REKORMON®
Active material: Epoetin Beta
When ATH: B03XA01
CCF: The stimulator of erythropoiesis
ICD-10 codes (testimony): D63, P 61.3
When CSF: 19.01.02.01
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Valium for drug of a solution for s / c administration in the form of homogeneous powder or porous mass of white colour: solvent – Colorless, transparent liquid; prepared solution of – Colorless, clear or slightly Opalescent fluid.
| 1 cartridge | |
| Epoetin beta | 10 000 ME |
| -“- | 20 000 ME |
Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine.
Solvent: benzyl alcohol, benzalkonium chloride, water d / and (1 ml).
Two-section cartridges with solvent (1) – packs cardboard.
The solution for I / O and p / to the introduction colorless, clear or slightly opalescent.
| 1 ampin | |
| Epoetin beta | 1000 ME |
| -“- | 2000 ME |
Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water d / and.
0.3 ml – ampin (3) complete with needles d/and (3 PC.) – packings Valium planimetric (2) – packs cardboard.
The solution for I / O and p / to the introduction colorless, clear or slightly opalescent.
| 1 ampin | |
| Epoetin beta | 10 000 ME |
| -“- | 20 000 ME |
Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water d / and.
0.6 ml – ampin (3) complete with needles d/and (3 PC.) – packings Valium planimetric (2) – packs cardboard.
The solution for I / O and p / to the introduction colorless, clear or slightly opalescent.
| 1 ampin | |
| Epoetin beta | 30 000 ME |
Excipients: urea, sodium chloride, sodium hydrogen phosphate, sodium dihydrogen, calcium chloride, polysorbate 20, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid, L-phenylalanine, water d / and.
0.6 ml – ampin (1) complete with needles d/and (1 PC.) – packings Valium planimetric (1) – packs cardboard.
0.6 ml – ampin (1) complete with needles d/and (1 PC.) – packings Valium planimetric (4) – packs cardboard.
Pharmacological action
Stimulator of hematopoiesis. Epoetin Beta – glikoproteid, consisting of 165 amino acids, which, as a mitogennym factor and hormone differentiation, promotes the formation of red blood cells from partly deterministic progenitor cells erythropoiesis.
Recombinant Epoetin beta, the resulting genetically engineered, at its amino and uglevodnomu composition is identical to human jeritropojetinu.
Epoetin beta after in/in and s/to the introduction increases the number of red blood cells, and, reticulocyte hemoglobin level, as well as the inclusion of iron speed (59Fe) in cells, specifically stimulates erythropoiesis, without affecting the leikopoez. Zitotoksicski epoetina beta on bone marrow or cells of human skin not found.
Pharmacokinetics
Absorption
Beta epoetina bioavailability when s/to the introduction 23-42%. When s/to the introduction of the drug to patients with uremyei long induction provides drug concentrations in the serum of plateau. Tmax – 12-28 no.
Distribution
Vd equal to or BCC 2 times exceeds its.
Deduction
In patients with uremyei and in healthy volunteers T1/2 with a / in the introduction of 4-12 no. T1/2 Terminal phase when s/to the introduction of more, After the on/in the introduction and averages 13-28 no.
Pharmacokinetics in special clinical situations
Beta epoetina pharmacokinetics in patients with hepatic insufficiency has not been studied.
Testimony
-symptomatic anemia in chronic kidney disease patients, dialysis;
-symptomatic anaemia kidney Genesis in patients, still not receiving dialysis;
— treatment of symptomatic anaemia in adults with solid and Hematological tumors nemieloidnymi, receiving chemotherapy;
-to increase blood donations, intended for subsequent autotransfuzii ((c) taking into account the risk of thromboembolitic phenomena registered and only for patients with moderate anaemia (Hb 100-130 g/l or 6.21-8.07 mmol / l), without iron deficiency), If you get enough blood cannot be, a planned major jelektivnoe surgery may require a large amount of blood (≥ 4 units for women or for men units 5 ≥);
-Prevention of anemia in preterm infants, born weighing 750-1500 g to 34 weeks of gestation.
Dosage regimen
Treatment of anemia in patients with chronic kidney disease
Enter n/a or/in during 2 m. Patients, in gemodialise after arteriovenoznyj shunt at the end of dialysis. Patients, not receiving hemodialysis, It is preferable to enter the drug s/c, to avoid puncture of peripheral veins.
The goal of treatment-hemoglobin index (Nr) 100-120 g / l. Nr should not exceed 120 g / l. When you raise more than Nr 20 g / l (1.3 mmol / l) for 4 weeks dose should be reduced. In patients with arterial hypertension, cardiovascular and cerebrovascular diseases weekly increase in hemoglobin and its targets should be determined individually, depending on the clinical. Should be careful monitoring of the patient in order to select the minimum dose, sufficient to ensure the maximum effect of the drug. Treatment Rekormonom® is held in 2 Phase.
Phase correction. P /, the initial dose – 20 IU / kg 3 times a week. With insufficient increase Nr (less 2.5 g/l per week) dose can be increased every 4 weeks 20 IU / kg 3 times a week. The total weekly dose of the drug can also be divided into daily introduction.
B /, the initial dose – 40 IU / kg 3 times a week. With insufficient increase Nr one month dose can be increased to 80 IU / kg 3 times a week. If necessary, further dose should be increased by 20 IU / kg 3 times a week, with monthly intervals.
Regardless of the method of introduction, the maximum dose should not exceed 720 IU/kg per week.
Maintenance therapy. To maintain target Nr (100-120 g / l) dose should be reduced in 2 times from the previous dose. Subsequently, supporting dose picked individually, at intervals of 2 or 4 of the week. When s/to the introduction weeks dose can be injected 1 or divide by 3 or 7 introductions/week. When you stabilize against the backdrop of the introduction 1 Once a week you can go to the introduction 1 once every 2 of the week, in this case, you might need to increase the dose.
Treatment Rekormonom®, usually, conducted long-term. If necessary, it can be interrupted at any time.
Treatment of symptomatic anemia in patients with solid and Hematological tumors nemieloidnymi, receiving chemotherapy
The drug is administered s / c, at an initial dose 30 000 IU per week (450 ME/kg per week), once or sharing the weekly dose 3 or 7 introduced.
Rekormonom Therapy® shows when Nr ≤ 110 g/l (6.83 mmol / l). Nr rate should not exceed 130 g / l (8.07 mmol / l).
While increasing the Nr 10 g / l (0.62 mmol / l) through 4 of the week – therapy should continue in the same dose.
When you raise less than Nr 10 g / l (0.62 mmol / l) through 4 of the week – dose should be doubled.
If there is no increase in Nr 10 g / l (0.62 mmol / l) through 8 weeks – treatment should be interrupted, tk. response to therapy Rekormonom® unlikely.
Treatment should be continued for 4 weeks after the end of chemotherapy.
The maximum dose does not exceed 60 000 ME in a week.
When it reaches the target of Nr for individual patient dose should be reduced by 25-50%.
To prevent a build-up of Nr more 130 g/l may require a further dose reduction.
As Hb more, than 20 g / l (1.3 mmol / l) per month, should be reduced dose Rekormona® on 25-50%.
Preparation of patients to take blood for subsequent autohemotransfusions
B / (during 2 m) or s /, 2 times a week throughout 4 weeks. Where, When hematocrit in a patient (≥ 33%) allows for blood sampling, Rekormon® You should enter at the end of the procedure.
Throughout the course of treatment should not exceed a hematocrit 48%.
Dose determine physician and surgeon transfuziolog individually, whichever, how much blood will be taken from the patient and from its jeritrocitarnogo reserve:
1. Blood volume, which will be taken from the patient, depends on the anticipated blood loss, available methods of preservation of blood and the general condition of the patient; It should be sufficient to, to avoid a blood transfusion from another donor.
2. Blood volume, which will be taken from the patient, is expressed in units of (1 unit equivalent 180 ml erythrocytes).
3. The possibility of donation depends, mainly, from the patient's blood volume and source hematocrit. Both indicators determine the endogenous red blood reserve, which is calculated by the following formula:
Endogenous red blood reserve = blood volume [ml] x (gematokrit – 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] (When body mass index ≥ 45 kg).
Indications for use Rekormona® and its single dose determined by accordance with nomograms, on the basis of the required blood volume and endogenous jeritrocitarnogo reserve. The maximum dose does not exceed 1600 IU/kg per week with on/in the introduction and 1200 IU/kg per week when s/to the introduction.
Preventing anemia in premature infants
The drug used only in spric-tubikah. Enter n / a dose of 250 IU / kg 3 times a week, as soon as possible, preferably from 3 days of life, during 6 weeks.
In Children and Adolescents drug dose depends on the age of the: usually, the smaller age, so higher doses of Rekormona® required. But because individual response to the drug cannot be predicted, It is advisable to start with the standard dosage. At treatment of anemia, associated with chronic kidney disease, Rekormon® nor should appoint Children up to 2 years.
In clinical studies in elderly patients need to change the doses is not defined.
Terms of use of the drug
Squirt-tube with the drug Rekormon® ready-to-eat. Its solution is sterile and contains no preservatives. Apply only light transparent or slightly Opalescent solution, containing no visible impurities. If after injection in spric-tube left some amount of drug, Re-introduction of its unacceptable.
Instructions for use a syringe-tubes
Before injection, you must wash your hands.
1. Remove one spric-tubik from its packaging and check that, that solution is transparent, is colourless and contains no visible impurities. Remove the CAP from the syringe.
2. Pull out one needle packing, wear it on the syringe and remove the protective cap from the needle.
3. Remove the air from the syringe and needles, holding syringe vertically, gently pushing the plunger up. Press the plunger until, While the sprite does not remain a necessary dose Rekormona®.
4. Clean the skin at the injection site with an alcohol cotton wool. Thumb and index finger take skin fold. Keeping closer to the syringe needle, introduce the needle under the skin. Enter the solution Rekormona®. Quickly remove the needle and push the place sterile injection dry cotton wool.
Cartridge with Rekormonom® for spric-rucki Reko-pen is a two-piece toner cartridge, containing liofilizat for solution to the p/to the introduction and solvent preservatives. Ready solution is obtained through the introduction of cartridge spric-Reko-pen handle in accordance with the instructions.
Rekormonom cartridges® should only be used in syringe handle Reko-pen. It is recommended that you use a needle for spric-rucki Reko-pen (eg, needle “Penfajn”). The prepared solution stored in the cartridge 1 month at a temperature from 2° to 8° c. After you install the cartridge syringe pen Reko-pen take out from the fridge only at the time of the injection.
Side effect
Cardio-vascular system: often – emergence or strengthening existing hypertension (>1%, <10%), especially in the case of rapid increase gematokrita; hypertonic Kriz events encephalopathy (headaches and confusion, sensory and motor disorders – speech disorders, gait, until tonico-klonicakih convulsing), thromboembolic complications in cancer patients (>0.1%, <1%) and patients, preparing for autotransfuzii (clear causal relationship with the drug is not installed).
CNS: >1%, <10% – headache, incl. sudden migraine-like headaches.
From the hematopoietic system: the sharp increase in the number of platelets (not outside the norms and disappear with continued therapy), especially after the on/in the introduction of the drug; <0.01% – thrombocytosis; >0.01%, <0.1% – pulmonary shunts (Perhaps if inadequate geparinizacii), especially in patients with a tendency towards lower hell or with complications of arteriovenous fistula (incl. stenosis, aneurysm).
Allergic reactions: rarely (of ≥ 1/10 000 to ≤ 1/1000) -skin rash, itch, hives; rarely (≤ 1/10 000) – anaphylactoid reactions.
From the laboratory parameters: reduction of the concentration of serum ferritin concentrations with increasing Hb, reduction of serum iron Exchange indicators; in patients with uremyei-passing hyperkalemia (clear causal link with the admission of the drug is not installed), giperfosfatemiя. In preterm infants – reduction of the concentration of serum ferritin (>10%), a slight increase in the number of platelets, especially with 12 on the 14th day of life.
Other: reactions at the injection site; flu-like symptoms (especially early in treatment; usually expressed as weakly or moderately and disappear after a few hours or days), incl. fever, chills, headache, pain in the limbs or bones, general malaise.
Postmarketingovoe monitoring: While therapy Rekormonom® registered individual cases (0.107 accidents 10 000 patient-years when applying Rekormona® for the treatment of anemia in renal Genesis/in and c/a and 0.158 accidents 10 000 patient-years when s/to the introduction Rekormona® for the treatment of anaemia kidney Genesis) partial krasnokletochnoj aplazii (PKKA), caused by the formation of neutralizing anti-EPO antibodies.
Contraindications
-myocardial infarction or stroke during the preceding month;
— unstable angina or an increased risk of deep vein thrombosis (When venous thromboembolism history) -When assigning to increase donor blood for autotransfusion;
- Uncontrolled hypertension;
- Children up to age 3 years (for cartridges with liofilizatom for solution to the p/to the introduction);.
- Hypersensitivity to the drug;
-hypersensitivity to benzoic acid-metabolitu benzyl alcohol (When applying Rekormona® for spric-rucki Reko-pen).
FROM caution apply when in the presence of anemia refractor blasttransformirovannyh cells, thrombocytosis, epilepsy and chronic liver failure; birth weight less than 50 kg to increase blood donations for further autotransfuzii.
Pregnancy and lactation
Rekormona safety information® Pregnancy, at the time of birth and lactation (breast-feeding) received in postregistracionnom application.
During pregnancy or during childbirth, Rekormon® It should be administered with caution, because sufficient experience of use in pregnancy and during delivery is not.
Endogenous erythropoietin secretiruetsa in breast milk and completely absorbed from the digestive tract of the newborn. The choice between the continuation of breastfeeding or continuation therapy Rekormonom® make, bearing in mind the need for mothers and the benefits of breastfeeding for the child
IN experimental studies shows, that Epoetin Beta has no teratogenicity in animals.
Cautions
Inadequate application of healthy people (eg, as doping) may cause a sharp increase in Hb, accompanied by life-threatening complications from the circulatory system.
Because in some cases there were anaphylactoid reactions, the first dose should be under the supervision of a physician.
Should regularly monitor the performance of platelets, Hematocrit and Hb while therapy Rekormonom®.
You should be wary of Rekormon® When in the presence of anemia refractor blasttransformirovannyh cells, epilepsy, trombozitoze and chronic liver failure. Prior to the start of treatment Rekormonom® You must exclude vitamin B deficiency12 and folic acid, t. to. they reduce the effectiveness of the therapy.
Should exclude iron deficiency prior to the start of treatment Rekormonom®, as well as during the entire period of therapy. If necessary, can be assigned additional therapy drugs iron in accordance with clinical recommendations.
In the treatment of patients with severe forms of phenylketonuria should take into account the presence of phenylalanine as excipient: each squirt-tube-up to 0.3 mg (at dosages 1000 ME, 2000 ME ) or to 0.6 mg (10 000 ME, 20 000 ME, 30 000 ME), in each cartridge – to 0.5 mg.
Lack of effect. The most common causes of partial response to treatment means, stimulates erythropoiesis, are iron deficiency and inflammation (as a result of uremia or progressive metastatic cancer). The following condition will reduce the effectiveness of treatment means, stimulates erythropoiesis: Chronic blood loss, fibrosis of the bone marrow, a sharp increase in the concentration of aluminum, due to hemodialysis, deficiency of folic acid or vitamin B12, gemoliz. If all of the listed status of the excluded and the patient is observed a sudden decrease of Hb, reticulocytopenia and have antibodies to erythropoietin, a study of bone marrow to exclude PKKA. With the development of Rekormonom therapy PKKA® must stop, and patients should not be transferred to other therapy with erythropoiesis stimulants. PKKA, caused by the same anti-EPO antibodies, can be associated with therapy with erythropoiesis stimulants, incl. and with Rekormonom therapy® (0.107 accidents 10 000 patient-years when applying Rekormona® for the treatment of anemia in renal Genesis/in and c/a; 0.158 accidents 10 000 patient-years when s/to the introduction Rekormona® for the treatment of anaemia kidney Genesis). It is not recommended to transfer patients to therapy Rekormonom® When suspected, or when confirmed the presence of neutralizing antibodies to erythropoietin.
Effect on tumor growth. Jepojetiny are growth factors, that basically stimulates the formation of red blood cells. Erythropoietin receptors may be present on the surface of various tumor cells. You cannot delete the, that means, stimulating erythropoiesis, can stimulate the growth of any type of malignancy.
In clinical research in the treatment of anemia in cancer patients epoetinom beta statistically sound deterioration of survival and progression of tumors is not registered.
In patients with chronic kidney disease or malignant tumors, receiving chemotherapy, may experience episodes of raising HELL and deterioration of the current existing hypertension, especially when sharp increase Hb content. The ad can be eliminated with medication, in the absence of the effect a temporary break in treatment Rekormonom®. It is recommended that you regularly monitor ad (especially early in treatment), incl. between sessions of dialysis in patients with renal anemia Genesis. Some patients with chronic kidney disease may occur with symptoms of encephalopathy hypertensive crisis even at normal or low AD. Require immediate medical consultation and especially if you encounter sudden acute headaches migrenepodobnykh.
During treatment Rekormonom® It is recommended to periodically monitor the level of potassium in the blood serum. When you need to temporarily cancel giperkaliemii Rekormon® to normalize the concentration of potassium.
Patients with chronic kidney disease an increase dose heparin during hemodialysis session due to higher content of Hb. Possible occlusion of PD system with inadequate geparinizacii. We recommend early shunt revision and timely prevention of thrombosis (eg, admission of acetylsalicylic acid).
Perhaps a moderate dose-dependent increase in platelet count within normal limits, especially after the on/in the appointment Rekormona®, with the subsequent independent return to normal values with continued therapy. First 8 weeks of therapy required weekly tally of uniform and, especially, Platelet.
If Rekormon® appointed before the fence autologous blood donations, should follow the recommendations of the donation procedure:
– blood can be taken only in patients with hematocrit value ≥ 33% (or at least haemoglobin 110 g / l (6.83 mmol / l));
– special caution should be exercised in patients weighing less than 50 kg;
– blood volume, at zabiraemyj, should not exceed 12% from the calculated blood volume of the patient.
The increase in the number of platelets in the patients, receiving Rekormon® before the fence autologous blood donations, Therefore, you should monitor the number of platelets downloads. Treatment Rekormonom® interrupts at increase platelets more than 150 h 109/l or at trombozitoze.
Treatment Rekormonom® shows only those patients, which is most important to avoid homologous blood transfusion, taking into account the ratio risk-polza when homologous transfusion.
Perhaps a slight increase in the number of platelets in preventing anemia in preterm infants (up to 12-14 day), It is therefore recommended to regularly monitor the platelets.
The decision to use Rekormona® in patients with nefrosklerozom, not receiving dialysis, must be taken individually, tk. It is impossible to completely exclude the possibility of a more rapid deterioration of the kidney.
In most cases, with increasing hemoglobin serum ferritin concentration decreases. Therefore, all patients with renal anemia Genesis and serum ferritin concentration less than 100 µg/l or transferrine saturation less than 20% recommended oral iron supplementation (Fe2+) dose 200-300 mg / day.
Patients with cancer and haematological diseases therapy drugs iron hold on the same principles, patients with mielomna disease, started chemotherapy or chronic lymphocytic leukemia with transferrine saturation less than 25% You can enter 100 mg Fe3+ per week/in. Premature children oral therapy drugs iron dose 2 mg Fe2+ per day should be appointed as soon as possible (at the latest – on the 14th day of life). Dose iron adjust depending on the level of serum ferritin. If he remains firmly below the 100 mcg/ml or have other signs of iron deficiency, dose iron supplementation should be increased to 5-10 mg/day and conduct therapy to relieve the symptoms of iron deficiency.
Patients with moderate anemia before the planned major operational intervention product shall, taking into account the benefits of the epoetina beta and increased risk of thromboembolic complications.
Patients, preparing to give blood for subsequent autotransfuzii, because they've got a instructions for a temporary iron deficiency, oral therapy drugs iron (Fe2+) dose 300 mg/day should begin simultaneously with therapy Rekormonom® and to continue to normalize indicators ferritin. If, Despite oral substitution therapy iron, develop signs of iron deficiency (ferritin level ≤ 20 µg/l or transferrine saturation less than 20%), You must consider additional on/in the introduction of iron. Solution Rekormona® cartridge contains benzyl alcohol as a preservative, able to cause newborn neurological and other complications, sometimes with fatal consequences.
Effects on ability to drive vehicles and management mechanisms
Study on the influence of the drug on the ability to drive and work with the mechanisms have not been conducted. Based on the mechanism of action and safety profile, Rekormon® has no such action.
Overdose
Therapeutic index Rekormona® very wide, However, one should take into account the individual response to therapy at the beginning of treatment. Chance of excessive pharmacodynamic response, ie. excessive eritropoez with life-threatening cardiovascular complications.
If you have a high rate of Hb you need to temporarily interrupt therapy Rekormonom®. If necessary, it can be carried phlebotomy.
Drug Interactions
The data received so far did not show any interaction Rekormona® with other drugs.
To avoid incompatibility or reduce the activity of the drug, you can't use other solvent and mix the drug with other drugs or injectable solutions
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.
Autoinjector Reko-pen with an inserted cartridge can be stored for 1 months at a temperature of 2-8° c.
