Vero-Epoetin - instructions for use, dose, side effects, contraindications

Composition:Recombinant human erythropoietin 1000 ME 2000 ME 4000 ME 10000 ME, Polyvinylpyrrolidone low molecular weight medical (povidone), citrate-phosphate buffer to obtain a solution with a pH of 6.9.

Description:Porous amorphous mass of white or almost white color

Pharmacotherapeutic group:Hematopoiesis stimulant

ATX: & nbsp

B.03.X.A Other stimulators of hemopoiesis

Pharmacodynamics:Epoetin beta-glycoprotein, specifically stimulating erythropoiesis, activates the mitosis and maturation of erythrocytes from the progenitor cells of the erythrocyte series. Recombinant epoetin beta is synthesized in mammalian cells in which a gene encoding human erythropoietin is inserted. By its composition, biological and immunological properties epoetin beta is identical to natural human erythropoietin. The introduction of epoetin beta leads to an increase in hemoglobin and hematocrit, an improvement in the blood supply of tissues and the work of the heart. The most pronounced effect of epoetin beta 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 Vero-epoetin in healthy individuals and patients with uremia, the half-life period is 5-6 hours. With subcutaneous administration of epoetin beta, its concentration in the blood increases slowly and reaches a maximum in the period from 12 to 28 hours after administration, the half-life is 13- 28 hours. With intravenous administration, the elimination half-life is 4-12 hours. The bioavailability of Vero-epoetin with subcutaneous administration is 25-40%.

Indications:

Symptomatic anemia in chronic kidney disease in patients on dialysis.

Symptomatic anemia of renal genesis in patients not yet receiving dialysis. Prevention and treatment of anemia in patients with solid tumors, anemia in which was the result of anti-tumor therapy.

Prevention and treatment of anemia in HIV-infected patients (AIDS), caused by the use of zidovudine.

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

Treatment and prevention of anemia in premature infants born with a low body weight of up to 1.5 kg.

To reduce the volume of blood transfused with extensive surgical interventions and acute blood loss

Contraindications:

Hypersensitivity to the drug or its components, partial red cell aplasia after the earlier of the therapy in any erythropoietin, uncontrolled, hypertension, impossibility of adequate anticoagulant therapy, myocardial infarction within a month after the events, unstable angina, or an increased risk of deep vein thrombosis and thromboembolism in the framework of predreezopotnoy program for collecting blood before surgery, porphyria.

Carefully:

In patients with thrombosis (in the anamnesis), with malignant neoplasms, with sickle cell disease, in patients with moderate anemia without iron deficiency, in patients with refractory anemia, epilepsy and chronic hepatic insufficiency.

Pregnancy and lactation:Since there is no sufficient experience with the use of erythropoietin in pregnancy and lactation in humans, Vero-epoetin should be prescribed only if the expected benefits from its use exceed the possible risk to the fetus and mother.

Dosing and Administration:

Intravenously and subcutaneously.

A solution of Vero-epoetin is prepared by adding 1 ml of physiological solution to the lyophilizate.

Treatment of anemia in patients with chronic kidney disease

Vero-epoetin is administered subcutaneously or intravenously (for 2 minutes). Patients on hemodialysis - through the arteriovenous shunt at the end of the dialysis session.

Patients who do not receive hemodialysis, preferably administer the drug subcutaneously, to avoid puncture of peripheral veins. The goal of the treatment is a hemoglobin (Hb) value of 100-120 g / l. Hb should not exceed 120 g / l. When Hb is increased by more than 20 g / l (1.3 mmol / l), the dose of the drug should be reduced in 4 weeks.In patients with hypertension, cardiovascular and cerebrovascular diseases, the weekly increase in Hb and its targets should be determined individually, depending on the clinical picture. Careful observation of the patient should be carried out in order to select the minimum dose sufficient to ensure the maximum effect of the drug.

Treatment with Vero-epoetin includes two stages:

1. Correction phase: With subcutaneous injection of the drug Vero-epoetin, the initial single dose is 20 IU / kg 3 times a week. If there is insufficient increase in Hb (less than 2.5 g / L per week), the dose can be increased every 4 weeks by 20 IU / kg 3 times a week. The total weekly dose of the drug can also be divided into daily injections. When intravenously administered Vero-epoetin, the initial dose is 40 IU / kg 3 times a week. When insufficient increase of Hb In a month, the dose can be increased to 80 IU / kg 3 times a week.

If necessary, in the future, the dose should be increased by 20 IU / kg 3 times a week at a monthly interval.

Regardless of the method of administration, the maximum dose should not exceed 720 IU / kg per week.

2. Stage of maintenance therapy: For maintaining the target Hb (100-120 g / l), the dose should first be reduced 2 times from the previous dose. Then the maintenance dose of the drug Vero-epoetin is selected individually, with an interval of 2 or 4 weeks. When administered subcutaneously, the dose can be administered in 1 dose or divided into 3 or 7 administrations per week. After stabilization against a background of a single administration per week, you can switch to a single injection at a two-week interval, in which case an increase in dose may be necessary.

Treatment, as a rule, is long. If necessary, it can be interrupted at any time.

Prevention and treatment of anemia in patients with solid tumors

Before treatment is recommended to determine the level of endogenous erythropoietin. When the serum erythropoietin concentration is less than 200 IU / ml, the initial dose of Vero-epoetin is 150 IU / kg for the intravenous route. With the subcutaneous route of administration, the initial dose of Vero-epoetin can be reduced to 100 IU / kg. If there is no response, an increase in the dose to 300 IU / kg is possible. Further increase in the dose seems inappropriate.It is not recommended to appoint erythropoietin to patients with an endogenous erythropoietin content in the serum above 200 IU / ml.

Prevention and treatment of anemia in patients with HIV infection

Intravenous administration of epoetin beta in a dose of 100-150 IU / kg 3 times a week is effective in HIV patients receiving Zidovudine, provided that the serum endogenous erythropoietin level of the patient is less than 500 IU / ml and the Zidovudine dose is less than 4200 mg / a week. When administered subcutaneously, the dose of Vero-epoetin can be reduced by a factor of 1.5.

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

In these patients, the appropriateness of epoetin beta treatment is due to inadequate synthesis of endogenous erythropoietin against the background of anemia. If the hemoglobin content is below 100 g / l and the serum erythropoietin is below 100 IU / ml, Vero-epoetin is administered subcutaneously at a starting dose of 100 IU / kg three times a week. Laboratory monitoring of hemodynamic parameters is carried out weekly. If necessary, the dose of epoetin beta 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 beta 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 pro-inflammatory cytokines. Treatment of anemia in these patients is carried out by Vero-epoetin with subcutaneous administration at a dose of 50-75 IU / kg 3 times a week. With an increase in hemoglobin content of less than 10 g / L after 4 weeks of treatment, the dose of Vero-epoetin 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 infants, born with low body weight

Vero-epoetin is administered subcutaneously in a dose of 250 IU / kg three times a week starting from the 3rd day of life until the target hemoglobin and hematocrit are reached, but not more than 6 weeks.

Prevention of anemia with extensive surgical interventions and acute blood loss

Vero-epoetin is administered intravenously or subcutaneously three times a week at a dose of 100-150 IU / kg until the hematocrit normalizes and the hemoglobin content

Side effects:

The cardiovascular system: the occurrence or strengthening of an existing arterial hypertension, especially in the case of a rapid increase in hematocrit; hypertensive crisis with the phenomena of encephalopathy (headaches and confusion, sensory and motor disorders - speech disorders, gait, up to tonic-clonic seizures); thromboembolic complications in cancer patients and in patients preparing for autotransfusion (there is no clear causal relationship with the drug). Nervous system: headache, incl. sudden migraine-like headache.

The system of hematopoiesis: dose-dependent increase in the number of platelets (not exceeding the norm and disappearing with the continuation of therapy), especially after intravenous administration of the drug; thrombocytosis, thrombosis of shunts (possibly with inadequate heparinization), especially in patients with a tendency to lower blood pressure (BP) or complications of arteriovenous fistula (for example, stenosis, aneurysm, etc.).

Laboratory indicators: decline serum ferritin concentrations concomitantly with elevated hemoglobin, a decrease in serum iron metabolism. Patients with uremia have hyperphosphataemia.

In preterm infants: decline concentration of serum ferritin, a small increase in the number of platelets, especially up to 12-14th day of life.

Other: skin allergic reactions: rash, itching, hives, reactions at the injection site; anaphylactoid reactions; influenza-like syndrome (especially at the beginning of therapy): fever, chills, headache, pain in the extremities or bones, malaise

Overdose:

With an overdose of Vero-epoetin, there may be an increase in side effects. Treatment: symptomatic, with a high level of hemoglobin and hematocrit bloodletting is indicated.

Interaction:

With the simultaneous use of cyclosporine, it may be necessary to adjust the dose of the latter due to an increase in its binding by erythrocytes.

The experience of clinical use of Vero-epoetin has not yet revealed the facts of its pharmacological incompatibility with other drugs. Nevertheless, in order to avoid possible incompatibility or decrease in activity, Vero-epoetin should not be mixed with solutions of other medications.

Special instructions:

During treatment, it is necessary to monitor blood pressure weekly and conduct a general blood test, including determination of hematocrit, platelets and ferritin. In patients with uremia who are on hemodialysis because of the increase in hematocrit, it is often necessary to increase the dose of heparin, in addition, timely prevention of thrombosis and early revision of the shunt is necessary. In the pre- and postoperative period, Hb should be monitored more often if its baseline was less than 140 g / l. It must be remembered that Vero-epoetin does not replace blood transfusion, but it reduces the volume and frequency of its use. Patients with controlled arterial hypertension or with thrombotic complications may require an increase in the dose of antihypertensive and / or anticoagulant drugs. With the development of hypertensive crisis, urgent measures are taken to provide medical care to the patient, treatment with Vero-epoetin should be interrupted. When Vera-epoetin is prescribed, patients with hepatic insufficiency may have a slower metabolism and a marked increase in erythropoiesis. The safety of Vero-epoetin in this group of patients has not been established.Nor can we rule out the possibility of interaction Vero epoetin the growth of some types of tumors, including bone marrow tumors. One should take into account the possibility that preoperative increase in Hb level may serve as a predisposing factor to the development of thrombotic complications. Before the treatment to exclude possible causes of an inadequate response to a drug (iron deficiency, folic acid tsianokobalomina, severe poisoning A13 +, concomitant infection, inflammation and injury, hidden hemorrhage, hemolysis, bone marrow fibrosis of various etiologies) and adjust treatment as necessary. In most patients with uremia, oncological and HIV-infected patients, the serum ferritin level decreases simultaneously with an increase in hematocrit. The level 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 (for children 100-200 mg / day). 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 pre-or post-operative period should also receive adequate therapy with iron preparations at a dose of up to 200 mg / day. In patients with uremia, correction of anemia with epoetin beta can cause an improvement in appetite and an increase in absorption of potassium and proteins. In this regard, periodic correction of hemodialysis parameters may be required to maintain the levels of urea, creatinine and K + within normal limits. These patients also need to monitor the level of electrolytes in the blood serum. When using epoetin beta in women of reproductive age, 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. During the treatment period, before the optimal maintenance dose is established, patients with uremia should avoid practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, because of the increased risk of high blood pressure at the beginning of therapy.Given the possible more pronounced effect of epoetin beta, 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 according to the above scheme.

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

Packaging:For 1, 5 or 10 bottles together with instructions for use in a pack of cardboard.

Storage conditions:

In a dry, dark place at a temperature of 2 ° C to 8 ° C. Keep out of the reach of children!

Shelf life:

2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000258

Date of registration:18.05.2010

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp02.02.2017

Illustrated instructions

Instructions

Vero-epoetin (Vero-Epoetin)