Lucrin depot emulsion lyophilisate 3.75mg, vials set 1pc

Composition

Active ingredient:

leuprorelin acetate 3.75 mg.

Auxiliary substances:

gelatin-0.65 mg;

lactic and glycolic acid copolymer-33.1 mg;

mannitol-6.6 mg.

Solvent (in ampoule):

carmellose sodium-10 mg;

mannitol-100 mg;

polysorbate 80-2 mg;

water for injection-up to 2 ml

Pharmacological action

Pharmacodynamics

Leuprorelin, a GnRH agonist, is an effective inhibitor of gonadotropin secretion when taken for a long time in therapeutic doses. In humans, the use of leuprorelin leads to an initial increase in LH and FSH concentrations, which leads to a transient increase in the concentrations of sex hormones (testosterone and dihydrotestosterone in men, estrone and estradiol in women). However, long-term use of leuprorelin leads to a decrease in the concentrations of LH, FSH and sex hormones. In men, testosterone concentration decreases to post-castration or prepubertal levels. In pre-menopausal women, estrogen concentrations drop to postmenopausal levels. These hormonal changes occur within a month of starting therapy with the drug in the recommended doses.

Suppression of steroidogenesis in the ovaries and testicles is reversible and stops after the end of therapy.

Pharmacokinetics

The bioavailability of the drug with subcutaneous and intramuscular use is comparable. The approximate value of absolute bioavailability when the drug is administered at a dose of 7.5 mg is 90%.

After a single intravenous and subcutaneous use of leuprorelin in patients with prostate cancer at doses of 3.75 and 7.5 mg, the average plasma concentrations of the drug by the end of the first month were 0.7 and 1 ng/ml, respectively.

The serum leuprorelin concentration of 3.75 mg was determined for 12 months in 11 patients with premenopausal breast cancer. The average concentration of leuprorelin exceeded 0.1 ng / ml after 4 weeks and remained stable after repeated use (at 8 and 12 weeks). No accumulation of the drug was observed.

Medium V_ss – 27 liters. Binding to plasma proteins is 43-49%. The system clearance is 7.6 l/h. T_1/2 – about 3 h. Leuprorelin, being a peptide, undergoes metabolic degradation, mainly by peptidase, to shorter inactive peptides-pentapeptide (metabolite I), tripeptides (metabolites II and III) and dipeptide (metabolite IV). The time to reach the_cmax of the main metabolite M-I is 2-6 hours and corresponds to 6% of the_cmax of leuprorelin. 1 week after injection, the average plasma concentration of M-I is 20% of the average leuprorelin concentration.

After use of 3.75 mg of leuprorelin, the content of leuprorelin and M-I in the urine was less than 5% of the administered dose 27 days after use of the drug.

Pharmacokinetics in special clinical cases

, the pharmacokinetics of the drug in patients with impaired liver or kidney function have not been studied.

Indications

• Advanced prostate cancer (palliative care), including when orchiectomy or estrogen therapy is not shown, or are not applicable in this patient;
• endometriosis (for the period up to 6 months as the primary therapy or adjunct to surgical treatment);
• fibromyoma of the uterus (for the period up to 6 months as a preoperative preparation for the removal of fibroids or Comfrey Woundwort, as well as for the symptomatic treatment of and improve the condition of women in menopause who refuse surgical intervention);
• breast cancer in perimenopausal period, in combination with hormone therapy;
• children with precocious puberty (PPP) of Central origin.

Contraindications

• Hypersensitivity to leuprorelin similar drugs protein or to any other auxiliary substance included in the composition of the dosage form;
• surgical castration;
• pregnancy;
• lactation breast;
• vaginal bleeding of unknown etiology;
• cancer of the prostate (gormononezawisimy);
• children’s age (under 18), except for children with a PPP of Central origin;
• women older than 65 years.

Caution: patients with spinal metastases, urinary tract obstruction, or hematuria.

Side effects

From the cardiovascular system: edema, angina, palpitation, bradycardia, tachycardia, arrhythmia, congestive heart failure, ECG changes, increased or decreased blood pressure, myocardial infarction, phlebitis, pulmonary embolism, stroke, thrombosis, transient ischemic attacks, varicose veins.

From the digestive system: change (increase, decrease or absence) of appetite, changes in taste perception, dry mouth, thirst, dysphagia, nausea, vomiting, diarrhea or constipation, flatulence, increase or decrease in body weight, impaired liver function, abnormal liver function tests, jaundice.

Endocrine system disorders: breast pain and sensitivity, gynecomastia, lactation, thyroid enlargement, impotence, decreased libido, diabetes mellitus, androgen-like effects-virilization, acne, seborrhea, hirsutism, voice changes.

From the blood and hematopoietic organs: anemia, thrombocytopenia, leukopenia, leukocytosis, neutropenia, increased PV and partial thromboplastin time.

From the musculoskeletal system: bone pain, joint disorders, retroperitoneal fibrosis, arthralgia, myalgia, increased muscle tone; decreased bone density.

From the central and peripheral nervous system: headache, dizziness, fainting, sleep disorders (insomnia), increased irritability, anxiety, pituitary apoplexy (in patients with pituitary adenoma), depression, paresthesia, memory impairment, hallucinations, hyperesthesia, hypesthesia, emotional lability, personality disorders, impaired neuromuscular transmission, peripheral neuropathy, drowsiness. Very rarely, there were cases of suicidal thoughts and suicide attempts in patients.

From the respiratory system: cough, shortness of breath, nosebleeds, hemoptysis, pharyngitis, pleural effusion, fibrotic formations in the lungs, infiltrates in the lungs, respiratory disorders.

From the skin and its appendages: dermatitis, dry skin, photosensitization reactions, pruritus, rash, erythema, urticaria, ecchymoses (skin hemorrhages), alopecia, pigmentation, striae, acne in women, changes in hair formation (hair growth/loss).

From the sensory organs: visual and hearing disorders, ringing in the ears, dry eyes, amblyopia.

From the genitourinary system: dysuria, dysmenorrhea, breakthrough and prolonged vaginal bleeding, dryness of the vaginal mucosa, vaginitis, vaginal odor, leucorrhoea, prostate pain, testicular atrophy, testicular pain, hematuria, penile edema. Changes in laboratory parameters: increased blood urea nitrogen, increased content of calcium, creatinine, bilirubin, uric acid; hyperlipidemia (increased concentration of total cholesterol, LDL cholesterol, triglycerides), hyperphosphatemia, hypoglycemia, hyponatremia, hypoproteinemia, hypokalemia.

Local reactions: tissue compaction, hyperemia, inflammation and pain at the injection site.

Other: allergic reactions (including anaphylactic shock), flu-like syndrome, flushes of blood to the skin of the face and upper chest, increased sweating, enlarged lymph nodes, chills, fever, a lump in the throat, asthenia, dehydration.

Interaction

Pharmacokinetic studies on the drug interaction of Lucrin depo® with other drugs have not been conducted.

However, since leuprorelin is a substance of a peptide nature and undergoes primary degradation under the influence of peptidase, and not cytochrome P 450 enzymes, and about 46% of the drug binds to plasma proteins, drug interaction is unlikely.

How to take, course of use and dosage

I / m or p / c,1 time per month. The injection site should be changed periodically. The suspension for injection is prepared immediately before use using the supplied solvent at a concentration of 3.75 mg/1 ml.

For prostate or breast cancer, a single dose is 3.75 mg. The duration of treatment is determined by the doctor.

With endometriosis, uterine fibromyomas, a single dose is 3.75 mg

. Women of reproductive age receive the first injection on the 3rd day of menstruation. Duration of treatment is not more than 6 months.

In children with PPS, the initial dose is 0.3 mg / kg (minimum 7.5 mg) once every 4 weeks.

The initial dose can be determined based on the child’s body weight:

Note: If 2 or more injections are required to obtain the desired total dose, they should be administered simultaneously.

Maintenance dose for PPS

If complete suppression of disease progression is not achieved, the dose should be increased by 3.75 mg every 4 weeks.

Discontinuation of Lucrin depot should be considered before the age of 11 years in girls and 12 years in boys.

Instructions for preparing the suspension and injecting the drug Lucrin depot® in vials:

1. Take 1 ml of solvent from the ampoule into the syringe with the needle provided in the kit and insert it into the lyophilizate bottle (the remaining solvent should be disposed of).

2. Shake the bottle well until a homogeneous suspension is obtained. The suspension becomes milky in color.

3. Immediately after dilution, collect the entire contents of the vial (or 2 vials) in a syringe (maximum-2 ml per syringe) and make a subcutaneous or intramuscular injection. Although the prepared suspension of Lucrin Depot remains stable for 24 hours after dilution, it should be used immediately after preparation. The remainder of the drug must be disposed of.

Instructions for injecting the drug Lyukrin depot® in two-chamber syringes:

1. Screw the white plunger into the end plug until the plug starts to rotate.

2. Keep the syringe in an upright position. Insert the solvent by slowly pressing (for 6-8 seconds) on the plunger, until the first plug is on the blue line in the middle of the syringe.

3. Continue to hold the syringe upright. Carefully mix the lyophilizate with the solvent until a homogeneous suspension is formed. The suspension becomes milky in color.

4. Hold the syringe upright. With the other hand, remove the needle cap upwards without unscrewing it.

5. Hold the syringe upright. Push the plunger forward to remove air from the syringe.

6. Immediately after the suspension is formed, immediately inject the entire contents of the syringe intravenously or subcutaneously, as the suspension settles very quickly.

Overdose

There are no data on overdose of leuprorelin in humans. use of leuprorelin to patients with prostate cancer at a dose of up to 20 mg / day for 2 years did not cause the development of adverse events other than those observed with the use of the drug at a dose of 1 mg/day.

In case of overdose, the patient should be prescribed symptomatic treatment.

Special instructions

Lucrin depot® should only be used under medical supervision.

Prostate cancer

In most patients, the testosterone concentration increases from baseline during the first week, and then decreases to or below the baseline concentration by the end of the second week of treatment. Post-castration concentration is achieved within 2-4 weeks and is maintained throughout the entire period of regular use of the drug.

During the first few weeks of treatment with Lucrin Depot, transient symptoms of worsening of the condition may develop or additional signs and symptoms of the underlying disease may appear. In a small number of patients, bone pain may increase, which is stopped with symptomatic treatment. Increased symptoms of deterioration during the first few weeks of treatment with Lucrin depot® in patients with spinal metastases, urinary tract obstruction, or hematuria may lead to neurological problems, such as temporary weakness of the lower extremities, paresthesia, and increased urological symptoms. As with other GnRH analogues, there have been isolated cases of urinary tract obstruction and spinal cord compression, which can be complicated by paralysis with/without a fatal outcome, when using Lucrin depot®. Therefore, during the first few weeks of treatment, patients with spinal metastases and severe urinary tract obstruction should be carefully monitored.

Endometriosis/Uterine fibromyoma

At the very beginning of the course of treatment, a transient increase in the concentration of sex hormones is usually noted, which causes physiological manifestations of the drug’s action. Some aggravation of symptoms at the beginning of therapy with Lucrin depot® passes quickly enough with continued treatment with adequately selected doses of the drug. Severe vaginal bleeding requiring conservative or surgical treatment has been reported.

During treatment and before the restoration of menstruation, non-hormonal methods of contraception should be used.

The ability to fertilize or fertility suppressed as a result of therapy is restored in the period up to 24 weeks after the end of treatment.

The decrease in bone density during bone densitometry in women as a result of a decrease in the concentration of estrogens is reversible, and after discontinuation of treatment with leuprorelin, bone density is restored.

The use of Lucrin depo® in women causes suppression of the function of the pituitary-gonadotropic system. After the end of treatment, the function is restored in 3 months. However, diagnostic tests that indicate the function of the pituitary gland or sex glands performed during treatment and up to 3 months after its completion may be distorted.

The drug is prescribed for the treatment of PPS, based on the following criteria::

1. Clinical diagnosis of PPS (idiopathic or neurogenic) with the appearance of secondary sexual characteristics up to 8 years in girls and up to 9 years in boys.

2. The diagnosis should be confirmed by a GnRH stimulation test, and it should also be taken into account that the bone age is one year ahead of the biological age.

3. The initial examination includes:

• measurement of height and weight;
• determination of the concentration of sex hormones;
• determination of the concentration of adrenal steroids to exclude congenital adrenal hyperplasia;
• determination of the concentration of human chorionic gonadotropin to exclude the presence of a tumor that secretes chorionic gonadotropin;
• Ultrasound of the small pelvis and adrenal glands to exclude a steroid-producing tumor;
• computed tomography of the head to exclude an intracranial tumor.

The dose of Lucrin depo® for the preparation of depo suspension should be individualized for each child. The dose is based on the ratio of the amount of the drug to body weight (mg / kg). Younger children require higher doses in terms of mg/kg.

When using any dosage form, a follow-up examination of the child should be performed 1 or 2 months after starting therapy or changing the dose, with a GnRH stimulation test, sex hormones, and a Timer staging test to confirm suppression. Bone age advance measurements should be performed every 6-12 months. The dose should be titrated until there is no progression of the disease, according to clinical and / or laboratory studies.

The first dose, which was found to be sufficient to maintain adequate suppression, can be maintained throughout therapy in most children. However, there is no sufficient data to establish an adjusted dose when patients move to higher weight categories after starting therapy at a very young age and using low dosages.

Confirmation of adequate suppression is recommended in patients whose weight has increased significantly during treatment.

Discontinuation of Lucrin depot should be considered before the age of 11 years in girls and 12 years in boys.

Violations of the drug regimen or an incorrectly selected dose can lead to inadequate control of the puberty process. The consequences of inadequate control include the recurrence of pubertal symptoms, such as menstruation, breast development, and testicular growth. The long-term consequences of inadequate control of gonadal steroid secretion are unknown, but may include subsequent growth disruption in adulthood.

Laboratory tests

Monitoring of response to therapy with Lucrin depot® should be performed 1 or 2 months after the start of therapy using a GnRH stimulation test and determination of sex hormone concentrations. Bone age advance should be measured every 6-12 months.

The concentration of sex hormones may increase above the limits of prepubertal levels in the case of an inadequate dose. After setting the therapeutic dose, the concentration of gonadotropins and sex hormones will decrease to prepubescent levels.

Information for parents

Before starting therapy with Lucrin depot®, parents or guardians should be warned about the importance of continuous therapy.

During the first 2 months of therapy, girls may have menstruation or spotting. If the bleeding continues for more than 2 months, you should inform your doctor. Your doctor should immediately report any irritation at the injection site and any unusual symptoms or signs.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

There is no data on the effect on the ability to drive a car and work with mechanisms. Due to the possibility of side effects such as drowsiness, dizziness, etc. (see “Side effects”) it is recommended to refrain from driving a car and engaging in other activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Lyophilizate for the preparation of a suspension for intramuscular and subcutaneous use of prolonged action

Storage conditions

At a temperature of 15-25 °C (do not freeze)

Shelf life

3 years

Active ingredient

Leuprorelin

Conditions of release from pharmacies

By prescription

Dosage form

lyophilizate for solution preparation