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 subcutaneous administration of prolonged action
    Composition:

    The camera with lyophilizate contains:

    Active substance: leuprorelin acetate - 30 mg.

    Excipients: polymer of lactic acid - 270.0 mg, mannitol - 52.9 mg.

    The chamber with the solvent contains: carmellose sodium 5.0 mg, mannitol 50.0 mg, polysorbate 80-1.0 mg, acetic acid 0 to 0.05 mg, water for injection up 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.

    Purpose leuprorelin leads to an initial increase in the concentration of luteinizing (LH) and follicle stimulating hormone (FSH), hormones that is expressed in the transient increase of concentrations of sex steroids (testosterone and dihydrotestosterone in men, estrone and estradiol in women of reproductive age).

    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 usually occur within 2-4 weeks from the beginning of drug therapy at the recommended doses. Postastratsionnye concentrations of testosterone in patients with prostate cancer persist for more than five years.

    Pharmacokinetics:

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

    Suction

    After a single subcutaneous injection of the drug Lucrin Depot® 30 mg (1 time in 6 months), its concentration in the blood plasma increases rapidly, followed by a decrease to a plateau level for several days. Within two hours, the maximum plasma concentrations of the drug are 100 ng / ml. Leiprorelin continued to be determined in blood plasma for> 180 days after the last administration.

    Distribution

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

    Metabolism

    The average system clearance is 7.6 l / h, half-life (T1/2) about 3 hours.

    Leuprorelin, being a peptide undergoes metabolic degradation mainly peptidase inactive to shorter peptides - pentapeptide (metabolite I), tripeptides (metabolite II and III) and dipeptide (metabolite IV). The time to reach maximum concentration main metabolite M-1 (6% of the maximum concentration leuprorelin) - 2-6 h After 1 week after injection the average concentration of M-1 in plasma -. 20% from the average concentration of leuprolide.

    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:

    - Prostate cancer, in cases where it is necessary to reduce testosterone to the castration level.

    Contraindications:

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

    - Surgical castration.

    - Prostate cancer (hormone independent).

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

    Carefully:

    Patients with metastatic spinal cord injury and / or obstruction of the urinary tract should be carefully monitored during the first few weeks of treatment.

    Pregnancy and lactation:The drug Lucrin Depot® 30 mg is not indicated for use in women.
    Dosing and Administration:

    The drug Lucrin Depot ® should be used only under the supervision of a doctor.The drug is injected once subcutaneously at a dose of 30 mg once every six months. The place of administration should be periodically changed.

    Since the drug does not contain preservatives, the suspension should be used immediately after preparation.

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

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

    - 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.

    - 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.

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

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

    - Immediately after the formation of the suspension, immediately enter the entire contents of the syringe 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): effect of "tumor outbreak", progression of prostate cancer.

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

    From the nervous system: headache, muscle weakness, loss or decrease of sexual desire, increased sexual desire.

    From the cardiovascular system: vasodilation, hot flashes, lowering of arterial pressure, orthostatic hypotension.

    From the skin and subcutaneous tissue: dry skin, hyperhidrosis, rash, hives, abnormal hair growth, hair disorders, night sweats, hypotrichosis, pigmentation disorders, cold sweat, hirsutism.

    On the part of the reproductive system: gynecomastia, tenderness of the mammary glands, erectile dysfunction, pain in the testicles, enlargement of the mammary glands, pain in the mammary glands, pain in the prostate gland, swelling of the penis, testicular atrophy.

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

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

    Below are the side effects observed in clinical studies and post-marketing observations. For most side effects, the cause-and-effect relationship with taking the drug has not been established.

    In most patients in the first week of treatment, the testosterone concentration rises, and by the end of the second week - decreases to baseline or lower.

    In patients with metastases in the vertebrae and / or urinary tract obstruction or hematuria, symptoms may increase in the first few weeks of treatment, which can lead to neurologic disorders, such as temporary weakness and / or paresthesia of the lower extremities, or aggravation of urination disorders.

    Infections and infestations: infection, including infection of the urinary tract, pharyngitis, pneumonia.

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

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

    From the immune system: anaphylactic reactions.

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

    From the side of metabolism: diabetes, increased appetite, hypoglycemia, dehydration, hyperlipidemia, hyperphosphatemia, hypoproteinemia, excessive weight gain.

    From the nervous system: mood swings, nervousness, decreased / increased sex drive, insomnia, sleep disorders, depression, anxiety, delirium, suicidal thoughts, suicide attempts, dizziness, headache, including migraine, paresthesia, lethargy, memory disorders, dysgeusia, hypoesthesia, peripheral neuropathy, cerebrovascular disorders, loss of consciousness, including fainting, transient ischemic attack, neuromyopathy, convulsions, paralysis.

    From the sense organs: visual impairment, including amblyopia, dry eyes, ringing in the ears, hearing impairment.

    From the cardiovascular system: heart failure, including congestive heart failure, arrhythmia, myocardial infarction, angina pectoris, tachycardia, bradycardia, sudden cardiac death, lymphedema, increased blood pressure,phlebitis, thrombosis, lowering of arterial pressure, varicose veins.

    On the part of the respiratory system: pleural friction noise, pulmonary fibrosis, epistaxis, dyspnea, hemoptysis, cough, pleural effusion, pulmonary infiltration, respiratory disorders, nasal congestion, acute pulmonary edema, pulmonary embolism, interstitial lung disease.

    On the part of the digestive system: constipation, nausea, vomiting, gastrointestinal bleeding, bloating, diarrhea, dysphagia, dryness of the oral mucosa, duodenal ulcer, peptic ulcer, rectal polyp, liver function disorder, jaundice.

    From the skin and subcutaneous fat: alopecia, ecchymosis, rash, dry skin, photosensitization reactions, urticaria, hyperhidrosis, dermatitis, hair growth disorders, itching, night sweats, hypotrichosis, pigmentation disorders, skin damage.

    From the musculoskeletal system: myalgia, decreased bone density, arthropathy, arthralgia, ankylosing spondylitis, tenosynovitis.

    From the genitourinary system: urinary incontinence, pollakiuria, imperative urges to urinate, hematuria, urinary retention, bladder spasm, urinary tract disorders, urinary tract obstruction, gynecomastia, breast tenderness, erectile dysfunction, testicular atrophy, testicular pain, chest pain, swelling of the penis, pain in the prostate gland.

    Other: pain, edema, peripheral edema, asthenia, fatigue, fever, reactions at the injection site, chills, nodules in the larynx, thirst, inflammation, retroperitoneal fibrosis, vertebral fracture.

    Deviations of laboratory indicators: increasing the concentration of blood urea nitrogen, increasing the concentration of uric acid, increasing the concentration of blood creatinine, increasing the concentration of calcium in the blood, disturbances in the electrocardiogram, signs of myocardial ischemia on the ECG, deviation from the norm of the results of functional liver 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, increased activity of "hepatic" transaminases,noise in the heart, increasing the concentration of low-density lipoproteins, increasing the concentration of triglycerides in the blood, increasing the concentration of bilirubin in the blood.

    Overdose:

    Data on the overdose of leuprorelin are absent. In case of an overdose, the patient should be given symptomatic treatment.

    Interaction:

    Pharmacokinetic studies of 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 cytochrome P-450 enzymes, and about 46% of the drug binds to plasma proteins, drug interaction is unlikely.

    Special instructions:

    The drug Lucrin Depot® 30 mg is not indicated for use in women.

    Pay attention to worsening of symptoms during the first few weeks of treatment in patients with metastatic spine injury and / or urinary tract obstruction or hematuria, as aggravation of these conditions can lead to neurological problems such as temporary weakness and / or paresthesia of the lower extremities, or to worsening symptoms of urinary tract damage.

    Leuprorelin, like other Gn-RH agonists, during the first week of treatment causes a rise in plasma concentrations of testosterone, up to 50% higher than the original ones. Sometimes, during the first few weeks of treatment with Lucrin Depot® 30 mg, transient symptoms of impairment may develop, or additional signs and symptoms of prostate cancer may appear. In a small number of patients, it is possible to increase pain in the bones, which require symptomatic treatment. As with the use of other Gn-RH agonists, there were isolated cases of urinary tract obstruction or spinal compression, including fatal.

    In men receiving treatment with agonists Gn-RG, there was hyperglycemia and an increased risk of developing diabetes. 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 Gn-RG, it is necessary to periodically monitor the concentrations of glucose and glycosylated hemoglobin (HbAlc) blood and treat hyperglycemia or diabetes.

    In men receiving treatment with agonists Gn-RG, there was an increased risk of myocardial infarction, sudden cardiac death and stroke. According to the available data, the level of risk is low, nevertheless, it should be carefully evaluated, taking into account the risk factors for cardiovascular disease, with the appointment of Gn-RH agonists in patients with prostate cancer. It is necessary to monitor the condition of patients receiving Gn-RH agonists, carefully monitoring the appearance of symptoms indicative of 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 interval lengthening QT, abnormalities in the electrolyte indices or chronic heart failure, as well as in patients taking antiarrhythmic drugs of the 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: patients with seizures, epilepsy, cerebrovascular disorders, developmental abnormalities or tumors of the central nervous system, as well as patients taking concomitant medications 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.

    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.

    Control of laboratory indicators

    Activity of the drug Lucrin Depot® 30 mg should be monitored by measuring the concentrations in the plasma of testosterone, as well as the prostate-specific antigen (PSA). In most patients, testosterone concentrations rose to above normal levels during the first week of therapy, then decreasing to normal or lower by the end of the second week of treatment.In men, within 2-4 weeks, the concentration of testosterone reached postastratsionnyh levels and was maintained on them during the entire period of receiving injections.

    The use of Lucrin Depot® in therapeutic doses leads to the inhibition of the pituitary-gonadotropic system. Normal function is usually restored within three months after cessation of treatment. Therefore, the results of diagnostic functional tests of the pituitary gland and gonads, performed during treatment with the drug and within three 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 subcutaneous administration of prolonged action of 30 mg.
    Packaging:

    352.9 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 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 first autopsy 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-001652
    Date of registration:13.04.2012
    The owner of the registration certificate:Abbott Laboratories SAAbbott Laboratories SA Spain
    Manufacturer: & nbsp
    Representation: & nbspABBOTT LABORATORIES LLC ABBOTT LABORATORIES LLC Russia
    Information update date: & nbsp03.11.2015
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