Description
Release form
Solution for intravenous and subcutaneous administration
Packaging
6 syringes.
Indications
Anemia associated with chronic renal failure in adults and children, including patients undergoing hemo- or peritoneal dialysis.
Anemia in cancer patients with non-myeloid tumors (for prevention and treatment).
Anemia in HIV-infected patients receiving zidovudine therapy with an endogenous erythropoietin level of less than 500 IU / ml.
As part of the pre-deposit program, prior to extensive surgery in patients with a hematocrit level of 33-39%, to facilitate the collection of autologous blood and reduce the risk associated with the use of allogeneic blood transfusions, if the expected need for transfused blood exceeds the amount that can be obtained by the autologous method collection without the use of epoetin alfa.
Before carrying out an extensive operation with an expected blood loss of 900-1800 ml (2-4 units) for adult patients without anemia or with mild to moderate anemia (hemoglobin level 100-130 g / l) to reduce the need for allogeneic blood transfusions and facilitate recovery erythropoiesis.
Contraindications
Hypersensitivity to the components of Eprex
uncontrolled arterial hypertension
patients with severe pathology of coronary, carotid, cerebral and peripheral vessels, including recent myocardial infarction or acute cerebrovascular accident (circulatory system) pregnancy
lactation
patients for any reason, patients with partial red cell aplasia who received therapy with any erythropoietin who are unable to receive adequate preventive antithrombotic therapy
(the use of Eprex and all other erythropoietins is contraindicated).
Special instructions
Before and after starting treatment with Eprex, blood pressure should be adequately controlled. Eprex should be used with caution in the presence of untreated or poorly controlled hypertension. During therapy with Eprex, the appointment of antihypertensive therapy may be necessary. If it is not possible to reduce the pressure with antihypertensive drugs, Eprex therapy should be discontinued.
Epoetin alfa should also be used with caution in patients with chronic liver failure. The safety of epoetin alfa in patients with impaired liver function has not been established. Due to the decreased metabolism in patients with impaired liver function, an increase in erythropoiesis may occur with the use of epoetin alpha.
In patients receiving erythropoietin stimulating drugs, an increase in the frequency of thrombotic vascular events, such as venous and arterial thrombosis and embolism (including several fatal cases), such as deep vein thrombosis, pulmonary embolism, was observed retinal thrombosis and myocardial infarction. In addition, cerebrovascular accidents (including cerebral infarction, intracerebral hemorrhage and transient ischemic attacks) were noted. The noted risk of thrombotic vascular events and the benefit of treatment with epoetin alfa should be carefully compared, especially in patients with risk factors.
All patients should be closely monitored for hemoglobin levels due to the potentially increased risk of thromboembolic events and deaths observed in patients with elevated hemoglobin levels when treated with Eprex.
Safety and efficacy of epoetin alfa therapy in patients with background hematologic diseases, such as hemolytic anemia, sickle cell anemia, thalassemia have not been studied.
During treatment with Eprex, regular monitoring of platelet count is required, especially during the first 8 weeks, since a dose-dependent relative increase in platelet count may develop, which will normalize later without canceling therapy, in rare cases an absolute increase in platelet count is noted.
Before starting treatment with epoetin alfa, as well as when deciding to increase its dose, other causes of anemia should be evaluated and treated (deficiency of iron, folic acid or vitamin B12, aluminum intoxication, infection or inflammation, blood loss, hemolysis and bone marrow fibrosis of any genesis ) In most cases, serum ferritin levels decrease simultaneously with an increase in hematocrit. To achieve an optimal response to epoetin alfa, adequate iron stores should be provided, with the introduction of iron supplements if necessary: Patients with chronic renal failure are advised to take iron supplements (elemental iron 200-300 mg / day orally in adults and 100-200 mg / day orally in children) in case of serum ferritin level below 100 ng / ml.
Patients with cancer are advised to take additional iron supplements (elemental iron 200-300 mg / day orally) if transferrin is less than 20% saturated.
Patients of the autologous blood collection program are advised to take additional iron supplements (elemental iron 200 mg / day orally) for several weeks before the start of autologous blood collection, in order to achieve large iron stores before starting epoetin alfa therapy, as well as during the entire course of epoetin therapy alpha.
Patients who are scheduled for a large planned orthopedic operation are advised to take an additional iron supplement (elemental iron 200 mg / day orally) throughout the course of therapy with epoetin alfa. If possible, the use of iron-containing preparations should be started before the start of therapy with epoetin alfa in order to create sufficient reserves of iron.
Very rarely in patients treated with epoetin alfa, exacerbations of porphyria were observed at the beginning of treatment. In patients with porphyria, epoetin alfa should be used with caution.
Means stimulating erythropoiesis are not necessarily equivalent. Therefore, it should be clarified that patients should be transferred from one drug that stimulates erythropoiesis (such as Eprex) to another only with the approval of the attending physician.
In patients with chronic renal failure who received treatment with subcutaneous administration of epoetin, it was very rare, after months and years of treatment, that antibody-mediated true erythrocytic aplasia (IEA) was observed.
Occasionally, there have also been cases of this disease in patients with hepatitis C treated with interferon and ribavirin, when erythropoietin was treated with stimulant drugs at the same time, so they are not approved for the treatment of anemia, associated with hepatitis C.
In patients with chronic renal failure who have a sudden decrease in efficacy, defined by a decrease in hemoglobin (1-2 g / dl per month) with an increase in the need for transfusions, it is necessary to count the number of reticulocytes and examine for typical reasons for the lack of response (for example, deficiency of iron, folic acid or vitamin B12, aluminum intoxication, infection or inflammation, blood loss, hemolysis and bone marrow fibrosis of any origin). If the reticulocyte count adjusted for anemia (ie, the reticulocyte index) is low (3 or
) If an IEA mediated by anti-erythropoietin antibodies is suspected, epoetin alpha therapy should be stopped immediately. You should not start treatment with any other erythropoietin stimulating drugs, since there is a risk of a cross-reaction. If indicated, patients may be given appropriate therapy, such as a blood transfusion. Patients with chronic renal failure during treatment with Eprex should regularly measure the level of hemoglobin until the hemoglobin level reaches stable values, with periodic monitoring in the future.
To reduce the risk of arterial hypertension, the rate of increase in hemoglobin level should be approximately 10 g / l (maximum 20 g / l) per month. The dose should be reduced when the hemoglobin level reaches 120 g / l.
In patients with chronic renal failure, the sustained hemoglobin level should not exceed the upper limit of the indicated range of hemoglobin levels. Hemoglobin levels of 130 g / L or higher may lead to an increased risk of cardiovascular events, including death.
Patients with chronic renal failure and an insufficient hemoglobin response to erythropoietin therapy with stimulant drugs may be at even greater risk of cardiovascular events and mortality than other patients.
Based on the currently available information, the use of epoetin alfa in patients prior to dialysis (end-stage renal failure) does not increase the rate of progression of renal failure.
Shunt thrombosis occurred in hemodialysis patients, in particular, in patients with a tendency to hypotension, or with complications from arteriovenous fistulas (for example, stenosis, aneurysm, etc.). In these patients, early screening of the shunt and prevention of thrombosis by administering, for example, acetylsalicylic acid, are recommended.
In some cases, hyperkalemia was observed, although its causal relationship with the use of the drug has not been established. In patients with chronic renal failure, serum electrolytes should be monitored. If the serum potassium level is increased or increasing, then, in addition to the proper treatment of hyperkalemia, consideration should be given to stopping the administration of epoetin alpha until the serum potassium level is adjusted.system.
In some patients with chronic renal failure, menstruation was resumed during treatment with Eprex. The possibility of pregnancy and the need for contraceptive measures should be discussed with the patient before starting therapy.
Erythropoiesis stimulants are growth factors that stimulate, in the first place, the formation of red blood cells. Erythropoietin receptors can be expressed on the surface of many tumor cells. As with all growth factors, there are doubts that erythropoiesis stimulants can stimulate tumor growth.
From the point of view of the above, the decision to administer a recombinant erythropoietin preparation should be made on the basis of an assessment of the risk-benefit ratio involving a particular patient, and must take into account the specific clinical situation. Factors to be considered in this assessment include: type and stage of the tumor, severity of anemia, life expectancy, conditions under which the patient receives treatment for the patient s preferences.
In cancer patients receiving chemotherapy, when evaluating the suitability of epoetin alfa therapy (especially in patients at risk of transfusion), a delay of 2-3 weeks between the administration of erythropoiesis stimulating agents and the appearance of erythropoietin-stimulated red blood cells should be considered.
If an HIV-infected patient does not respond or the response to epoetin alfa therapy is insufficient, other possible causes of anemia should be considered, including iron deficiency.
In patients associated with the autologous blood collection program and receiving additional treatment with epoetin alfa, all special warnings and special precautions should be taken into account, especially the mandatory replenishment of the volume.
In the pre- and postoperative period, proper standards for monitoring blood counts should always be observed.
Patients who are scheduled for a large planned orthopedic operation should receive antithrombotic prophylaxis, since surgical patients may experience thrombotic and vascular events, especially patients with underlying cardiovascular disease. In addition, special precautions should be observed in patients with a predisposition to the development of thrombotic complications. Moreover, in patients with an initial hemoglobin level> 130 g / l (8, 1 mmol / l) the possibility that treatment with epoetin alfa may be associated with an increased risk of postoperative thrombotic vascular events cannot be ruled out. Therefore, in patients with an initial hemoglobin level> 130 g / l (8.1 mmol / l), the use of epoetin alpha is not recommended.
Dosage and administration
Before use, carefully examine the solution for visible particles or discoloration. The drug should not be shaken, because this can lead to denaturation of the glycoprotein and loss of activity of the drug. Eprex does not contain preservatives, therefore, individual packaging is intended for single use.
Intravenous administration. The duration of the injection is at least 15 minutes. Slower administration is preferred for patients in which there is a flu-like syndrome on the introduction of the drug. For hemodialysis patients, the drug is injected through a needle into the fistula at the end of the dialysis procedure. To wash the connecting tubes, as well as to ensure a satisfactory introduction of the drug into the circulation system after injection of Eprex, 10 ml of isotonic sodium chloride solution is administered (only for intravenous and subcutaneous solutions of 1000, 2000, 4000 and 10000 IU).
It is forbidden to introduce the drug as an intravenous infusion or mix it with other drugs.
Subcutaneous injection. The maximum volume of one subcutaneous injection should not exceed 1 ml, if necessary, the introduction of large volumes should use several points of introduction. The drug is administered under the skin of the shoulder, thigh, anterior abdominal wall.
When changing the method of administration, the drug is administered at the previous dose, then the dose is adjusted if necessary (to achieve the same therapeutic effect with subcutaneous administration, a dose of 20-30% is required than with intravenous administration) (for solution for intravenous and subcutaneous administration of 1000, 2000 , 4000 and 10000 IU).
Patients with cancer are subcutaneous.
The optimal hemoglobin content should be 100120 g / l in men and women and should not be exceeded.
The initial dose for the prevention or treatment of anemia should be 150 IU / kg body weight 3 times a week s / c. Alternatively, the initial dose may be 40,000 IU once a week subcutaneously.
If, after 4 weeks of treatment, the hemoglobin content has increased and is at least 10 g / l, or the number of reticulocytes increased by more than 40,000 cells / ?l above the original, the dose of Eprex remains the same.
If, after 4 weeks of treatment, the increase in hemoglobin is less than 10 g / l and the increase in the number of reticulocytes is less than 40,000 cells / ?l compared to the initial one, then over the next 4 weeks the dose is increased to 300 IU / kg body weight 3 times a week or 60,000 IU once a week.
If after an additional 4 weeks of treatment at a dose of Eprex 300 IU / kg 3 times a week or 60,000 IU once a week, the hemoglobin content has increased and is at least 10 g / l or the number of reticulocytes has increased by more than 40,000 cells / ?l, then keep the existing dose of Eprex.
If after 4 weeks of treatment at a dose of 300 IU / kg of body weight or 60,000 IU once a week, the hemoglobin content increases by less than 10 g / l and the increase in the number of reticulocytes is less than 40,000 cells / ?l compared to the initial one, treatment should be discontinued.
If the hemoglobin content increases by more than 20 g / l for 1 month or if the hemoglobin content reaches 120 g / l, the dose should be reduced by 25%. If the hemoglobin content exceeds 120 g / l, it is necessary to suspend treatment until it drops below 120 g / l and then continue the administration of Eprex in a dose 25% lower than the original.
Eprex therapy should be continued for 1 month after completion of chemotherapy.
Adult patients participating in an autologous blood collection program before surgery, – intravenously.
Epoetin alfa should be administered at the end of the blood collection procedure.
Before prescribing Eprex, all contraindications to the collection of autologous blood should be considered. At each visit to the doctor, a portion of blood is taken from the patient (if the hematocrit level is 3339% and / or the hemoglobin level is 100130 g / l) and stored for autologous transfusion. The recommended dose of Eprex is 600 IU / kg iv twice a week for 3 weeks before surgery.
Serum ferritin level (or serum iron level) must be determined in all patients before and during treatment with Eprex. If necessary, an additional intake of iron is prescribed.
If there is anemia, its cause must be established before starting Eprex therapy.
Patients in the pre- and postoperative period, not participating in the autologous blood collection program – subcutaneously.
It is recommended to use the drug at a dose of 600 IU / kg per week for 3 weeks prior to surgery (21, 14 and 7 days before surgery), and on the day of surgery. If necessary, when for medical reasons it is necessary to shorten the preoperative period, Eprex can be prescribed daily at a dose of 300 IU / kg for 10 days before surgery, on the day of surgery and for 4 days after surgery.
With a hemoglobin content of less than 130 g / l, it is recommended to prescribe Eprex at a dosage of 300 IU / kg per day. If the hemoglobin content reaches 150 g / l and above, the use of epoetin should be discontinued.
Solution for intravenous or subcutaneous administration, 1000, 2000, 4000 and 10000 IU (optional)
Patients with chronic renal failure, – intravenously, subcutaneously.
IV administration of the drug is preferred for patients on hemodialysis. Patients with chronic renal failure who are not receiving dialysis or are on peritoneal dialysis, the drug can be administered sc.
The optimal level of hemoglobin for adult patients is 100120 g / l, for children – 95110 g / l.
If patients have concomitant clinically severe coronary artery disease or chronic heart failure, the supported hemoglobin level should not exceed the upper limit of the optimal value.
The dose of the drug is 50 IU / kg. In the process of selection, the dose of Eprex increases if the hemoglobin level rises by less than 10 g / l / month.
Adult hemodialysis patients – intravenously.
Treatment is divided into 2 phases – anemia correction phase and maintenance phase.
Anemia correction phase: Eprex is administered at a rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks) by 25 IU / kg 3 times a week until the optimal hemoglobin level is reached.
Maintenance phase: The usual dose to maintain optimal hemoglobin levels is 30100 IU / kg 3 times a week. Available data suggest that patients with severe anemia (hemoglobin content less than 60 g / l) require a higher maintenance dose.
Adult patients undergoing peritoneal dialysis – intravenously, subcutaneously.
Anemia correction phase: the drug is administered at a rate of 50 IU / kg 2 times a week. If necessary, the dose can be gradually increased (not more than 1 time in 4 weeks) by 25 IU / kg 2 times a week until the optimal hemoglobin level is reached.
Maintenance phase: the usual dose to maintain an optimal hemoglobin level is 25-50 IU / kg 2 times a week.
Adult patients with chronic renal failure who do not receive dialysis – intravenously, subcutaneously.
Anemia correction phase: Eprex is administered at a rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks) by 25 IU / kg 3 times a week until the optimal hemoglobin level is reached.
Maintenance phase: the usual dose to maintain an optimal hemoglobin level is 1733 IU / kg 3 times a week.
Children undergoing hemodialysis, regardless of age, are given intravenously.
Anemia correction phase: Eprex is administered at a rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks) by 25 IU / kg 3 times a week until the optimal hemoglobin level is reached.
Maintenance phase: children with a body weight of up to 30 kg usually require a higher maintenance dose than adults and children with a body weight of more than 30 kg. In clinical trials, after the 6-month treatment with Eprex, the following maintenance doses of epoetin alfa were established:
Body weight, kg Dose, IU / kg 3 times a week
Normal maintenance Median
75150100
10306015075
> 3030 10033
Available data suggest that patients with severe anemia (hemoglobin level –
HIV-infected patients receiving zidovudine therapy – intravenously, subcutaneously.
It is recommended to determine the initial level of endogenous erythropoietin in the blood serum before starting treatment with Eprex. Studies have shown that with an erythropoietin level of more than 500 IU / ml, the effect of Eprex therapy is unlikely.
Anemia correction phase: the drug is prescribed at a dose of 100 IU / kg 3 times a week for 8 weeks. If after 8 weeks of therapy it was not possible to achieve a satisfactory effect (for example, to reduce the need for blood transfusions or to increase the level of hemoglobin), the dose can gradually increase (not more than 1 time in 4 weeks) by 50-100 IU / kg 3 times a week. If it was not possible to achieve a satisfactory effect of Eprex therapy at a dose of 300 IU / kg 3 times a week, then a response to further therapy at higher doses is unlikely.
Support phase: after achieving a satisfactory effect in the phase of correction of anemia, the maintenance dose should provide a hematocrit level of 3035%, depending on the change in the dose of zidovudine, the presence of concomitant infectious or inflammatory diseases. With a hematocrit of more than 40%, the administration of Eprex should be discontinued until the hematocrit decreases to 36%. When resuming therapy, the dose of epoetin alpha should be reduced by 25%, followed by adjustment to maintain the required level of hematocrit.
The hemoglobin content in HIV-infected patients receiving zidovudine therapy should not exceed 120 g / l.
Serum ferritin level (or serum iron level) must be determined in all patients before and during treatment with Eprex. If necessary, an additional intake of iron is prescribed.
Side effects of
During therapy with Eprex, the most frequently observed dose-dependent increase in blood pressure or worsening of the course of existing hypertension.
It is necessary to adequately control blood pressure, especially at the beginning of Eprex therapy. Diarrhea, nausea, fever, and vomiting were also very common. Flu-like syndrome was most often observed at the beginning of therapy.
In patients receiving erythropoietin stimulating drugs, an increased frequency of thrombotic vascular events was observed.
Hypersensitivity reactions have been reported, including rash, urticaria, anaphylactic reactions, and angioedema.
Hypertensive crisis with encephalopathy and seizures requiring intensive care was observed during the treatment with Eprex in patients who previously had normal or low blood pressure. It is recommended that you carefully monitor the occurrence of sudden migraine-like headaches.
The following are adverse reactions observed in patients. The frequency of adverse reactions was classified as follows: very frequent (? 10%), frequent (? 1% and <10%), infrequent (? 0.1% and rare (? 0.01% and very rare (unknown frequency). Disorders of the circulatory and lymphatic systems: is very rare – erythropoietin antibody-mediated partial red cell aplasia, thrombocytopenia. Disorders from the nervous system: frequent – headache, cramps, of unknown frequency – cerebrovascular cases (including stroke, including cerebral infarction and intracerebral hemorrhage), transient ischemic attack, hypertensive encephalopathy. Ophthalmic Disorders: of unknown frequency – retinal thrombosis. Disorders from the cardiovascular system: frequent – arterial hypertension (including hypertensive crisis), arterial and venous (including fatal cases) thrombosis and embolism: deep vein thrombosis, arterial thrombosis (including including myocardial infarction) thrombosis of arteriovenous aneurysm shunt, pulmonary embolism. Disorders of the gastrointestinal tract: is very common – nausea, diarrhea, vomiting. Disorders of the respiratory system: frequent – cough, of unknown frequency – nasal congestion. Skin disorders: frequent – rash, of unknown frequency – urticaria, angioedema. Disorders of the musculoskeletal system and connective tissue: frequent – myalgia, arthralgia, bone pain, pain in the limbs. Disorders of metabolism and nutrition: infrequent – hyperkalemia Others: very frequent – fever, frequent – flu-like syndrome, chills, peripheral edema, reactions at the injection site, shunt thrombosis (including a component of dialysis). Drug Interactions There is no data on the interaction of epoetin alfa with other drugs. Drugs that reduce erythropoiesis can weaken the effect of erythropoietin alpha. However, it is possible to influence the concentration of cyclosporine with simultaneous use, therefore, additional control of the level of cyclosporin in the blood serum is required, followed by its correction. You can t dilute and transfer the drug from the original to any other container, you can not enter Eprex in a mixture with other drugs. In patients with metastatic breast cancer who are prescribed concomitant administration of epoetin alpha at a dose of 40,000 IU / ml and trastuzumab at a dose of 6 mg / kg, administration of epoetin alpha does not affect the pharmacokinetics of trastuzumab. Overdose of When an overdose of epoetin alfa occurs, effects reflecting the extreme severity of its pharmacological action. With a very high hemoglobin content, bloodletting is possible. Storage Conditions At 2 to 8 ° C, in a dark place. Do not shake or freeze. Expiration 1.5 years. active substance Epoetin alfa Conditions of release from pharmacies Prescription lekarstvennaja form Solution for and infusions
