Vepox

Vepox is a biogenic type stimulant.

Indications Vepoxa

It is used for anemia caused by chronic renal failure (adults undergoing peritoneal dialysis or hemodialysis procedures), as well as for people in the pre-dialysis period and children who also undergo hemodialysis sessions.

It is used to treat anemia and reduce the volume of required blood transfusions in adults who require chemotherapy due to solid tumors, malignant lymphomas or multiple myeloma.

In addition, the drug is prescribed for anemia in people with HIV who are taking zidovudine and have intrinsic erythropoietin levels of ≤500 U/ml.

The drug can be used during the pre-deposit program, which occurs before major surgeries in individuals with hematocrit values of 33-39%. This is necessary to simplify the collection of autologous blood and reduce the risks associated with the use of allogeneic blood transfusions. It is used in cases where the probable need for transfused blood is higher than the volumes that can be obtained using autologous collection, which does not use α-epoetin.

It is prescribed for moderate to mild anemia in adults (hemoglobin values are approximately 100-130 g/l) who need to undergo a major surgical procedure where blood loss of 2-4 U of hemoglobin (approximately 0.9-1.8 l of blood) is expected. The use of Vepox reduces the need for allogeneic blood transfusion and simplifies the process of restoring erythropoiesis.

Release form

The product is available in the form of injection liquid:

• form 2000 – 0.5 ml of substance inside a syringe equipped with a needle, with a volume of 1 ml, which is packed in a blister – 1 piece inside a box;
• form 4000 – 0.4 ml of medicine inside a syringe with a needle, with a capacity of 1 ml and packed in a blister pack – 1 syringe per pack;
• Form 10000 – 1 ml of the drug inside a 1 ml syringe equipped with a needle, packed in a blister cell – 1 piece per box.

Pharmacodynamics

Erythropoietin is a purified glycoprotein that has the ability to stimulate erythropoiesis processes. The amino acid composition of α-epoetin, produced using genetic engineering technologies, is similar to human erythropoietin isolated from the urine of people with anemia. The protein makes up about 60% of the total molecular weight, and it contains 165 amino acids. Four carbohydrate chains are attached to this protein - among them three N-glycosidic and one O-glycosidic bond.

The molecular volume of α-epoetin is about 30 thousand daltons. The biological characteristics of this element are similar to the properties of human erythropoietin. The introduction of α-epoetin increases the indices of reticulocytes with erythrocytes, hemoglobin values, and the rate of absorption of 59 Fe. This element selectively stimulates erythropoiesis processes, but does not affect leukopoiesis.

The drug does not have a cytotoxic effect on bone marrow cells.

Pharmacokinetics

The half-life of the drug after intravenous injection is approximately 5-6 hours (regardless of the type of disease). The distribution volume is approximately equal to the volume of blood plasma.

Plasma values of Vepox after subcutaneous administration are much lower than those after intravenous injection. Plasma drug levels increase slowly, reaching a peak within 12-18 hours after injection. The half-life of the drug after subcutaneous injection is about 24 hours, the bioavailability index is approximately 25%.

Dosing and administration

The medication is administered intravenously or subcutaneously (if intravenous administration is not possible and therapy is needed urgently).

Existing general treatment regimens:

• in case of chronic renal failure in adults - at the beginning of therapy, the weekly dose is 50-100 IU/kg, administered three times a week (intravenously or subcutaneously); the size of the maintenance weekly dose is 25 IU/kg (the dose should be reduced after hemoglobin reaches optimal levels);
• an adult at the pre-dialysis stage - the initial dose per week: three times intravenous/subcutaneous administration of 50-100 IU/kg of the drug; the maintenance dose is 17-33 IU/kg with three times administration over 7 days;
• an adult undergoing hemodialysis - the initial weekly dose is 50-100 IU/kg (three times a week); maintenance - 3 times a week 30-100 IU/kg;
• Adult undergoing peritoneal dialysis sessions - the initial dose is 50 IU/kg, administered 3 times a week;
• a child undergoing hemodialysis - the initial dosage is 50 IU/kg (intravenously), 3 times a week; maintenance - 25-50 IU/kg, 3 times a week;
• a person with oncology - the initial dose is 150 IU/kg (subcutaneously) with three-time administration over 3 weeks; the sizes of maintenance doses: if the hemoglobin level increases by less than 10 g/l in 1 month, the dose should be doubled, and if this indicator increases by more than 20 g/l, it should be reduced by 25%;
• a person with HIV taking zidovudine - the initial dosage is 100 IU/kg, three times a week (intravenously or subcutaneously) for 8 weeks;
• an adult participating in a program with preliminary autologous blood collection before surgical procedures - intravenous administration of 600 IU/kg twice a week, for 21 days before the procedure;
• a person not participating in the above program, in the periods before and after the operation - subcutaneous injections of 600 IU/kg, once a week, for 21 days before the procedure, and then on the day of the procedure. A scheme with daily administration of 300 IU/kg for 10 days before and on the day of the procedure, and then for another 4 days after can also be used.

Persons with chronic renal failure.

When treating people with CRF, the drug is recommended to be administered intravenously. Optimal hemoglobin levels are 100-120 g/l (adult) and 95-110 g/l (child). In people with CRF, as well as coronary heart disease or congestive heart failure, the maintained hemoglobin levels should not be higher than the upper limit of its optimal levels. Ferritin levels should be determined for each patient before starting to use Vepox.

The dosage of the drug should be increased if the hemoglobin levels do not increase by at least 10 g/l over the past month. A clinically significant increase in hemoglobin levels is usually noted at least 14 days after the start of the therapeutic course (in some people, this occurs after 6-10 weeks). Once the required hemoglobin values are reached, the dose is reduced by 25 IU/kg - this is necessary to avoid exceeding the optimal level. If hemoglobin levels exceed 120 g/l, treatment with the drug should be temporarily stopped.

During hemodialysis.

For adults undergoing hemodialysis, the drug is administered intravenously. The therapy is carried out in 2 stages.

Correction stage: 50 IU/kg of the substance is administered intravenously three times a week. If necessary, the dose is gradually increased (maximum once per month) by 25 IU/kg (this dose is also administered three times a week until the required hemoglobin level is achieved).

Maintenance phase: the recommended weekly dose is in the range of 75-300 IU/kg. Often, a single dose used to maintain optimal hemoglobin values is 30-100 IU/kg, given 3 times a week. Current information suggests that people with severe anemia (hemoglobin level ≤60 g/L) require a higher maintenance dose than people with less severe disease.

During peritoneal dialysis.

For adults undergoing peritoneal dialysis, the drug is recommended to be administered intravenously. The therapy is carried out in 2 stages.

Corrective stage: a dosage of 50 IU/kg is administered twice a week.

Maintenance phase: when adjusting the dose to maintain the required hemoglobin levels of 100-120 g/l (approximately 6.2–7.5 mmol/l), it is necessary to administer 25-50 IU/kg twice a week (in equal doses).

Adults with renal failure.

In such a disorder in people in the pre-dialysis period, the drug is also administered intravenously, if possible. The therapy is carried out in 2 stages.

Correction stage: three times administration of 50 IU/kg per week. Then the portion (if necessary) is gradually increased by 25 IU/kg with 3 times use per week until the desired result is achieved (correction should be gradual and continue for at least 1 month).

Maintenance phase: dosage adjustments are made to maintain hemoglobin levels within 100-120 g/l (approximately 6.2-7.5 mmol/l). The medication is administered three times a week in a dose of 17-33 IU/kg. A single dose of the drug should not exceed 200 IU/kg.

Children on hemodialysis.

Correction stage: intravenous administration of 50 IU/kg of the substance, three times a week. If necessary, a single dose can be gradually increased (maximum once a month) by 25 IU/kg until the optimal hemoglobin level is achieved.

Maintenance phase: A child weighing less than 30 kg is often prescribed a higher maintenance portion than a child weighing more than 30 kg or an adult.

After conducting clinical trials based on six-month treatment, the following maintenance doses of α-epoetin were selected:

• weight ≤10 kg – the average dosage is 100 IU/kg (three times a week), and the maintenance dosage is 75-150 IU/kg;
• weight within 10-30 kg – average portion is 75 IU/kg, maintenance – 60-150 IU/kg;
• weight from 30 kg – the average portion is 33 IU/kg, maintenance – 30-100 IU/kg.

Based on the available information, it can be concluded that people with extremely low (≤60 g/L or ≤4.25 mmol/L) initial hemoglobin levels may require higher doses of the drug to maintain normal values of this substance than people with higher initial levels (from 68 g/L or 4.25 mmol/L).

Oncological diseases.

In people with oncological disorders, the optimal hemoglobin level is approximately 120 g/L. The drug is used in people with symptomatic anemia, and in addition to this, to prevent anemia in people who have previously undergone chemotherapy and have low initial hemoglobin levels (≤110 g/L).

In addition, the drug can be prescribed to patients who have had a significant decrease in hemoglobin values during the first chemotherapy cycle (for example, the hemoglobin level decreased by 10-20 g/l from the initial values of 110-130 g/l or decreased by 20+ g/l from the initial hemoglobin values of 130+ g/l).

The initial dose, which is used to prevent the development or to treat anemia, should be 150 IU/kg with three subcutaneous injections per week. If after 1 month of therapy the hemoglobin levels have increased by less than 10 g/l, the Vepox dose should be increased to 300 IU/kg for the next month. If a month of therapy using a dosage of 300 IU/kg also does not increase the hemoglobin levels by more than 10 g/l, it is concluded that the effect has not been achieved and the therapy is discontinued.

If hemoglobin values increase by 20+ g/L over a period of 1 month, the dose size of the drug should be reduced by approximately 25%. If hemoglobin values are 140+ g/L, therapy should be stopped until hemoglobin decreases to 120 g/L, and then the drug should be administered again in a reduced dose (by 25% compared to the initial dose).

It is necessary to evaluate the need for continued treatment from time to time, for example, after the end of a chemotherapy cycle. Before starting to use Vepox, as well as during therapy, it is necessary to monitor iron levels, providing additional iron saturation of the body if necessary. Before prescribing the drug, it is necessary to exclude the presence of other possible factors for the development of anemia.

Patients with HIV.

In people with HIV who are treated with zidovudine, it is necessary to determine the baseline values of endogenous erythropoietin in the serum before starting therapy with Vepox. According to the data from the tests, it became known that at values of this substance amounting to 500 IU/ml, Vepox will most likely be ineffective.

Correction stage: administration (subcutaneously or intravenously) of 100 IU/kg of the substance 3 times a week for 8 weeks. If at the end of 8 weeks of treatment the reaction to the drug is unsatisfactory (for example, it was not possible to reduce the body's need for blood transfusions or achieve an increase in hemoglobin values), the dosage of the drug is increased by 50-100 IU/kg (three times a week during the 1st month). If there is no result after using dosages of 300 IU/kg, one should not expect a positive effect from further treatment using higher doses.

The maintenance phase should ensure hematocrit values of 30-35%, taking into account changes in the zidovudine portion, as well as the presence of concomitant inflammations or infections. If the hematocrit values are more than 40%, it is necessary to stop the administration of the drug until the hematocrit decreases to 36%. After resuming treatment, the Vepox portion size is reduced by 25%, and hematocrit values are monitored.

Ferritin values should be determined in each patient before and during therapy. If necessary, additional iron supplementation may be prescribed.

Patients who undergo blood sampling.

In adults who are participants in a program for the collection of autologous blood prior to surgical procedures, it is necessary to consider the contraindications related to this program before using the drug.

Before the procedure, the drug is administered twice a day for 3 weeks. During each visit to the doctor, a small amount of blood is taken from the patient (with hematocrit values within 33-39% or hemoglobin values equal to 110 g / l) and saved for autologous transfusion. The recommended dosage of the drug is 600 IU / kg. It is administered intravenously, twice a week for 21 days before the surgical procedure. Treatment with α-epoetin reduces the likelihood of prescribing homologous blood by 50% compared to people who do not use the drug.

People who require less stimulation of erythropoiesis processes should be given the drug twice a week in doses of 150-300 IU/kg. This will increase the volume of collected autologous blood and prevent a subsequent decrease in hematocrit.

Serum iron levels should be determined before starting therapy for each patient. If iron deficiency is detected, these levels should be restored first and only then blood should be collected. In case of anemia, the cause of the disease should be determined before starting therapy. It is necessary to achieve adequate iron intake as quickly as possible (take 0.2 g of iron orally per day), and then maintain these levels at the same level throughout the entire therapeutic cycle.

People from whom blood is not drawn.

For adults who are not participants in the above-mentioned collection program, the drug is administered subcutaneously. The dosage of 600 IU/kg is administered once a week for 21 days before the surgical procedure (on the 21st, 14th, and 7th days) and on the day of the procedure.

If it is necessary to shorten the preoperative period as prescribed by the doctor, Vepox is used daily in a dose of 300 IU/kg for 10 days before the procedure, on the day of the operation, and then for another 4 days after it.

As with other parenteral drugs, the injection fluid must be carefully examined for visible particles or color changes before use. The drug must not be shaken, as this may cause glycoprotein denaturation and loss of medicinal activity.

Individual packaging of the drug can only be used once.

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Use Vepoxa during pregnancy

The use of Vepox in pregnant or lactating women is permitted only in situations where the benefit of therapy is more likely than the risk of developing consequences in the child/fetus.

There are no data on whether α-epoetin is excreted in human milk.

Contraindications

Main contraindications:

• the presence of intolerance to medicinal elements;
• uncontrolled increase in blood pressure;
• lesions affecting the peripheral, coronary, and carotid arteries, and having a severe degree of severity (this includes people with cerebrovascular diseases, as well as those who have recently suffered a myocardial infarction).

Side effects Vepoxa

The use of drugs may provoke a dose-dependent increase in blood pressure or worsening of existing hypertension. Often, such an effect develops in people with chronic renal failure.

Occasionally, the use of the drug causes:

• complications in the vascular area – development of blood clots (infarction or myocardial ischemia);
• complications of a cerebrovascular nature (strokes or hemorrhages);
• transient ischemic attacks;
• thrombosis in the area of arteries (retinal or peripheral) and deep veins;
• aneurysm, pulmonary embolism and thrombosis in the dialyzer area.

In some patients undergoing hemodialysis, thrombosis may develop in the shunt area (this is especially true for people with a tendency to low blood pressure or with complications affecting the arteriovenous fistula, such as aneurysm, stenosis, etc.).

Eczema, rash, itching, urticaria, or angioedema have been reported following use of α-epoetin.

People with CRF may develop hyperphosphatemia or hyperkalemia, increased levels of creatinine, urea nitrogen, and uric acid in the blood.

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Overdose

Vepox has an extremely broad spectrum of medicinal activity. In case of intoxication with this agent, signs may develop that reflect the highest intensity of the therapeutic effect of the hormone. At extremely high hemoglobin values, phlebotomy may occur. In such situations, symptomatic procedures should be performed.

Interactions with other drugs

The medicine must not be administered as an intravenous infusion or mixed with other drugs.

At present, there is no information indicating the ability of α-epoetin to affect the metabolic processes of other drugs.

When combining the drug with cyclosporine, it is necessary to monitor the blood levels of the latter and adjust the dose of cyclosporine if necessary.

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Storage conditions

Vepox must be kept in a dark place, out of the reach of small children. Do not freeze or shake the medicine. Temperature values are within 2-8°C.

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Shelf life

Vepox can be used within 24 months from the date of release of the therapeutic agent.

Analogues

Analogues of the drug are the drugs Epobiocrin, Erythrostim and Recormon with Vero-Epoetin and Shanpoetin, and also Shanpoetin-Health and Erythroetin.