Vepox 4000.

Vepox 4000 is an antianemic drug.

Indications Vepoxa 4000.

It is used in the following situations:

• anemia caused by chronic renal failure in adults undergoing peritoneal dialysis or hemodialysis procedures, as well as in people during the pre-dialysis period, and in children undergoing hemodialysis procedures;
• anemia in individuals (who are undergoing or not undergoing chemotherapy) with oncology (non-myeloid tumors), and also prevention of anemia in individuals with oncology (non-myeloid tumors) who are undergoing chemotherapy;
• anaemia in people with HIV who have used zidovudine and have intrinsic erythropoietin levels of £500 U/ml;
• as a pre-deposit course before major surgical procedures in individuals with hematocrit values of 33-39%. This is necessary in order to facilitate autologous blood collection and to reduce the risks that exist due to the use of allogeneic blood transfusions in the event of a probable need for transfused blood exceeding the volumes that can be obtained through the autologous method of collection without the introduction of α-epoetin;
• moderate or mild anemia (haemoglobin >10-£13 g/L) prior to major adult surgery where moderate blood loss (2-4 U haemoglobin or 0.9-1.8 L of blood) is expected. This is to reduce the need for allogeneic transfusions and to facilitate the restoration of erythropoiesis.

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Release form

The medicinal element is released in the form of an injection liquid - 0.5 ml of the substance per 1 ml (form 2000), 0.4 ml/1 ml (form 4000) and 1 ml/1 ml (form 10000) inside a syringe equipped with a needle. The pack contains 1 such syringe.

Pharmacodynamics

Erythropoietin is a glycoprotein in a purified form that is a stimulator of erythropoiesis. The amino acid structure of α-epoetin, created by genetic engineering procedures, is identical to human erythropoietin and is secreted from the urine of people with anemia. The protein component is approximately 60% of the molecular weight; it contains 165 amino acids. Four carbohydrate chains are attached to the protein - via three N-glycosidic and one O-glycosidic linker.

The molecular weight of α-epoetin is approximately 30 thousand daltons. The biological characteristics of α-epoetin are similar to human erythropoietin. When using α-epoetin, hemoglobin values, the volume of reticulocytes with erythrocytes, and the rate of absorption of the element 59Fe increase. In addition, α-epoetin selectively stimulates erythropoiesis processes without affecting ongoing leukopoiesis.

The α-epoetin component does not have a cytotoxic effect on bone marrow cells.

Pharmacokinetics

Intravenous injections.

The half-life after intravenous injection of doses of the drug within 50-100 U/kg is approximately 4 hours. In individuals with renal failure, after using doses of 50, 100 or 150 U/kg, this figure is about 5 hours. The half-life of the drug in a child is approximately 6 hours.

Subcutaneous injections.

Plasma values of the drug after subcutaneous administration are much lower than after intravenous injection. Plasma values increase slowly, reaching the Cmax mark within 12-18 hours after administration.

The half-life after subcutaneous injection is almost 24 hours. The bioavailability values of the drug with this method of administration are about 20%.

Dosing and administration

The medicine is administered intravenously. If intravenous access is impossible, but there are strict indications, it is allowed to administer the solution subcutaneously.

The most commonly used general treatment regimens are:

• adults with chronic renal failure - the drug is first used in a dose of 50-100 IU/kg, 3 times a week, intravenously or subcutaneously. Then a maintenance weekly dosage is used - a decrease in the dose by 25 IU/kg when the required hemoglobin level is obtained;
• adults who do not undergo dialysis - first, 50-100 IU/kg of the substance is administered subcutaneously or intravenously, 3 times a week. Then, a maintenance dose of 17-33 IU/kg is used 3 times a week;
• adults on hemodialysis - first, 50-100 IU/kg of the drug is administered (subcutaneously or intravenously), 3 times a week. Later, a maintenance dose of 30-100 IU/kg is used, 3 times a week;
• adults undergoing peritoneal dialysis – the initial dosage is 50 IU/kg; administered subcutaneously, 3 times a week;
• Children on hemodialysis - initially, 50 IU/kg of the drug is administered intravenously 3 times a week. The maintenance dosage is 25-50 IU/kg, with 3 intravenous administrations per week;
• people with oncology – initially, 3 times a week, subcutaneous administration of 150 IU/kg of the drug is required. Later, the maintenance dose per week is doubled (if the monthly hemoglobin values have increased by <10 g/l) or reduced by 25% (if this indicator has increased by >20 g/l);
• HIV-infected individuals using zidovudine – the initial dose is 100 IU/kg, administered intravenously or subcutaneously, 3 times a week for 2 months;
• adults who are participants in the autologous blood program, prior to surgery, are administered 600 IU/kg of the substance intravenously, 2 times a week within 21 days before the surgical procedure;
• people during the pre- and postoperative period who are not participants in the autologous program - 1-time subcutaneous application of 600 IU/kg per week during the 21st day before surgery, and also on the day of the procedure. In addition, a scheme with daily administration of 300 IU/kg of the substance for 10 days before surgery, on the day of the operation, and for another 4 days can be used.

People with chronic renal failure.

In such cases, the medication is administered intravenously, if possible.

Optimal hemoglobin values are about 100-120 g/l (for adults) and 95-110 g/l (for children).

In individuals with chronic renal failure, clinical form of ischemic heart disease or cardiac failure of a congestive nature, maintenance hemoglobin values must remain below the upper limit of the designated optimal hemoglobin level.

Before starting Vepox administration, any patient should have their ferritin levels (or serum iron levels) determined.

During dose adjustment, the dose of the drug can be increased if the hemoglobin volume does not increase by at least 1 g/dL within a month.

A clinically significant increase in the hemoglobin index is usually noted after at least 14 days of therapy (in some people - after 1.5-2.5 months). Upon reaching the required hemoglobin values, the dose is reduced by 25 IU/kg to prevent exceeding the optimal value. If the hemoglobin values are more than 12 g/dl, treatment should be temporarily discontinued.

Adults undergoing hemodialysis procedures.

For such people, the medicine is administered intravenously. The therapy process consists of 2 phases.

Corrective stage.

Administration of 50 IU/kg of the drug 3 times a week, intravenously. If necessary, the dosage can be gradually increased (adjustment is made no more than once a month) by 25 IU/kg with 3 times a week until the optimal hemoglobin level is achieved.

Supporting stage.

It is recommended to administer 75-300 IU/kg of the medicinal substance per week. Most often, a single dose used to maintain optimal hemoglobin values is 30-100 IU/kg with 3-time administration per week. Existing information allows us to conclude that people with severe anemia (hemoglobin level - <6 g/l) require an increased maintenance dose (compared to people with less severe anemia).

Adults who require peritoneal dialysis sessions.

In these cases, if possible, the medication is administered intravenously. If intravenous administration is unavailable, it is necessary to determine the degree of benefit and risk in the case of subcutaneous administration of the substance (separately for each patient). Therapy consists of 2 phases.

Corrective stage.

Administration of 50 IU/kg of the drug twice a week.

Maintenance stage.

The dose can be adjusted to maintain the required hemoglobin level of 10-12 g/l (corresponding to 6.2-7.5 mmol/l) within the range of 25-50 IU/kg, with 2-fold use per week (administration of 2 equal portions of the drug).

Adults with kidney failure who are not on dialysis.

For people during the pre-dialysis period, the drug is administered intravenously if possible. If intravenous administration is unavailable, it is necessary to analyze the benefits and risks of administering the drug subcutaneously (individually for each patient). The therapeutic course consists of 2 stages.

Corrective stage.

A 3-times per week administration of 50 IU/kg of the drug is required. Later, if necessary, the dose is gradually increased by 25 IU/kg with 3-times per week administration until the desired effect is achieved (correction is performed gradually and over at least 1 month).

Supporting stage.

The serving size that maintains the required hemoglobin level of 10-12 g/dL (equivalent to 6.2-7.5 mmol/L) is 17-33 IU/kg, administered 3 times per week.

The maximum permissible size of a single portion is 200 IU/kg. It can be administered 3 times a week.

Children undergoing hemodialysis procedures.

Corrective stage.

The drug is administered at a dose of 50 IU/kg 3 times a week. If necessary, the dosage can be increased in 2 phases (maximum 1 time per month), by 25 IU/kg, with 3 times a week until the optimal hemoglobin level is achieved.

Maintenance stage.

In general, children weighing less than 30 kg require a higher dosage than a child weighing more than 30 kg and an adult. In clinical trials after six months of therapy, the following maintenance doses of α-erythropoietin were determined:

• weight <10 kg – the average portion is 100 IU/kg, and the maintenance portion is within 75-150 IU/kg;
• weight within 10-30 kg – average dosage is 75 IU/kg, maintenance dosage is 60-150 IU/kg;
• weight >30 kg – the average dose is 33 IU/kg, maintenance dose is 30-100 IU/kg.

The medicine is administered 3 times a week.

Current information suggests that individuals with very low baseline haemoglobin levels (<60 g/L or <4.25 mmol/L) may require a higher dose of Vepox to maintain haemoglobin levels than individuals with other levels (>68 g/L or >4.25 mmol/L).

For people with oncology, the optimal hemoglobin level should be approximately 120 g/l.

The drug is approved for use in people with symptomatic anemia.

The medication can also be used to prevent anemia in people who have undergone chemotherapy procedures and had low initial hemoglobin values (<11 g/dl). In addition, it is prescribed to people whose hemoglobin level has dropped significantly during the first chemotherapy cycle (for example, a decrease of 10-20 g/l in hemoglobin levels with initial values equal to 110-130 g/l, or a decrease of 20+ g/l when the initial value was more than 130 g/l).

The initial dose for prevention or treatment of anemia is 150 IU/kg, administered subcutaneously 3 times per week. If hemoglobin values increase by less than 10 g/l during 1 month of therapy, the dose should be doubled (300 IU/kg). If hemoglobin values increase by less than 1 g/dl after 1 month of use of this dose, it is concluded that the effect has not been achieved, and treatment is discontinued.

If the hemoglobin level increases above 2 g/dl per month, the dose should be reduced by approximately 25%. If the hemoglobin level increases to more than 14 g/dl, therapy should be discontinued until this figure decreases to 12 g/dl, after which the medication should be administered in a dose reduced by 25% from the original.

The need for continued treatment should be assessed periodically, for example after completion of a course of chemotherapy.

Before using the drug, as well as during therapy, it is necessary to monitor iron levels and ensure, if necessary, its additional intake into the body. Also, before starting to use the drug, it is necessary to exclude other possible factors for the development of anemia.

People with HIV who used zidovudine.

Before starting therapy, before transfusion, it is necessary to determine the baseline value of internal serum erythropoietin. The data of such tests show that if erythropoietin is above 500 IU/ml, the medicinal effect of Vepox will be extremely low.

Corrective stage.

Use 100 IU/kg 3 times a week, intravenously or subcutaneously, for 2 months.

If the response to 2-month treatment is unsatisfactory (for example, the need for blood transfusions could not be reduced, or the hemoglobin level did not increase), the dose of the drug is increased by 50-100 IU/kg with 3-times use per week, for 1 month. If the use of a dosage of 300 IU/kg also did not produce an effect, the treatment can be discontinued, because the probability of obtaining a response to the introduction of higher doses is extremely low.

Supporting stage.

Upon reaching the desired result at the correction stage, a maintenance dose is required to ensure hematocrit values within the range of 30-35%, taking into account some other factors (change in the zidovudine dose, presence of concomitant infections or inflammations). If the hematocrit value is over 40%, the drug should be discontinued until it decreases to 36%. After resuming treatment, the Vepox dose is reduced by 25%, then adjusted to maintain hematocrit values.

Ferritin levels (or serum iron levels) should be measured in all patients before and during therapy. Iron should be supplemented if necessary. Other possible factors for anemia should also be excluded before therapy.

Adults who are participants in the autologous program and who will undergo surgery.

Before administering the drug, it is necessary to take into account existing contraindications regarding the autologous blood collection program. Before performing the operation, the drug is administered 2 times a day for 14 days. During each visit to the doctor, a portion of blood is taken from the patient (with hematocrit values within 33-39% or hemoglobin values equal to 11 g / l), preserving it for autologous transfusion.

The recommended dose of the drug is 600 IU/kg, administered twice a week for 21 days before surgery. The use of α-epoetin reduces the likelihood of using homologous blood by 50% (compared to individuals not using α-epoetin).

People who require less stimulation of erythropoiesis are required to use the drug in a dosage of 150-300 IU/kg 2 times a week. This increases autologous collection and prevents a decrease in hematocrit values.

Serum iron levels should be determined in each patient before the start of therapy. If iron deficiency is noted, measures required to restore its values are taken before the start of the autologous program. If anemia is present, its cause should be determined. It is necessary to ensure the required amount of iron as quickly as possible (oral intake for an adult is 0.2 g of iron per day) and maintain it at this level throughout the therapeutic cycle.

Adults during the pre- and postoperative period (not participating in the autologous blood program).

The drug is administered subcutaneously.

The drug is used in a dose equal to 600 IU/kg per week, for 21 days before the operation (on the 21st, 14th, and 7th day), and also on the day of the procedure.

In situations where medical indications require a reduction in the preoperative period, the medication is administered daily in a dose of 300 IU/kg, for 10 days before the operation, on the day of the procedure, and also for 4 days after it.

All people using Vepox should be provided with the required amount of iron (oral administration of 0.2 g iron per day) throughout the entire therapeutic cycle. If possible, an option with additional oral intake of iron should be provided before the start of treatment to ensure the necessary accumulation of this component.

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Use Vepoxa 4000. during pregnancy

The administration of Vepox is permitted during lactation or pregnancy only in situations where the probable benefit from therapy is more expected than the risk of developing negative consequences in the fetus.

There is no information regarding whether α-epoetin passes into breast milk, so it should be used with extreme caution during lactation.

Contraindications

Main contraindications:

• true red cell aplasia that occurs due to the use of erythropoietin;
• elevated blood pressure values that cannot be controlled;
• presence of strong sensitivity to the components of the drug;
• It is also necessary to take into account all existing contraindications that are prescribed for the autologous program (for individuals receiving α-epoetin).

People who will undergo elective orthopedic surgery and are not in an autologous program are not prescribed α-epoetin in the following cases:

• diseases of a peripheral-arterial, coronary, cerebrovascular or carotid nature (severe forms);
• recent stroke or myocardial infarction.

Do not use in surgical patients who are prohibited from receiving adequate antithrombotic prophylaxis due to some factors.

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Side effects Vepoxa 4000.

At the initial stages of therapy, signs of a cold may appear - a feeling of drowsiness and lethargy, fever, dizziness, pain in the muscles and joints, and headaches.

Sometimes the development of thrombocytosis was noted.

In some individuals using erythropoietin agents, vascular-related thrombotic complications have occurred - myocardial infarction or ischemia, cerebrovascular complications (stroke, cerebral hemorrhage, etc.), TIA, deep vein or arterial thrombosis, pulmonary embolism, retinal thrombosis, aneurysms, and also occlusion affecting the dialysis system.

There are data on manifestations on the epidermis in the injection area (more often occur in the case of subcutaneous injection, not intravenous). The appearance of moderate or mild pain around the injection area and reddening of the skin are distinguished.

Immune damage after using Vepox is observed only rarely. There are reports of intolerance and allergic symptoms; sometimes the development of anaphylactic manifestations and Quincke's edema was recorded.

The occurrence of true type erythrocyte aplasia (erythroblastopenia) was noted in isolated cases with many months or many years of subcutaneous administration of α-epoetin.

People with renal insufficiency.

A dose-dependent increase in blood pressure or worsening of existing hypertension is often observed with α-epoetin. This reaction mainly occurs in people with chronic renal failure.

Hypertensive crises or encephalopathic manifestations (feeling of confusion, severe headaches, etc.) as well as generalized tonic-clonic seizures have developed in some individuals. Particular attention should be paid to the occurrence of sudden migraine attacks or headaches (they may be a warning signal). Blood pressure readings should be monitored from the very beginning of drug use.

In some individuals undergoing hemodialysis (especially patients prone to hypotension or those with complications associated with arteriovenous fistula (such as aneurysms, stenosis, etc.)), shunt thrombosis has occasionally developed.

Persons with oncological diseases.

Because of the potential for increased blood pressure with α-epoetin, hemoglobin levels and blood pressure should be closely monitored during therapy.

Thrombotic complications have been reported in people treated with erythropoietin agents, including α-epoetin.

Tests conducted in women with metastatic breast carcinoma to determine the effectiveness of overall treatment without adjustment for anaemic conditions found that overall mortality rates, disease progression-related mortality rates, and fatal thromboembolism rates were higher with α-epoetin than with placebo.

Surgical patients (adults) who are participants in the autologous collection program.

Without reference to the prescribed treatment with α-epoetin, vascular and thrombotic complications may develop in such people in the presence of any concomitant cardiovascular pathologies and repeated phlebotomies.

All existing warnings and precautions related to the autologous blood program (including the process of compensating the amount of circulating blood) apply to people using α-epoetin.

Surgical patients (adults) who are not participants in the autologous collection program.

Patients with persistent hemoglobin levels >13 g/dL (equivalent to 8.1 mmol/L) and who require elective orthopaedic surgery are at significantly increased risk of developing vascular or thrombotic complications associated with α-epoetin therapy. Therefore, patients with such risk factors should not use Vepox.

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Overdose

The drug has a significant range of therapeutic effects. Poisoning with α-epoetin leads to the appearance of signs reflecting the strong expression of the medicinal effect of the hormone.

In case of extremely high hemoglobin levels, phlebotomy may be used. After that, symptomatic measures are carried out.

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Interactions with other drugs

The medication must not be administered by intravenous infusion or mixed with other medicinal substances.

There is no information indicating that the use of α-epoetin can affect the metabolic processes of other drugs.

When using Vepox in combination with cyclosporine, it is necessary to monitor the blood levels of the latter, adjusting its dose if necessary.

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Storage conditions

Vepox should be kept in a dark place out of reach of children. Do not freeze or shake the bottle with the medicine. Temperature marks are within 2-8°C.

Shelf life

Vepox can be used within 24 months from the date of manufacture of the drug.

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Analogues

The following substances are analogs of the drug: Recormon, Erythrostim, Shanpoetin, Epoetin with Epobiocrin, as well as Epoetal and Eprex.