, visual impairment (side effects of treatment or a consequence of the underlying disease), the ability to drive a car and operate machinery may deteriorate. Leuprorelin acetate, like other gonadotropin-releasing hormone agonists, causes a transient increase in serum concentrations of testosterone, dihydrotestosterone and acid phosphatase during the first week of treatment. Patients may experience worsening or new symptoms, such as bone pain, neurological disorders, hematuria, ureteral obstruction, or bladder outlet obstruction. These symptoms usually go away with continued treatment. Ureteral obstruction and spinal cord compression have been reported with the use of gonadotropin-releasing hormone agonists, which may lead to paralysis with or without fatal complications. In cases of spinal cord compression or renal failure, standard treatment for these complications is carried out. Careful monitoring should be carried out during the first few weeks of treatment in patients with metastases in the spine and/or brain, as well as patients with urinary tract obstruction. An additional antiandrogen should be prescribed 3 days before starting leuprorelin therapy and used during the first 2–3 weeks of treatment (to prevent the consequences of the initial increase in serum testosterone levels). In case of a hormone-resistant tumor (lack of clinical improvement despite a decrease in testosterone levels), further therapy with Eligard does not make sense. There have been reports of decreased bone density in men who have undergone bilateral orchiectomy or who have been treated with a gonadotropin-releasing hormone agonist. Antiandrogen therapy increases the risk of fractures due to osteoporosis. In addition to long-term testosterone deficiency, the development of osteoporosis can also be influenced by the following factors: old age, smoking, alcohol consumption, excess body weight, and insufficient exercise. Changes in glucose tolerance have been observed in some patients treated with gonadotropin-releasing hormone agonist, so patients with diabetes mellitus require careful monitoring. After surgical castration, Eligard does not lead to a further decrease in serum testosterone levels in men.

Packaging, expiration date, storage conditions

The syringes are packaged in polyester cells covered with laminated aluminum foil. One syringe A (complete with a piston and a desiccant) and one syringe B (complete with an injection needle and a desiccant) in cells packed in a cardboard box along with instructions for use.

Store in original packaging at 2–8 °C.

Shelf life: 2 years.

Our company operates both in Kazakhstan and delivers to neighboring countries. Contact us for advice by contact numbers.

Eligard 45 mg 1 piece lyophilisate for the preparation of solution for subcutaneous administration Astellas Pharma Europe bv

Pharmacological properties of the drug Eligard

Use of the drug Eligard

Description

Side effects of the drug Eligard

Special instructions for the use of Eligard

Packaging, expiration date, storage conditions

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