LYUKRIN DEPOT
Active material: Leuprorelin
When ATH: L02AE02
CCF: An analogue of gonadotropin-releasing hormone – depot
ICD-10 codes (testimony): C61, D25, N80
When CSF: 15.07.04.01
Manufacturer: ABBOTT LABORATORIES S.A. (Spain)
Pharmaceutical form, composition and packaging
Lyophilisate for preparation of suspension for injection in the form of a powder of white color; prepared suspension of white color; when standing, a white precipitate is formed, which is easily resuspended with shaking.
| 1 fl. | |
| leyprorelina acetate | 3.75 mg |
Excipients: gelatin, copolymer D,L-lactic and glycolic acids, mannyt.
Solvent: sodium carboxymethylcellulose, mannyt, polysorbate-80, water d / and (to 2 ml).
Bottles (1) together with the solvent (amp. 1 PC.) and a set for one-time administration (needle – 2 PC., disposable sterile propylene syringe – 1 PC., napkin, alcohol-soaked – 1 PC.) – packs cardboard.
Pharmacological action
Anticancer drug, synthetic peptide analogue of GnRH. Has a more pronounced activity, than a natural hormone. Interacts with pituitary gonadorelin receptors, causes their short-term stimulation with subsequent long-term inhibition of their activity.
Reversibly inhibits the production of LH and FSH by the pituitary gland, reduces the concentration of testosterone in the blood in men and estradiol – female, causes desensitization of receptors after short-term initial stimulation.
After the first i / m injection within 1 weeks concentration of sex hormones as in men, so it increases in women (physiological response). During the same period, the concentration of acid phosphatase in plasma increases., which recovers to 3-4 week of treatment. K 21 the day after the first injection, the concentration of sex hormones decreases below the initial values: in men, the concentration of testosterone reaches the post-castration level, in women, the concentration of estradiol decreases to a level, corresponding to oophorectomy or postmenopause. This condition persists during the entire period of treatment., which leads to inhibition of growth and the reverse development of hormone-dependent tumors (uterine fibroids, prostate cancer).
After stopping treatment, the physiological secretion of hormones is restored.
Pharmacokinetics
Absorption
Leiprorelin acetate is inactive when taken orally.
The bioavailability of the drug with s / c and i / m administration is comparable.
Bioavailability in men – 98%, female – 75%.
Distribution
Average Vd at equilibrium – 27 l. Plasma protein binding – 43-49%.
Metabolism and excretion
Systemic clearance – 7.6 l.
Leuprorelin, being a peptide, undergoes metabolic degradation mainly with the participation of peptidase to shorter inactive peptides – pentapeptide (metabolite I), tripeptides (metabolites II and III) and the dipeptide (metabolite IV).
The time to reach Cmax in blood plasma of the main metabolite (М-I) is 2-6 h and corresponds 6% from Cmax leuprorelin. Through 1 week after injection, the average concentration of M-I in plasma is 20% from the average concentration of leuprorelin. Css achieved through 7-14 days after injection.
Leiprorelin and M-I are excreted by the kidneys: less 5% from the imposed dose within 27 days after injection.
Testimony
- progressive prostate cancer (palliative care), incl. when orchiectomy or estrogen treatment is not indicated or applicable in the patient;
- Endometriosis (for a period up to 6 months as the main therapy or addition to surgical treatment);
-uterine fibroids (for a period up to 6 months as a preoperative preparation for the removal of fibroids or hysterectomy, as well as for symptomatic treatment and improvement of the condition in women during menopause, who refuse surgery).
Dosage regimen
Enter i / m or s / c 1 times / month. The injection site should be changed every month..
At prostate cancer single dose – 3.75 mg or 7.5 mg.
At endometriosis and uterine fibroids the recommended single dose is 3.75 mg. The first injection is made on the 3rd day of menstruation.. Duration of treatment – no more 6 Months.
Women of reproductive age the first injection is performed on 3 day of menstruation. Duration of treatment is not more 6 Months.
The solution for injection is prepared immediately prior to administration. Are recruiting 1 ml of the supplied solvent and injected into the vial, comprising 3.75 mg leuprorelin acetate.
Side effect
Cardio-vascular system: swelling, angina, heartbeat, bradycardia, tachycardia, arrhythmia, congestive heart failure, ECG changes, increased blood pressure, myocardial infarction, phlebitis, embolism pulmonary artery branches, stroke, thrombosis, transient ischemic attacks.
From the digestive system: change (increase, decrease or absence) appetite and taste, dry mouth or hypersalivation, thirst, dysphagia, nausea, vomiting, diarrhea or constipation, flatulence, increase or reduction of body weight, increase in liver transaminases and alkaline phosphatase.
On the part of the endocrine system: pain in the milk glands, gynecomastia, enlargement of the thyroid gland, androgen-like effects – virilization, acne, seborrhea, increased hair growth, voice alteration.
From the hematopoietic system: anemia, thrombocytopenia, leukopenia, neutropenia, increased prothrombin time and APTT.
On the part of the musculoskeletal system: ostealgias, arthralgia, myalgia, increase in muscle tone, changes in bone density during bone densitometry in women as a result of a decrease in estrogen levels (after stopping treatment with leuprorelin acetate, bone density is restored).
From the central and peripheral nervous system: headache, dizziness, fainting, sleep disturbance (insomnia), irritability, depression, fatigue, paresthesia, memory impairment, hallucinations, hyperesthesia, stupor, emotional lability, personality changes, neuromuscular disorders, perifericheskaya neuropathy; rarely – suicidal thoughts and suicidal attempts.
The respiratory system: cough, breathlessness, nose bleed, pharyngitis, pleural effusion, fibrous lesions in the lungs, pulmonary infiltrates, respiratory disorders.
Dermatological reactions: dermatitis, xerosis, itching, rash, ecchymosis, alopecia, giperpigmentatsiya, nail changes; female – acne, hypertryhoz.
From the senses: conjunctivitis, impaired vision and hearing, noise in ears.
From the urinary system: dizurija.
On the part of the reproductive system: dysmenorrhoea, vaginal bleeding, dryness of the vaginal mucosa, vaginitis, white, pain in the prostate gland, testicular atrophy, pain in the testicles, decreased libido.
From the laboratory parameters: increase in blood urea nitrogen, hypercalcemia, giperkreatininemiя, hyperlipidemia (increase in total cholesterol, LDL-C, TG), giperfosfatemiя, gipoglikemiâ, giponatriemiya, hyperuricemia.
Local reactions: thickening of tissues, hyperemia and pain at the injection site.
Other: allergic reactions (incl. anaphylactic shock), peripheral edema, change in body odor, flu-like symptoms, rush of blood to the face and upper chest, increased sweating, hyperadenosis (in the first week of treatment), acute urinary retention and / or spinal cord compression (in men in the first 2 week of treatment).
Contraindications
- Hirurgicheskaya castration;
- Pregnancy;
- Lactation;
- Vaginal bleeding of unknown etiology;
- Prostate cancer (hormone independent);
- hypersensitivity to leuprorelin and other components of the drug;
- hypersensitivity to similar preparations of protein origin.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Cautions
Lucrin depot® should only be used under medical supervision.
Prostate Cancer
During the first few weeks of treatment with Lukrin Depot® transient worsening symptoms may develop or additional symptoms of the underlying disease may appear. A small number of patients may have increased bone pain., which are stopped with symptomatic treatment. Intensification of symptoms of deterioration during the first few weeks of treatment with Lukrin Depot® in patients with spinal metastases, with urinary tract obstruction or with hematuria, may lead to neurological problems, such as temporary weakness of the lower limbs, paresthesias and weighting of urological symptoms.
Therefore, during the first few weeks of treatment, patients with spinal metastases and severe urinary tract obstruction require careful monitoring..
Endometriosis / uterine fibroids
At the very beginning of the course of treatment, a transient increase in the concentration of sex steroid hormones is usually noted., what determines the physiological manifestations of the drug's action. Some aggravation of symptoms at the beginning of therapy with Lukrin Depot® passes quickly enough with continued treatment with adequately selected doses of the drug.
Non-hormonal methods of contraception should be used during treatment and until menstruation is restored..
Fertility or fertility, suppressed by therapy, recovering in the period before 24 weeks after treatment.
Application of Lukrin depot® in women caused inhibition of the function of the pituitary-gonadotropic system. After the end of treatment, the function is restored after 3 of the month. However, diagnostic tests, indicative of the function of the pituitary or gonads, carried out during treatment and during 3 months after its end may be distorted.
Overdose
There are no data on overdose in humans.
In the case of an overdose should be symptomatic therapy.
Drug Interactions
Pharmacokinetic studies of drug interactions Lucrin depot® with other drugs was not carried out.
Leiprorelin acetate is a substance of a peptide nature and undergoes primary degradation under the influence of peptidase, not enzymes of the cytochrome P450 system. Besides, about 46% the drug binds to blood plasma proteins, therefore, the drug interaction of Lukrin depot® unlikely.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of the reach of children at a temperature not exceeding 25 °; Do not freeze. Shelf life – 3 year.
