Eligard, lyophilizate 7.5 mg syringes 2 pcs

Pharmacodynamics

The gonadotropin-releasing hormone analogue is a depo-form. Leuprorelin is a synthetic non-peptide analogue of natural GnRH which, with long-term use, inhibits pituitary gonadotropin secretion and suppresses testicular steroidogenesis in men. The analog is more effective than the natural hormone and its effects are reversible when treatment is discontinued. Leuprorelin administration initially leads to increased levels of circulating LH and FSH, resulting in a temporary increase in male gonadal steroids, testosterone, and dihydrotestosterone. With prolonged use of leuprorelin, LH and FSH levels decrease. In men, testosterone levels decrease to castration levels (≤50 ng/dL) within 3-5 weeks after starting treatment. Mean testosterone levels after 6 months of treatment are 6.1 (±0.4) ng/dL for the 7.5 mg dose; 10.1 (±0.7) ng/dL for the 22.5 mg dose and 10.4 (±0.53) ng/dL for the 45 mg dose. These values are comparable to testosterone levels after bilateral orchiectomy.

Pharmacokinetics

Intake Distribution

After the first injection, after 4-8 h the mean leuprorelin concentration level (C_max) determined in serum increases to 25.3 ng/dL, 127 ng/dL, and 82 ng/dL when leuprorelin doses of 7.5 mg, 22.5 mg, and 45 mg are used, respectively. After an initial increase (plateau phase is 2 to 28 days for 7.5 mg doses; 3 to 84 days for 22.5 mg doses; 3 to 168 days for 45 mg doses), serum leuprorelin levels remained relatively stable (0.2 to 2 ng/mL). No data were available on the accumulation of the substance with repeated injections.

The binding to plasma proteins is 43-49%.

Elevation

In administration of 1 mg of leuprorelin acetate by IV to healthy male volunteers, it was found that using a dual-chamber model, mean clearance was 8.34 L/h with a final T_1/2 of approximately 3 h. No studies of elimination of Eligard have been performed.

Indications

Hormone-dependent prostate cancer.

Active ingredient

Composition

1 dose (1 syringe (B)) contains:

Active ingredients:

Leuprorelin acetate 7.5 mg (10.6 mg)*.

Solvent (syringe A):

Poly-D copolymer,

L-lactide-co-glycolide:PLGH (50:50) – 117 mg,

N-methyl-2-pyrrolidone – 226 mg.

* – The drug contains an excess of the active ingredient to compensate for losses in the syringe and needle.

There are 2 syringes in a cell pack.

The carton pack contains 2 syringes.

How to take, the dosage

Eligard is administered by injection 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 injected solution forms a drug depot which ensures continuous release of leuprorelin for a specified period. The treatment is prolonged. If PSA level rises against the background of castration of testosterone, treatment with Eligard should be discontinued.

The injection site should be changed periodically. Avoid getting the drug in an artery or vein.

There are no clinical data on the use of Eligard in patients with hepatic or renal impairment.

Rules for preparing the solution

The contents of two pre-filled sterile syringes must be mixed immediately prior to administration.

The mixture is prepared as follows:

1. Before use, take the package out of the refrigerator and keep it at room temperature until the package reaches room temperature.

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

3. Remove the caps from Syringe A (solvent to prepare the solution) and Syringe B (lyophilized leuprorelin acetate) and carefully combine the syringes. Mix the solution by alternately pressing the plunger of syringe A and syringe B 60 times to obtain a homogeneous solution. The ready to use mixture should be colorless or light yellow.

4. Add the mixture to syringe B. Remove syringe A while continuing to push the plunger all the way in. You might see some small bubbles. This is normal and will not affect the depot formation after injection. Insert a sterile needle into the B syringe.

5. The mixture is ready for injection.

6. The solution must be injected immediately after mixing. The solution is for single use only. Unused solution must be destroyed.

Interaction

No studies on pharmacokinetic interaction of the drug Eligard with other drugs have been conducted.

The interaction of Eligard with other medicinal products has not been reported.

Special Instructions

Eligard should be used under the supervision of a physician experienced in the use of antitumor therapy.

Eligard, like other GnRH agonists, causes transient increases in serum testosterone, dihydrotestosterone and acid phosphatase concentrations during the first week of treatment, which may cause increased or new symptoms in patients, such as bone pain, neurological disorders, hematuria, ureteral obstruction or infravesical obstruction. These symptoms usually go away with continued therapy. Cases of spinal cord compression have also been reported with GnRH agonists. Standard treatment for these complications should be given if necessary.

Patients with spinal and/or brain metastases and those with urinary tract obstruction should be monitored closely during the first few weeks of treatment.

The additional administration of an appropriate anti-androgen 3 days before starting therapy with Eligard and continuing its administration for the first two or three weeks of treatment prevents the effects of an initial increase in testosterone levels.

The anti-androgen therapy increases the risk of bone fractures as a result of osteoporosis. In addition to long-term testosterone deficiency, advanced age, smoking, alcohol consumption, excess body weight, and lack of exercise may also contribute to the development of osteoporosis.

Because of a possible decrease in glucose tolerance, patients with diabetes mellitus need more careful monitoring when treated with Eligard.

After surgical castration, use of Eligard does not further decrease serum testosterone.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

Some adverse reactions of the drug, such as increased fatigue, dizziness, visual disturbances, may adversely affect the ability to drive and perform potentially hazardous activities requiring increased concentration and rapid psychomotor reactions.

Contraindications

Side effects

The side effects observed with Eligard are mainly caused by the pharmacological action of the drug.

Cardiovascular system disorders: hot flashes, increased or decreased BP, fainting; in some cases – peripheral edema, pulmonary embolism, palpitations, dyspnea.

CNS and peripheral nervous system disorders: hypoesthesia, dizziness, headache, insomnia, taste disorders, olfactory disorders, involuntary movements; in some cases – sleep disorders, depression, peripheral vertigo, amnesia, visual disturbances and skin hypersensitivity.

Digestive system disorders: nausea/vomiting, diarrhea, dyspepsia, constipation, dry mouth, belching, flatulence, increased ALT.

Respiratory system: rhinorrhea, difficulty in breathing.

Urogenital system disorders: dysuria, nycturia, oliguria, urinary tract infection, difficult urination, bladder spasms, hematuria, acute urinary retention, testicular atrophy, testicular pain, infertility, impotence, reduced libido.

Endocrine system: pain in the breasts, gynecomastia.

Muscular system disorders: arthralgia, back pain, pain in the extremities, myalgia, muscle cramps, muscle weakness.

In patients with surgical or medical castration, there is a decrease in bone density. Note that long-term use of Eligard may also lead to decreased bone density and progression of osteoporosis.

With the hematopoietic system: decrease in the number of red blood cells, hemoglobin and hematocrit level; rarely – thrombocytopenia, leukopenia.

With the coagulation system: increased clotting time, increased prothrombin time.

Laboratory findings: increased CPK in blood, increased triglycerides in blood.

Local reactions: burning/tingling, pain, redness, bruising and itching at the injection site; rarely – thickening and ulceration at the injection site.

Others: feeling of malaise, increased fatigue, weakness, skin rash, alopecia, increased sweating, chills, changes in glucose tolerance, weight gain. In the first weeks after the start of therapy with Eligard, an exacerbation of symptoms of the disease may be observed.

Overdose

There are no data on overdose in humans. In case of overdose, the patient should be treated symptomatically.