Epostim®
The patient's medical documentation should indicate the trade name and batch number of the drug. Replacing the drug Epostim with any biological drug requires agreement with the attending physician. Inappropriate use of the drug by healthy people (for example, as a doping agent) can cause a sharp increase in Hb, accompanied by life-threatening complications from the cardiovascular system. Since anaphylactoid reactions have been reported in isolated cases, the first dose of the drug should be administered under the supervision of a physician. Platelet counts, hematocrit and Hb should be regularly monitored during therapy with Epostim. The drug Epostim should be used with caution in refractory anemia in the presence of blast-formed cells, epilepsy, thrombocytosis and chronic liver failure. Before starting treatment with Epostim, it is necessary to exclude deficiency of vitamin B12 and folic acid, since it reduces the effectiveness of therapy. Iron deficiency should be excluded before starting treatment with Epostim, as well as during the entire period of therapy. If necessary, additional therapy with iron supplements may be prescribed in accordance with clinical recommendations.
Lack of response: The most common causes of incomplete response to treatment with erythropoiesis-stimulating agents are iron deficiency and inflammation (as a result of uremia or advanced metastatic cancer). The following conditions reduce the effectiveness of treatment with drugs that stimulate erythropoiesis: chronic blood loss, bone marrow fibrosis, a sharp increase in aluminum concentration due to hemodialysis, deficiency of folic acid or vitamin BP, hemolysis. If all of these conditions have been excluded and the patient has a sudden decrease in Hb, reticulocytopenia and antibodies to erythropoietin are detected, a bone marrow examination should be performed to exclude partial red cell aplasia (PRCA). If PRCA develops, therapy with Epostim should be discontinued and patients should not be transferred to therapy with other erythropoiesis stimulants. PRCA caused by neutralizing anti-erythropoietin antibodies may be associated with therapy with erythropoiesis stimulants, including therapy with Epostim. It is not recommended to transfer patients to therapy with Epostim if the presence of erythropoietin neutralizing antibodies is suspected or confirmed.
Effect on tumor growth: Epoetins are growth factors that primarily stimulate the formation of red blood cells. Erythropoietin receptors may be present on the surface of various tumor cells. It cannot be ruled out that drugs that stimulate erythropoiesis can stimulate the growth of any type of malignant tumor. In clinical studies of the treatment of anemia in cancer patients with epoetin beta, a statistically significant deterioration in survival rate and tumor progression was not recorded.
Patients with chronic kidney disease or malignant tumors receiving chemotherapy may experience episodes of increased blood pressure and worsening of existing arterial hypertension, especially with a sharp increase in Hb. Increased blood pressure can be eliminated with medication; if there is no effect, a temporary break in treatment with Epostim 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 renal origin. In some patients with chronic kidney disease, a hypertensive crisis with symptoms of encephalopathy may occur even with normal or low blood pressure. Immediate consultation with a physician is necessary, especially if sudden acute migraine-like headaches occur. Increased serum potassium levels have been reported in patients with chronic kidney disease, but a causal relationship with epoetin beta has not been established. During treatment with Epostim, it is recommended to periodically monitor the level of potassium in the blood serum. If hyperkalemia occurs, Epostim should be temporarily discontinued until potassium concentration normalizes. Patients with chronic kidney disease require an increase in the dose of heparin during a hemodialysis session due to an increase in Hb. Occlusion of the dialysis system is possible with inadequate heparinization. Early revision of the shunt and timely prevention of thrombosis (for example, taking acetylsalicylic acid) are recommended. A moderate dose-dependent increase in platelet count within normal limits is possible, especially after intravenous administration of epoetin beta, followed by an independent return to normal values with continued therapy. In the first 8 weeks of therapy, weekly counts of blood cells, especially platelets, are necessary. If Epostim is prescribed before collecting autologous donor blood, you should follow the recommendations for the donation procedure:
- blood can only be taken from patients with a hematocrit ≥33% (or hemoglobin of at least 110 g/L (6.83 mmol/L));
- Particular care should be taken in patients weighing less than 50 kg;
- the volume of blood taken at one time should not exceed 12% of the patient’s estimated blood volume.
It is possible that platelet counts may increase within the normal range in patients receiving epoetin beta before autologous blood donation, so platelet counts should be monitored weekly. Treatment with epoetin beta is interrupted if platelets increase by more than 150x109/l or thrombocytosis. Treatment with Epostim is indicated only for those patients for whom it is most important to avoid homologous blood transfusion, taking into account the risk-benefit ratio of homologous transfusion. A slight increase in the platelet count is possible when preventing anemia in premature newborns (up to 12-14 days), therefore regular platelet monitoring is recommended. The decision to use the drug Epostim in patients with nephrosclerosis who are not receiving dialysis must be made individually, since the possibility of a more rapid deterioration of renal function cannot be completely excluded. In most cases, along with an increase in hemoglobin, the concentration of ferritin in the serum decreases. Therefore, all patients with anemia of renal origin and with a serum ferritin concentration of less than 100 μg/L or transferrin saturation of less than 20% are recommended to take oral iron supplements (Fe2+) at a dose of 200-300 mg/day. Patients with oncological and hematological diseases are treated with iron supplements according to the same principles, while patients with multiple myeloma, non-Hodgkin's lymphomas or chronic lymphocytic leukemia with transferrin saturation less than 25% can be administered 100 mg Fe2+ per week intravenously. For premature infants, oral iron therapy at a dose of 2 mg Fe2+ per day should be prescribed as early as possible (at the latest on the 14th day of life). The dose of iron is adjusted depending on the level of serum ferritin. If it persistently remains at a level below 100 mcg/ml or there are other signs of iron deficiency, the dose of iron supplements should be increased to 5-10 mg/day and therapy should be continued until the signs of iron deficiency are relieved. In patients with moderate anemia before planned major surgery, the drug is prescribed taking into account the benefits of using epoetin beta and the increased risk of thromboembolic complications. In patients preparing to donate blood for subsequent autotransfusion, since they have indications of temporary iron deficiency, oral therapy with iron preparations (Fe2+) at a dose of 300 mg per day should be started simultaneously with therapy with Epostim and continued until ferritin levels normalize. If, despite oral iron replacement therapy, signs of iron deficiency develop (ferritin concentration <20 mcg/L or transferrin saturation <20%), additional intravenous iron supplementation should be considered.
Hypersensitivity to human albumin If there is hypersensitivity to human albumin, which is an excipient in the composition of the drug Epostim, the drug should be discontinued. If continued treatment is necessary, another epoetin beta preparation that does not contain human albumin should be used.
Excipients The sodium content in one dose of the drug 2000 IU, 5000 IU, 10000 IU is 3.66 mg.
Instructions for use of EPOSTIM
Inappropriate use of the drug by healthy people (for example, as doping) can cause a sharp increase in Hb, accompanied by life-threatening complications from the cardiovascular system.
Since anaphylactoid reactions have been reported in isolated cases, the first dose of the drug should be administered under the supervision of a physician.
Platelet counts, hematocrit and Hb should be regularly monitored during Epostim therapy.
Epostim should be used with caution in refractory anemia in the presence of blast-transformed cells, epilepsy, thrombocytosis and chronic liver failure. Before starting treatment with Epostim, it is necessary to exclude deficiency of vitamin B12 and folic acid, since they reduce the effectiveness of therapy. Iron deficiency should be excluded before starting treatment with Epostim, as well as during the entire period of therapy. If necessary, additional therapy with iron supplements may be prescribed in accordance with clinical recommendations.
No effect:
The most common causes of incomplete response to treatment with erythropoiesis-stimulating agents are iron deficiency and inflammation (as a result of uremia or advanced metastatic cancer). The following conditions reduce the effectiveness of treatment with erythropoiesis-stimulating agents:
- chronic blood loss, bone marrow fibrosis, a sharp increase in aluminum concentration due to hemodialysis, deficiency of folic acid or vitamin B12, hemolysis. If all of the above conditions are excluded and the patient experiences a sudden decrease in Hb, reticulocytopenia, and antibodies to erythropoietin are detected, it is necessary to conduct a bone marrow examination to exclude partial red cell aplasia (PRCA). If PRCA develops, therapy with Epostim should be discontinued and patients should not be transferred to therapy with other erythropoiesis stimulants. PRCA caused by neutralizing anti-erythropoietin antibodies may be associated with therapy with erythropoiesis stimulants, including therapy with Epostim. It is not recommended to transfer patients to Epostim therapy if the presence of erythropoietin neutralizing antibodies is suspected or confirmed.
Effect on tumor growth:
Epoetins are growth factors that primarily stimulate the formation of red blood cells. Erythropoietin receptors may be present on the surface of various tumor cells. It cannot be ruled out that drugs that stimulate erythropoiesis can stimulate the growth of any type of malignant tumor. In clinical studies of the treatment of anemia in cancer patients with epoetin beta, a statistically significant deterioration in survival rate and tumor progression was not recorded.
In patients with chronic kidney disease or cancer receiving chemotherapy,
Episodes of increased blood pressure and worsening of existing arterial hypertension may occur, especially with a sharp increase in Hb. Increased blood pressure can be eliminated with medication; if there is no effect, a temporary break in treatment with Epostim 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 renal origin. In some patients with chronic kidney disease, a hypertensive crisis with symptoms of encephalopathy may occur even with normal or low blood pressure. Immediate consultation with a physician is necessary, especially if sudden acute migraine-like headaches occur.
During treatment with Epostim, it is recommended to periodically monitor the level of potassium in the blood serum. If hyperkalemia occurs, Epostim should be temporarily discontinued until potassium concentration normalizes.
Patients with chronic kidney disease require an increase in the dose of heparin during a hemodialysis session due to an increase in Hb. Occlusion of the dialysis system is possible with inadequate heparinization. Early revision of the shunt and timely prevention of thrombosis (for example, taking acetylsalicylic acid) are recommended. A moderate dose-dependent increase in the number of platelets within normal limits is possible, especially after intravenous administration of Epostim, followed by an independent return to normal values with continued therapy. In the first 8 weeks of therapy, weekly counts of formed elements and, especially, platelets are necessary.
If Epostim is prescribed before autologous donor blood collection,
You should follow the recommendations for the donation procedure:
- blood can only be taken from patients with a hematocrit ≥33% (or hemoglobin of at least 110 g/l (6.83 mmol/l));
- special caution should be observed in patients weighing less than 50 kg;
- the volume of blood taken at one time should not exceed 12% of the patient’s estimated blood volume.
It is possible that the platelet count may increase within the normal range in patients receiving Epostim before autologous donor blood collection, so the platelet count should be monitored weekly. Treatment with Epostim is interrupted if platelets increase by more than 150x109/l or with thrombocytosis. Treatment with Epostim is indicated only for those patients for whom it is most important to avoid homologous blood transfusion, taking into account the risk-benefit ratio of homologous transfusion.
Possible slight increase in platelet count when preventing anemia in preterm infants
(up to 12-14 days), therefore regular platelet monitoring is recommended.
The decision to use Epostim in patients with nephrosclerosis who are not receiving dialysis must be made individually, since the possibility of a more rapid deterioration of renal function cannot be completely excluded.
In most cases, along with an increase in hemoglobin, the concentration of ferritin in the serum decreases. Therefore, all patients with anemia of renal origin and with a serum ferritin concentration of less than 100 mcg/l or transferrin saturation of less than 20% are recommended to take oral iron supplements (Fe2+) at a dose of 200-300 mg/day. Patients with oncological and hematological diseases are treated with iron supplements according to the same principles, while patients with multiple myeloma, non-Hodgkin's lymphomas or chronic lymphocytic leukemia with transferrin saturation less than 25% can be administered 100 mg Fe3+ per week intravenously. Premature infants receive oral iron therapy at a dose of 2 mg Fe2+ per day. should be prescribed as early as possible (at the latest on the 14th day of life). The dose of iron is adjusted depending on the level of serum ferritin. If it persistently remains at a level below 100 mcg/ml or there are other signs of iron deficiency, the dose of iron supplements should be increased to 5-10 mg/day and therapy should be continued until the signs of iron deficiency are relieved.
In patients with moderate anemia before planned major surgery, the drug is prescribed taking into account the advantages of using epoetin beta and the increased risk of thromboembolic complications.
In patients preparing to donate blood for subsequent autotransfusion, since they have indications of temporary iron deficiency, oral therapy with iron preparations (Fe2+) at a dose of 300 mg/day should be started simultaneously with Epostim therapy and continued until ferritin levels normalize. If, despite oral iron replacement therapy, signs of iron deficiency develop (ferritin level ≤20 mcg/L or transferrin saturation less than 20%), additional IV iron supplementation should be considered.
Impact on the ability to drive a car and operate machinery
Studies have not been conducted to study the effect of the drug on the ability to drive a car and operate machinery.
Based on the mechanism of action and safety profile, Epostim does not have such an effect.
Epostim, 2000 IU/ml, solution for intravenous and subcutaneous administration, 1 ml, 10 pcs.
Treatment of anemia in patients with chronic renal failure: Epostim is administered intravenously or subcutaneously. For hemodialysis patients, the drug is administered through an arteriovenous shunt at the end of the dialysis session. When changing the method of administration, the drug is administered at the same dose, then the dose is adjusted if necessary (with the subcutaneous route of administration of Epostim, to achieve the same therapeutic effect, a dose of 20-30% less is required than with intravenous administration). Treatment
Epostim includes two stages: 1. Correction stage: For subcutaneous administration of Epostim, the initial single dose is 30 IU/kg 3 times a week. When Epostima is administered intravenously, the initial single dose is 50 IU/kg. The correction period lasts until the optimal level of hemoglobin (100-120 g/l in adults and 95-110 g/l in children) and hematocrit (30-35%) is achieved. These indicators must be monitored weekly. The following situations are possible: 1) Hematocrit increases from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved. 2) The rate of increase in hematocrit is less than 0.5% per week. In this case, it is necessary to increase the single dose by 1.5 times. 3) Growth rate of more than 1.0% per week. In this case, it is necessary to reduce the single dose of the drug by 1.5 times. 4) Hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.
The effectiveness of therapy depends on a correctly selected individual treatment regimen.
2. Stage of maintenance therapy: To maintain the hematocrit at the level of 30-35%, the dose of Epostim achieved at the correction stage should be reduced by 1.5 times. Then the maintenance dose of Epostim is selected individually, taking into account the dynamics of hematocrit and hemoglobin. After stabilization of hemodynamic parameters, it is possible to switch to administering Epostim once every 1-2 weeks.
Prevention and treatment of anemia in patients with solid tumors: Before starting treatment, it is recommended to determine the level of endogenous erythropoietin. When the concentration of erythropoietin in the serum is less than 200 IU/l, the initial dose of Epostim is 150 IU/kg 3 times a week for intravenous administration. When administered subcutaneously, the initial dose of Epostim can be reduced to 100 IU/kg 3 times a week. If there is no response, the dose may be increased to 300 IU/kg 3 times a week. Further increase in dose seems inappropriate. It is not recommended to prescribe erythropoietin to patients with serum endogenous erythropoietin levels above 200 IU/L.
During therapy with Epostim, it is undesirable to increase the hemoglobin level by more than 20 g/l per month or above 140 g/l. If the hemoglobin level increases by more than 20 g/l per month, the dose of Epostim should be reduced by 2 times. If the hemoglobin level exceeds 140 g/L, Epostim is discontinued until the hemoglobin level decreases to ≤120 g/L, after which treatment is resumed at a dose equal to 50% of the dose at which the drug was discontinued.
Prevention and treatment of anemia in patients with HIV infection: Intravenous administration of Epostima at a dose of 100-150 IU/kg 3 times a week is effective in HIV-infected patients receiving zidovudine therapy, provided that the level of endogenous erythropoietin in the patient's serum is less than 500 IU/L, and the dose of zidovudine is less than 4200 mg per week. When administered subcutaneously, the dose of Epostim can be reduced by 1.5 times.
Prevention and treatment of anemia in patients with multiple myeloma, low-grade non-Hodgkin lymphomas and chronic lymphocytic leukemia: In these patients, the advisability of treatment with epoetin beta is determined by inadequate synthesis of endogenous erythropoietin against the background of the development of anemia. When the hemoglobin content is below 100 g/l and serum erythropoietin is below 100 IU/l, Epostim is administered subcutaneously at a starting dose of 100 IU/kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of Epostim is adjusted upward or downward every 3-4 weeks. If after 4 weeks the hemoglobin level increases by 10 g/l, treatment is continued at the same dose. If after 4 weeks hemoglobin increases by less than 10 g/l, the dose may be increased to 300 IU/kg 3 times a week. If after 8 weeks of treatment with Epostim the hemoglobin level has not increased by at least 10 g/l, the development of an effect is unlikely and the drug should be discontinued.
If during 4 weeks of therapy the hemoglobin level increases by more than 20 g/l, the dose of Epostim should be reduced by 2 times. If the hemoglobin level exceeds 140 g/L, treatment with Epostim is suspended until the hemoglobin level decreases to ≤ 130 g/L, after which therapy is continued at a dose equal to 50% of the dose at which therapy was suspended.
For chronic lymphocytic leukemia, treatment with Epostim is continued for up to 4 weeks after the end of chemotherapy. The maximum dose should not exceed 300 IU/kg 3 times a week.
Treatment should only be restarted if the most likely cause of anemia is insufficient production of endogenous erythropoietin.
Prevention and treatment of anemia in patients with rheumatoid arthritis: In patients with rheumatoid arthritis, suppression of the synthesis of endogenous erythropoietin is observed under the influence of increased concentrations of proinflammatory cytokines. Treatment of anemia in these patients is carried out with Epostim when administered subcutaneously at a dose of 50-75 IU/kg 3 times a week. If the hemoglobin level increases by less than 10 g/l after 4 weeks of treatment, the dose of Epostim is increased to 150-200 IU/kg 3 times a week. Further increase in dose seems inappropriate.
Treatment and prevention of anemia in premature infants born with low body weight: For the prevention and treatment of anemia in premature newborns, the administration of Epostim should begin as early as possible, preferably from the 3rd day of life at a dose of 200 IU/kg body weight intravenously or subcutaneously 3 times per week and last no more than 6 weeks. The effect of the drug in premature newborns who have already undergone blood transfusions is somewhat less than in those who have not undergone blood transfusions.
Preparing patients for surgical interventions with planned large blood loss: The recommended dose of Epostim is 450-600 IU/kg once a week subcutaneously for 3 weeks preceding surgery (21, 14 and 7 days before surgery) and on the day of surgery. If it is necessary to reduce the time of preoperative preparation, it is possible to use Epostim at a dose of 300 IU/kg subcutaneously daily 10 days before surgery, on the day of surgery and 4 days after surgery.
If the hemoglobin level in the preoperative period is ≥150 g/l, the use of Epostim should be discontinued.
All patients should receive oral iron supplements at a dose of 200 mg/day throughout the course of treatment. If possible, additional oral administration of iron supplements should be provided before starting Epostim therapy to create an iron depot in the patient's body.
Epostim - reviews
During treatment, it is necessary to monitor blood pressure weekly and perform a complete blood count, including determination of hematocrit, platelets and ferritin. In patients with uremia who are on hemodialysis due to an increase in hematocrit, it is often necessary to increase the dose of heparin; in addition, timely prevention of thrombosis and early revision of the shunt are necessary. In the pre- and postoperative period, hemoglobin should be monitored more often if its initial level was <140 g/l. It must be remembered that epoetin beta does not replace blood transfusion, but reduces the volume and frequency of its use. In patients with controlled arterial hypertension or with thrombotic complications, an increase in the dose of antihypertensive and/or anticoagulant drugs may be required. If a hypertensive crisis develops, urgent measures are taken to provide medical care to the patient; treatment with epoetin beta should be interrupted. When prescribing epoetin beta to patients with liver failure, a slowdown in its metabolism and a pronounced increase in erythropoiesis is possible. The safety of epoetin beta in this group of patients has not been established. We also cannot exclude the possibility of epoetin beta influencing the growth of certain types of tumors, incl. bone marrow tumors. The possibility that a preoperative increase in hemoglobin levels may predispose to the development of thrombotic complications should be considered. Before starting treatment, it is necessary to exclude possible causes of an inadequate reaction to the drug (deficiency of iron, folic acid, cyanocobalamin, severe Al3+ poisoning, concomitant infections, inflammatory processes and injuries, hidden blood loss, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust treatment. In most patients with uremia, cancer and HIV-infected patients, plasma ferritin levels decrease simultaneously with an increase in hematocrit. Ferritin levels must be determined throughout the course of treatment. If it is <100 ng/ml, oral iron replacement therapy is recommended at a rate of 200–300 mg/day (for children 100–200 mg/day). In premature infants, oral iron therapy at a dose of 2 mg/day should be prescribed as early as possible. Patients who donate autologous blood and are in the pre- or postoperative period should also receive adequate therapy with iron supplements in a dose of up to 200 mg/day. In patients with uremia, correction of anemia with epoetin beta may result in improved appetite and increased absorption of potassium and protein. In this regard, periodic adjustment of hemodialysis parameters may be required to maintain the level of urea, creatinine and K + within normal limits. Serum electrolyte levels should also be monitored in these patients. When using epoetin beta in women of reproductive age, menstruation may resume. The patient should be warned about the possibility of pregnancy and the need to use reliable methods of contraception before starting therapy. During the treatment period, until the optimal maintenance dose is established, patients with uremia should avoid engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to an increased risk of increased blood pressure at the beginning of therapy. Considering the possible more pronounced effect of Epostim®, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first 2 weeks, the dose is not changed, the dose/response ratio is assessed. After this, the dose can be reduced or increased according to the scheme presented above.
