NEORECORMON 2000 IU 0.3 ml. 1 syringes
NEORECORMON amp. 2 IU 0.3 ml. 6 syringes
Epoetin beta e recombinant human erythropoietin produced by recombinant DNA technology CHO cell line ( ovarian cells of Chinese hamster) .
Epoetin beta is identical in its amino acid and carbohydrate composition of EPO which has been isolated from the urine of anemic patients.
Erythropoietin is a glycoprotein that stimulates the formation of erythrocytes from the stem cell precursors . It acts as a mitosis stimulating factor and differentiation hormone .
Studies of the cell culture of cells from human bone marrow cells showed that epoetin beta stimulates erythropoiesis specifically and does not affect leucopoiesis. Not Cytotoxic actions of epoetin beta on bone marrow or on human skin cells . Preclinical and clinical studies have shown no effect of epoetin beta on tumor progression .
Treatment of anemia associated with chronic renal failure (renal anemia ) in patients on dialysis .
Treatment of symptomatic renal anemia in patients who have not been on dialysis.
* Prevention of anemia of prematurity in infants with a birth weight of 750 to 1500 g and gestational age less than 34 weeks .
* Prevention and treatment of anemia in adult patients with solid tumors treated with chemotherapy , based on the platinum which can induce anemia ( cisplatin : 75 mg/m2 per cycle , Carboplatin 350 mg/m2 per cycle ) .
Treatment of anemia in adult patients with multiple myeloma, low grade non-Hodgkin 's lymphoma or chronic lymphocytic leukemia , which have a relative deficiency of erythropoietin obtained and anti-tumor therapy . Deficiency is defined as an inappropriately low serum erythropoietin level in terms of the degree of anemia .
* Increasing the yield of autologous blood from patients in a program of collection . Its use in this indication must be balanced against the reported risk of thromboembolic events. Treatment should only be given to patients with moderate anemia (Hb 10-13 g / dl [6.21 mmol / L - 8.07 mmol / L], no iron deficiency ), if not possible blood conserving procedures or insufficient when the scheduled major surgery requires a large volume of blood ( 4 or more units of blood for females or 5 or more units for males ) .
HOW TO USE
NeoRecormon therapy should be initiated by a physician experienced in the treatment of the above mentioned indications. Since in some cases anaphylactoid reactions were observed , it is recommended that the first dose be administered under medical supervision.
NeoRecormon in pre-filled syringe is ready for use. Can be injected which are clear or slightly opalescent, colorless and practically free of visible particles.
NeoRecormon in pre-filled syringe is a sterile but unpreserved . In no case should inject more than one dose syringe .
Treatment of anemic patients with chronic renal failure
The solution may be administered subcutaneously or intravenously. In case of intravenous administration, the solution should be injected over about 2 min, for example . in hemodialysis patients via the arterio- venous fistula at the end of dialysis.
In patients not on dialysis , should always preferably subcutaneous administration , in order to prevent puncture of peripheral veins .
The goal of treatment is to increase the hematocrit of 30-35% , such as weekly increase should be at least 0.5% (volume percent ) . Should not exceed a value of 35%.
In the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral vascular diseases, the weekly increase in the PCV and the target PCV should be determined individually taking into account the clinical picture. In some patients, the optimal hematocrit may be lower than 30 %.
Treatment with NeoRecormon is divided into two stages .
1. Correction phase
* Subcutaneous administration: The initial dosage is 3 x 20 IU / kg body weight per week. The dosage may be increased every 4 weeks by 3 x 20 IU / kg per week if the increase in hematocrit is not adequate ( <0.5% per week).
The weekly dose can also be divided into daily doses.
* Intravenous administration: The initial dosage is 3 x 40 IU / kg body weight per week. The dose may be increased after 4 weeks to 80 IU / kg - three times a week and if necessary further increase , it should be 20 IU / kg, three times a week, every month.
For both routes of administration, the maximum dose should not exceed 720 IU / kg per week .
2 . Maintenance phase
To maintain a hematocrit between 30% and 35% , the dose is initially reduced to half of the previously administered amount . Thereafter, the dosage is adjusted at intervals of one or two weeks for the patient ( maintenance dose).
In the case of subcutaneous administration , the weekly dose can be given as one injection per week or in divided doses three or seven times a week. Patients who are stable on a once weekly dosing regimen may be switched to once every two weeks. In this case you may need a dose increase .
Results of clinical studies in children have shown that on average, the younger the patient , the higher the NeoRecormon doses required . Nevertheless, the recommended dosing schedule should be followed as the individual response can not be predicted.
NeoRecormon therapy is usually long . However, it can be interrupted, if necessary, at any time. Data on the once weekly dosing is based on a clinical trial with a 24 week duration of the treatment.
Prevention of anemia of prematurity
The solution was administered subcutaneously at a dose of 3 x 250 IU / kg bw week. NeoRecormon therapy should begin as soon as possible in advance , preferably by day 3 of life. Unlikely Premature infants who have already been transfused before the start of treatment with NeoRecormon, to benefit as much as those without blood transfusion. Treatment should continue for six weeks .
Treatment of patients with solid tumors
The solution was administered subcutaneously , the weekly dosage may be divided into 3 to 7 unit dosages.
NeoRecormon therapy is indicated if the hemoglobin ? 13 g / dl (8.1 mmol / l) at the start of chemotherapy. The recommended starting dose is 450 IU / kg body weight per week . If after 4 weeks the patient does not show a satisfactory response to the hemoglobin , then the dose should be doubled. Treatment should be continued until three weeks after the end of chemotherapy.
If the hemoglobin is lowered by more than 1 g / dl (0.63 mmol / l) in the first cycle of chemotherapy despite concomitant NeoRecormon, further treatment may not be effective.
The increase in hemoglobin of greater than 2 g / dl (1.24 mmol / l) per month, or more than 14 g / dl (8.69 mmol / l) should be avoided . If the hemoglobin increases by more than 2 g / dl per month , the dose of NeoRecormon must first be reduced by 50%. If values exceed 14 g / dl (8.69 mmol / l), NeoRecormon therapy should be interrupted until a value <12 g / dl (7.45 mmol / l) and then restarted at 50% of the previous weekly dose .
Treatment of patients with multiple myeloma, low grade non-Hodgkin 's lymphoma or chronic lymphocytic leukemia
Patients with multiple myeloma , non-Hodgkin's lymphoma or chronic lymphocytic leukemia should have a relative erythropoietin deficiency . Deficiency is defined as an inappropriately low serum erythropoietin level in terms of the degree of anemia :
- Serum erythropoietin level <100 mU / ml with hemoglobin > 9 and <10 g / dl
(> 5.58 to <6.21 mmol / l);
- Serum erythropoietin level ? 180 mU / ml in hemoglobin of> 8 to < 9 g / dl
(> 4.96 to <5.58 mmol / l);
- Serum erythropoietin level ? 300 mU / ml in hemoglobin ? 8 g / dl (? 4.96 mmol / l).
The above values should be measured at least 7 days after the last transfusion and the last cycle of cytotoxic chemotherapy.
The solution was administered subcutaneously. The weekly dose can be given as one injection per week, or can be divided into 3 to 7 unit dosages.
The recommended starting dose is 450 IU / kg body weight per week . If, after 4 weeks of therapy , the hemoglobin value has increased by at least 1 g / dl (0.62 mmol / l), should be continued with this dose. If the hemoglobin has not increased by at least 1 g / dl (0.62 mmol / l), you may consider increasing the dose to 900 IU / kg body weight per week . If after 8 weeks of therapy , the hemoglobin value has not increased by at least 1 g / dl (0.62 mmol / l), it is unlikely to get a response and treatment should be discontinued.
Clinical studies have shown that the response to treatment with epoetin beta is delayed by about 2 weeks to patients with chronic lymphocytic leukemia in comparison with patients with multiple myeloma , non-Hodgkin's lymphoma and solid tumors. Treatment should be continued up to 4 weeks after the end of chemotherapy.
The maximum dose should not exceed 900 IU / kg body weight per week .
If the hemoglobin increases by more than 2 g / dl (> 1.24 mmol / l) in 4 weeks , the dose of NeoRecormon should be halved . If the hemoglobin exceeds 14 g / dl (8.69 mmol / l), NeoRecormon therapy should be interrupted until the value? 13 g / dl (? 8.07 mmol / l). Then therapy should be restarted at 50 % of the dose from the previous week.
Treatment should be started again if the erythropoietin deficiency is the most likely cause of anemia.
Treatment for increasing the amount of autologous blood
The solution was administered intravenously over approximately 2 minutes or subcutaneously.
NeoRecormon is administered twice weekly for 4 weeks. Where PCV allows blood sampling , i.e. PCV ? 33 %, NeoRecormon is administered at the end of blood donation .
Throughout the treatment period should not exceed hematocrit of 48%.
The dosage should be determined by the surgical team individually for each patient as a function of the required amount of blood that must be decided in advance and the endogenous red cell reserve cells :
1. Required amount of blood that must be taken in advance, depending on the anticipated blood loss, use of blood conserving procedures and the physical condition of the patient .
This amount should be that quantity which is expected to be sufficient to avoid homologous blood.
The required amount of pre- donated blood is expressed in units whereby nomogram is equivalent to 180 ml of red blood cells.
2 . Ability to donate blood depends predominantly on patient's blood volume and baseline PCV . Both variables determine the endogenous reserves of red blood cells, which can be calculated by the following formula :
Endogenous reserve of red blood cells = blood volume [ml] x ( RSV - 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].
(body weight? 45 kg)
Single dose thus determined is administered twice weekly for 4 weeks. The maximum dose should not exceed 1600 IU / kg bw week for intravenous or 1200 IU / kg bw week for subcutaneous administration.
NeoRecormon should not apply to poorly controlled hypertension and known hypersensitivity to the active substance or to any of the excipients.
In the indication "increasing the yield of autologous blood " NeoRecormon should not be administered to patients one month before treatment had a myocardial infarction or stroke in patients with unstable angina or patients at risk of deep vein thrombosis , such as patients with a history of thromboembolic disease .
Special warnings and special precautions for use
NeoRecormon should be used with caution in the presence of refractory anemia with excess blasts in transformation, epilepsy , thrombocytosis, and chronic liver failure. Should be excluded deficiency of folic acid and vitamin B12, as this reduces the effectiveness of NeoRecormon.
Severe aluminum overload due to treatment of renal failure may compromise the effectiveness of NeoRecormon.
The indication for NeoRecormon treatment of patients with nephrosclerosis not yet undergoing dialysis should be defined individually, as it can certainly be possible acceleration of progression of renal failure.
Patients who developed anti -erythropoietin antibodies and pure red blood cells during treatment with another erythropoietic product should not be switched to treatment with NeoRecormon due to possible cross-reactivity of antibodies to erythropoietin all substances.
In patients with chronic renal failure during treatment with NeoRecormon may be a moderate dose-dependent rise in the platelet count within the normal range , especially with intravenous administration . It decreases with continued therapy. It is recommended that the platelet count be monitored regularly during the first 8 weeks of treatment.
In premature infants there may be a slight increase in the number of platelets , especially day 12th - 14th of life and therefore platelets should be monitored regularly .
In patients with cancer, platelet counts should be monitored at regular intervals during treatment with NeoRecormon.
Patients in the program opt- autologous blood may be an increase in platelet count , mostly within the normal range. It is therefore recommended in these patients, the platelet count be determined at least once a week. If elevations in platelet counts above 150 x 109 / l or if platelets rise above the normal range, treatment with NeoRecormon should be discontinued .
In patients with chronic renal failure during treatment with NeoRecormon often requires an increase in heparin dose during hemodialysis due to increased hematocrit . Possible Occlusion of the dialysis system if heparinisation is not optimum.
Early shunt revision and thrombosis prophylaxis by administration of acetylsalicylic acid , for example , should be given in patients with chronic renal failure who are at risk of shunt thrombosis .
Serum potassium levels should be monitored closely during treatment with NeoRecormon. There are reports of an increase in potassium in some uremic patients receiving NeoRecormon, although not established a causal link. If an elevated or rising potassium level should be given to discontinuation of NeoRecormon to the correct level .
With NeoRecormon program for opt- autologous blood should be given to official guidance on the principles of blood , in particular:
* Only patients with hematocrit ? 33% (hemoglobin ? 11 g / dl [6.83 mmol / l]) should donate ;
* You should pay special attention to patients weighing less than 50 kg;
* Single volume drawn should not exceed approximately 12% of estimated blood volume of the patient.
Treatment should be reserved for patients who are considered to be particularly important to avoid homologous blood transfusion taking into consideration the risk / benefit assessment for homologous blood.
Misuse by healthy persons may lead to an excessive increase in hematocrit . This may be associated with life-threatening complications of the cardiovascular system .
NeoRecormon in pre-filled syringe contains up to 0.3 mg phenylalanine syringe as an excipient. This should be considered in patients with severe phenylketonuria.
Interaction with other medicaments and other forms of interaction
The clinical results obtained so far do not indicate any interaction of NeoRecormon with other substances.
Animal experiments have shown that epoetin beta does not increase the myelotoxicity of cytostatic agents such as etoposide, cisplatin, cyclophosphamide , and fluorouracil.
Pregnancy and lactation
Animal studies have shown no teratogenic effect of epoetin beta in treatment regimens that do not lead to abnormally high hematocrit . Not collected enough clinical experience of pregnancy and lactation in humans , but potential risk appears to be minimal under therapeutic conditions.
Driving and using machines
No effects on ability to drive and use machines.
Generally objectionable side effects
Based on results from clinical trials involving 1725 patients expected approximately 8% of patients treated with NeoRecormon, to experience adverse reactions. Adverse effects during treatment with NeoRecormon are observed predominantly in patients with chronic renal failure or malignancy as underlying disease and are most commonly an increase in blood pressure or aggravation of existing hypertension and headache.
* Anemic patients with chronic renal failure
The most frequent adverse reaction during treatment with NeoRecormon is an increase in blood pressure or aggravation of existing hypertension, especially in cases of rapid PCV . This increase in blood pressure can be treated with drugs . If blood pressure can not be controlled with medication , it is recommended the temporary discontinuation of NeoRecormon. Regular monitoring of blood pressure, especially at the beginning of treatment, including between dialyses .