Eligard - instructions for use, dose, side effects, contraindications

Name component	Dosage 7.5 mg	Dosage: 22.5 mg	Dosage of 45 mg
Copolymer poly-D,L lactide-co-glycolide: PLGA (50:50)	117 mg	-	-
PLG (75:25)	-	206 mg	-
PLG (85:15)	-	-	217 mg
Nmethyl-2- pyrrolidone	226 mg	251 mg	217 mg

1 syringe B contains:

active substance: leuprorelin acetate *

dosage 7.5 mg: 10.6 mg

dosage of 22.5 mg: 29.2 mg

dosage of 45 mg: 59.2 mg

Excipients: no

* 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.

Description:

Syringe A (solvent)

Dosage 7.5 mg : From light yellow to light yellow with a brownish tinge, a clear, viscous liquid, with no visible foreign particles. Air bubbles are allowed.

Dosages of 22.5 mg and 45 mg: From colorless to light yellow, transparent, viscous liquid, with no visible foreign particles.Air bubbles are allowed.

Syringe B (lyophilizate leuprorelin acetate)

Liofilizate from white to almost white, without visible foreign particles.

The reconstituted solution

Dosage 7.5 mg: from light yellow to light yellow with a brownish tint viscous liquid without visible foreign particles. Air bubbles are allowed.

Dosages of 22.5 mg and 45 mg: from colorless to light yellow viscous liquid with no visible foreign particles. Air bubbles are allowed.

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:

Leiprorelin is a synthetic, non-peptide analogue of the natural gonadotropin releasing hormone (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.

The appointment of leuprorelin first leads to an increase in the level of circulating luteinizing hormone (LH) andfollicle-stimulating hormone (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 dosage 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.

Pharmacokinetics:

After the first injection, after 4-8 hours, the average level of leuprorelin (Cmoch), determined in serum, increased to 25.3 ng / dl, 127 ng / dL and 82 ng / dl with leuprorelin at a dose of 7, 5 mg, 22.5 mg and 45 mg, respectively.

After the initial increase (the plateau phase is from 2 to 28 days for dosing 7,5 mg; 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 (0.2-2 ng / ml). Data on the accumulation of substance with repeated injections are absent.

Communication with plasma proteins - 43% - 49%.

When 1 mg leuprorelin acetate was injected intravenously to healthy volunteers, it was found to men that when using a two-chamber model, the average clearance was 8.34 l / h with a terminal half-life of about 3 hours.

Studies on the Eligard preparation were not carried out.

Indications:

Hormone-dependent prostate cancer.

Contraindications:

Hypersensitivity to leuprorelin, other GnRH agonists or to any auxiliary substance included in the formulation.

Surgical castration.

Contraindicated in women and children.

Dosing and Administration:

Eligard is administered as a subcutaneous injection once a month at a dosage of 7.5 mg, once every three months at a dosage of 22.5 mg and once every six months at a dosage of 45 mg. The injected solution forms the drug depot, which ensures the continuous release of leuprorelin during this period. Treatment is long. When increase in the level of prostate-specific antigen (PSA) against the background of castration levels of testosterone treatment Eligard should be discontinued.

The injection site should be periodically changed. Avoid getting into the artery or vein.

Dose adjustment for specific patient populations

Clinical data on the use of Eligard in patients with hepatic or renal insufficiency do not.

Recommendations for the preparation of a solution for administration

The contents of two pre-filled sterile syringes should be mixed immediately before administration. Preparation of the mixture is as follows:

1. Before use, the package is removed from the refrigerator and kept at room temperature until the temperature of the package reaches room temperature.

2. Remove syringe A and syringe B from the packages. Remove the short piston from the syringe B with the second stop, remove the long piston from the package with the syringe A and insert it into the syringe B.

3. Remove the caps from the syringe A (solvent for solution) and the syringe B (lyophilized leuprorelin acetate) and carefully connect the syringes. Mix the solution by alternately pressing the plunger of the syringe A and the syringe B 60 times to obtain a uniform solution. Ready-to-use mixture should be colorless or light yellow.

4. Enter the resulting mixture into the syringe B. Remove the syringe A, continuing to press down on its piston. Note: Small bubbles may appear. This is normal and does not affect the formation of the depot after administration. Insert a sterile needle into the syringe.

5. The mixture is ready for subcutaneous administration.

6. The solution should be introduced immediately after mixing.

Only for single use. Unused solution must be disposed of.

Side effects:

The side effects observed with the use of Eligard are mainly due to the pharmacological action of the drug.

From the cardiovascular system: hot flushes, increased or decreased blood pressure, fainting. In some cases peripheral edema, embolism of the branches of the pulmonary artery, palpitation, dyspnea were noted.

From the nervous system: hypoesthesia, dizziness, headache, insomnia, taste disorders, smell disorders, involuntary movements. In some cases, sleep disorders, depression, peripheral dizziness, amnesia, visual impairment and skin hypersensitivity were noted.

From the digestive system: nausea / vomiting, diarrhea, indigestion, constipation, dry mouth, belching, flatulence.

From the respiratory system: rhinorrhea, shortness of breath.

From the genitourinary system: dysuria, nocturia, oliguria, urinary tract infection, difficulty urinating, bladder spasms, hematuria, acute urinary retention, testicular atrophy, testicular pain, infertility, impotence, decreased libido.

From the endocrine system: pain in the mammary glands, gynecomastia.

From the musculoskeletal system: arthralgia, back pain, pain in the extremities, myalgia, muscle cramps, muscle weakness.

In patients with surgical or drug castration, a decrease in bone density is observed. It should be borne in mind that prolonged reception of Eligard can also lead to a decrease in bone density and the progression of osteoporosis.

Violations from laboratory indicators: decrease in the number of erythrocytes, hemoglobin and hematocrit, increased blood creatine phosphokinase, increased blood coagulation time, increased alanine aminotransferase, elevated triglycerides in the blood, increased prothrombin time, and rare cases of thrombocytopenia and leukopenia.

Local reactions: burning / pricking, pain, redness, bruising and itching at the injection site; rarely - compaction and ulceration at the injection site.

Other: feeling of malaise, increased fatigue, weakness, skin rash, alopecia, increased sweating, chills, changes in glucose tolerance, weight gain. In the first weeks after the beginning of Eligard's therapy, the symptoms of the disease may worsen.

Overdose:

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

Interaction:

Studies to study the pharmacokinetic interaction of the drug Eligard with other drugs have not been conducted. Eligard's interaction with other drugs was not reported.

Special instructions:

Eligard should be used under the supervision of a doctor who has experience in the use of antitumor therapy.

Eligard, like other drugs-agonists GnRH, during the first week of treatment causes a short-term increase in the concentration of testosterone, dihydrotestosterone and acid phosphatase in the blood serum, in this connection, patients may have symptoms or develop new ones such as bone pain,neurological disorders, hematuria, ureteral obstruction, or infravesical obstruction. These symptoms usually go away with the continuation of therapy. When GnRH agonists were used, there were also reported cases of compression of the spinal cord. If necessary, a standard treatment for these complications should be performed.

Patients with metastases in the spine and / or brain, as well as patients with obstruction of the urinary tract, should be carefully monitored during the first few weeks of treatment.

The additional appointment of an appropriate anti-androgen three days before the start of Eligard's therapy and the continuation of its administration during the first two or three weeks of treatment prevents the effects of an initial increase in testosterone levels. Antiandrogen therapy increases the risk of bone fractures due to osteoporosis. In addition to the prolonged testosterone deficiency, the development of osteoporosis can be influenced by advanced age, smoking, alcohol consumption, excess weight and insufficient physical activity.

In connection with the possible decrease in glucose tolerance, patients suffering from diabetes mellitus need more careful observation when treated with Eligard.

After surgical castration, the use of Eligard does not lead to a further decrease in testosterone in the serum.

Effect on the ability to drive transp. cf. and fur:

Some side effects of the drug, such as increased fatigue, dizziness, visual impairment, can adversely affect the ability to drive and perform potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Lyophilizate for the preparation of a solution for subcutaneous administration (7.5 mg, 22.5 mg, 45 mg) complete with a solvent.

Packaging:

Two sterile pre-filled syringes of polypropylene or a cyclic olefin copolymer, one (syringe B) contains leuprolilin acetate (10.6 mg for a dosage of 7.5 mg, 29.2 mg for a dosage of 22.5 mg, 59.2 mg for dosages of 45 mg), in the other (syringe A) - a solvent (343 mg for a dosage of 7.5 mg, 457 mg for a dosage of 22.5 mg, 434 mg for a dosage of 45 mg). Content two The syringe is a combined system.

The syringe A together with the plunger for the syringe B and the sachet with the desiccant (silica gel) is placed in one polyester cell package,covered with aluminum laminated foil. Syringe B with injection needle 0.9 x 12.3 mm "monoject" (No. 20 for doses of 7.5 mg and 22.5 mg, No. 18 for a dosage of 45 mg) in a transparent plastic case and a bag of desiccant (silica gel) is placed in a cell package covered with aluminum laminated foil.

One cell pack with a syringe A complete with a piston and a bag with a desiccant and one cell pack with a syringe B complete with an injection needle and a bag with a desiccant along with an instruction in a cardboard bundle.

Storage conditions:

List B.

At a temperature of 2 ° C to 8 ° C in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

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

The prepared solution is chemically and physically stable for 30 minutes at a temperature of 25 ° C.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006156/09

Date of registration:29.07.2009

The owner of the registration certificate:Astellas Farma Europe BVAstellas Farma Europe BV Netherlands