Active substanceLeiprorelinLeiprorelin
Similar drugsTo uncover
  • Lucrin Depot®
    lyophilizate w / m PC 
  • Lucrin Depot®
    lyophilizate PC 
  • Lucrin Depot®
    lyophilizate w / m PC 
  • Eligarde
    lyophilizate PC 
    Astellas Farma Europe BV     Netherlands
  • Dosage form: & nbsplyophilizate for the preparation of a suspension for intramuscular and subcutaneous administration of prolonged action
    Composition:

    For 1 two-chamber syringe.

    The camera with lyophilizate contains:

    Active substance: leuprorelin acetate - 11.25 mg.

    Excipients: the polymer of lactic acid - 99,30 mg, mannitol - 19,45 mg.

    The chamber with the solvent contains: carmellose sodium - 5,0 mg, mannitol - 50,0 mg, polysorbate-80 - 1,0 mg, acetic acid - q.s. to a pH of 5.0 to 7.0, water for injection to 1.0 ml.

    Description:

    Lyophilizate: White powder.

    Solvent: colorless clear solution.

    Finished suspension: a suspension of white color. Upon settling, a white precipitate forms, which is easily resuspended by shaking.

    Pharmacotherapeutic group:An antineoplastic agent, a gonadotropin-releasing hormone analog
    ATX: & nbsp

    L.02.A.E   Analogues of gonadotropin-releasing hormone

    L.02.A.E.02   Leiprorelin

    Pharmacodynamics:

    Leuprorelin, a gonadotropin-releasing hormone agonist (GnRH), is an effective inhibitor of gonadotropin secretion with long-term admission in therapeutic doses.After initial stimulation, prolonged use of leuprorelin leads to suppression of steroidogenesis in the ovaries and testes. This effect is reversible and discontinues after the end of therapy.

    In humans, the appointment of leuprorelin leads to an initial increase in the concentrations of luteinizing (LH) and follicle-stimulating (FSH) hormones, which is expressed in a transient increase in the concentrations of sex steroidstestosterone and dihydrotestosterone in men, estrone and estradiol in women of reproductive age). These hormonal changes usually occur within 2-4 weeks from the beginning of drug therapy at the recommended doses.

    However, a longer-term appointment of leuprorelin leads to a decrease in the concentrations of LH, FSH and sex steroid hormones. In men, the concentration of testosterone is reduced to the castration or prepubertal level. In women who are in a state before menopause, estrogen concentrations drop to the postmenopausal level. These hormonal changes occur within a month from the beginning of therapy with the drug in the recommended doses.

    Pharmacokinetics:

    Leiprorelin is not active when ingested.Bioavailability of the drug with subcutaneous and intramuscular injection is comparable.

    Suction

    After a single injection of leuprorelin at a dose of 11.25 mg every 3 months, a rapid increase in its concentration in the blood plasma is observed. The maximum concentration was observed three hours after the administration: 21.82 (± 11.24) ng / ml. The concentrations of leuprorelin reach the plateau from 7 to 14 days after administration. In the fourth week, the average concentration of leuprorelin in the blood plasma is 0.26 (± 0.10) ng / ml and then decreases to 12 weeks to 0.17 (± 0.08) ng / ml.

    In women after a single injection of leuprorelin at a dose of 11.25 mg, the average concentration of the drug is 36.3 ng / ml achieved within 4 hours. By the third week after the concentration of leuprorelin reaches the plateau and then gradually decreases to the lower limit by the 12th week. The average concentration of leuprorelin from 3 to 12 weeks is 0.23 ± 0.09 ng / ml. The initial release followed by a rapid decrease to constant levels was similar to that of Lucrin Depot® 3.75 mg.

    Distribution

    The average volume of distribution is 27 liters. In vitro binding to plasma proteins - 43% - 49%.

    Metabolism

    The average value of the system clearance is 7.6 l / h, half-life (T1/2) for about 3 hours. Leiprorelin, being a peptide, undergoes metabolic degradation mainly by peptidase to shorter inactive peptides - pentapeptide (metabolite I), tripeptides (metabolites II and III) and dipeptide (metabolite IV). The time to reach the maximum concentration of the main metabolite M-1 is 2-6 hours and corresponds to 6% of the maximum concentration of leuprorelin. 1 week after the injection, the average plasma concentration of M-1 is 20% of the average concentration of leuprorelin.

    Excretion

    After the administration of Lucrin Depot® 3.75 mg to three patients, the content of leuprorelin and M-1 in urine was less than 5% of the administered dose 27 days after drug administration.

    Special Groups

    Pharmacokinetics of the drug in patients with impaired liver or kidney function has not been investigated.

    Indications:

    - Progressive cancer of the prostate (palliative treatment), incl. when orchiectomy or treatment with estrogens are not shown or are not applicable in this patient.

    - Endometriosis (for up to 6 months as the main therapy or addition to surgical treatment). Initial therapy of endometriosis and recurrence of endometriosis or its symptoms in combination with hormone replacement therapy.

    - Fibromyoma of the uterus (for up to 6 months as a preoperative preparation for the removal of fibroids or hysterectomy, as well as for symptomatic treatment and improvement in women during menopause who refuse surgery).

    - Breast cancer in the perimenopausal period in combination with hormone therapy.

    Contraindications:

    - Hypersensitivity to leuprorelin, similar to preparations of protein origin or to any auxiliary substance included in the composition of the dosage form.

    - Surgical castration.

    - Pregnancy and lactation.

    - Vaginal bleeding is not established etiology.

    - Prostate cancer (hormone independent).

    - Age to 18 years (effectiveness and safety not established).

    - Women over 65 years.

    Carefully:

    Patients with metastases in the spine, with obstruction of the urinary tract or with hematuria.

    Pregnancy and lactation:

    The drug is contraindicated in pregnancy. The safety of leuprorelin in pregnant women has not been clinically proven. Before the use of the drug is recommended to exclude the presence of pregnancy.

    There are no data on the excretion of leuprorelin and milk in women, so the drug is contraindicated during breastfeeding.

    Dosing and Administration:

    The drug Lucrin Depot ® should be used only under the supervision of a doctor.

    Enter single-intramuscularly or subcutaneously at a dose of 11.25 mg once every three months. Although the prepared suspension of Lucrin Depot® remains stable for 24 hours after dilution, since the product does not contain preservatives, the suspension should be used immediately after preparation.

    Instructions for injection of Lucrin Depot® in two-chamber syringes:

    1. Screw the white piston into the end plug until the plug starts to rotate.

    2. Hold the syringe in the VERTICAL POSITION. Enter the solvent, SLOWLY (for 6-8 seconds) by pressing ON the piston, until the first plug is on the blue line in the middle of the syringe.

    3. Continue to hold the syringe VERTICALLY. With gentle rocking, mix the lyophilizate thoroughly with the solvent until a uniform suspension (suspension) is formed. The suspension becomes milky.

    4. Hold the syringe VERTICALLY.With the other hand, remove the needle cap from the top, without unscrewing it.

    5. Hold the syringe VERTICALLY. Push the piston forward to remove air from the syringe.

    6. Immediately after the formation of the suspension, immediately enter the entire contents of the syringe intramuscularly or subcutaneously, since the suspension settles very quickly.

    Side effects:

    The following side effects are associated with the pharmacological action of leuprorelin on steroidogenesis:

    Neoplasms benign, malignant and unspecified (including cysts and polyps): progression of prostate cancer.

    From the side of metabolism: increase or decrease in body weight.

    From the nervous system: headache, muscle weakness, increased emotional lability.

    From the side of the vascular system: vasodilation, "hot flashes", lowering of arterial pressure, orthostatic hypotension.

    From the skin and subcutaneous tissue: acne, seborrhea, dry skin, hyperhidrosis, rash, urticaria, abnormal skin odor, abnormal hair growth, hair disorders, night sweats, hypotrichosis, pigmentation disorders, cold sweat, hirsutism, eczema, nail abnormalities.

    From the reproductive system and the breast: gynecomastia, vaginal bleeding, menstrual irregularities, breast tenderness, mammary gland congestion, mammary atrophy, vaginal discharge, breast enlargement, mammary gland pain, galactorrhea, metrorrhagia, menopause symptoms, dyspareunia, vaginitis, menorrhagia, pain in the prostate gland, swelling of the penis, testicular atrophy, erectile dysfunction, pain in the testicles, loss or decrease of sexual desire, increased sexual desire.

    Other: dryness of mucous membranes, a feeling of heat, irritability, a decrease in bone density, an increase in the concentration of PSA (prostate-specific antigen).

    Long exposure (6-12 months): diabetes mellitus, impaired glucose tolerance, increased total cholesterol concentration, increased LDL (low-density lipoprotein) concentration, increased triglyceride concentration, and osteoporosis.

    Below are the side effects observed in clinical studies and post-marketing observations.

    Since the drug Lyukrin Depot® has several indications for use, not all of the side effects listed below can be attributed to each patient.For most side effects, the cause-and-effect relationship with taking the drug has not been established.

    Infections and infestations: infection, bronchitis, pyelonephritis, boils, urinary tract infection, bladder infection, viral infection, candidiasis, sepsis, influenza.

    Neoplasms benign, malignant and unspecified (including cysts and polyps): pseudolymphoma.

    From the side of the blood and lymphatic system: anemia, eosinophilia.

    From the immune system: hypersensitivity reactions.

    From the side of metabolism: anorexia, increased appetite, hyperglycemia, hypoglycaemia, dehydration, hypercholesterolemia, excessive weight gain, excessive weight loss.

    From the nervous system: mood swings, personality disorders, nervousness, decreased sexual desire, insomnia, depression, anxiety, delirium, confusion, euphoria, hostility, apathy, dizziness, headache, paresthesia, drowsiness, fainting, migraine, hypertonia, ataxia, tremor, simple partial seizures, peripheral neuropathy.

    From the sense organs: decreased visual acuity, visual impairment, including amblyopia, dry eyes, eye pain, vestibular dizziness.

    From the side of the cardiovascular system: stenocardia, tachycardia, heart failure, palpitations, bradycardia, atrioventricular blockade, "hot flashes", vasodilation, lymphedema, increased blood pressure, thrombophlebitis, aneurysm, vascular collapse, hematoma.

    On the part of the respiratory system: nose bleeding, shortness of breath, hemoptysis, emphysema, cough, asthma, bronchospasm, chronic obstructive pulmonary disease (COPD).

    On the part of the digestive system: constipation, nausea, vomiting, gastritis, gastrointestinal bleeding, flatulence, bloating, diarrhea, indigestion, gingival hemorrhage, dry mouth, abdominal pain, impaired liver function, tenderness in the liver, hepatic cholestasis, hepatocellular lesions.

    From the skin and subcutaneous fat: alopecia, ecchymosis, maculopapular rash, dry skin, acne, seborrhea, photosensitivity reactions, hyperhidrosis, hirsutism, hair growth disorders, itching.

    From the musculoskeletal system: pain in the bones, myalgia, arthralgia, back pain, arthritis, stiff neck, muscle weakness, pain in the extremities, muscle spasms.

    From the genitourinary system: urinary incontinence, dysuria, pollakiuria, hematuria, nocturia, urinary retention, urinary disorders, gynecomastia, erectile dysfunction, pain in the mammary glands, enlargement of mammary glands, mammary atrophy, breast engorgement, galactorrhea, vaginitis, genital excretion, pelvic pain , swelling of the penis, pain in the prostate gland.

    Other: pain, chest pain, edema, peripheral edema, facial edema, gravitational edema, lower extremity edema, dry mucous membranes, asthenia, fatigue, reaction at the injection site, compaction at the injection site, pain at the injection site, edema at the injection site, elevated sensitivity at the injection site, chills, thirst, malaise, flu-like condition, gait disturbance.

    Deviations of laboratory indicators: increased erythrocyte sedimentation rate, increased alkaline phosphatase activity in the blood, increased lactate dehydrogenase activity in the blood,an increase in the concentration of the prostate-specific antigen, an increase in the activity of alanine aminotransferase (ALT), an increase in activity of aspartate aminotransferase (ACT), increased gamma-glutamyltranspeptidase activity, abnormalities in the electrocardiogram, increased testosterone concentration in the blood, abnormal liver function tests, decreased platelet count, decreased potassium levels in the blood, increased prothrombin time, increased activated partial thromboplastin time, heart murmur, increased lipoprotein concentration low density, an increase in the concentration of triglycerides in the blood, an increase in the concentration of bilirubin in the blood.

    Postmarketing research

    Below are the side effects observed in post-marketing studies; the incidence of these side effects is unknown.

    Infections and infestations: pharyngitis, pneumonia.

    Neoplasms benign, malignant and unspecified (including cysts and polyps): skin cancer.

    From the immune system: anaphylactic reactions.

    From the endocrine system: goiter, apoplexy of the pituitary gland.

    From the side of metabolism: diabetes mellitus, hyperlipidemia, hyperphosphatemia, hypoproteinemia.

    From the nervous system: mood swings, increased libido, sleep disorders, suicide attempts, lethargy, memory impairment, including amnesia, dysgeusia, hypoesthesia, peripheral neuropathy, cerebrovascular disorders, unconsciousness, including syncope, transient ischemic attack, seizures, paralysis, neuromyopathy.

    From the sense organs: decreased visual acuity, dry eyes, ringing in the ears, hearing impairment.

    From the side of the cardiovascular system: congestive heart failure, arrhythmia, myocardial infarction, sudden cardiac death, phlebitis, thrombosis, lowering of arterial pressure, varicose veins.

    On the part of the respiratory system: pleural friction noise, pulmonary fibrosis, hemoptysis, effusion in the pleural cavity, lung infiltration, sinus congestion, pulmonary embolism, interstitial lung disease.

    On the part of the digestive system: gastrointestinal bleeding, dysphagia, ulcer dvenadza digestive ulcer, a peptic ulcer, polyps of the rectum, a violation of liver function, severe hepatic insufficiency, jaundice.

    From the skin and subcutaneous fat: hives, dermatitis, hair growth disorders, pigmentation disorders, rashes on the skin.

    From the musculoskeletal system: swelling of the bones, arthropathy, ankylosing spondylitis, tenosynovitis.

    From the genitourinary system: persistent urination, bladder spasm, urinary tract obstruction, breast tenderness, vaginal bleeding, menstrual irregularities, metrorrhagia, testicular atrophy, testicular pain, swelling of the penis, pain in the prostate gland.

    Other: fever, reaction at the injection site, inflammation at the injection site, compaction at the injection site, aseptic abscess at the injection site, hematoma at the injection site, nodule, inflammation, intracelastic fibrosis, vertebral fracture.

    Deviations of laboratory indicators: increase in the concentration of blood urea nitrogen, increase in the concentration of blood creatinine, an increase in the concentration of calcium in the blood, signs of myocardial ischemia on the ECG, deviation from the norm of liver function tests, a decrease in the number of platelets, a decrease in the concentration of potassium in the blood, an increase in the number of leukocytes, a decrease in the number of leukocytes, an increase in prothrombin time,increased activated partial thromboplastin time, noise in the heart, increased concentration of low-density lipoproteins, increased concentration of triglycerides in the blood, increased concentrations of bilirubin in the blood.

    Men's

    Serious cases of venous and arterial thromboembolism were noted, including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke and transient ischemic attack. Although in some cases, a temporary connection was noted, in most cases, there were risk factors or the taking of concomitant medications. It is not known whether there is a causal relationship between the use of GnRH agonists and these events.

    Women

    Changes in bone density

    In a clinical study in patients with endometriosis who received Lucrin Depot® 3.75 mg for 6 months, the density of the spine bones was measured by X-ray absorptiometry (DEXA) and there was a decrease of an average of 3.9% compared with the level of density before treatment. In patients examined 6 or 12 months after the end of treatment, the average bone density of the tissue was restored to the original (± 2%).When using Lucrin Depot® 3.75 mg for three months in patients with uterine myoma, the mineral density of the sponge bones of the spine was assessed by the quantitative X-ray method (QDR) and was 2.7% lower than the original. Six months after the cessation of treatment, there was a tendency for recovery.

    Overdose:

    Data on the overdose of leuprorelin in humans is not available. In case of an overdose, the patient should be given symptomatic treatment.

    Interaction:

    Pharmacokinetic studies on the drug interaction of leuprorelin with other drugs have not been conducted. However, since leuprorelin is a substance of a peptide nature and undergoes primary decomposition under the influence of peptidase, rather than enzymes of cytochrome P-450 and about 46% of the drug binds to blood plasma proteins, drug interaction is unlikely.

    Special instructions:

    In men receiving treatment with GnRH agonists, hyperglycemia and an increased risk of developing diabetes were observed. Hyperglycemia may be a sign of the development of diabetes mellitus or the deterioration of glycemic control in patients with diabetes.In patients receiving treatment with GnRH, it is necessary to periodically monitor the concentration of glucose in the blood and the concentration of glycosylated hemoglobin (HbAlc) and treat hyperglycemia or diabetes.

    In men receiving treatment with GnRH agonists, there was an increased risk of myocardial infarction, sudden cardiac death and stroke. Based on the available data, the level of risk is low, and its evaluation should be carefully evaluated, taking into account the risk factors for the development of cardiovascular diseases, when prescribing treatment for patients with prostate cancer. It is necessary to monitor the condition of patients receiving GnRH agonists, paying special attention to symptoms that signal the development of cardiovascular diseases, and apply the treatment in accordance with current clinical practice.

    Influence on the interval QT /QTc

    In patients receiving long-term antiandrogen therapy, an interval elongation was observed QT. Doctors should correlate the benefits of antiandrogen therapy with risks in patients with congenital syndrome of lengthening the interval QT, abnormalities in terms of electrolytes or chronic cardiacdeficiency and in patients taking antiarrhythmic drugs of class IA (eg, quinidine, procainamide) or class III (for example, amiodarone, sotalol).

    Convulsions

    Post-marketing messages about convulsions were received on the background of the use of leuprorelin. Seizures were observed in patients of the following categories: women; children; patients with convulsions, epilepsy, cerebrovascular disorders, developmental anomalies or tumors of the central nervous system, as well as patients who simultaneously took drugs that can cause seizures, for example, bupropion or selective serotonin reuptake inhibitors (SSRIs). Cases of seizures in patients without any of the described conditions are also described.

    Prostate Cancer

    In most patients, testosterone concentrations rose above normal during the first week, then decreased to normal values ​​or lower by the end of the second week of treatment.

    During the first few weeks of treatment with Lucrin Depot®, transient symptoms of impairment may develop or additional signs and symptoms of the underlying disease may appear.The possible worsening of symptoms during the first few weeks of treatment concerns patients with metastatic spinal cord injury and / or urinary tract obstruction or hematuria, which, if aggravated, can lead to neurological problems such as temporary weakness and / or paresthesia of the lower extremities or to worsening of symptoms of urinary tract damage . In a small number of patients, pains in the bones that can stop with symptomatic treatment may increase. As with other gonadotropin-releasing hormone analogues, with the application of Lucrin Depot®, there have been isolated cases of obstruction of the urinary tract and spinal cord compression, which can be complicated by paralysis with / without fatal outcome. Therefore, during the first few weeks of treatment, patients with metastases in the spine and severe obstruction of the urinary tract require careful observation.

    Endometriosis / Fibromyoma of the uterus

    At the very beginning of the course of treatment, a transient increase in the concentration of sex steroid hormones is usually noted, which determines the physiological manifestations of the effect of the drug.Some aggravation of symptoms at the beginning of therapy with the drug Lyukrin Depot® passes quickly enough with the continuation of treatment with adequately selected doses of the drug. However, with the continuation of therapy, cases of severe vaginal bleeding, requiring conservative or surgical treatment, are also reported.

    The drug Lucrin Depot® is not a contraceptive. If contraception is required, nonhormonal methods of protection from pregnancy should be used.

    Density of bone tissue

    Changes in bone density may appear against any hypoestrogenic background. The loss of bone density can be reversible after the abolition of leuprorelin.

    Laboratory testing

    The adequacy of the response to leuprorelin treatment should be monitored by the determination of serum testosterone and PSA concentrations. In most patients, the testosterone concentration rises compared to the baseline during the first week, and then decreases to or below the baseline by the end of the second week of treatment. Postcastration level is achieved within 2-4 weeks and maintained throughout the period of regular use of the drug.

    The use of Lucrin Depo® in women causes oppression of the function of the pituitary-adrenal system. After the end of treatment, the function is restored after 3 months. However, diagnostic tests that testify to the function of the pituitary gland or gonads, carried out during treatment and up to 3 months after its termination, may be distorted.

    Effect on the ability to drive transp. cf. and fur:Data on the effect of the drug on the ability to drive and work with mechanisms there. However, since it is possible the occurrence of such side effects as drowsiness, dizziness, etc., it is recommended to refrain from driving and doing other activities that require an increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:Lyophilizate for the preparation of a suspension for intramuscular and subcutaneous administration of prolonged action 11,25 mg.
    Packaging:

    130.0 mg of lyophilizate and 1 ml of solvent in different chambers of a two-chamber syringe consisting of an anterior complex with a planted needle, a closed plastic cap, a glass cartridge with rubber stoppers and a finger rest.

    A kit for single-dose administration contains the components necessary for one intramuscular or subcutaneous injection:

    - one two-chamber syringe containing lyophilizate in the chamber nearest to the needle, and in the chamber nearest to the piston, a solvent;

    - one plastic piston;

    - one or two napkins impregnated with 70% isopropyl alcohol, in laminated polyethylene paper.

    One set together with instructions for use in a plastic case with a first-opening control system.

    Storage conditions:

    At a temperature of 15 to 25 ° C. Do not freeze.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use the drug after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002532
    Date of registration:15.07.2014
    Expiration Date:15.07.2019
    The owner of the registration certificate:Abbott Laboratories SAAbbott Laboratories SA Spain
    Manufacturer: & nbsp
    Representation: & nbspEbbVi Ltd.EbbVi Ltd.Russia
    Information update date: & nbsp21.03.2018
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