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

Active substanceEpoetin alfaEpoetin alfa

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FarmSirma Soteks, ZAO Russia

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FarmSirma Soteks, ZAO Russia

Eralfon®

solution in / in PC

FarmSirma Soteks, ZAO Russia

Dosage form: & nbspsolution for intravenous and subcutaneous administration

Composition:

1 ampoule (1 ml) contains as active substance Epoetin alfa (REPOETIN-SP - recombinant human erythropoietin) 1000 ME, 2000 ME, 4000 ME or 10 000 ME

1 syringe (0.3 ml) contains, as an active substance, Epoetin alfa (REPOETHIN-SP - recombinant human erythropoietin) 1000 ME or 2000 ME

1 syringe (0.5 ml) contains, as an active substance, Epoetin alfa (REPOETHIN-SP - recombinant human erythropoietin 2000 ME

1 syringe (0.4 ml) contains as active substance Epoetin alfa (REPOETIN-SP - recombinant human erythropoietin) 4000 ME

1 syringe (0.6 ml) contains as active substance Epoetin alfa (REPOETIN-SP - recombinant human erythropoietin) 10 000 ME

1 syringe (1 ml) contains as active substance Epoetin alfa (REPOETIN-SP - recombinant human erythropoietin) 10 000 ME

Excipients: albumin solution, sodium citrate pentasecovihydrate 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 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 of 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:

- 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 level 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 patients with rheumatoid arthritis;

- treatment and prevention of anemia in premature infants born with a low body weight of up to 1.5 kg;

- in the context of the pre-op program before the extensive surgicalintervention 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 level 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 coronary, carotid, cerebral and peripheral arteries and their consequences, including acute and recently transferred myocardial infarction and acute cerebrovascular accident (within the limits of the pre-collection program of blood collection beforesurgical 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 exceed the possible risk to the fetus and the mother. It is not known whether epoetin alfa with breast milk.

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 mode of administration is changed, the drug is administered in the previous dose, then the dose is corrected if necessary (with a subcutaneous route of administration, the dose is 20-30% less than for intravenous administration to achieve the same therapeutic effect). Treatment with the drug includes two stages:

1. Correction phase: when administered subcutaneously, the initial single dose is 30 IU / kg 3 times a week. With intravenous administration of the drug, the initial single dose is 50 IU / kg 3 times a week. The correction period lasts until the optimal hemoglobin level 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 before increasing the dose of the drug.

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

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 levels.

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

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

The maintenance dose is 17-33 U / kg 3 times a week.

Prevention and treatment of anemia in patients with solid tumors

Before the start of treatment it is recommended to carry out a determination of the level of endogenous erythropoietin. When the serum erythropoietin concentration is less than 200 IU / ml, the initial dose of the drug is 150 IU / kg 3 times a week for intravenous administration. If, after 4 weeks of treatment, the hemoglobin level increased and is at least 10 g / l or the amount of reticulocytes increased by more than 40,000 cells / μl from the baseline, the dose remains the same (150 IU / kg body weight 3 times a week).

If, after 4 weeks of treatment, an increase in hemoglobin level is less than 10 g / L and an increase in the number of reticulocytes is less than 40,000 cells / μl compared to baseline, then over the next 4 weeks the dose is increased to 300 IU / kg body weight 3 times a week . If, after an additional 4 weeks of treatment with a dose of 300 IU / kg, the hemoglobin level 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 3 times a week). If after 4 weeks of treatment at a dose of 300 IU / kg body weight the hemoglobin level rises by less than 10 g / l and the increase in the number of reticulocytes is less than 40,000 cells / μl compared to baseline, treatment should be discontinued. If the hemoglobin level is increased by more than 20 g / L during the month, the dose of the drug should be reduced by 25%. If the hemoglobin level exceeds 140 g / l, it is necessary to suspend the treatment until the hemoglobin level drops below 120 g / l and then continue the drug administration at a dose 25% below the initial level.

The drug should be continued 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 drug treatment. If necessary, an additional iron intake is prescribed.

Prevention and treatment of anemia the of patients with HIV infection

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

1. Correction phase: the drug is given at a dose of 100 IU / kg 3 times per 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 level), the dose can be incremented (not more often than once every 4 weeks) by 50-100 IU / kg 3 times a week. If the satisfactory effect of therapy with Eralfon® at a dose of 300 IU / kg is not achieved 3 times a week, then the response to further therapy at higher doses is unlikely.

2. Stage of maintenance therapy: after reachinga satisfactory effect in anemia correction phase maintenance dose should provide a hematocrit level in the range of 30-35% depending on the dose of zidovudine changes, presence of concomitant infections or inflammatory diseases. With a hematocrit more than 40%, the drug should be discontinued until the hematocrit is reduced to 36%. When resuming epoetin alfa therapy dose should be reduced by 25% with subsequent adjustments to maintain the desired level of hematocrit. The serum ferritin level (or serum iron level) should be determined in all patients before and during drug treatment. If necessary, an additional iron intake 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 appropriateness of treatment with epoetin alfa is due to inadequate synthesis of endogenous erythropoietin in the background of anemia.

When the hemoglobin level below 100 g / l and serum erythropoietin below 100 IU / ml is administered subcutaneously into Eralfon® startrvoy 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 no increase in hemoglobin is observed when a weekly dose of 600 IU / kg is reached, further use of epoetin alfa should be discontinued as ineffective.

Prevention and treatment of anemia in patients with rheumatoid arthritis

In patients with rheumatoid arthritis, the synthesis of endogenous erythropoietin is suppressed under the influence of an increased concentration of anti-inflammatory cytokines. Treatment of anemia in these patients is carried out with a drug administered subcutaneously at a dose of 50-75 IU / kg 3 times a week. When the hemoglobin level is increased by less than 10 g / l after 4 weeks of treatment, the dose of the drug is increased to 150-200 IU / kg 3 times a week. Further increase in the dose seems inappropriate.

Treatment and prevention of anemia in premature babies born with low body weight

Eralfon ® is administered subcutaneously in a dose of 200 IU / kg three times a week, starting from the 6th day of life, to the achievement of hemoglobin and hematocrit targets, but no more than 6 weeks.

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, the patient receives a blood sample (if hematocrit> 33% and / or hemoglobin> 110 g / l) and stored for autologous transfusion. The recommended dose of Eralfon ® is 600 IU / kg body weight 2 times a week. The serum ferritin level (or serum iron level) should be determined in all patients before and during drug treatment. If necessary, an additional iron intake is 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 administering an iron preparation orally at a dose of 200 mg / day (based on ferrous 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 level 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 (orally 200 mg / day based on ferrous iron) throughout the course of treatment. If possible, an additional oral intake of iron should be provided before epoetin alfa therapy begins to provide an adequate depot of iron in the patient's body.

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

1. Before injection

2. After injection

Components:

1. Stock

2. Clamps

3. Protective cover

4.Protective cap

5. Needle

6. Pre-filled glass syringe

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.

Carefully inspect the pre-filled glass syringe with the protective device. 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 introduced

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: a dose-dependent increase in blood pressure, worsening of arterial hypertension (most often in patients with chronic renal failure patients), in some cases - a 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, - shunt thrombosis or arteriovenous fistula (in hemodialysis patients with a tendency to hypotension or aneurysm, stenosis, etc.), germ cell aplasia erythrocyte.

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, hemoglobin levels should be monitored more often if the initial level 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.

Patients with controlled arterial hypertension or thrombotic complications in a history may require higher doses of antihypertensive drugs and / or anticoagulants, respectively. 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 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 level 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, severe aluminum salt poisoning, concomitant 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-dialysis 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 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 this, the dose can be reduced or increased according to the above scheme.

Form release / dosage:Solution for intravenous and subcutaneous administration 1000 ME, 2000 ME, 4000 ME or 10 000 ME.

Packaging:

1 ml per ampoule of colorless neutral glass with a color fracture ring or with a colored dot and a notch.

One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric encoding or without additional color rings, a two-dimensional bar code, an alphanumeric code,digital encoding.

5 ampoules in a contoured cell pack of a polyvinylchloride film and aluminum foil foil or a multilayered film, or without foil and film.

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

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

For 0.3 ml of 1000 ME; 0.4 ml 4000 ME in a sterile glass syringe graduated with a needle, protective cap, with an additional automatic or non-automatic device to protect the needle after using the syringe or without it.

1, 2 or 3 syringes in a contiguous cell pack of a polyvinylchloride or polyethylene terephthalate film and a multilayer or polypropylene or polyethylene film, or a polymer-coated packaging paper, or a paper for packaging medical products, or an aluminum lacquered foil.

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

The pack is glued from both sides with stickers of self-adhesive material to control the opening.

For 0.3 ml of 2000 ME; 0.5 ml 2000 IU; 0.6 ml 10000 IU; 1.0 ml to 10000 ME per sterile glass syringe graduated with a needle, protective cap, with an additional automatic or non-automatic device to protect the needle after using the syringe or without it.

1, 2 or 3 syringes in a contoured cell pack of a polyvinylchloride or polyethylene terephthalate film and a multilayer or polypropylene or polyethylene film or a polymer wrapping paper, or a paper for packaging medical products, or an aluminum lacquered foil.

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

5 contour squares per 2 syringes without needle protection device, along with instructions for use in a pack of cardboard.

The pack is glued from both sides with stickers of self-adhesive material to control the opening.

A solution of 10,000 IU / ml in 0.25 ml (2500 ME); 0.6 ml (6000 IU); 0.8 ml (8000 ME) into a sterile glass syringe graduated with a needle, protective cap, with an additional automatic or non-automatic device to protect the needle after using the syringe or without it.

3 syringes in a contour acrylic package from a polyvinyl chloride or polyethylene terephthalate film and a multilayer or polypropylene or polyethylene film or a polymer wrapping paper or paper for packaging medical products or aluminum lacquered foil.

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

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

Storage conditions:

PIn the temperature range from 2 to 8 ° C.

Keep out of the reach of children.

Shelf life:

Solution for intravenous and subcutaneous

introduction in ampoules - 2 years.

Solution for intravenous and subcutaneous injection in syringes - 3 years.

Do not use the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006663/08