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

Auxiliary substances: Albumin solution in terms of dry albumin - 0.75 mg, sodium citrate pentasecvhydrate - 1.74 mg or sodium citrate dihydrate - 1.4328 mg, sodium chloride - 1.752 mg, citric acid monohydrate - 0.0171 mg, water for injections - up to 0.3 ml.

1 syringe (0.5 ml) contains epoetin alfa (human recombinant erythropoietin) as active ingredient 20,000 IU.

Excipients: Albumin solution in terms of dry albumin, 1.25 mg, sodium citrate pentasecvhydrate - 2.9 mg or sodium citrate dihydrate - 2.388 mg, sodium chloride - 2.92 mg, citric acid monohydrate - 0.0285 mg, water for injections - up to 0.5 ml.

1 syringe (0.6 ml) contains epoetin alfa (human recombinant erythropoietin) as active ingredient 20,000 IU.

Excipients: albumin solution in terms of dry albumin - 1.5 mg, sodium citrate pentasecylhydrate - 3,48 mg or sodium citrate dihydrate - 2,8656 mg, sodium chloride - 3,504 mg, citric acid monohydrate - 0.0342 mg, water for injections - up to 0,6 ml.

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 the long-term use of erythropoietin for the therapy of anemic conditions, the formation of neutralizing antibodies to erythropoietin with the development of partial red cell aplasia or without it.

Pharmacokinetics:

With intravenous administration of epoetin alfa in healthy individuals and patients with uremia, the half-life period 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 half-life is 16-24 hours. Bioavailability of epoetin alfa with subcutaneous administration is 25-40%. Do not cumulate.

Indications:

- anemia in patients with chronic renal failure, including those on hemodialysis;

- 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 infected with the human immunodeficiency virus (HIV) caused by zidovudine, with an endogenous erythropoietin concentration of less than 500 IU / ml;

- 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 transferred myocardial infarction and acute disturbance of the cerebralblood circulation (as part of a preship 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 from its use for the mother 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:

Treatment of anemia in patients with chronic renal failure

Adult patients on hemodialysis

Eralfon® is administered subcutaneously or intravenously at the end of a dialysis session. When the method of administration is changed, the drug is administered in the previous dose, then, if necessary, correct the dose (with a subcutaneous route of administration, a dose 20-30% less than for intravenous administration is required to achieve the same therapeutic effect).Treatment with the drug includes two stages:

Correction phase: with subcutaneous administration of the drug, the initial single dose is 30 IU / kg 3 times a week. When administered intravenously, the initial single dose is 50 IU / kg. The correction period lasts until the optimal hemoglobin content is reached (100-120 g / L in adults and 95-110 g / L in children) and hematocrit (30-35%). These indicators need to be monitored weekly.

The following situations are possible:

1) The hematocrit rises from 0.5 to 1.0% per week. In this case, the dose is not changed until optimal values are achieved.

2) The growth rate of hematocrit is less than 0.5% per week. In this case it is necessary to increase the single dose by 1.5 times.

3) The growth rate is more than 1.0% per week. In this case, it is necessary to reduce the single dose of the drug by a factor of 1.5.

4) The hematocrit remains low or decreases. It is necessary to analyze the causes of resistance.

The effectiveness of therapy depends on a properly selected individual treatment regimen.

1. The stage of maintenance therapy: to maintain the hematocrit at 30-35% dose of the drug used in the correction phase should be reduced by 1.5 times. Then the maintenance dose of the drug is selected individually, taking into account the dynamics of hematocrit and hemoglobin.

With subcutaneous administration, a weekly dose can be administered in 1 dose or divided into 3 injections per week. When the condition is stabilized against the background of administration once a week, you can go to the administration once every 2 weeks, in which case an increase in the dose may be necessary.

In children on hemodialysis, the initial single dose is 50 IU / kg 3 times a week, subcutaneously or intravenously. If necessary, a single dose is increased 1 time per 4 weeks by 25 IU / kg until the optimal concentration of hemoglobin is achieved. The maintenance single dose in children weighing less than 10 kg is 75-150 IU / kg (average 100 IU / kg), 10-30 kg - 60-150 IU / kg (average 75 IU / kg), more than 30 kg - 30-100 IU / kg (an average of 33 IU / kg) 3 times a week.

Adult pre-dialysis patients the initial dose is administered subcutaneously or intravenously 3 times 50 IU / kg per week. If necessary, a single dose is increased once every 4 weeks by 25 IU / kg until the optimal concentration of hemoglobin is reached. The maintenance dose is 17-33 IU / kg 3 times a week either subcutaneously or intravenously.

Prevention and treatment of anemia in patients with solid tumors

Before starting treatment, it is recommended that the concentration of endogenous erythropoietin is determined. When the serum erythropoietin concentration is less than 200 IU / ml, the initial single dose of the drug is 150 IU / kg three times a week for intravenous administration.If, after 4 weeks of treatment, the hemoglobin concentration increased and is at least 10 g / l or the amount of reticulocytes increased by more than 40,000 cells / μl above the initial value, the dose of the drug remains the same (150 IU / kg of body weight). If after 4 weeks of treatment the increase in hemoglobin concentration is less than 10 g / L and the increase in the number of reticulocytes is less than 40 000 cells / μl compared to the initial, then during the next 4 weeks the dose is increased to 300 IU / kg of body weight. If, after an additional 4 weeks of treatment with a dose of 300 IU / kg, the hemoglobin concentration increased and is not less than 10 g / L or the amount of reticulocytes increased by more than 40 000 cells / μl, then maintain the existing dose of the drug (300 IU / kg body weight) . If, after 4 weeks of treatment at a dose of 300 IU / kg body weight, the hemoglobin concentration 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 baseline, treatment should be discontinued. If the hemoglobin concentration is increased by more than 20 g / L during the month, the dose of the drug should be reduced by 25%. If the concentration of hemoglobin exceeds 140 g / l,it is necessary to suspend the treatment until the concentration drops below 120 g / l and then continue the administration of the drug at a dose 25% lower than the original.

The drug should be continued for one month after the end of the course of chemotherapy.

The serum ferritin content should be determined in all patients before and during treatment with the drug. If necessary, an iron preparation is additionally prescribed.

Prevention and treatment of anemia in patients with HIV infection

It is recommended to determine the initial content of endogenous erythropoietin in the blood serum before starting treatment with Eralfon®. Studies have shown that with an erythropoietin content of more than 500 IU / ml, the effect of drug therapy is unlikely.

1. Correction phase: the drug is given in a single dose of 100 IU / kg 3 times a week, subcutaneously or intravenously for 8 weeks. If after 8 weeks of therapy a satisfactory effect has not been achieved (for example, to reduce the need for blood transfusions or to increase the hemoglobin concentration), the dose can be incremented (not more often than once every 4 weeks) by 50-100 IU / kg 3 times in a week.If the satisfactory effect of Eralfon® therapy in a single dose of 300 IU / kg was not achieved 3 times a week, then the response to further therapy at higher doses is unlikely.

2. Stage of maintenance therapy: after achieving a satisfactory effect in the phase of correction of anemia, the maintenance dose should provide hematocrit within 30-35%, depending on the change in the dose of zidovudine, the presence of concomitant infectious or inflammatory diseases. With a hematocrit more than 40%, the drug should be discontinued before the 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 serum ferritin content should be determined in all patients before and during treatment with the drug. If necessary, an iron preparation is additionally 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.With a hemoglobin concentration below 100 g / L and an erythropoietin level in the serum below 100 IU / mL, Eralfon® is administered subcutaneously at a starting single dose of 100 IU / kg three times a week. 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 when a weekly dose of 600 IU / kg is reached, further use of epoetin alfa should be discontinued as ineffective.

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

It is recommended to use intravenous administration of the drug. Epoetin alfa should be administered at the end of the blood collection procedure. Before prescribing the drug, all contraindications to collection of autologous blood should be taken into account. Before surgery, Eralfon® should be administered 2 times a week for 3 weeks. At each visit to the doctor, a portion of blood is taken from the patient (if the hematocrit is> 33% and / or the hemoglobin concentration is> 110 g / l) and stored for autologous transfusion.The recommended single dose of Eralfon ® is 600 IU / kg body weight 2 times a week.

The serum ferritin content should be determined in all patients before and during treatment with the drug. If necessary, an iron preparation is additionally prescribed. In the presence of anemia, its cause should be established before the initiation of epoetin alfa therapy. It is necessary to provide an adequate intake of iron into the body as soon as possible, by prescribing an iron preparation at a dose of 200 mg / day (based on elemental iron) and maintaining the intake of iron 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 injection of the drug at a dose of 600 IU / kg body weight per week for 3 weeks preceding surgery (21st, 14th and 7th days before surgery) and on the day of surgery. If necessary, when the preoperative period should be reduced for medical reasons, Eralfon® can be administered 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 concentration in the pre-operative period reaches 150 g / l and above, the use of epoetin alfa 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 prior to the initiation of epoetin alfa therapy to provide an adequate iron depot 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:

Stock

Clamps

Protective cover

Protective cap

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

Procedure for the operation of a syringe with a non-automatic needle protector

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 seizures.

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

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. At a high concentration 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 perform a general blood test (including platelet count), determination of hematocrit and serum ferritin levels. 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 a preoperative increase in hemoglobin concentration may serve as a predisposing 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 response to the drug should be excluded (iron deficiency, folic acid, cyanocobalamin, severe aluminum salt poisoning, concomitant infections, inflammatory processes and trauma, latent bleeding, hemolysis,fibrosis of the bone marrow 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 100ng / 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 insufficiency, it is necessary to control the content of electrolytes in the blood serum.

According to available data, the use of epoetin alfa in pre-dialysis patients can prevent 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 attention 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:

Solution for intravenous and subcutaneous administration 3000 ME, 5000 ME or 20 000 ME.

Packaging:

For 0.3 ml 3000 ME; 0,3 ml of 5000 ME; 0.5 ml or 0.6 ml 20 000 ME in syringes with an additional automatic or non-automatic device to protect the needle after using the syringe or without it.

1 or 3 syringes are placed in a contoured, cellular package with a coating.

1 or 2 contour mesh packages with instructions for use are placed in a pack of cardboard.

The packet is glued on both sides by stickers of self-adhesive material to control the opening.

Storage conditions:

At a temperature of 2 to 8 FROM.

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-000971/10

Date of registration:15.02.2010

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