Eligard

Eligard is an analogue of gonadotropin-releasing hormone – it acts as a depot form.

Indications Eligarda

It is used in the treatment of hormone-dependent prostate cancer.

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Release form

Released in the form of a lyophilisate for the preparation of a solution administered subcutaneously. The volume of syringes with the drug is 7.5, 22.5, and 45 mg. The package contains one of these syringes, complete with a second syringe - with a special solvent inside it.

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Pharmacodynamics

Leuprorelin is an artificial analogue of natural GnRH (non-peptide). With prolonged administration, it slows down the release of pituitary gonadotropin and inhibits the process of male testicular steroidogenesis. This analogue has a more powerful effect than the natural hormone, and its effect is reversible if the drug is discontinued. As a result of the use of the substance leuprorelin, an increase in LH and FSH levels is initially observed, due to which testosterone levels along with gonadal steroids and dihydrotestosterone increase in men for some time.

With further continuation of the course, the FSH and LH levels decrease. The testosterone values in men decrease to castration levels (≤50 ng/dl) within 3-5 weeks after the start of the course. The average testosterone level after six months of therapy is:

• 6.1±0.4 ng/dL at 7.5 mg serving size;
• 10.1±0.7 ng/dl at a dosage of 22.5 mg;
• 10.4±0.53 ng/dl at a dosage of 45 mg.

These figures can be compared with testosterone levels after a bilateral orchidectomy procedure.

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Pharmacokinetics

After the administration of the 1st dose of the drug, an increase in the average serum leuprorelin levels to 25.3 ng/dl is observed after 4-8 hours, as well as 127 ng/dl or 82 ng/dl after the administration of the drug in doses of 7.5, 22.5, and 45 mg, respectively.

With the initial increase (the plateau stage is 2-28 days at a dosage of 7.5 mg; 3-84 days at 22.5 mg, and 3-168 days at a dose of 45 mg), the serum values of the leuprorelin component remain in a fairly stable state (approximately 0.2-2 ng/ml). There is no information on the accumulation of the drug after repeated administration.

The synthesis of the substance with plasma protein is 43-49%.

Following intravenous injection of 1 mg leuprorelin acetate into male volunteers, the mean clearance was 8.34 L/h with a terminal half-life of approximately 3 hours using a 2-compartment model.

Eligard excretion tests have not been performed.

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Dosing and administration

Eligard is required to be administered subcutaneously once a month in the amount of 7.5 mg. It is also administered once every 3 months in the amount of 22.5 mg, and also once every six months in the amount of 45 mg. The solution that gets under the skin forms a depot of the drug, which ensures regular release of the active component during the entire specified period. The treatment process is long-term.

If an increase in PSA levels is observed with castration testosterone levels, the use of the drug should be stopped.

It is necessary to periodically change the injection site of the solution. It is also necessary to avoid penetration of the medicine into the vein or artery.

There is no medicinal information regarding the use of drugs in people with kidney or liver failure.

The process of making the solution.

The contents of the two syringes must be mixed immediately before the injection procedure. The mixture must be prepared as follows:

• take the medicine package out of the refrigerator and keep it in room conditions so that the packaging matches the temperature of the medicine;
• remove syringes A and B from the blisters. Then remove the small piston with the 2nd limiter from the B-syringe, after which a long special piston is removed from the blister with the A-syringe and inserted into the B-syringe;
• remove the stoppers from both syringes (the A-syringe contains the solvent, and the B-syringe contains the lyophilisate of the drug) and carefully connect them. Next, the solution must be mixed, using the syringe plungers in turn (60 presses), until a homogeneous mixture is obtained. The solution, which is allowed to be used for administration, acquires a light yellow or colorless hue;
• the prepared mixture is injected into the B-syringe, and the empty A-syringe is removed, pressing the piston all the way in. Small bubbles may appear during the procedure. This phenomenon is absolutely normal and does not affect the formation of the depot after the drug injection. After this, a sterile needle is inserted into the B-syringe;
• After this, the mixture can be administered subcutaneously. In this case, the prepared solution must be administered immediately after the mixing procedure. If it was not used immediately, it can no longer be administered after a while. The medicine is intended for single use.

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Contraindications

Main contraindications:

• surgical castration;
• intolerance to leuprorelin, as well as other GnRH hormone agonists or additional components of the drug;
• use in childhood or women.

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Side effects Eligarda

As a result of taking the drug, the following side effects may develop:

• dysfunction of the cardiovascular system: increase or decrease in blood pressure, hot flashes, development of fainting. Sometimes peripheral edema, dyspnea, palpitations, and pulmonary embolism may occur;
• reactions from the PNS and CNS: headaches, taste or olfactory disturbances, dizziness, hypoesthesia, involuntary movements, and insomnia. Sometimes depression, amnesia, various sleep or vision disorders, peripheral dizziness, and, in addition, skin hypersensitivity may develop;
• gastrointestinal disorders: diarrhea, vomiting or nausea, constipation, dyspeptic symptoms, belching, dry mouth, bloating and increased ALT levels;
• manifestations from the respiratory system: breathing problems or rhinorrhea;
• reactions of the urogenital system: development of nocturia, dysuria or oliguria, as well as the appearance of infection in the urinary tract. In addition, pain in the testicles or their atrophy, problems with urination, hematuria, spasms in the bladder, acute urinary retention, as well as decreased libido, impotence and infertility;
• dysfunction of the endocrine system: development of gynecomastia and pain in the mammary glands;
• manifestations in the area of muscle and bone structure: pain in the limbs or back, arthralgia, muscle cramps or weakness, and myalgia. People with drug or surgical castration may develop a weakening of bone tissue density. It should be taken into account that prolonged administration of the solution can also reduce bone density and contribute to the progression of osteoporosis;
• disorders in the functioning of the hematopoietic system: decreased hematocrit values with hemoglobin, decreased number of erythrocytes. Thrombocyto- or leukopenia is occasionally observed;
• blood clotting disorders: prolongation of the time interval required for blood clotting, as well as an increase in the PT indices;
• changes in laboratory test values: increased levels of CPK in the blood, as well as elevated triglyceride levels;
• local manifestations: occurrence of pain, tingling or burning sensation, as well as redness, itching and bruising at the injection site. Occasionally, small ulcers or compactions appear at the injection site;
• others: increased feeling of fatigue, feeling of extreme weakness or malaise, and in addition to this, the appearance of alopecia, chills, skin rashes, hyperhidrosis, weight gain and changes in glucose tolerance.

In the early stages of treatment, signs of pathology may worsen.

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Storage conditions

Eligard must be kept at a temperature of 2-8°C.

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Special instructions

Eligard, according to patients, demonstrated an increase in the manifestations of the disease at the initial stage of therapy. In addition, there were pains in the bone area, blood in the urine, and neurological disorders. Such signs develop due to a surge in the release of gonadotropic hormones. During subsequent treatment, they are suppressed. During prolonged use, according to reviews of individual people, there were hot flashes of moderate or mild severity, as well as nausea, burning in the area of administration and gynecomastia.

But at the same time, the medicine is unique, as it uses a special Atrigel system (a biodegradable polymer used as a solvent), which helps form a drug depot inside the subcutaneous layer for a period of 1-3-6 months, and also provides a stable result. Such a system helps reduce testosterone levels in 95% of those treated.

Among the advantages of Eligard, it should also be noted that thanks to the use of a 6-month depot, the frequency of local manifestations is reduced, and the need for frequent visits to the doctor disappears.

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Shelf life

Eligard can be used for a period of 2 years from the date of release of the drug.