Universal reference book for medicines
Product name: ELIGARD (ELIGARD)

Active substance: leuprorelin

Type: Gonadotropin-releasing hormone analogue - depot form

Manufacturer: ASTELLAS PHARMA EUROPE (Netherlands) manufactured (syringe A) TOLMAR (USA) manufactured (syringe B) TOLMAR (USA) ASTELLAS PHARMA EUROPE (Netherlands), issuing quality control ASTELLAS PHARMA EUROPE (Netherlands)
Liofilizate for the preparation of a solution for s / s injection (syringe B) from white to almost white, without visible foreign particles. The applied solvent (syringe A) is a clear, viscous liquid from light yellow to light yellow with a brownish hue, without visible foreign particles; air bubbles are allowed. The reconstituted solution is a viscous liquid from light yellow to light yellow with a brownish hue, without visible foreign particles; air bubbles are allowed.
1 dose 1 Syringe B
leuprorelin acetate * 7.5 mg 10.6 mg
Solvent (syringe A): (copolymer poly-D, L-lactide-co-glycolide: PLGH (50:50) -117 mg, N-methyl-2-pyrrolidone-226 mg) -343 mg.
Syringes of polypropylene or a copolymer of a cyclic olefin [syringe A complete with a piston for a syringe B and a sachet with a desiccant placed in a contour polyester cell packaging covered with aluminum foil laminated; syringe B complete with injection needle and sachet with dehumidifier, packed in a polyethylene cell loop, covered with aluminum foil laminated] (2) - packs of cardboard.
Liofilizate for the preparation of a solution for s / s injection (syringe B) from white to almost white, without visible foreign particles. The applied solvent (syringe A) is a clear, viscous liquid from colorless to light yellow in color, with no visible foreign matter; air bubbles are allowed. The reconstituted solution is a viscous liquid from colorless to light yellow color, with no visible foreign particles; air bubbles are allowed.
1 dose 1 Syringe B
leuprorelin acetate * 22.5 mg 29.2 mg
Solvent (syringe A): (copolymer poly-D, L-lactide-co-glycolide: PLG (75:25)-206 mg, N-methyl-2-pyrrolidone 251 mg) 457 mg.
Syringes of polypropylene or a copolymer of a cyclic olefin [syringe A complete with a piston for a syringe B and a sachet with a desiccant placed in a contour polyester cell packaging covered with aluminum foil laminated; syringe B complete with injection needle and sachet with dehumidifier, packed in a polyethylene cell loop, covered with aluminum foil laminated] (2) - packs of cardboard.
Liofilizate for the preparation of a solution for s / s injection (syringe B) from white to almost white, without visible foreign particles. The applied solvent (syringe A) is a clear, viscous liquid from colorless to light yellow in color, with no visible foreign matter; air bubbles are allowed. The reconstituted solution is a viscous liquid from colorless to light yellow color, with no visible foreign particles; air bubbles are allowed.
1 dose 1 Syringe B
leuprorelin acetate * 45 mg 59.2 mg
Solvent (syringe A): (copolymer poly-D, L-lactide-co-glycolide: PLG (85:15) -217 mg, N-methyl-2-pyrrolidone-217 mg) -434 mg.
Syringes of polypropylene or a copolymer of a cyclic olefin [syringe A complete with a piston for a syringe B and a sachet with a desiccant placed in a contour polyester cell packaging covered with aluminum foil laminated; syringe B complete with injection needle and sachet with dehumidifier, packed in a polyethylene cell loop, covered with aluminum foil laminated] (2) - packs of cardboard.
* excess leuprorelin acetate compensates for losses in the syringe and needle. The reconstituted solution (administered dose) contains 7.5 mg, 22.5 mg or 45 mg of leuprorelin acetate.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
An analogue of gonadotropin-releasing hormone is a depot form. Leiprorelin is a synthetic non-peptide analogue of natural GnRH, which, with prolonged use, inhibits the secretion of the pituitary gonadotropin and suppresses testicular steroidogenesis in men. The analog is more effective than the natural hormone, and its effect is reversible upon discontinuation of treatment. However, the time to restore testosterone concentration may vary among patients.
The appointment of leuprorelin first leads to an increase in the level of circulating LH and FSH, resulting in a temporary increase in the level of gonadal steroids, testosterone and dihydrotestosterone in men. With prolonged use of leuprorelin, the level of LH and FSH decreases. In men, testosterone levels drop to the castration level (≥50 ng / dl) within 3-5 weeks after the start of treatment. The average level of testosterone after 6 months of treatment is 6.1 (± 0.4) ng / dl for a dosage of 7.5 mg; 10.1 (± 0.7) ng / dl for a dosage of 22.5 mg and 10.4 (± 0.53) ng / dL for a dosage of 45 mg. These values ​​are comparable to the level of testosterone after a bilateral orchiectomy.
All patients in the clinical trial of Eligard 7.5 mg achieved castration levels of testosterone at week 6 of treatment; 94% of patients by day 28 and 98% of patients by day 35. All patients in the clinical trial of Eligard's 22.5 mg drug reached castration levels of testosterone at week 5; 99% of patients - by the 28th day. All patients (except one) in a clinical trial of Eligard's 45 mg drug reached castration levels of testosterone at week 4. In the vast majority of patients, testosterone concentrations decreased below 20 ng / dL, although the full benefit of these low levels of testosterone has not yet been established. The PSA concentrations decreased by 94% after 6 months of treatment with Eligard 7.5 mg, 98% with Eligard 22.5 mg, 97% with Eligard 45 mg.
Long-term studies have shown that constant therapy maintains testosterone concentrations below the castration level for up to 7 years and, most likely, indefinitely.
PHARMACOKINETICS
Suction distribution
After the first injection 4-8 hours, the average level of leuprorelin (C max ) concentration determined in the blood serum increases to 25.3 ng / dl, 127 ng / dL and 82 ng / dl with leuprorelin 7.5 mg, 22.5 mg and 45 mg, respectively. After the initial increase (the plateau phase is from 2 to 28 days for a 7.5 mg dosage, from 3 to 84 days for a dosage of 22.5 mg, from 3 to 168 days for a dosage of 45 mg), the level of leuprorelin in the serum remained relatively stable: 0.28-1.67 ng / ml for a dosage of 7.5 mg and 0.2-2 ng / ml for dosages of 22.5 and 45 mg. Data on the accumulation of substance with repeated injections are absent.
Mean V d in the equilibrium state after iv injection of leuprorelin to healthy volunteers for men was 27 liters. According to in vitro studies, binding to plasma proteins ranges from 43% to 49%.
Excretion
When 1 mg leuprorelin acetate was injected into / in healthy volunteers, it was found out that when using a two-chamber model, the average clearance was 8.34 l / h with a final T 1/2 of about 3 hours. Eligard was not tested. Studies on the drug metabolism of the drug Eligard was not carried out.
INDICATIONS
- hormone-dependent prostate cancer.
DOSING MODE
Eligard should only be used under the supervision of a health professional who has sufficient experience to evaluate the effectiveness of treatment.
Eligard is prescribed SC 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. The contents of two pre-filled sterile syringes should be mixed immediately before the injection of Eligard. The injected solution forms the drug depot, which ensures the continuous release of leuprorelin during this period.
Typically, the treatment of advanced prostate cancer using the Eligard drug involves long-term treatment and should not cease if there is an improvement or remission. Eligard can be used as neoadjuvant or adjuvant therapy in combination with radiotherapy in patients with localized high risk cancer and locally advanced prostate cancer.
The injection site should be periodically changed. It is necessary to avoid getting the drug into the artery or vein.
Clinical data on the use of Eligard in patients with hepatic or renal insufficiency do not.
In the case of a suspected or known mixing error in a patient, the concentration of testosterone should be determined due to the fact that as a result of improper preparation, mixing or administration of the drug, there may be cases of lack of clinical effectiveness.
Rules for the preparation of solution
If the drug was prepared in violation of the instructions, it should not be used because when improper preparation of the solution for p / c administration, there may be cases of lack of clinical effectiveness.
First, it is recommended to prepare the patient for the administration of the drug, and then proceed to prepare the solution in accordance with the recommendations presented below.
The packaging is removed from the refrigerator approximately 30 minutes before use and kept at room temperature.
After removal from the refrigerator, the drug can be stored in its original packaging at room temperature (not above 25 ° C) up to 4 weeks.
Step 1. Remove two contour squeezes from the box and open them by pulling the free edge of the aluminum foil, extract the contents of the cell packs and put them on a clean surface. It should be thrown bags with a desiccant.
Step 2. Take the syringe B and draw from it a short blue piston along with the stopper (do not unscrew the piston from the limiter).
Do not mix the contents of the syringes until the blue short piston is removed from the syringe B.
Step 3. Take the white piston for the syringe B and insert it into the syringe B from the side of the remaining gray stop, turn the piston clockwise to the stop.
Step 4. Remove the gray rubber cap from the syringe B and place the syringe.
Step 5. Take the syringe A and, keeping it in a vertical position, to avoid solvent leakage, unscrew the transparent cap from the syringe A.
Step 6. Connect the two syringes, the syringe A from below, and screw the syringe B into the syringe A clockwise until it is fully fixed.
Do not turn the syringes too tightly.
Step 7. Turn over the connected syringes so that the syringe B is on the bottom and press the plunger of the syringe A until the contents of the syringe A (solvent) are completely injected into the syringe B (containing leuprorelin acetate powder), the syringes should be held vertically.
Step 8. Hold the syringes in a strictly horizontal position, carefully mix the contents of both syringes,
alternately pressing gently on the piston of one or another syringe (approximately 60 times, which takes about 60 seconds) to obtain a homogeneous viscous solution.
You should avoid kinking the system (this can cause leakage, since syringes may not be tight enough).
After thorough mixing, the ready-for-use mixture should be colorless or light yellow (a white or pale yellow shade may be observed).
Important: it is necessary to use the solution immediately after preparation, as its viscosity increases with time. Freezing the finished product is prohibited.
The drug should be mixed as described in the instructions; shaking will not ensure proper mixing.
Step 9. Hold the syringes upright, syringe B - from the bottom. The syringes must be securely attached. Pressing the plunger of the syringe A, and slightly pulling down the plunger of the syringe B, move the entire contents into the syringe B.
Step 10. Unscrew the syringe A, while continuing to press the plunger of the syringe A. Make sure that the contents do not flow out of the syringe, It will not be possible to secure the needle properly in the event of a leak.
Step 11. Hold the syringe B vertically. Open the packaging with a sterile needle (folding the paper label) and remove the needle.
Attach the needle cartridge to the base of the syringe B and gently snap it by twisting the needle clockwise. Do not overtighten.
Step 12. Remove the protective cap from the needle before injection.
Important: Do not operate the needle protector before administering the drug.
Step 13. Remove large air bubbles from the syringe before starting the injection. Insert the preparation subcutaneously. It is necessary to make sure that the whole preparation is injected from the syringe B.
Step 14. After the injection, immediately activate the needle guard device in any of the two ways described below.
1 way. Closure on a flat surface
Place the syringe with the needle on a flat surface downward with the safety device lever and press the lever to activate the protective mechanism. Then move the lever to the front position until the tip of the needle is completely closed. It is necessary to make sure that the lever is moved to the extreme position and the tip of the needle is completely closed (until a characteristic click).
2 way. Hand Closure
Place the thumb on the lever, gently push it towards the tip of the needle with the lever moved to the forward forward position until the tip of the needle is fully closed. It is necessary to make sure that the lever is moved to the extreme position and the tip of the needle is completely closed (until a characteristic click).
Step 15. Immediately place the needle and syringe in the appropriate container for sharp objects.
SIDE EFFECT
The undesirable effects caused by taking Eligard are due mainly to the specific pharmacological action of leuprorelin, which causes an increase and decrease in the level of hormones. The most common side effects were: "hot flashes", malaise, nausea and weakness, irritation at the injection site. Weak or mild "hot flashes" were observed in approximately 58% of patients.
The following adverse events were recorded during clinical trials of Eligard in patients with advanced prostate cancer. The incidence of adverse reactions listed below is described in accordance with the following gradation: very often (> 1/10), often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (<1/10 000), is unknown (it is impossible to estimate based on available data).
Adverse events in the clinical trials of Eligard
Infectious and parasitic diseases: often - nasopharyngitis; infrequently, infection of the urinary tract, limited infection of the skin.
From the side of metabolism: infrequently the deterioration of the course of diabetes.
Mental disturbances: infrequently - sleep disorders, depression, decreased libido.
From the side of the nervous system: infrequently - dizziness, headache, hypoesthesia, insomnia, taste disorders, impaired sense of smell; rarely - involuntary pathological movements.
From the cardiovascular system: very often - "hot flashes"; infrequently - increased blood pressure, lower blood pressure; seldom - faint, collapse; unknown - elongation of the QT interval.
From the respiratory system: infrequently - rhinorrhea, dyspnoea.
From the digestive system: often - nausea, diarrhea; infrequently - constipation, dry mouth, indigestion, vomiting; rarely - flatulence, belching.
From the skin and subcutaneous tissue: very often - ecchymosis, erythema; often - itching, night sweats, cold sweat, increased sweating; rarely - alopecia, itchy skin.
From the musculoskeletal system: often - arthralgia, pain in the extremities, myalgia; infrequently - pain in the back, muscle cramps.
From the urinary system: often - a violation of urination, difficulty urinating, dysuria, nocturia, oliguria; infrequently - bladder spasm, hematuria, increased frequency of urination, delayed urination.
From the reproductive system and breast: often - breast tenderness, pain in the testicles, hypertrophy of the mammary glands, testicular atrophy, infertility; infrequently - gynecomastia, impotence, testicular disorders; rarely - chest pain.
On the part of the hematopoiesis system: often - hematological changes (deviation from the norm of the number of blood cells, deviation from the norm of the MHO index.
From the indicators of laboratory and instrumental studies: often - increasing the concentration of creatinine and the activity of creatine phosphokinase, increasing coagulation time; infrequently - increased ALT, hypertriglyceridemia, increased prothrombin time, increased body weight.
Other: very often - increased fatigue, burning at the injection site, paresthesia at the injection site; often - malaise, pain at the injection site, bruising, burning, muscle rigidity, weakness; infrequently - itching at the injection site, lethargy, pain, pyrexia; rarely - the formation of ulcers at the injection site; very rarely - necrosis at the injection site.
Other adverse events associated with leuprorelin acetate include peripheral edema, pulmonary embolism, palpitations, myalgia, muscle weakness, dyskinesia, chills, dizziness, itching, amnesia, and visual impairment. There were rare reports of cases of a heart attack caused by pituitary apoplexy after taking short-term and long-acting antagonists of GnRH. Cases of thrombocytopenia and leukopenia, changes in glucose tolerance were also recorded.
Local reactions after administration Eligard same as when s / to the introduction of other drugs. In general, local reactions after administration is moderate and are short.
The change in bone density
in the publications was a decrease in bone density in men after orchiectomy or GnRH analogue therapy. It can be assumed that long-term therapy leuprorelin leads to increased symptoms of osteoporosis, which increases the risk of fractures.
Amplification symptoms and signs of disease
Leuprolide acetate therapy may exacerbate the disease symptoms during the first weeks of treatment. In the case of metastatic disease in the spine and / or obstruction of the urinary tract or hematuria may cause neurological complications such as weakness and / or paresthesia lower limbs or worsening symptoms of micturition disorders.
CONTRAINDICATIONS
- surgical castration;
- as the sole treatment for patients with prostate cancer with compression of the spinal cord or metastases in the spine;
- increased sensitivity leuprorelin, other GnRH agonists or any auxiliary substance, a part of the dosage form.
Is contraindicated in women and children.
PREGNANCY AND LACTATION
The drug is contraindicated in women.
APPLICATION FOR FUNCTIONS OF THE LIVER
Clinical data on the use of Eligarda in patients with renal insufficiency not.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Clinical data on the use of Eligarda in patients with hepatic impairment is not.
APPLICATION FOR CHILDREN
The drug is contraindicated in children.
SPECIAL INSTRUCTIONS
If the wrong solution for s / c administration may be observed instances of lack of clinical efficacy.
Eligard should be used under the supervision of a physician who has experience in anticancer therapy.
Response to therapy with Elegard necessary to monitor clinical parameters and measuring the concentration of prostate-specific antigen (PSA) in the blood serum. Clinical studies have shown that testosterone concentration increased during the first 3 days of treatment in most patients without orchiectomy, and then reduced to the level of drug katrsatsii within 3-4 weeks. Subsequently, these indicators remain unchanged with continued drug therapy. If the patient's response to treatment is inadequate, it is necessary to ensure that the concentration of testosterone in the blood serum is at or remains at castration level.
Androgen deprivation therapy may prolong the interval QT. Before assigning Eligard formulation should balance the benefits and risks (including the occurrence of ventricular tachycardia type "pirouette") patients instructions history or risk factors lengthening QT interval, taking medications that may prolong the interval QT.
Eligard, like other drugs, GnRH agonists, in the first week of treatment causes a transient increase in the concentration of testosterone, dihydrotestosterone and acid phosphatase in serum, due to which patients may worsen symptoms or cause new ones, such as bone pain, neurological disorders , hematuria, ureteral obstruction or bladder outlet obstruction. These symptoms usually disappear with continued therapy.
Antiandrogen appropriate supplementation for 3 days prior to initiation of therapy and continued Eligardom its reception over the first 2 or 3 weeks of treatment prevents the effects of the initial increase testosterone concentration.
After performing the surgical castration Eligarda use does not lead to a further reduction of testosterone in the blood serum.
In the application of GnRH agonists were also reported cases of urinary tract obstruction and spinal cord compression, which may lead to paralysis of both with or without fatal complications. In the case of spinal cord compression or renal failure should resort to standard therapy.
For patients with metastases to the spine and / or brain, as well as patients with urinary tract obstruction should be closely monitored during the first few weeks of treatment.
In a certain percentage of patients the tumor resistant to hormone therapy. No improvement of clinical parameters, despite the suppression of testosterone, diagnosed as a lack of efficiency in the further therapy with Eligard.
Antiandrogen therapy significantly increases the risk of bone fractures as a result of osteoporosis. Information on this issue is currently limited. Fractures related to osteoporosis were observed in 5% of patients receiving androgen deprivation therapy for 22 months, and in 4% of patients
treatment duration of 5 to 10 years. In general, the risk of bone fractures as a result of osteoporosis higher than that for pathological fractures. In addition to long-testosterone deficiency on the development of osteoporosis can affect old age, smoking, alcohol consumption, obesity and lack of exercise.
During the post-marketing period of the drug were reported cases of pituitary apoplexy (rare) (a clinical syndrome that occurs after myocardial pituitary), the majority of patients symptoms after taking the drug, GnRH agonists in 2 weeks after the first dose, some - for first hour. In this case, pituitary apoplexy manifested as symptoms such as headache, vomiting, visual disturbances, ophthalmoplegia, altered mental status, and cardiovascular disease, and requires immediate medical attention.
Hyperglycemia and increased risk of diabetes observed in men treated with GnRH agonist drugs. Hyperglycemia may be indicative of the development of diabetes mellitus or worsening of glycemic control in patients with diabetes mellitus. Periodically to monitor the concentration of glucose in the blood and / or glycosylated hemoglobin (HbA1c) in patients treated with GnRH agonist medications, as well as to the necessary selection of modern treatments for hyperglycemia or diabetes.
It reported an increased risk of myocardial infarction, sudden cardiac death and stroke in men receiving GnRH agonist drugs. This risk is not supported by a sufficient number of results within a generalized correlation indicators, and should be carefully evaluated together with the risk of cardiovascular disease when deciding on the method of treatment for patients suffering from prostate cancer. Patients taking drugs GnRH-agonists, should be screened for symptoms and signs indicating the development of cardiovascular disease, as well as undergo treatment based on modern principles of clinical practice.
Impact on the ability to drive vehicles and manage mechanisms
Some adverse drug reactions such as increased fatigue, dizziness, blurred vision, may adversely affect the ability to drive the car and the performance of potentially hazardous activities that require high concentration and psychomotor speed reactions.
OVERDOSE
Data on overdose are available. In case of overdose, the patient should be treated symptomatically.
DRUG INTERACTION
Pharmacokinetic studies of drug interactions Eligard with other drugs was conducted. About Eligarda interaction with other drugs have been reported.
Due to the fact that androgenic deprivation may lengthen the interval QT, should carefully weigh the simultaneous use of the drug Eligard with other drugs that prolong the interval QT, or agents capable of causing ventricular tachycardia type "pirouette" such as antiarrhythmics of class IA (e.g., quinidine , disopyramide) or a class III (e.g., amiodarone, sotalol, dofetelid, ibutilide), methadone, moxifloxacin, neuroleptics, etc.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in their original packaging in reach of children at a temperature of from 2 ° to 8 ° C. Shelf life - 2 years.
The finished solution is chemically and physically stable for 30 min at 25 ° C.
The information is provided for your information, do not self-medicate, it is dangerous for your health.
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