Vepoks

Vepox is a biogenic type stimulant.

Indications Vepox

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

Used to treat anemia and reduce the amount of required blood transfusions for adults who need chemotherapy because of solid neoplasms, malignant tumors or multiple type myeloma.

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

The medication can be used during the pre-infection program, which occurs before large surgical operations in persons 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 when the probable need for transfused blood is higher than those that can be obtained by means of an autologous collection in which α-epoetin is not used.

It is prescribed for anemia, which has a moderate or mild degree of severity, in an adult (hemoglobin - about 100-130 g / l), which needs a large surgical procedure, where blood loss is expected to be 2-4 units of hemoglobin (approximately 0.9- 1.8 liters of blood). The use of Vepox reduces the need for performing allogeneic blood transfusions and simplifies the process of restoring erythropoiesis. 

Release form

The release is realized as an injection liquid:

• Form 2000 - 0.5 ml of substance inside a syringe equipped with a 1 ml needle, which is packed in a blister - 1 piece inside the box;
• Form 4000 - 0.4 ml of medication inside a syringe with a needle, having a capacity of 1 ml and packed in a blister plate - 1 syringe in a pack;
• form 10000 - 1 ml of preparation inside a needle-equipped syringe with a volume of 1 ml, packed in a blister cell - 1 piece in a box.

Pharmacodynamics

Erythropoietin is a purified glycoprotein that has the ability to stimulate the processes of erythropoiesis. The amino acid composition of α-epoetin produced by genetic engineering is similar to human erythropoietin isolated from the urine of people with anemia. The protein in this case is about 60% of the total molecular weight, and it contains 165 amino acids. To this protein are attached 4 carbohydrate chains - among them 3 N-glycosidic, as well as 1 O-glycosidic linkage.

The molecular volume of α-epoetin is about 30,000 daltons. The biological characteristics of this element are similar to those of human erythropoietin. The introduction of α-epoetin increases the indices of reticulocytes with erythrocytes, the hemoglobin values, and the absorption rate of 59 Fe. This element selectively stimulates the processes of erythropoiesis, but does not affect leukopoiesis.

The drug has no 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 indices of the volume of blood plasma.

Plasma values of Vepox with subcutaneous injection are much lower than those for intravenous injection. The plasma level of the drug increases slowly, reaching a peak for 12-18 hours after the injection. The half-life of drugs after subcutaneous injection is about 24 hours, the bioavailability index is about 25%.

Dosing and administration

The medication is administered intravenously or subcutaneously (if there is no possibility of intravenous injection, and therapy is needed urgently).

Existing general treatment regimens:

• at chronic renal failure in an adult - at the beginning of therapy, the weekly dose is 50-100 IU / kg, with administration three times per week (intravenously or subcutaneously); the size of the maintenance weekly portion is 25 IU / kg (reduce the dose needed after the hemoglobin has reached the optimal values);
• an adult at the pre-dialysis stage - the initial portion for the week: a triple intravenous / subcutaneous injection of 50-100 IU / kg of the drug; the maintenance dose is 17-33 IU / kg with a triple injection for 7 days;
• Adult person undergoing hemodialysis - the initial weekly dose is 50-100 IU / kg (triple injections); supporting - 3-fold introduction for a week 30-100 IU / kg;
• adult, undergoing peritoneal dialysis sessions - the initial dose is 50 IU / kg with a 3-time application per week;
• the child undergoing hemodialysis - the initial dosage is 50 IU / kg (intravenously), 3 times a week; Supporting - 25-50 IU / kg, 3 times per week;
• a person with oncology - the initial dose is 150 IU / kg (subcutaneously) with a triple injection for 3 weeks; sizes of maintenance dosages: if the hemoglobin level is increased by less than 10 g / l for 1 month, the dose should be doubled, and if this value increases by more than 20 g / l, it should be reduced by 25%;
• a person with HIV who takes 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 pre-sampling of blood of an autologous type before surgical procedures - intravenous administration of 600 IU / kg twice a week, during the 21st day before the procedure;
• a person not participating in the above-described program, before and after the operation, subcutaneous injections of 600 IU / kg, once a week, during the 21st day before the procedure, and then on the day of the procedure. A scheme may also be used 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.

Persons with CRF.

When treating patients with CRF, the drug should be administered intravenously. The optimal parameters of hemoglobin - 100-120 g / l (adult) and 95-110 g / l (child). In individuals with CRF, as well as CHD or heart failure in stagnant form, the hemoglobin values maintained should not be higher than the upper limit of its optimal parameters. Values of ferritin should be determined for each patient before starting Vepox.

It should increase the dosage of drugs, if the hemoglobin does not increase by at least 10 g / l over the past month. Clinically significant increase in hemoglobin level is usually observed at least 14 days after the start of the therapeutic course (in individual people this occurs after 6-10 weeks). After reaching the required hemoglobin values, the dose is reduced by 25 IU / kg - this is necessary in order to avoid exceeding the optimal level. With hemoglobin values exceeding 120 g / l, treatment with medication should be temporarily stopped.

With hemodialysis.

Adults who undergo hemodialysis sessions receive the medication intravenously. The therapy is carried out in 2 stages.

Correction phase: three times per week intravenously injected 50 IU / kg of substance. If necessary, the portion is incrementally increased (maximum once per 1 month) by 25 IU / kg (this dose is also administered 3 times a week, until the required hemoglobin level is obtained).

Supporting stage: the size of the recommended weekly dose is in the range of 75-300 IU / kg. Often the single dose used to maintain the optimal hemoglobin values is 30-100 IU / kg with a 3-use weekly use. The current information suggests that people with severe anemia (hemoglobin level ≤ 60 g / l) need a stronger maintenance portion of drugs than people with less severe disease.

With peritoneal dialysis.

For adults who undergo peritoneal dialysis sessions, the medication should be administered intravenously. Therapy is carried out in 2 stages.

Correction phase: a dosage of 50 IU / kg is administered twice a week.

Supporting stage: when adjusting the portion to maintain the necessary hemoglobin values of 100-120 g / l (about 6.2-7.5 mmol / l), 25-50 IU / kg need to be administered 2 times a week (in equal portions ).

Adults with kidney failure.

With such a violation in people who are in the pre-dialysis period, the medication is also, if possible, administered intravenously. The therapy is carried out in 2 stages.

Correction phase: a triple introduction of 50 IU / kg per week. Then the portion (if necessary) is gradually increased by 25 IU / kg with a 3-use weekly use, until the desired result is obtained (the correction should be gradual and last for a minimum of 1 month).

Supporting step: dosage adjustment is performed to maintain hemoglobin values in the range of 100-120 g / l (approximately 6.2-7.5 mmol / l). The medication is administered three times per week in a dose of 17-33 IU / kg. A single dose of medicines should not exceed 200 IU / kg.

Children who are on hemodialysis.

Correction phase: intravenous administration of 50 IU / kg of substance, three times a week. If required, it is possible to gradually increase the single dose (at a maximum of 1 time per 1 month) by 25 IU / kg until the optimal level of hemoglobin is obtained.

Supporting stage: a child with a weight of less than 30 kg is often prescribed a higher maintenance dose than for a child weighing more than 30 kg or an adult.

After conducting clinical tests based on a six-month treatment, such maintenance doses of α-epoetin were selected:

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

According to available information, it can be concluded that people with extremely low hemoglobin levels (≤60 g / L or ≤4.25 mmol / L) may require higher portions of drugs to maintain normal values of this substance than those with an initial level higher (from 68 g / l or 4.25 mmol / l).

Oncological diseases.

In people with cancer, the optimal hemoglobin is about 120 g / l. The medicine is used for people with symptomatic anemia, and in addition to preventing anemia in people who have previously undergone chemotherapy and have low initial hemoglobin values (≤110 g / l).

In addition, the medication can be given to patients who have had a significant decrease in hemoglobin values during the 1st 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 values of hemoglobin, which amounted to 130 + g / l).

The initial dose, which is used to prevent development or for therapy of anemia, should be equal to 150 IU / kg with a triple subcutaneous administration per week. If after 1 month of therapy the hemoglobin values increased by less than 10 g / l, for a subsequent month it is required to increase the dose of Vepox to 300 IU / kg. If the month of therapy with a dosage of 300 IU / kg also did not increase hemoglobin values by more than 10 g / l, they conclude that the effect could not be achieved, and the therapy is canceled.

If the hemoglobin values increase by 20+ g / L for the period of the 1st month, the portion size of the drug should be reduced by approximately 25%. At hemoglobin values of 140+ g / L, it is necessary to stop therapy until the hemoglobin decreases to 120 g / l, and then again to inject the drug in a reduced (by 25% compared to the initial) portion.

It is necessary to assess the need for continuation of treatment from time to time, for example, after the end of the chemotherapy cycle. Before starting the application of Vepox, as well as during therapy, it is necessary to monitor the parameters of iron, providing, if necessary, additional saturation of the body with iron. Before the appointment of drugs it is necessary to exclude the presence of other possible factors for the development of anemia.

Patients with HIV.

People with HIV who are treated with zidovudine need to determine the initial values of endogenous erythropoietin inside the serum before starting therapy with Vepox. According to the tests conducted, it became known that with the index of this substance, which is 500 IU / ml, Vepox is likely to be ineffective.

Correction phase: administration (subcutaneously or intravenously) of 100 IU / kg of substance 3 times a week, for 8 weeks. If, at the end of the 8-week treatment, the response to the drug was unsatisfactory (for example, it did not reduce the body's need for blood transfusions or to increase the hemoglobin values), the dosage of the drug is increased by 50-100 IU / kg (three times a week for the period 1 month). If there is no result after using the dosages of 300 IU / kg, do not expect a positive effect of further treatment with higher portions.

The supporting stage should provide hematocrit values of 30-35%, taking into account the change in the dose of zidovudine, as well as the presence of concomitant inflammation or infections. At hematocrit values of more than 40%, it is required to stop the drug administration until the moment when the hematocrit drops to 36%. After the resumption of treatment, the size of the Vepox portion is reduced by 25%, and the hematocrit values are monitored.

Values of ferritin should be determined in each patient before the start of therapy and in the course of its management. If necessary, additional use of iron medicines may be prescribed.

Patients who are taking blood.

In adults who are participants in an autologous type blood collection program before performing surgical procedures, contraindications regarding the program before using drugs should be taken into account.

Before the procedure, the medication is administered 2 times a day for 3 weeks. During each visit to the doctor, the patient takes a little blood (at hematocrit values within 33-39% or hemoglobin values equal to 110 g / l) and save it for autologous transfusion. The recommended dosage of drugs is 600 IU / kg. It is administered intravenously, twice a week for 21 days before the procedure of surgery. Treatment with α-epoetin reduces the probability of prescribing homologous blood by 50% in comparison with people who do not use the drug.

People who need less stimulation of erythropoiesis should be given a medication in a dose of 150-300 IU / kg 2 times a week. Thanks to this, the volumes of collected blood of an autologous type will increase, and the subsequent reduction of the hematocrit will be prevented.

Serum iron values should be determined before starting therapy in each patient. If a lack of iron has been identified, it is necessary first to restore these parameters and only then to collect blood. When anemia before the beginning of therapy determine the cause of the development of this disease. It is required to achieve as quickly as possible an adequate intake of iron in the body (per day, take 0.2 g of iron per os), and then maintain these values at the same level throughout the therapeutic cycle.

People who do not take blood.

Adults who are not members of the above-mentioned collection program, the medication is administered subcutaneously. A dosage equal to 600 IU / kg is administered once weekly for the 21st day before the surgical procedure (on the 21st, 14th, and 7th days) and on the day of it.

If necessary, in reducing the pre-operative period as prescribed by the doctor, Vepox is applied daily in a 300 IU / kg dose for 10 days before the procedure, on the day of the operation, and then in the period of 4 more days after it.

As with other drugs injected parenterally, the injectable liquid must be carefully inspected before use for visible particles or a change in color. You can not shake the medicine, because it can cause the denaturation of glycoprotein and the loss of medication activity.

Individual packaging of the drug can be used only once.

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Use Vepox during pregnancy

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

There is no evidence as to whether α-epoetin passes into the mother's milk.

Contraindications

The main contraindications:

• the presence of intolerance with respect to the drug 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 myocardial infarction).

Side effects Vepox

The use of drugs can provoke an increase in blood pressure, depending on the size of the dosage, or worsening of the course of an existing hypertension. Often, this effect develops in people with CRF.

Occasionally, the use of medication causes:

• complications in the vascular region - development of thrombi (myocardial infarction or ischemia);
• complications of cerebrovascular nature (strokes or hemorrhages);
• transient ischemic attacks;
• thrombosis in the arteries (retina or peripheral) and deep veins;
• aneurysm, pulmonary embolism and thrombosis in the area of the dialyzer.

In some patients who undergo hemodialysis, there may be a development of thrombosis in the shunt area (especially for people with a tendency to decrease blood pressure or complications affecting arteriovenous fistula - among such an aneurysm, stenosis, etc.).

After the use of α-epoetin, the occurrence of eczema, rashes, itching, urticaria, or edema of Quincke was noted.

People with CRF may develop hyperphosphataemia or hyperkalemia, increase the values of creatinine, urea nitrogen, and also uric acid in the blood.

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Overdose

Vepox has an extremely wide spectrum of drug activity. When this drug is intoxicated, signs that reflect the highest intensity of the therapeutic effect of the hormone may develop. At extremely high values of hemoglobin, phlebotomy may occur. In such situations, symptomatic procedures should be followed.

Interactions with other drugs

Do not administer the medication in the form of intravenous infusions or mix it with other drugs.

At the moment 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 drug and adjust the dose of cyclosporine, if necessary.

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Storage conditions

Vepox is required to be kept in a dark place and closed from the infiltration of small children. Do not freeze or shake the medicine. The temperature is within 2-8 ° C.

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Shelf life

Vepox is allowed to be used within 24 months of the release of the therapeutic agent.

Analogues

The analogues of the medication are the drugs Epobiocrin, Erythrostim and Recormon with Vero-Epoetin and Shanpoethin, as well as Shapoetin-Health and Erythroetin.