Eprex - instructions for use, dose, side effects, contraindications

Active substance: epoetin alfa (recombinant) - 8.4 μg Auxiliary substances: polysorbate 80 - 0.15 mg, sodium chloride - 2.19 mg, sodium dihydrogen phosphate dihydrate - 0.58 mg, sodium hydrogen phosphate dihydrate - 1.12 mg, glycine - 2.50 mg, water for injection - up to 0.5 ml.

For a dosage of 2000 IU / 0.5 ml

Active substance: epoetin alfa (recombinant) 16.8 μg

Excipients: polysorbate 80, 0.15 mg, sodium chloride 2.19 mg, sodium dihydrogen phosphate dihydrate 0.58 mg, sodium hydrogen phosphate dihydrate 1.12 mg, glycine 2.50 mg, water for injection up to 0.5 ml

For dosage 4000 ME / 0.4 ml

Active substance: epoetin alfa (recombinant) - 33.6 μg

Excipients: polysorbate 80 - 0.12 mg, sodium chloride - 1.752 mg, sodium dihydrogen phosphate dihydrate - 0.464 mg, sodium hydrogen phosphate dihydrate - 0.896 mg, glycine - 2.00 mg, water for injection - up to 0.4 ml.

For a dosage of 10,000ME / 1, 0ml

Active substance: epoetin alfa (recombinant) - 84.0 μg

Auxiliary substances: polysorbate 80 - 0.30 mg, sodium chloride - 4.38 mg, sodium dihydrogen phosphate dihydrate - 1.16 mg, sodium hydrogen phosphate dihydrate - 2.24 mg, glycine - 5.00 mg, water for injection - up to 1 , 0 ml.

Description:Clear colorless solution

Pharmacotherapeutic group:hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:

Epoetin alfa is a purified glycoprotein that stimulates erythropoiesis; affects the division and differentiation of progenitor cells. It is produced by mammalian cells with a built-in gene that codes for the synthesis of human erythropoietin. By biological properties epoetin alfa does not differ from human erythropoietin.

The protein fraction is about 58% of the molecular weight and consists of 165 amino acids. Four hydrocarbon chains are attached to the protein by three N- glycosidic bonds and one O-glycosidic bond. The molecular weight of erythropoietin is approximately 32,000 - 40,000 daltons.

After the administration of the drug, the number of erythrocytes, reticulocytes, hemoglobin level and absorption rate ⁵⁹Fe are increasing. The culture of bone marrow cells showed that epoetin alfa selectively stimulates erythropoiesis without affecting leukopoiesis.

The half-life with intravenous administration is 5-6 hours, regardless of the severity of the disease. The volume of distribution is approximately equal to the volume of the plasma. The concentration of the drug in the blood serum with subcutaneous injection is much lower than with intravenous administration. The serum level of the drug rises slowly and reaches a maximum 12-18 hours after subcutaneous injection. Half-life with subcutaneous the introduction is approximately 24 hours. Bioavailability of the drug with subcutaneous injection is about 25%.

Epoetin alfa has a minimal ability to induce the formation of antibodies.

Carcinogenicity studies have not been conducted.

Epoetin alfa does not cause mutations of bacterial genes (Ames test), chromosomal aberrations in mammalian cells, and mutations of locus genes HGPRT.

In one study, there was no difference in the incidence of bone marrow fibrosis in patients who were on dialysis and who received epoetin alfa for three years, and in similar patients who did not receive epoetin alfa.

The teratogenicity of the drug in humans has not been studied, and teratogenic effects of epoetin alfa have not been detected in rats and rabbits.

Indications:

Anemia associated with chronic renal failure in adults and children, including those in patients on 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-op program before extensive surgical intervention 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 autologous collection without the use of epoetin alfa.

Before the extensive operation with the expected blood loss of 900-1800 ml (2-4 units), 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 the recovery of erythropoiesis .

Contraindications:

Eprex® is contraindicated:

with uncontrolled arterial hypertension;

- with increased sensitivity to the components of the drug;

patients with severe pathology of coronary, carotid, cerebral and peripheral vessels, including those who have recently undergone myocardial infarction or acute impairment of cerebral circulation (as part of a preshipter program for collecting blood before an extensive surgical operation);

- during pregnancy and lactation;

- patients, for whatever reason, unable to receive adequate preventive antithrombotic therapy.

- patients with partial red cell aplasia receiving therapy with some erythropoietin

Carefully:

Eprex® should be used with great care in patients with epilepsy, epileptic syndrome (including history) or with diseases that can trigger epileptic activity (eg, CNS infections or brain metastases), thrombocytosis, thrombosis (in anamnesis), obliterating diseases peripheral vascular and other vascular complications, gout, with sickle-cell anemia, iron, B12 or folic-deficient states, coronary heart disease.

If the amount of reticulocytes is less than 20,000 mm³ (or less than 20,000 / μL, or less than 0.5%), the number of platelets and white blood cells is normal and if there are no other reasons for the loss of efficacy, an analysis should be performed; for the presence of antibodies to erythropoietin and bone marrow examination for the diagnosis of partial red cell aplasia.

In case the diagnosis of partial red cell aplasia is suspected, epoetin alfa should be discontinued immediately. Do not prescribe similar drugs in connection with the possibility of cross-reacting antibodies to erythropoietin with other erythropoietins. According to the indications, appropriate therapy (blood transfusion) can be performed. Epoetin alfa, being a growth factor, can have a stimulating effect on certain types of tumors, especially on malignant neoplasms of the bone marrow

Dosing and Administration:

Before use, carefully inspect the solution for visible particles or discoloration. The drug should not be shaken, as this can lead to glycoprotein denaturation and loss of drug activity.Eprex® contains no preservatives, therefore the individual packaging is designed for single use.

Intravenous administration. The duration of the injection is at least 1 -5 minutes. Slower administration is preferable for patients who have an influenza-like syndrome for drug administration. Patients who are on hemodialysis, the drug is injected through the needle into the fistula at the end of the dialysis procedure. To flush the connecting tubes, and also to ensure a satisfactory introduction of the preparation into the circulation system after the injection of the preparation Eprex® 10 ml isotonic sodium chloride solution is introduced.

It is forbidden to administer the drug as an intravenous infusion or to mix it with other drugs. Subcutaneous injections. The maximum volume of one subcutaneous injection should not exceed 1 ml, if it is necessary to introduce large volumes, several injection points should be used. The drug is injected under the skin of the shoulder, thigh, anterior abdominal wall. When the mode of administration is changed, the drug is administered in the previous dose, then the dose is adjusted if necessary (to achieve the same therapeuticeffect with subcutaneous administration requires a dose of 20-30% less than with intravenous administration).

Patients with chronic renal failure.

In patients with chronic renal failure, Eprex® can be used intravenously and subcutaneously. Intravenous administration of the drug is preferred for patients on hemodialysis. In patients with chronic renal failure who are not receiving dialysis, and in patients on peritoneal dialysis, the drug can be administered subcutaneously. The optimal content of hemoglobin for adult patients is 100-120 g / l, for children - 95-110 g / l.

If patients have concomitant clinically severe ischemic heart disease or chronic heart failure, the hemoglobin level maintained should not exceed the upper limit of the optimal value.

The dose of the drug is 50 IU / kg body weight. During the selection process, the dose of Eprex® is increased if the hemoglobin level rises by less than 10 g / l per month.

Adult patients on hemodialysis

In patients on hemodialysis, Eprex® is preferably administered intravenously.

Treatment is divided into two phases - the phase of correction of anemia and the supporting phase.

Anemia correction phase:

Eprex® is administered at a rate of 50 IU / kg body weight three times a week. If necessary, the dose can be increased (no more than once every 4 weeks) by 25 IU / kg body weight three times in

week before reaching the hemoglobin content.

Supportive therapy:

The usual dose to maintain the optimal hemoglobin content is 30-100 IU / kg body weight three times a week. The available data suggest that patients with severe anemia (hemoglobin content less than 60 g / l) require a large maintenance dose.

Adult patients on peritoneal dialysis

Patients on peritoneal dialysis Both intravenous and subcutaneous route of Eprex® are possible.

Anemia correction phase:

The drug is administered at a rate of 50 IU / kg body weight twice a week. If necessary, the dose can be gradually increased by 25 IU / kg body weight (no more often than once every 4 weeks) twice a week until the optimal hemoglobin content is reached.

Support phase:

The usual dose to maintain optimal hemoglobin is 25 to 50 IU / kg body weight twice a week.

Adult patients with chronic renal failure who are not receiving dialysis.

In patients with chronic renal failure who are not receiving dialysis, both intravenous and subcutaneous administration of the preparation Eprex® is possible

Anemia correction phase:

Eprex® is administered at a rate of 50 IU / kg body weight three times a week. If necessary, the dose can be increased (no more than once every 4 weeks) by 25 IU / kg body weight three times a week until the optimal hemoglobin content is reached.

Supporting Phase:

The usual dose for maintaining the optimal hemoglobin content is from 17 to 33 IU / kg body weight three times a week.

Children who are on hemodialysis, regardless of age.

Anemia correction phase:

Eprex® is administered at a rate of 50 IU / kg body weight three times a week intravenously. If necessary, the dose can be increased (no more than once every 4 weeks) by 25 IU / kg body weight three times a week until the optimal hemoglobin content is reached.

Support phase:

Usually, children with a body weight of up to 30 kg require a larger maintenance dose than adults and children weighing more than 30 kg. In clinical trials after six months of therapy with Eprex®, the following maintenance doses of epoetin alfa were established:

Body weight, kg	Dose of the drug IU / kg body weight three times a week
Body weight, kg	Usual supportive	Median
<10	75-150	100
10-30	60-150	75
>30	30-100	33

The available data suggest that patients with severe anemia (hemoglobin less than 68 g / L) require a larger maintenance dose than patients with less severe anemia.

Patients suffering from oncological diseases

To treat anemia in adult oncological patients, Eprex® is administered subcutaneously.

The optimal hemoglobin content should be 100-120 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 three times per week subcutaneously. Alternatively, the initial dose may be 40,000 ME once a week, subcutaneously.

If, after four weeks of treatment, the hemoglobin content increased and is at least 10 g / L or the amount of reticulocytes increased by more than 40,000 cells / μl above the initial dose, the dose of Eprex® remains the same.

If, after four weeks of treatment, an increase in hemoglobin is less than 10 g / L and an increase in the number of reticulocytes is less than 40,000 cells / μl compared tothe initial amount for the next four weeks, the dose is increased to 300 IU / kg body weight three times a week or up to 60,000 ME once a week.

If after an additional four weeks of treatment with a dose of Eprex® 300 IU / kg 3 times a week or 60,000 ME Once a week, the hemoglobin content increased and is not less than 10 g / l or the amount of reticulocytes increased by more than 40,000 cells / μl, then Preserve the existing dose of Eprex®.

If after four weeks of treatment at a dose of 300 IU / kg body weight or 60,000 ME once a week, the content of hemoglobin rises by less than 10 g / l and the increase in the number of reticulocytes is less than 40,000 cells / μl in comparison with the initial amount, treatment should be discontinued.

In the case of an increase in hemoglobin more than 20 g / l for a month or achieving a hemoglobin content of 120 g / l dose of the drug should be reduced by 25%. If the hemoglobin content exceeds 120 g / L, it is necessary to suspend the treatment until the hemoglobin falls below 120 g / L and then continue the injection of Eprex® at a dose 25% below the original level.] Eprex® therapy should continue for one month after the end of the course of chemotherapy.

HIV-infected patients, who receive zidovudine therapy. It is recommended that the initial level of endogenous erythropoietin in the serum be determined before starting treatment with Eprex®. Studies have shown that with an erythropoietin level of more than 500 IU / ml, the effect of therapy with Eprex® is unlikely.

Anemia correction phase:

The drug is given in a dose of 100 IU / kg body weight three times a week subcutaneously or intravenously for eight weeks. If after eight weeks of therapy failed to achieve a satisfactory effect (for example, reduce the need for blood transfusions or achieve an increase in hemoglobin), the dose may gradually increase (not more than once every 4 weeks) by 50-100 IU / kg body weight three times in Week. If the satisfactory effect of therapy with the drug Eprex® at a dose of 300 IU / kg body weight three times a week was not achieved, then the appearance of a response! for further therapy in higher doses is unlikely.

Support phase:

After achieving a satisfactory effect in the anemia correction phase, the maintenance dose should provide a hematocrit in the range of 30-35%, depending on the dose change of zidovudine, the presence concomitant infectious or inflammatory diseases.If the hematocrit is more than 40%, Eprex® should be discontinued before hematocrit is reduced to 36%. When resuming therapy, the dose of epoetin alfa should be reduced by 25% with subsequent adjustment to maintain the required hematocrit.

The hemoglobin content of HIV-infected patients receiving zidovudine therapy should not exceed 120 g / l.

The serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with Eprex®. If necessary, an additional iron intake is prescribed.

Adult patients participating in the program of collection of autologous blood before surgical interventions

It is recommended to use the intravenous route of drug administration, Epoetin alfa should be administered at the end of the blood collection procedure.

Before prescribing Eprex®, all contraindications to 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 33-39% and / or the hemoglobin level is 100-130 g / l) and stored for autologous transfusion.The recommended dose of Eprex® is 600 IU / kg body weight intravenously twice a week for three weeks before surgery. The serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with Eprex®. If necessary, an additional iron intake is prescribed.

In the presence of anemia, its cause should be established before starting therapy with the drug Eprex®.

Patients in the pre- and postoperative period, not participating in the program of collection of autologous blood

It is recommended to use a subcutaneous route of administration of the drug at a dose of 600 IU / kg body weight per week for three weeks preceding surgery (21, 14 and 7 days before surgery) and on the day of surgery. If necessary, when for medical reasons it is necessary to reduce preoperative period, Eprex® can be given daily at a dose of 300 IU / kg body weight for 10 days before surgery, on the day of surgery and for 4 days after surgery. If the hemoglobin content is less than 130 g / l, it is recommended to prescribe Eprex® in a dosage of 300 IU / kg per day. If the hemoglobin content reaches 150 g / l and higher, epoetin should be discontinued.

Instructions for use

When administered subcutaneously Epreks® drug amount administered is usually less than a milliliter (1 ml) in a single injection. Eprex is administered separately, it is not allowed to mix it with other injectable solutions.

Do not shake the syringes with Eprex®. Continued intensive shaking can damage the product. If the product has been shaken violently, do not use it.

How to independently make an injection of the drug with a pre-filled syringe with a protection device. The syringes are equipped with a PROTECS ™ needle guard to prevent the needle from being injured after use (this is also indicated on the cardboard bundle).

Figure 1. Prefilled syringe

1. Remove the syringe from the refrigerator.

The solution must be brought to room temperature. Usually it takes from 15 to 30 minutes. Do not remove the protective cap of the needle until it reaches room temperature.

2.Check the syringe on the correct dosage, the shelf life, the absence of damage, as well as the transparency of the solution and the absence of its freezing.

3. Choose the injection site. Suitable injection sites are the upper thigh area and the anterior abdominal wall, except in the vicinity of the umbilical region. Every day alternate injection sites.

4. Wash your hands. Clean the injection site with a tampon with an antiseptic to disinfect it.

5. Hold the pre-filled syringe behind the syringe body with the needle closed up.

6. Do not hold the syringe behind the tip of the piston, the piston, the protective "wings" of the needle or the protective cap of the needle.

7. Do not pull on the piston.

8. Do not remove the protective cap from the pre-filled syringe until the drug is injected.

9. Remove the package from the syringe by holding the syringe body and pulling the package together without twisting it. Do not press the plunger, touch the needle, or shake the syringe.

10. Do not touch the protective clamps of the needle (shown as asterisks in Figure 1) to prevent the needle guard from being removed.

11. Form a skin fold between the thumb and forefinger. Do not tighten it.

12. Insert the entire length of the needle.

13. Push the piston to the end, to inject the entire solution. Press it effortlessly and evenly, continuing to clamp the skin fold.The PROTECS ™ needle protector is not activated until the full dose is given. You will hear a click when the PROTECS ™ needle guard is activated.

14. With the maximum possible advancement of the piston, remove the needle and straighten the skin fold.

15. Slowly remove the thumb from the piston. Allow the needle to move until completely covered with a protective cap.

16. After the needle is removed from the skin, there may be slight bleeding at the injection site. This is normal. You can press the tampon with the antiseptic to the injection site for a few seconds after it is completed.

17. Place the syringe you used in a safe container. Use only one dose from each syringe. If after the injection the solution remains in the syringe, you still need to throw the syringe, and do not reuse it.

Side effects:

During treatment with Eprex®, the most frequently observed dose-related increase in blood pressure or worsening of the current of the existing arterial hypertension. It is necessary to adequately control blood pressure, especially at the beginning of therapy with the drug Eprex®. Diarrhea, nausea, fever, and vomiting were also very common.

Grippopodobny syndrome was most often observed at the beginning of therapy In patients receiving erythropoietin stimulating drugs, there was an increased incidence of thrombotic vascular events.

Hypersensitivity reactions were noted, including rash, hives, anaphylactic reactions and angioedema. A hypertensive crisis with encephalopathy and convulsions requiring intensive therapy was observed during therapy with Eprex® in patients who had previously had normal or low blood pressure. It is recommended that the sudden occurrence of sudden migraine-like headaches.

The following are undesirable reactions, observed in patients. Frequency The undesired reactions were classified as follows: very frequent (>10%), frequent (>1 % and <10%), infrequent (> 0.1% and <1%), rare (>0,01 % and <0.1%), very rare (<0.01%) and of an unknown frequency.

Disorders from the blood and lymphatic systems: very rare - erythropoietin antibody-mediated partial red cell aplasia, thrombocytopenia

Nervous system disorders: frequent - headache, cramps, unknown frequency - cerebrovascular events (including stroke, including cerebral infarction and cerebral hemorrhage), transient ischemic attack, hypertensive encephalopathy

Ophthalmic Violation: an unknown frequency - retinal thrombosis

Disorders from the cardiovascular systems: frequent - arterial hypertension (including hypertensive crisis), arterial and venous (including fatal cases) thrombosis and embolism: deep vein thrombosis, arterial thrombosis (including myocardial infarction), thrombosis of arteriovenous shunt aneurysm, embolism pulmonary artery

Disorders from the gastrointestinal tract: very frequent - nausea, diarrhea, vomiting

Disturbances from the respiratory system: frequent - cough, unknown frequency - airway obstruction

Skin disorders: frequent - a rash, unknown frequency - urticaria, angioedema

Disturbances from the musculoskeletal system and connective tissue: frequent - myalgia, arthralgia, bone pain, pain in the extremities

Metabolic and nutritional disorders: infrequent - hyperkalemia

Other: very frequent - increase temperature, frequent - flu-like syndrome, chills, peripheral edema, reactions at the injection site, thrombosis of the shunt (including the dialysis component)

Overdose:When an epoetin alfa overdose occurs, effects reflecting the extreme degree of severity of its pharmacological action. With a very high hemoglobin content, it is possible to use bleeding

Interaction:

There are no data on the interaction of epoetin alfa with other drugs. Drugs that reduce erythropoiesis can weaken the action of erythropoietin alfa.

However, it is possible to influence the concentration of cyclosporine when used concomitantly, therefore, an additional one is required. control of the level of cyclosporine in the blood serum with subsequent correction.

Do not dilute and pour the preparation from the original into any other container, you can not inject Eprex® in a mixture with other medicines.

In patients with metastatic breast cancer who are concomitantly taking epoetin alfa subcutaneously at a dosage of 40,000 IU / mL and trastuzumab at a dosage of 6 mg/ kg, the administration of epoetin alfa does not affect the pharmacokinetics of trastuzumab.

Special instructions:

Before and after starting therapy with Eprex®, adequate to control blood pressure. Eprex® should be used with caution in the presence of untreated or poorly controlled hypertension. During therapy with Eprex®, an antihypertensive therapy may be necessary. If it is not possible to reduce pressure with antihypertensive agents, therapy with Eprex® should be discontinued.

Epoetin alfa also should be used with caution in patients with chronic hepatic insufficiency. Safety of epoetin alfa in patients with impaired liver function is not established. Due to reduced metabolism in patients with impaired liver function, the use of epoetin alfa may lead to an increase in erythropoiesis.

In patients receiving erythropoietin stimulant drugs, there was an increase in the frequency of thrombotic vascular events, for example, venous and arterial thromboses and embolisms (including several fatal cases), such as deep vein thrombosis, pulmonary embolism, retinal thrombosis and myocardial infarction.In addition, there were violations of cerebral circulation (including cerebral infarction, intracerebral hemorrhage and transient ischemic attacks). The noted risk of thrombotic vascular events and the benefits of epoetin alfa therapy should be carefully compared, especially in patients with risk factors.

All patients should carefully monitor hemoglobin levels because of the potentially increased risk of thromboembolic events and fatalities observed in patients with elevated hemoglobin levels in the case therapy with Eprex®.

The safety and efficacy of epoetin alfa therapy in patients with background hematologic diseases, such as, for example, hemolytic anemia, sickle cell anemia, thalassemia has not been studied.

When treating with Eprex®, regular monitoring of platelet levels is required, especially during the first 8 weeks, since it is possible to develop a dose-dependent relative increase in the number of platelets, which will normalize thereafter without discontinuing therapy; In rare cases, there is an absolute increase in the number of platelets.

Before the start of epoetin alfa therapy, and when deciding whether to increase its dose, other causes of anemia (iron, folic acid or vitamin B deficiency and iron deficiency, infection with aluminum, infection or inflammation, hemorrhage, haemolysis and bone marrow fibrosis of any origin ). In most cases, the serum levels of serum ferritin are reduced simultaneously with an increase in hematocrit. For an optimal response to epoetin alfa adequate supplies of iron should be provided, with the introduction; if necessary, additional intake of iron-containing preparations:

- Patients with chronic renal insufficiency are recommended an additional intake of iron-containing preparations (elementary iron 200-300 mg / day orally in adults and 100-200 mg / day orally in children) in the case of serum ferritin level below 100 ng / ml.

- Patients with oncological disease are recommended an additional intake of iron-containing preparations (elementary iron 200-300 mg / day orally) in case of transferrin saturation less than 20%.

- Patients in the autologous blood collection program are encouraged to take an additionaliron preparations (elemental iron 200 mg / day orally) for several weeks before starting the collection of autologous blood, in order to achieve large iron stores before starting epoetin alfa therapy, and throughout the course of epoetin alfa therapy.

- Patients who are assigned to a large planned orthopedic operation are advised to take an additional intake of iron-containing preparations (elementary iron 200 mg / day orally) throughout the course of epoetin alfa. If possible, the use of preparations containing iron should be started before the initiation of epoetin alfa therapy to create sufficient iron stores.

Very rarely in patients treated with epoetin alfa; At the beginning of treatment, porphyria exacerbations were observed. In patients with porphyria epoetin alfa use with caution.

The drugs that stimulate 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 with the approval of the attending physician.

In patients with chronic renal insufficiency treated with subcutaneous administration of epoetin, very rarely, months and years later, antibody-mediated true red cell aplasia (IEA) was noted.

Occasionally, cases of this disease were also observed in patients with hepatitis C treated with interferon and ribavirin, when erythropoietin was treated with stimulants simultaneously, and therefore they are not approved for the treatment of anemia associated with hepatitis C.

In patients with chronic renal failure, who experience a sudden decrease in efficacy, determined by the reduction of hemoglobin (1-2 g / dl per month), with an increase in the need for transfusions, the number of reticulocytes should be counted and examined for typical causes of non-response (eg iron deficiency, folate or vitamin B deficiency and, aluminum intoxication, infection or inflammation, hemorrhage, hemolysis and fibrosis bone marrow of any genesis). If the amount of reticulocytes corrected for anemia (ie, reticulocyte "index") is low (<20,000 / mm³ or <20000 / μL or <0.5%), and the number of platelets and leukocytes is normal, and if no other causes of the effect decrease are identified, the level of antibodies to erythropoietin should be determined and the possibility of studying the bone marrow for the diagnosis of IEA should be considered.

If there is a suspicion of IEA mediated by anti-erythropoietin antibodies, epoetin alfa therapy should be discontinued immediately. Do not start treatment with any other erythropoietin stimulants, because there is a risk of a cross-reaction. If there is evidence, patients can receive appropriate therapy, such as blood transfusion. Patients with chronic renal insufficiency against the background of treatment with Eprex®, it is necessary to regularly check 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 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 hemoglobin level maintained should not exceed the upper limit of this hemoglobin level range. The level of hemoglobin, 130 g / l [or higher, can lead to an increased risk of cardiovascular events, including death. Patients with chronic renal failure and 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 information available at the moment, the use of epoetin alfa in patients before starting dialysis (terminal stage of renal failure) does not increase the rate of progression of renal failure.

Patients on hemodialysis had thrombotic shunts, especially in patients with a tendency to hypotension, or with complications from arteriovenous fistulas (eg, stenosis, aneurysms, etc.). These patients recommend an early check of the shunt and prevention of thrombosis by introducing, for example, acetylsalicylic acid.

In some cases, hyperkalemia was observed, although its cause-and-effect relationship with the use of the drug was not established. In patients with chronic renal failure, serum electrolytes should be monitored. If serum potassium levels are elevated or increased, then in addition to proper treatment of hyperkalemia, consideration should be given to stopping epoetin alfa administration until the serum potassium level is adjusted.

Due to the increase in hematocrit against the background of therapy with Eprex®, patients on hemodialysis may require an increase in the dose of heparin, otherwise it is possible occlusion of the dialysis system.

In some patients with chronic renal failure against the background of treatment with Eprex®, the resumption of menstruation was noted. The possibility of pregnancy and the need for contraceptive measures should be discussed with the patient before starting therapy.

Means stimulating erythropoiesis are growth factors that stimulate, in first of all, the formation of red blood cells. The erythropoietin receptors may expressed on the surface of many tumor cells.As with all growth factors, there are doubts that the agents that stimulate erythropoiesis can stimulate tumor growth. From the point of view of the foregoing, the decision to administer a recombinant erythropoietin preparation should be taken; based on an assessment of the relationship between risk and benefit with the participation of a specific patient, and should take into account a specific clinical situation. Factors to be considered in this evaluation include: the type and stage of the tumor; severity of anemia; the expected life expectancy; conditions in which the patient receives treatment; preferences patient.

In patients with oncological disease receiving chemotherapy, in assessing fitness of therapy epoetics of alpha (especially in patients at risk of transfusion) should take into account a delay of 2-3 weeks between administration of funds, stimulating erythropoiesis and the appearance of stimuli with erythropoietin erythrocytes.

If the HIV-infected patient does not respond or the response to epoetin alfa therapy is insufficient, consider other possible causes of anemia, including iron deficiency.

In patients associated with the autologous blood collection program and receiving additional epoetin alfa treatment, all special warnings and special precautionary measures should be considered, in particular - the mandatory completion of the volume.

In the pre- and postoperative period, the proper standards for monitoring blood levels should always be observed.

Patients assigned to a large planned orthopedic operation should undergo antithrombotic prophylaxis, as surgical patients may experience thrombotic and vascular events, especially in patients with background cardiovascular disease. In addition, special precautions should be taken in patients with a predisposition to thrombotic complications. Moreover, in patients with baseline hemoglobin> 130 g / l (8.1 mmol / L), the possibility that epoetin alfa treatment may be associated with an increased risk of postoperative thrombotic vascular events can not be ruled out. Therefore, in patients with baseline hemoglobin> 130 g / l (8.1 mmol / l) epoetin alfa is not recommended.

Form release / dosage:

Solution for intravenous and subcutaneous administration of 1000 IU / 0.5 mL, 2000 IU / 0.5 mL, 4000 IU / 0.4 mL, 10,000 IU / 1 mL

Packaging:

For 0.4 ml, 0.5 ml or 1 ml in a borosilicate glass syringe (type I).

3 pre-filled syringes are put in a contour mesh box made of PVC

For 2 contour-cell packs containing 3 syringes, with instruction for use put in a cardboard box, or

For 0.4 ml, 0.5 ml or 1 ml in a borosilicate glass syringe (type I).

The syringes are provided with a PROTECS ™ needle guard to prevent needle injury after use.

3 pre-filled syringes are put in a contour mesh box made of PVC

2 contour-cell packs containing 3 syringes are placed in a cardboard box with instructions for use.

Storage conditions:

At a temperature of 2 to 8 ° C, in a dark place. Do not shake and do not freeze.

Keep out of the reach of children.

Shelf life:

1,5 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N013583 / 01

Date of registration:17.08.2007

The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia

Manufacturer: & nbsp

Vetter Pharma-Fertigung, GmbH & Co. KG. KG Germany

CILAG, AG Switzerland

Information update date: & nbsp23.11.2015

Illustrated instructions

Instructions

Eprex® (Eprex®)