Active substanceEpoetin betaEpoetin beta
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  • Vero-epoetin
    lyophilizate in / in PC 
    VEROPHARM SA     Russia
  • Recormon®
    solution in / in PC 
    Hoffmann-La Roche Ltd.     Switzerland
  • Recormon®
    lyophilizate PC 
    Hoffmann-La Roche Ltd.     Switzerland
  • Epostim®
    solution in / in PC 
    FARMAPARK, LLC     Russia
  • Epoetin beta
    solution in / in PC 
  • Erythropoietin
    solution in / in PC 
    BINNOFARM, CJSC     Russia
  • Dosage form: & nbsplyophilizate for the preparation of a solution for subcutaneous administration
    Composition:

    One syringe tube (0.3 ml) with a solution for intravenous and subcutaneous injection contains:

    epoetin beta 1 LLC ME, 2000 ME

    auxiliary substances: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-treonine, L- glutamic acid, Lphenylalanine, water for injection.

    One syringe tube (0.6 ml) with a solution for intravenous and subcutaneous injection contains:

    epoetin beta 10,000 ME, 20000 ME, 30000 ME

    auxiliary substances: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-treonine, L- glutamic acid, Lphenylalanine, water for injection.

    One two-section cartridge with lyophilizate for the preparation of a solution for subcutaneous administration contains:

    The first section:

    epoetin beta 10,000 ME, 20000 ME

    auxiliary substances: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen phosphate, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-treonine, L- glutamic acid. L-phenylalanine.

    Second section:

    solvent: benzyl alcohol, benzalkonium chloride, water for injection.

    Description:

    Solution for intravenous and subcutaneous administration - colorless, clear or slightly opalescent liquid.

    Lyophilizate - homogeneous powder or porous mass of white or almost white color. Solvent - colorless, clear liquid.

    The reconstituted solution - colorless, clear or slightly opalescent liquid
    Pharmacotherapeutic group:hematopoiesis stimulant
    ATX: & nbsp

    B.03.X.A   Other stimulators of hemopoiesis

    Pharmacodynamics:

    Epoetin beta is a glycoprotein consisting of 165 amino acids, which, being a mitogenic factor and a differentiation hormone, promotes the formation of erythrocytes from partially determined progenitor cells of erythropoiesis.

    Recombinant epoetin beta, obtained by genetic engineering, is identical in its amino acid and carbohydrate composition to human erythropoietin.

    Epoetin beta after intravenous and subcutaneous administration increases the number of erythrocytes, reticulocytes and hemoglobin level, as well as the rate of iron incorporation (59Fe) in cells, specifically stimulates erythropoiesis, without affecting leukopoiesis. The cytotoxic effect of epoetin beta on the bone marrow or on human skin cells has not been revealed.

    Pharmacokinetics:

    Suction

    With subcutaneous administration of the drug to patients with uraemia, prolonged absorption provides a plateau of the drug concentration in the serum, the time to reach a maximum concentration of -12-28 h.

    Bioavailability of epoetin beta with subcutaneous injection is 23-42% compared with intravenous administration.

    Distribution

    The volume of the distribution is equal to the volume of the circulating plasma, or 2 times its volume. Excretion

    In patients with uremia and in healthy volunteers, the elimination half-life with intravenous administration is 4-12 hours. The half-life of the terminal phase with subcutaneous injection is greater than after intravenous administration and is on the average 13-28 hours.

    Pharmacokinetics in specific patient groups

    The pharmacokinetics of epoetin beta in patients with hepatic insufficiency has not been studied.
    Indications:

    - Symptomatic anemia in chronic kidney disease in patients on dialysis.

    - Symptomatic anemia of renal genesis in patients not yet receiving dialysis.

    - Treatment of symptomatic anemia in adult patients with solid and hematologic non-myeloid tumors receiving chemotherapy.

    - An increase in the volume of donor blood intended for subsequent autotransfusion. The registered risk of thromboembolic events should be taken into account. The use according to this indication is only shown in patients with moderate anemia (HB 100-130 g / L (6.21-8.07 mmol / L), without iron deficiency) if it is not possible to obtain a sufficient amount of preserved blood, and a planned large elective surgery may require a large blood volume (> 4 units for women or> 5 units for men).

    - Prevention of anemia in premature newborns born with a body weight of 750-1500 g until the 34th week of pregnancy.

    Contraindications:

    Increased sensitivity to epoetin beta or any of the components of the drug (with the use of Recormon for the Reko-Pen syringe pen - also an increased sensitivity to benzoic acid - a metabolite of benzyl alcohol); uncontrolled arterial hypertension.

    Myocardial infarction or stroke during the previous month, unstable angina or an increased risk of deep vein thrombosis (with a history of venous thromboembolism) - with an appointment to increase the volume of donor blood for autohemotransfusion.

    Age up to 3 years for cartridges with lyophilizate for the preparation of a solution for subcutaneous administration.

    Carefully:

    Refractory anemia in the presence of blast-transformed cells, thrombocytosis, epilepsy and chronic hepatic insufficiency.

    Body weight less than 50 kg to increase the volume of donor blood for subsequent autotransfusion.

    Pregnancy and lactation:

    Epoetin beta does not have teratogenic effects on animals. Information on the safety of the use of Rekormon during pregnancy, during childbirth and the period of breastfeeding is obtained by post-marketing use of the drug. In pregnancy or during childbirth, Recormon should be administered with caution, since there is not sufficient experience in pregnancy and during childbirth. Endogenous erythropoietin is secreted into breast milk and completely absorbed in the newborn's gastrointestinal tract.The choice between continuing breastfeeding or continuing with Rekormon therapy is done taking into account the benefits of therapy for the mother and the benefits of breastfeeding for the baby.

    Dosing and Administration:

    Treatment of anemia in patients with chronic kidney disease

    Subcutaneously or intravenously (within 2 minutes). Patients on hemodialysis - through the arteriovenous shunt at the end of the dialysis session. Patients who do not receive hemodialysis, preferably administer the drug subcutaneously, to avoid puncture of peripheral veins. The goal of the treatment is a hemoglobin (Hb) value of 100-120 g / l. Hb should not exceed 120 g / l. With an increase in Hb by more than 20 g / l (1.3 mmol / L) in 4 weeks, the dose of the drug should be reduced. In patients with hypertension, cardiovascular and cerebrovascular diseases, weekly increase in Hb and its targets should be determined individually, depending on the clinical picture. Careful observation of the patient should be carried out in order to select the minimum dose sufficient to ensure the maximum effect of the drug.

    Treatment Rekormon is carried out in 2 stages.

    Correction stage

    Subcutaneously - The initial dose is 20 IU / kg 3 times a week.With an insufficient increase in Hb (less than 2.5 g / L per week), the dose can be increased every 4 weeks by 20 IU / kg 3 times a week. The total weekly dose of the drug can also be divided into daily injections.

    Intravenously - The initial dose is 40 IU / kg 3 times a week. With an insufficient increase in Hb in a month, the dose can be increased to 80 IU / kg 3 times a week. If necessary, in the future, the dose should be increased by 20 IU / kg 3 times a week, with a monthly interval. Regardless of the route of administration, the maximum dose should not exceed 720 IU / kg per week.

    Supportive therapy.

    To maintain the target Hb value (100-120 g / l), the dose should first be reduced 2 times from the previous one. Subsequently, the maintenance dose is selected individually, with an interval of 2 or 4 weeks. With subcutaneous administration, a weekly dose can be administered in 1 dose or divided into 3 or 7 administrations per week. When the condition stabilizes against a background of a single injection per week, you can switch to a single injection at a two-week interval, in which case an increase in dose may be necessary.

    Treatment Rekormon, as a rule, is long. If necessary, it can be interrupted at any time.

    Treatment of symptomatic anemia in patients with solid and hematological non-myeloid tumors receiving chemotherapy

    The drug is administered subcutaneously, in an initial dose of 30000 ME per week (450 IU / kg per week), a single or weekly dose can be divided into 3 or 7 injections.

    Rekormon therapy is indicated for Hb <110 g / l (6.83 mmol / l). The Hb should not exceed 130 g / l (8.07 mmol / l).

    When Hb is increased by 10 g / l (0.62 mmol / L) after 4 weeks, therapy should be continued at the same dose.

    With a rise in Hb of less than 10 g / L (0.62 mmol / L) after 4 weeks - the dose should be doubled. In the absence of an increase in Hb by 10 g / l (0.62 mmol / l) after 8 weeks - treatment should be interrupted, as. response to therapy Rekormon unlikely.

    Treatment should continue for 4 weeks after the end of chemotherapy. The maximum dose should not exceed 60,000 ME in Week.

    When the target Hb for a particular patient is reached, the dose of the drug should be reduced by 25-50%.

    To prevent an increase in Hb greater than 130 g / L, a further dose reduction may be required.

    When Hb increases by more than 20 g / l (1.3 mmol / L) per month, the dose of Rekormon should be reduced by 25-50%.

    Preparation of patients for the collection of donor blood for subsequent autohemotransfusion. Intravenously (for 2 minutes) or subcutaneously, 2 times a week for 4 weeks. In those cases where the hematocrit value of the patient (> 33%) allows blood sampling, the Recormon should be entered at the end of the procedure.

    Throughout the course of treatment, the hematocrit should not exceed 48%.

    The dose of the drug is determined by the transfusiologist and the surgeon individually, depending on how much blood is taken from the patient and from his erythrocyte reserve:

    1. The amount of blood that will be taken from the patient depends on the estimated blood loss, the available methods of blood preservation and the general condition of the patient; it should be sufficient to avoid transfusion of blood from another donor.

    2. The volume of blood that will be taken from the patient is expressed in units (one unit is equivalent to 180 ml of erythrocytes).

    3. The possibility of donation depends mainly on the volume of blood in this patient and the initial hematocrit. Both indices determine the endogenous red blood cell, which is calculated by the following formula:

    Endogenous erythrocyte reserve = blood volume [ml] x (hematocrit 33): 100 Women: blood volume [ml] = 41 [ml / kg] x body weight [kg] + 1200 [ml]

    Men: blood volume [ml] - 44 [ml / kg] x body weight [kg] + 1600 [ml] (with body weight> 45 kg).

    Indication for the use of Recormon and its single dose are determined from nomograms, based on the required volume of donor blood and the endogenous red blood cell. The maximum dose should not exceed 1600 IU / kg per week with intravenous administration and 1200 IU / kg per week with subcutaneous injection.

    Prevention of anemia in premature newborns (only syringe-Tubics with the drug Recormon).

    Subcutaneously, 250 IU / kg 3 times a week, as early as possible, preferably from the 3rd day of life, for 6 weeks.

    Dosing in special patient groups

    Children and teens

    In children and adolescents, the dose of the drug depends on age: as a rule, the smaller the age, the higher the dose of Recormon is required. But, since it is impossible to predict the individual response to a drug, it is advisable to start with the standard dosage regimen (see "Treatment of anemia in patients with chronic kidney disease" and "Prevention of anemia in premature infants").

    When treating anemia associated with chronic kidney disease, Rekormon should not be prescribed to children under 2 years of age.

    Elderly age

    In clinical trials, the need for dose changes is not defined.

    Mode of application

    Syringe tube with the drug Recormon is ready for use. The solution contained in it is sterile and does not contain preservatives. Apply only light clear or slightly opalescent solution that does not contain visible inclusions. If after the injection in the syringe tube a certain amount of the drug remains, the repeated administration of it is unacceptable.

    Instructions for the use of a syringe tube

    Before injection, wash hands

    1. Remove one syringe from the package and make sure that the solution is clear, colorless and contains no visible inclusions. Remove the cap from the syringe.

    2. Remove one needle from the package, put it on the syringe and remove the protective cap from the needle.

    3.Remove air from the syringe and needle, holding the syringe upright, gently pushing the piston upward. Press the plunger until the required dose of Recormon is left in the syringe.

    4.Wipe the skin at the injection site with alcohol moistened with cotton wool. With a thumb and forefinger, take the skin into a crease. Holding the syringe body closer to the needle, insert the needle under the skin. Introduce the solution of Rekormon. Quickly remove the needle and squeeze the injection site with a sterile dry cotton wool.

    Cartridge with the Recormon for the syringe handle Reco-Pen is a two-section cartridge containing lyophilizate for the preparation of a solution for subcutaneous administration and a solvent with preservatives. The prepared solution is obtained by inserting the cartridge into the Reco-Pen syringe-pen in accordance with the instructions for Reco-Pen. Cartridges with Recormon should only be used in the Reco Pen syringe pen. It is recommended to use needles for the Reco Pen syringe (for example, the Penfine needle). The solution prepared in the cartridge is stored for 1 month at a temperature of 2-8 ° C. After installing the cartridge, the Reco-Pen syringe pen is removed from the refrigerator only at the time of the injection.

    Side effects:

    The cardiovascular system. Frequent: occurrence or strengthening of an existing arterial hypertension (> 1%, <10%), especially in the case of a rapid increase in hematocrit; hypertensive crisis with the phenomena of encephalopathy (headaches and confusion, sensory and motor disorders - speech disorders, gait, up to tonic-clonic seizures), thromboembolic complications in cancer patients (> 0.1%, <1%) and in patients preparing for autotransfusion (there is no clear causal relationship with the drug).

    Nervous system. Headaches (> 1%, <10%), incl.sudden migraine headaches.

    The hematopoiesis system. Dose-dependent increase in the number of platelets (not exceeding the norm and disappearing with the continuation of therapy), especially after intravenous administration of the drug. Rare: thrombocytosis (<0.01%). Shunt thrombosis (> 0.01%, <0.1%) (possibly with inadequate heparinization), especially in patients with a tendency to lower blood pressure (BP) or complications of arteriovenous fistula (eg, stenosis, aneurysm, etc.).

    Laboratory indicators. Reduction of serum ferritin concentration concomitant with an increase in hemoglobin, a decrease in serum iron metabolism. In patients with uremia - transient hyperkalemia (a clear causal relationship with the drug is not established), hyperphosphatemia.

    In premature newborns. Reduction of ferritin concentration in serum (> 10%), a slight increase in the number of platelets, especially up to the 12-14th day of life.

    Other. Rare (from> 1/10000 to <1/1000) - skin allergic reactions: rash, itching, urticaria; reactions at the injection site.

    Very rare (<1/10000) - anaphylactoid reactions; influenza-like symptoms (especially at the beginning of therapy) are usually mild or moderate and disappear after a few hours or several days: fever, chills, headaches,pain in the extremities or bones, malaise.

    Post-marketing surveillance: (0.107 cases per 10000 patient-years with the use of Recormon for the treatment of anemia of renal genesis intravenously and subcutaneously and 0.158 cases per 10,000 patient-years with subcutaneous administration of Rekormon for the treatment of anemia of renal genesis) of partial red cell aplasia caused by formation neutralizing anti-erythropoietin antibodies (see "Special instructions").

    Overdose:

    Therapeutic index of Rekormona is very wide, however, individual response to therapy at the beginning of treatment should be taken into account. An excessive pharmacodynamic response is possible, i. E. excessive erythropoiesis with life-threatening cardiovascular complications. With a high Hb, temporarily discontinue therapy with Rekormon (see "Method of administration and dose"). If necessary, phlebotomy can be performed.

    Interaction:

    The data obtained so far have not revealed any interactions of Rekormon with other drugs. To avoid incompatibility or decrease in drug activity, another solvent should not be used and mixeddrug with other drugs or injection solutions.

    Special instructions:

    Inadequate use of the drug by healthy people (for example, as a dope) can cause a sharp increase in Hb, accompanied by life-threatening complications of the cardiovascular system.

    Since anaphylactoid reactions were noted in some cases, the first dose of the drug should be administered under the supervision of a doctor.

    Platelets, hematocrit and hemoglobin should be monitored regularly against the background of Rekormon therapy.

    Caution should be applied to Recormon in refractory anemia in the presence of blast-transformed cells, epilepsy, thrombocytosis and chronic liver failure. Before starting treatment with Recormon, vitamin B deficiency should be eliminated12 and folic acid, because they reduce the effectiveness of therapy.

    Iron deficiency should be eliminated before starting treatment with Rekormon, and also during the entire therapy period. If necessary, additional iron therapy may be prescribed in accordance with clinical recommendations.

    When treating patients with severe forms of phenylketonuria, one should take into account the presence of phenylalanine as an auxiliary substance: in each syringe tube - up to 0.3 mg (in dosages of 1000 ME, 2000 ME) or up to 0.6 mg (10,000 ME, 20000 ME, 30000 ME), in each cartridge - up to 0.5 mg.

    Lack of effect: the most common causes of incomplete response to drugs that stimulate erythropoiesis are iron deficiency and inflammation (as a result of uremia or progressive metastatic cancer). The following conditions reduce the effectiveness of treatment with agents that stimulate erythropoiesis: chronic blood loss, bone marrow fibrosis, a sharp increase in the concentration of aluminum due to hemodialysis, a deficiency of folic acid or vitamin B12, hemolysis. If all these conditions are excluded and the patient has a sudden decrease in Hb, reticulocytopenia and antibodies to erythropoietin are detected, bone marrow examination to exclude partial red cell aplasia (PKAA) should be performed. With the development of PKAA therapy, Recormon should be discontinued and patients should not be transferred to therapy with other stimulants of erythropoiesis.

    PKKA caused by neutralizing anti-erythropoietin antibodies, it may be associated with erythropoiesis stimulant therapy, including treatment with NeoRecormon (0.107 cases per 10,000 patient-years using NeoRecormon to treat anemia of renal origin intravenously and subcutaneously; 0.158 cases per 10,000 patsiento- years with subcutaneous administration of Rekormon for the treatment of anemia of renal genesis). It is not recommended to transfer patients to Rekormon therapy if there is a suspicion of the presence or with the confirmed presence of antibodies neutralizing erythropoietin.

    Effect on tumor growth: epoetins are growth factors, which mainly stimulate the formation of erythrocytes. Erythropoietin receptors may be present on the surface of various tumor cells. It can not be ruled out that drugs that stimulate erythropoiesis can stimulate the growth of any type of malignant formation.

    In clinical studies in the treatment of anemia in cancer patients epoetin beta, there was no statistically significant deterioration in survival and tumor progression.

    In patients with chronic kidney disease or with malignant tumors receiving chemotherapy, there may be episodes of increased blood pressure and worsening of the current arterial hypertension, especially with a sharp increase in hemoglobin. The increase in blood pressure can be eliminated medically, in the absence of effect, a temporary break in treatment with Rekormon is necessary. It is recommended to regularly monitor blood pressure (especially at the beginning of therapy), including between dialysis sessions in patients with anemia of kidney genesis. Individual patients with chronic kidney disease may develop a hypertensive crisis with encephalopathy, even with normal or low blood pressure. Immediate consultation of the therapist is necessary and especially when sudden sudden migraine headaches occur.

    During treatment with Rekormon it is recommended to periodically monitor the potassium level in the blood serum. When hyperkalaemia occurs, it is necessary to temporarily abolish Rekormon until the potassium concentration is normalized.

    Patients with chronic kidney disease require an increase in the dose of heparin during the hemodialysis session due to elevation of Hb. Possible occlusion of the dialysis system with inadequate heparinization.Early shunt revision and timely prevention of thrombosis (eg, acetylsalicylic acid) is recommended.

    A moderate dose-dependent increase in the number of platelets within normal limits is possible, especially after the administration of Rekormon, with subsequent independent return to normal values ​​while continuing therapy. In the first 8 weeks of therapy, a weekly count of the elements and, especially, of the platelets is needed.

    If Recormon is appointed before fetching autologous donor blood, follow the recommendations for the procedure of donation:

    - blood can be taken only in patients with a hematocrit value> 33% (or hemoglobin of at least 110 g / l (6.83 mmol / l));

    - special care should be taken in patients with a body weight of less than 50 kg;

    - the volume of blood taken at one time should not exceed 12% of the estimated volume of the patient's blood.

    It is possible to increase the number of platelets within the norm in patients receiving Recormon before taking autologous donor blood, therefore, the number of platelets should be monitored weekly. Treatment with Recormon is interrupted by increasing platelets by more than 150x10[1]/ l or with thrombocytosis.

    Rekormon treatment is indicated only for those patients who are most important to avoid homologous blood transfusion, taking into account the risk-benefit ratio for homologous transfusion.

    Possible a slight increase in the number of platelets in the prevention of anemia in premature newborns (up to 12-14 days), therefore regular monitoring of platelets is recommended.

    The decision to use Rekormona in patients with nephrosclerosis, who are not receiving dialysis, must be taken individually, since the possibility of a faster deterioration of kidney function can not be completely ruled out.

    In most cases, concomitantly with an increase in hemoglobin, the concentration of serum ferritin decreases. Therefore, all patients with anemia of renal genesis and with a serum ferritin concentration of less than 100 μg / l or a transferrin saturation of less than 20% are recommended to receive oral iron (Fe2+) in a dose of 200-300 mg / day. Patients with oncological and hematologic diseases receive iron therapy according to the same principles, while patients with myeloma, non-Hodgkin's lymphomas or chronic lymphocytic leukemia with transferrin saturation of less than 25% can be administered 100 mg Fe3+ per week intravenously.Preterm children with oral iron therapy at a dose of 2 mg Fe2+ a day should be prescribed as soon as possible (at the latest - on the 14th day of life). The dose of iron is corrected depending on the level of serum ferritin. If it persistently remains below 100 mcg / ml or there are other signs of iron deficiency, the dose of iron preparations should be increased to 5-10 mg / day and therapy should be performed until the symptoms of iron deficiency are relieved.

    Patients with mild anemia before the planned large operative intervention, the drug is prescribed taking into account the benefits of epoetin beta and the increased risk of thromboembolic complications.

    In patients who are preparing to donate blood for subsequent autotransfusion, because they have indications for temporary iron deficiency, oral iron therapy

    (Fe2+) in a dose of 300 mg per day should be started simultaneously with Rekormon therapy and continue until the normalization of ferritin values. If oral iron replacement therapy develops (ferritin level <20 μg / L or transferrin saturation less than 20%), additional intravenous iron preparations should be considered.

    The Recormon solution in the cartridge contains benzyl alcohol as a preservative, which can cause neurological and other complications in neonates, which can sometimes be fatal.

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

    Studies to study the effect of the drug on the ability to drive and work with mechanisms were not conducted. Based on the mechanism of action and the safety profile, Recormon does not have such an effect.

    Form release / dosage:

    Syringe tubes 1000 IU / 0.3 ml. 2000 IU / 0.3 ml. 10,000 IU / 0.6 ml. 20000 IU / 0.6 ml. 30000 IU / 0.6 ml

    Packaging:

    1000 IU / 0.3 ml, 2000 IU / 0.3 ml, 10,000 IU / 0.6 ml, 20000 IU / 0.6 ml, 30000 IU / 0.6 ml in syringe tubes, the body of which is made of colorless glass of hydrolytic class 1 (EF), closing with one side with a piston made of plastic, at the end of which there is a disk of bromobutyl rubber laminated with fluorine rubber; on the other hand - a gray cap made of bromobutyl rubber, laminated with fluorine rubber. The needle for injection is placed in a plastic container sealed with a PVC / PE / A1 triplex.

    3 syringe tubes together with 3 needles for injection (1000 IU / 0.3 ml, 2000 IU / 0.3 ml, 10,000 IU / 0.6 ml,20000 IU / 0.6 ml) are individually packaged (1 syringe and 1 needle) into a polyvinyl chloride film and paper with a laminated coating. 2 contour packagings along with the instruction are placed in a cardboard box.

    1 A syringe tube together with 1 injection needle (30000 IU / 0.6 mL) is packaged individually (1 syringe and 1 needle) into a contourcell pack. 1 or 4 contour squares, together with instructions for use, are placed in a cardboard box.

    Cartridges two-piece 10000 ME. 20000 ME

    The cartridge is made of colorless glass (hydrolytic class 1 EF) and consists of two sections separated by a disk of bromobutyl rubber. The first section contains 10000 ME or 20000 ME lyophilizate; in the second section - 1 ml of solvent. The sections are closed with plungers made of bromobutyl rubber; The section containing the lyophilizate is covered with an aluminum cap. 1 cartridge, together with the instruction for use, is placed in a cardboard box.

    Storage conditions:Syringe Tubes - at a temperature of 2-8 ° C, in a place protected from light. Do not freeze. Keep out of the reach of children
    Shelf life:

    2 of the year. The drug should not be used after the expiry date indicated on the package.

    Cartridges - at a temperature of 2-8 ° C, in a place protected from light. Do not freeze. Keep out of the reach of children.

    A Reco Pen syringe with an inserted cartridge can be stored for 1 month at a temperature of 2-8 ° C.

    Terms of leave from pharmacies:On prescription
    Registration number:П N014262 / 01
    Date of registration:29.07.2008
    The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland
    Manufacturer: & nbsp
    Representation: & nbspF.Hoffmann-La Roche Ltd. F.Hoffmann-La Roche Ltd. Switzerland
    Information update date: & nbsp16.11.2015
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