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

Active ingredient: epoetin alfa recombinant 40,000 ME (336 μg). Excipients: polysorbate 80 - 0.30 mg, sodium chloride - 4.38 mg, sodium hydrogen phosphate dihydrate 2.23 mg, sodium dihydrogen phosphate dihydrate 1.16 mg, glycine 5.00 mg, water for injection up to 1 ml

Description:

A clear, colorless solution.

Pharmacotherapeutic group:hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:

Epoetin-alpha 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, obtained by the genetic engineering method, 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 linkage. 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. The half-life for subcutaneous administration 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 in adult oncological patients with non-myeloid tumors, malignant lymphoma or multiple myeloma (for prevention and treatment).

Within the limits of the pre-opiate program, before extensive surgical intervention in adult 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 content 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 who, for whatever reason, do not have the opportunity to receive adequate preventive antithrombotic therapy.

The use of the preparation Eprex® and all other erythropoietins is contraindicated in patients with partial red cell aplasia receiving therapy with any 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 loss of efficacy, an analysis should be made 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 bone marrow neoplasms.

Pregnancy and lactation:

Use of the drug Eprex® during pregnancy and lactation is only possible if the potential benefit from its use exceeds the possible risk to the fetus or the baby. Erythropoietin is present in breast milk. However, it is not known whether epoetin alfa in breast milk. The drug Eprex® should be used with caution in lactation. It is not recommended to use Eprex® during pregnancy and lactation if a woman participates in an autologous blood collection program.

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. 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.

Adult patients with oncological diseases To treat anemia in adult cancer patients, Eprex® is introduced 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, the original 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 with the initial amount over the next four weeks, the dose is increased to 300 IU / kg body weight three times a week or up to 60000 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 the existing dose of Eprex® is preserved. .

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

If the hemoglobin content is increased by more than 20 g / l within a month or the hemoglobin content reaches 120 g / l, the dose of the drug should be reduced by 25%. If the hemoglobin content exceeds 130 g / l, it is necessary to suspend the treatment until the hemoglobin falls below A 20 g / L and then continue the injection of Eprex® in a dose 25% below the initial dose.

Therapy with Eprex® should be continued for one month after the end of the course of chemotherapy.

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

It is recommended that intravenous way administration of the drug. 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 shelter.

It is recommended that subcutaneous route of administration of the drug at a dose of 600 IU / kg of 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 the preoperative period should be reduced for medical reasons, 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 reaches 150 g / l and higher, epoetin should be discontinued.

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

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

How to make an injection by yourself preparation with the help of filled syringe with the device protection. Syringes are supplied with a needle protection device PROTECS™to prevent injury to the needle after use (this is also indicated on the cardboard bundle)

Figure 1. Pre-filled 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 for correct dosage, shelf life, no damage, as well as the clarity 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 protection device is activated.

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

15. Slowly remove the large grains 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 an antiseptic to the injection site for a few seconds after its completion.

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. The flu-like syndrome was most often observed at the beginning of therapy.

Patients receiving erythropoietin-stimulating drugs had 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 normal or low blood pressure earlier. It is recommended to detect cases of sudden migraine headaches in a timely manner.

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

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

Disturbances from the nervous system: frequent - headache, cramps, unknown frequency - cerebrovascular cases (including stroke, including cerebral infarction and intracerebral haemorrhage), transient ischemic attack, hypertensive encephalopathy,

Ophthalmic disorders: unknown frequency - retinal thrombosis

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

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

Disturbances from the respiratory system: frequent - cough, unknown frequency - obstruction of the respiratory tract (including the upper respiratory tract)

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 Disorders of metabolism and nutrition: nsparse - Hyperkalemia

Other: very frequent - temperature increase, 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, bleeding can be used.

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 with simultaneous application, therefore additional control of the level of cyclosporine in the blood serum is required, followed by its 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 concurrently administered 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®, you need to adequately monitor your blood pressure. The drug 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-stimulating drugs, there was an increase in the frequency of thrombotic vascular events, for example,venous and arterial thrombosis and embolism (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 haemorrhage 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 deaths observed in patients with elevated hemoglobin levels in the case of 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 treated 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 normalizes thereafter without the abolition of therapy; In rare cases, there is an absolute increase in the number of platelets.

Before starting epoetin alfa therapy, and when deciding whether to increase its dose, it is necessary to evaluate and treat other causes of anemia (iron, folic acid, or vitamin B deficiency12, intoxication with aluminum, infection or inflammation, hemorrhage, hemolysis and bone marrow fibrosis of any genesis). 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, of an 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 intakeiron 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 iron supplements (iron iron 200 mg / day orally) for several weeks before starting autologous blood collection 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 encouraged to take an additional intake of iron-containing preparations (elemental iron 200 mg / day orally) throughout the course of epoetin alfa therapy. 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, porphyria exacerbations were observed at the beginning of treatment. 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, after months and years of treatment, 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 a decrease in hemoglobin (1 to 2 g / dl per month) with an increase in the need for transfusions, a count of the number of reticulocytes should be made and examined for the typical reasons for the absence of a response (for example, deficiency of iron, folic acid or vitamin B12, intoxication with aluminum, infection or inflammation, hemorrhage, hemolysis and bone marrow fibrosis of any genesis).If the amount of reticulocytes corrected for anemia (ie, reticulocyte "index") is low (<20,000 / mm³ or <20,000 / μL or <0.5%), and the number of platelets and leukocytes is normal, and if no other cause of the effect is identified, a determination of the level of antibodies to erythropoietin should be made and the possibility of examining 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 stopped immediately. Do not start treatment with any other erythropoietin stimulants, because there is a risk of a cross-reaction. In the presence of indications, patients may undergo appropriate therapy, such as blood transfusion.

Means stimulating erythropoiesis are growth factors that stimulate, in the first place, the formation of erythrocytes. The erythropoietin receptors can be 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 the recombinant erythropoietin preparation should be made on the basis of an assessment of the risk-benefit relationship involving a particular patient, and should take into account the specific clinical situation. Factors to be considered in this evaluation include: the type and stage of the tumor; severity of anemia; life expectancy; conditions in which the patient receives treatment; preferences of the patient.

In patients with oncological disease 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 erythrocytes should be considered.

In patients associated with a program for collecting autologous blood and receiving additional epoetin alfa treatment, all special warnings and special precautions should be taken into account, 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.

Effect on the ability to drive transp. cf. and fur:

There is no information that epoetin alfa affects the ability to drive and other mechanisms.

Form release / dosage:Solution for intravenous and subcutaneous administration, 20000 IU / 0.5 mL and 40,000 IU / 1 mL;

Packaging:

For 0.5 or 1.0 ml in a borosilicate glass syringe (type I). For 1, 2 or 3 pre-filled syringes in a contour mesh box made of PVC.Syringes are supplied with a needle protection device Protecs to prevent injury to the needle after use. 1 contour pack containing 1 syringe or 2 contour packs containing 2 or 3 syringes, with instructions for use in a cardboard box.

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:LS-002439

Date of registration:15.12.2011

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

Manufacturer: & nbsp

CILAG, AG Switzerland

Representation: & nbspJohnson & Johnson LLC Johnson & Johnson LLC Russia

Information update date: & nbsp17.11.2015

Illustrated instructions

Instructions

Eprex® (Eprex®)