Active substanceDegarelixDegarelix
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  • Firmagon
    lyophilizate PC 
  • Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration
    Composition:

    1 the vial contains:

    active substance: Degarelix in the form of acetate 88.2 * mg (equivalent to 80 mg deharrelix) or 128.0 * mg (equivalent to 120 mg deharrelix);

    Excipients: mannitol.

    * Includes an excess of active substance to provide a recoverable amount of degarelix 80 or 120 mg respectively (concentrations of 20 and 40 mg / ml).

    Composition of 1 vial or 1 disposable syringe with solvent

    Bottle: water for injection 6 ml.

    Disposable syringe: water for injection 4.2 ml (for a dosage of 80 mg) or 3 ml (for a dosage of 120 mg).

    Description:

    Lyophilizate: white or almost white lyophilized mass.

    Solvent: clear, colorless liquid.

    Pharmacotherapeutic group:gonadotropin-releasing hormone antagonist
    ATX: & nbsp

    L.02.B.X   Other hormone antagonists and similar drugs

    L.02.B.X.02   Degarelix

    Pharmacodynamics:

    Degarelix is ​​a selective antagonist of gonadotropin-releasing hormone (GnRH), capable of competitively and reversibly binding pituitary GnRH receptors, drastically reducing the release of gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Thus, the secretion of testosterone in the testes decreases.Prostate cancer is considered a hormone-dependent tumor and is treatable, aimed at reducing the production of male sex hormones. Unlike GnRH agonists, the antagonists of this hormone do not induce LH release, followed by activation of testosterone release, tumor development and possible symptomatic exacerbation after the initiation of treatment.

    A single injection of 240 mg deharrelix and subsequent maintenance therapy at a dose of 80 mg, conducted during the month, quickly reduces the concentration of LH, FSH and, as a consequence, testosterone. The concentration of dihydrotestosterone (DHT) in blood plasma is reduced similar to testosterone.

    When deharelix is ​​administered, a decrease in the testosterone content and maintenance of its concentration at a level lower than with castration (0.5 ng / ml) is observed. Supportive monthly therapy at a dose of 80 mg resulted in prolonged suppression of testosterone in 97% of patients for at least 1 year. The average testosterone concentration after annual treatment was 0.087 ng / ml.

    The development of antibodies against degarelix was observed in 10% of patients after 1 year of treatment.There is no evidence of the effect of the resulting antibodies on the efficacy or safety of Degarelix treatment.

    Pharmacokinetics:

    Suction

    After subcutaneous administration of 240 mg of degarelix (at a concentration of 40 mg / ml) to patients with prostate cancer, the area under the concentration-time curve (AUC0-28) was 635 (602-668) day * ng / ml, the maximum concentration (CmOh) - 66.0 (61.0-71.0) ng / ml, the time to reach the maximum concentration (TmOh) - 40 (37-42) h. Degarelix is deduced in two stages, the average terminal half-life (t1/2) about 43 days for the initial dose and 28 days for the maintenance dose. Long t1/2 after subcutaneous administration is a consequence of the slow release of degarelix from the depot formed at the injection sites. Pharmacokinetics of the drug depends on the concentration of the solution upon administration. Thus, CmOh and bioavailability decrease with increasing drug concentration, while t1/2 increases. Therefore, do not enter in concentrations above the recommended levels.

    Distribution

    The distribution volume is approximately 1 l / kg. The connection with plasma proteins is approximately 90%.

    Metabolism

    Degarelix undergoes simple peptide degradation when passing through the hepatobiliary system and is released, mainly,in the form of peptide fragments with feces. Significant metabolites are not found. Research in vitro showed that deharrelix It is not a substrate of the cytochrome P450 system and does not inhibit or induce isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5.

    Excretion

    Approximately 20-30% of a single dose is excreted in the urine, 70-80% is released by the hepatobiliary system.
    Indications:

    Progressing hormone-dependent prostate cancer in adult men.

    Contraindications:

    Hypersensitivity to degarelix or mannitol.

    Female patients, children and adolescents (due to the lack of indications for use in this population).

    Carefully:

    In renal and hepatic insufficiency, in patients with an elongated interval Q-T or while taking medications that extend the interval Q-T, with polymorphic ventricular tachycardia of the "pirouette" type, diabetes mellitus.

    Dosing and Administration:

    Subcutaneously. DO NOT INSERT INSIDE! The efficacy and safety of intramuscular injection of Firmagona have not been studied.

    Injections are administered subcutaneously to the abdomen. The injection site must be changed periodically.It is necessary to avoid places that are subjected to pressure (for example, near the belt or belt and near the ribs).

    The initial dose is 240 mg, which is administered in two injections of 120 mg.

    A maintenance dose of 80 mg is given one month after the initial dose. Injections are carried out monthly.

    Special patient groups

    Elderly patients

    Specific recommendations for changing the dose of the drug for this population are absent.

    Patients with impaired renal or hepatic function

    With mild or moderate violations of kidney or liver function, there is no need to adjust the dose of the drug. Data on the use of degarelix in patients with severe renal or hepatic impairment are absent.

    Recommendations for solution preparation and injection

    It is recommended to use only a freshly prepared solution!

    For the solvent in the vial

    120 mg (initial dose)

    1. The dissolution needle (green needle 21G/ 0.8 x 50 mm), collect 3.0 ml of solvent. Remove residual solvent.

    2. Slowly introduce the solvent into the vial with lyophilizate 120 mg. VALVE HOLD VERTICALLY! The degarelix content in 1 ml of the prepared solution is 40 mg.

    3. Mix the contents of the vial in circular movements until a clear solution is obtained. Dissolution usually occurs in 15 minutes. The presence of undissolved particles is not allowed! If necessary, the bottle can be tipped gently. DO NOT BLINK! It is permissible to form small air bubbles on the surface of the liquid. Slightly tilt the bottle. DO NOT TURN! The needle should be at the bottom of the vial.

    5. Collect 3.0 ml of the solution. Replace the green needle with a white one for deep subcutaneous injection (27G/0,4 x 25 mm). Remove air bubbles from the syringe.

    6. Insert the needle at an angle of at least 45 ° deep into the skin fold on the abdomen.

    7. Make sure that the blood does not get into the syringe with the drug. If the blood gets into the syringe, the drug should not be used. In this case, it is necessary to interrupt the procedure and prepare a new dose of the drug!

    8. Prepare the second dose as described above. Choose a new place and add another 3.0 ml of the drug solution.

    80 mg (maintenance dose)

    1. The dissolution needle (green needle 21G/0,8 x 50 mm), collect 4.2 ml of solvent. Remove residual solvent.

    2. Slowly introduce the solvent into a vial of 80 mg lyophilizate. VALVE HOLD VERTICALLY!

    3. Mix the contents of the vial in circular movements until a clear solution is obtained. Dissolution usually occurs in 15 minutes. The presence of undissolved particles is not allowed! If necessary, the bottle can be tipped gently. DO NOT BLINK! It is permissible to form small air bubbles on the surface of the liquid. Slightly tilt the bottle. DO NOT TURN! The needle should be at the bottom of the vial.

    4. Collect 4.0 ml of the solution. Replace the green needle with a white one for deep subcutaneous injection (27G/0,4 x 25 mm). Remove air bubbles from the syringe.

    5. Perform the injection as described above.

    For solvent in a disposable syringe

    1. Remove the protective cap from the vial with lyophilizate.

    2. Tightly put the adapter on the bottle - the sharp end of the adapter must pierce the rubber bottle cap.

    3. Remove the protective cap from the syringe with the solvent. Connect the syringe to the vial with lyophilizate by screwing it onto the adapter.

    4. Slowly introduce the entire volume of solvent into the vial.

    5. Gently stir the contents of the vial until a clear solution is obtained. Dissolution usually occurs in 15 minutes. The presence of undissolved particles is not allowed.If necessary, the bottle can be tilted slightly. DO NOT BLINK! It is permissible to form small air bubbles on the surface of the liquid.

    5. Turn the vial and collect 3.0 ml of the solution (or 4.0 ml for a dosage of 80 mg).

    6. Disconnect the adapter and put the injection needle on the syringe. Perform the injection as described above.

    Side effects:

    Adverse reactions are listed according to the following gradation frequency of their occurrence: very often (> 10%); often (> 1% to <10%); infrequently (> 0.1% to <1%).

    From the hematopoiesis: often - anemia *; in isolated cases - febrile neutropenia.

    On the part of the digestive system: often - diarrhea, nausea, increased activity of "liver" transaminases; infrequent - constipation, vomiting, decreased appetite, abdominal pain, discomfort in the abdominal cavity, dry mouth, increased bilirubin concentration, increased activity of alkaline phosphatase.

    From the cardiovascular system: very often - "tides" *; infrequent - arrhythmias (including atrial fibrillation), palpitations, atrioventricular block of degree I, increased interval Q-T*, increased blood pressure, vasovagal syncope, varicose veins; in isolated cases - myocardial infarction, acute heart failure.

    From the respiratory system: infrequently - shortness of breath, cough.

    From the nervous system and psyche: often - dizziness, headache, insomnia; infrequently - hypostasis, irritability, decreased intellectual activity, depression, ringing in the ears, decreased libido *.

    From the urinary system: very often - an increase in the concentration of urea in the blood serum; often - increased serum creatinine concentration; infrequent - frequent urination, mandatory urination, dysuria, nocturia, urinary incontinence, renal insufficiency.

    From the skin and skin appendages: often - increased sweating (including night sweats) *, skin rash; infrequently - urticaria rash, alopecia, skin itch, erythema, hyperpigmentation of the skin, softening of the nail plates.

    From the musculoskeletal system: often - musculoskeletal pain; infrequently - osteoporosis / osteopenia, muscle weakness, muscle cramps, swelling and joint stiffness.

    On the part of the reproductive system: often - gynecomastia *, testicular atrophy *, erectile dysfunction *; infrequent - soreness of the testicles, tenderness of the mammary glands, pain in the pelvic region, irritation of the genitals, frustration of the ejaculation.

    From the immune system: infrequently - hypersensitivity.

    Local reactions: very often - redness and pain at the injection site; often - swelling, condensation in the area of ​​injection.

    Metabolic disorders: often - hyperkalemia; infrequently - hyperglycemia, diabetes mellitus, increased cholesterol concentration, changes in calcium concentration in the blood serum.

    Other: often - fever, chills, fatigue *, flu-like syndrome, weight gain *; infrequent - a feeling of malaise, peripheral edema, weight loss, decreased visual acuity.

    * - reactions associated with the suppression of testosterone production, which are of a temporary nature and, as a rule, do not require withdrawal of the drug.

    Overdose:

    Data on the symptoms of acute overdose of degarelix are absent. In case of an overdose, follow the patient and, if necessary, use maintenance therapy.

    Interaction:

    The firmage should not be mixed with other medicines in the same syringe!

    Since the use of degarelix may increase the interval Q-T, it should be assessed the need for simultaneous use of deharelix and drugs that cause lengthening of the interval Q-T or ventricular tachycardia (e.g., quinidine, disopyramide), neuroleptics, antiarrhythmic drugs (for example, amiodarone, sotalol, dofetilide, ibutilide), as well as methadone, cisapride and moxifloxacin.

    Clinically significant pharmacokinetic interaction of deharelix and drugs in the metabolism of which the cytochrome P450 system participates is unlikely, since studies in vitro showed that deharrelix It is not a substrate of the cytochrome P450 system and does not inhibit or induce isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4/5.

    Special instructions:

    The therapeutic effect of Firmagon should be monitored by the clinical parameters and serum prostate-specific antigen (PSA) level.

    Suppression of testosterone (T) occurs immediately after the initial dose, while testosterone levels in the blood plasma drop to the castration level (T <0.5 ng / ml) in 96% of patients after three days, in 100% of patients - in a month. Long-term, up to 1 year, maintenance therapy provides suppression of testosterone (T <0.5 ng / ml) in 97% of patients.If the patient's therapeutic effect is not sufficiently expressed, it should be ensured that the serum testosterone concentration remains sufficiently low. Firmagon does not cause fluctuations in testosterone concentration, so there is no need to take anti-androgenic drugs at the beginning of treatment.

    The change in bone mineral density in the application of Firmagon has not been studied, however, in patients who underwent orchiectomy or who took GnRH agonists, a decrease in the bone mineral density is observed. Therefore, due to the suppression of testosterone caused by taking Firmagon, a decrease in bone mineral density is possible.

    The effect of Firmagon on the concentration of insulin and glucose in the blood has not been studied. However, in patients who underwent orchiectomy or who took GnRH agonists, there was a decrease in glucose tolerance and possibly development or exacerbation of diabetes mellitus. Therefore, in the treatment of Firmomon, regular monitoring of the concentration of glucose in the blood is recommended.

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

    Data on the effect of Degarelix therapy on the ability to drive a vehicle and work with mechanisms are lacking,However, some side effects of the drug, such as increased fatigue and dizziness, can adversely affect the ability to drive and perform potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Lyophilizate for the preparation of a solution for subcutaneous administration, 80 mg and 120 mg.

    Packaging:

    - 80 mg deharrelix per bottle of colorless glass, ukuporenny brombutilovoy stopper with aluminum obkatkoy and plastic cap type "flip-off."

    For 6 ml of water for injection into a bottle of colorless glass type 1, sealed with chlorobutyl stopper with aluminum obkatkoy and plastic cap type "flip-off."

    1 bottle with lyophilizate, 1 vial with solvent, 1 syringe, 1 needle for solution and 1 injection needle (all components are placed in a plastic tray), along with instructions for use in a cardboard pack.

    - 80 mg deharrelix per colorless glass bottle, sealed with a bromobutyl stopper with aluminum rolling and a plastic cap of the "flip-off" type.

    For 4.2 ml of water for injection in a disposable syringe of colorless glass type 1, with a bromobutyl seal on the piston, with a tip of styrene-butadiene rubber type II. The syringe may be packaged in assembled or disassembled form (piston separately).

    1 bottle with lyophilizate, 1 syringe with solvent, 1 adapter and 1 injection needle (all components are placed in a plastic tray), along with instructions for use in a cardboard pack.

    - On 120 mg deharrelix in a bottle of colorless glass, ukuporenny brombutilovoy stopper with aluminum obakkoy and plastic cap type "flip-off."

    For 6 ml of water for injection into a bottle of colorless glass type 1, sealed with chlorobutyl stopper with aluminum obkatkoy and plastic cap type "flip-off."

    2 vials with lyophilizate, 2 vials with solvent, 2 syringes, 2 needles for solution and 2 needles for injection (all components are placed in plastic pallets) together with instructions for use in a cardboard pack.

    - 120 mg deharrelix per colorless glass bottle, sealed with bromobutyl stopper with aluminum rolling and plastic cap of "flip-off" type.

    For 3 ml of water for injection in a disposable syringe of colorless glass type 1, with a bromobutyl seal on the piston, with a tip of styrene-butadiene rubber type II. The syringe may be packaged in assembled or disassembled form (piston separately).

    2 vials with lyophilizate, 2 syringes with a solvent, 2 adapters and 2 needles for injection (all components are placed in plastic pallets) together with instructions for use in a cardboard pack.

    Storage conditions:

    Store at a temperature not exceeding 25 ° C.

    Keep out of the reach of children.

    The finished solution should not be stored for more than 2 hours, at a temperature not exceeding 25 ° C.

    Shelf life:

    Lyophilizate: 3 years.

    Solvent: 3 years.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-007449/10
    Date of registration:30.07.2010
    The owner of the registration certificate:Ferring Pharmaceuticals A / SFerring Pharmaceuticals A / S Denmark
    Manufacturer: & nbsp
    Representation: & nbspFERRING PHARMACEUTICALS LLCFERRING PHARMACEUTICALS LLCRussia
    Information update date: & nbsp29.12.2015
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