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

Excipients: albumin solution, sodium citrate pentasquihydrate or sodium citrate dihydrate, sodium chloride, citric acid monohydrate, water for injection.

Description:clear colorless liquid

Pharmacotherapeutic group:hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:

Epoetin alfa-glycoprotein, specifically stimulating erythropoiesis, activates the mitosis and maturation of erythrocytes from the progenitor cells of the erythrocyte series. Recombinant epoetin alfa is synthesized in mammalian cells in which a gene encoding human erythropoietin is inserted. By its composition, biological and immunological properties epoetin alfa is identical to natural human erythropoietin. The introduction of epoetin alfa leads to an increase in hemoglobin and hematocrit levels, an improvement in the blood supply of tissues and the work of the heart. The most pronounced effect of the use of epoetin alfa is observed in anemia caused by chronic renal insufficiency. In very rare cases, with prolonged use of erythropoietin for the therapy of anemic conditions, the formation of neutralizing antibodies to erythropoietin may be observed with the development of partial red cell aplasia or without it.

Pharmacokinetics:

With intravenous administration of epoetin alfa in healthy individuals and with uremia, the half-life is 5-6 hours. With subcutaneous administration of epoetin alfa, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 18 hours after administration, the elimination half-life is 16-24 hours. Bioavailability of epoetin alfa with subcutaneous administration is 25-40 %. Do not cumulate.

Indications:

- prevention and treatment of anemia in patients with solid tumors, whose anemia was the result of antitumor therapy;

- prevention and treatment of anemia in patients with myeloma, low-grade non-Hodgkin's lymphomas, chronic lymphocytic leukemia;

- in the context 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 carrying out extensive surgery with the expected blood loss of 900-1800 ml in adult patients without anemia or with mild to moderate anemia (hemoglobin concentration 100-130 g / l) to reduce the need for allogeneic blood transfusions and facilitate the recovery of erythropoiesis.

Contraindications:

- hypersensitivity to the drug or its components;

- partial red cell aplasia after previous therapy with an erythropoietin;

- uncontrolled arterial hypertension;

- impossibility of conducting adequate anticoagulant therapy;

- with severe occlusive diseases of the coronary, carotid, cerebral and peripheral arteries and their consequences, including acute and recently suffered myocardial infarction and acute impairment of cerebral circulation (within the limits of the pre-surgical blood collection program before surgical operations).

Carefully:

Malignant neoplasms, epileptic syndrome (including in the presence of anamnesis), thrombocytosis, thrombosis (in the anamnesis), sickle cell anemia, iron, B12- or folic deficiency states, porphyria, chronic hepatic insufficiency.

Pregnancy and lactation:

Since there is insufficient experience of using erythropoietin in pregnancy and lactation in humans, epoetin alfa should be prescribed only if the expected benefits for the mother from its use exceed the possible risk to the fetus. It is not known whether epoetin alfa with breast milk, so when treating the drug Eralfon® it is necessary to stop breastfeeding.

Dosing and Administration:

Prevention and treatment of anemia in patients with solid tumors

To treat anemia in cancer patients, it is recommended to administer Eralfon® subcutaneously. The optimal concentration of hemoglobin should be 120 g / l in men and women and should not be exceeded.

Eralfon® can be given to patients with symptomatic anemia, for the prevention of anemia in patients receiving chemotherapy and having an initial low hemoglobin concentration during the first course of chemotherapy (for example, a baseline hemoglobin content of 110-130 g / l or a decrease of more than 20 g / l with initial hemoglobin over 130 g / l).

Before starting treatment, it is recommended that the concentration of endogenous erythropoietin is determined. When the concentration of erythropoietin in the blood serum is less than 200 IU / ml, the initial single dose of the drug is 150 IU / kg intravenously, 3 times a week, subcutaneously. Alternatively, the initial dose may be 40,000 ME once a week, subcutaneously.

If, after four weeks of treatment, the hemoglobin concentration has increased and is at least 10 g / L, or the number of reticulocytes has increased by more than 40,000 cells / μl over the original amount, the dose of Eralfona® remains unchanged.

If, after four weeks of treatment, an increase in hemoglobin concentration is less than 10 g / L and an increase in the number of reticulocytes is less than 40,000 cells / μl compared to the initial amount, then over 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 Eralfon ® 300 IU / kg 3 times a week or 60 000 ME Once a week the concentration of hemoglobin increased and is not less than 10 g / l, or the number of reticulocytes increased by more than 40 000 cells / μl, then maintain the existing dose of Eralfona ®.

If after four weeks of treatment at a dose of 300 IU / kg body weight or 60 000 ME once a week the concentration 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.

If the hemoglobin concentration is increased by more than 20 g / l during the month or the hemoglobin concentration reaches 120 g / l, the dose of the drug should be reduced by 25%. If the hemoglobin content exceeds 120 g / l, the treatment should be suspended until the hemoglobin concentration is lower than 120 g / L and then the administration of Eralfon® at a dose 25% below the original dose is continued.

Therapy with Eralfon® should continue for one month after the end of the course of chemotherapy.

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

Prevention and treatment of anemia in patients with multiple myeloma, non-Hodgkin's lymphoma, low-grade and chronic lymphocytic leukemia

In these patients, the expediency of epoetin alfa treatment is due to an inadequate synthesis of endogenous erythropoietin against the background of anemia. When hemoglobin concentration below 100 g / l and serum erythropoietin below 100 IU / ml Eralfon® administered subcutaneously in the starting single dose of 100 IU / kg three times a week or once a week week dose. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of the drug is adjusted upwards or downwards every 3-4 weeks. If the increase in hemoglobin concentration is not observed after reaching a weekly dose of 600 IU / kg, then the use of epoetin alfa should be abolished as ineffective.

Adult patients participating in the autologous blood collection program 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 Eralfona®, all contraindications to collection of autologous blood should be taken into account. Before surgery, Eralfon® should be administered twice a week for three weeks. At each visit to the doctor, the patient receives a blood sample (if hematocrit> 33% and / or hemoglobin> 110 g / l) and stored for autologous transfusion. The recommended dose of Eralfona® is 600 IU / kg of body weight intravenously twice a week. The serum ferritin level (or serum iron level) should be determined in all patients before and during the treatment with Eralfon®. If necessary, an additional iron intake is prescribed.

In the presence of anemia, its cause should be established before the start of therapy with Eralfon ®. It is necessary to ensure an adequate intake of iron in the body as soon as possible, by prescribing an iron preparation at a dose of 200 mg / day (based on elemental iron) and maintaining iron intake at this level throughout the course of therapy.

Patients in the pre- and postoperative period who do not participate in the autologous blood collection program.

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 the preoperative period should be reduced for medical reasons, Eralfon® can be given daily at a dose of 300 IU / kg of body weight for 10 days before the operation, on the day of the operation and for 4 days after the operation. If the hemoglobin content in the pre-operative period reaches 150 g / l and above, the use of epoetin should be discontinued. Before starting epoetin alfa therapy, you need to make sure that the patients do not have iron deficiency.

All patients should receive an adequate amount of iron (200 mg / day based on elemental iron) throughout the course of treatment. If possible, additional iron should be provided before the therapy with Eralfon® begins to provide adequate iron stores in the patient's body.

Instructions for use

The device and the order of operation of the syringe with the automatic device of protection of a needle

1. Before injection

2. After the injection

Components:

1. Stock

2. Clamps

3. Protective cover

4. Protective cap

5. Needle

After completion of the injection, the needle and syringe will move back to the protective device.

Attention! Avoid contact with the clamps during the preparation of the syringe! The device is activated by pressing the rod to the terminals.

Inspect the pre-filled glass syringe with the protective device carefully. Remove the protective cap from the needle.

Carry out the injection according to the standard procedure.

Push the rod with your thumb and hold until the entire dose of the drug has been injected. The protective device is not activated until the entire dose of the drug has been injected.

Remove the needle, release the stem, allow the protective casing to move forward until the needle is completely protected and locked in place.

Operating procedure syringe with non-automatic needle guard

Carry out the injection according to the standard procedure. Attention! When carrying out the injection, keep your fingers on the protective cover to prevent premature activation of the protective device.

After the injection, move the protective device along the needle. An audible click will indicate the correctness of the action.During the entire procedure, the fingers should be behind the needle.

Side effects:

At the beginning of treatment may be noted influenza-like symptoms: dizziness, drowsiness, febrile condition, headache, myalgia, arthralgia.

From the cardiovascular system: dose-dependent increase in blood pressure, worsening of the course of arterial hypertension (most often in patients with chronic renal failure), in some cases - hypertensive crisis, a sharp increase in blood pressure with symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic surrogates.

From the hematopoiesis: thrombocytosis, in some cases - thrombosis shunt or arteriovenous fistula (in patients on hemodialysis with a tendency to arterial hypotension or an aneurysm, stenosis, etc.), aplasia of the erythrocyte sprout.

Allergic reactions: skin rash (mild or moderate), eczema, urticaria, itching, angioedema.^-

Local reactions: hyperemia, burning, mild or moderate soreness at the injection site (most often occur with subcutaneous injection).

From the laboratory indicators: a decrease in serum ferritin, with uremia - hyperkalemia, hyperphosphataemia.

Other: complications associated with impaired breathing or with a decrease in blood pressure, immune reactions (induction of antibody formation), exacerbation of porphyria.

Overdose:

Symptoms: increased side effects.

Treatment: symptomatic. With a high level of hemoglobin - bleeding.

Interaction:

Reduces the concentration of cyclosporine due to an increase in the degree of its binding to erythrocytes (there may be a need for correction of the dose of cyclosporine). Pharmaceutically incompatible with solutions of other drugs

Special instructions:

During treatment, it is necessary to monitor blood pressure weekly and conduct a general blood test (including platelets, hematocrit, ferritin). In the pre- and postoperative period, the concentration of hemoglobin should be monitored more often if the initial concentration is less than 140 g / l. It must be remembered that epoetin alfa in the treatment of anemia does not replace blood transfusion, but reduces the need for its reuse.

In patients with controlled arterial hypertension or thrombotic complications, an increase in the dose of antihypertensive drugs and / or anticoagulants, respectively, may be required. When appointing patients with hepatic insufficiency, it is possible to slow the metabolism of epoetin alfa and a marked increase in erythropoiesis. The safety of the drug in this category of patients is not established. Although the drug stimulates erythropoiesis, it is impossible to completely exclude the possibility of the effect of epoetin alfa on the growth of some types of tumors, incl. bone marrow.

It should be taken into account the possibility that preoperative hemoglobin elevation can serve as a contributing factor to the development of thrombotic complications. Before the planned surgical intervention, patients should receive adequate preventive antiplatelet therapy. In the pre- and postoperative period, the drug is not recommended for patients with a baseline hemoglobin level of more than 150 g / l.

In adult patients with chronic renal failure, clinically severe coronary heart disease or chronic heart failure, the hemoglobin concentration should not exceed 100-120 g / l.

Before starting treatment, the possible causes of inadequate reaction to the drug should be excluded (iron, folic acid, cyanocobalamin deficiency, heavy aluminum salt poisoning, concurrent infections, inflammatory processes and trauma, latent bleeding, hemolysis, bone marrow fibrosis of various etiologies) and, if necessary, adjust the treatment .

Before the start of treatment should assess the iron stores in the body. In most patients with chronic renal failure, oncological and HIV-infected patients, the concentration of ferritin in the plasma decreases simultaneously with an increase in the level of hematocrit. The concentration of ferritin should be determined throughout the course of treatment. If it is less than 100 ng / ml, substitution therapy with iron for oral administration is recommended at the rate of 200-300 mg / day (100-200 mg / day for children). For preterm infants, oral iron therapy at a dose of 2 mg / day should be given as soon as possible. Patients who take autologous blood and are in the pre- or postoperative period should also receive an adequate amount of iron inside at a dose of 200 mg / day.

In patients with chronic renal failure, correction of anemia can cause an improvement in appetite and an increase in absorption of potassium and proteins. Periodic correction of dialysis parameters may be required to maintain the concentration of urea, creatinine and potassium within normal limits.

In patients with chronic renal failure, it is necessary to monitor the level of electrolytes in the blood serum.

According to available data, the use of epoetin alfa in pre-patients does not accelerate the progression of chronic renal failure. Because of the increase in hematocrit, it is often necessary to increase the dose of heparin during hemodialysis. With inadequate heparinization, blockage of the dialysis system, thrombosis of vascular access, especially in patients with a tendency to hypotension or with complications of arteriovenous fistula (stenosis, aneurysm, etc.) is possible. In such patients, prevention of thrombosis is recommended.

When women are of reproductive age with anemia against a background of chronic renal failure, it is possible to resume menstruation. The patient should be warned about the possibility of pregnancy and the need for reliable methods of contraception before the start of therapy.In experimental studies on rats and rabbits, there was no teratogenic effect when administered intravenously at doses up to 500 U / kg body weight per day; in higher doses, a weak, statistically insignificant decrease in fertility was noted.

During the treatment period, before the optimal maintenance dose is established, patients with chronic renal insufficiency should be careful when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions (increased risk of high blood pressure at the beginning of therapy).

Given the possible more pronounced effect of the drug, its dose should not exceed the dose of recombinant erythropoietin used in the previous course of treatment. During the first two weeks, the dose is not changed, the dose / response ratio is evaluated. After that, the dose can be reduced or increased (see section "Method of administration and dose").

Form release / dosage:

The solution for intravenous and subcutaneous administration is 40,000 IU / ml.

Packaging:

For 0.3 ml (12,000 IU) and 1.0 ml (40,000 IU) per syringe with an additional automatic or non-automatic device forprotection of the needle after using the syringe or without it.

1, 2 or 3 syringes in a contoured, coated cell.

1 contour mesh package for 1, 2 or 3 syringes or 2 contour packs for 2 or 3 syringes together with instructions for use in a pack of cardboard with stickers to control the opening.

Storage conditions:

At a temperature of 2 to 8 ° C.

Keep out of the reach of children.

Shelf life:

2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008793/10

Date of registration:26.08.2010

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

FarmSirma Soteks, ZAO Russia

Information update date: & nbsp18.11.2015