Vepox 4000

Vepox 4000 is an anti-anemic drug.

Indications Vepox 4000

It is used in such situations:

• chronic anemia caused by insufficiency of the renal function in adults who are in peritoneal dialysis sessions or hemodialysis procedures, and also in people during the predialysis period, and in children undergoing hemodialysis procedures;
• anemia in persons (who are given or not chemotherapy) with oncology (non-myeloid tumors), and in addition the prevention of anemia in people with oncology (non-myeloid tumors) who are undergoing chemotherapy;
• anemia in people with HIV who used zidovudine and have internal erythropoietin rates of £ 500 U / ml;
• as a pre-deposit course before performing essential surgical procedures in individuals with hematocrit values equal to 33-39%. This is necessary in order to facilitate autologous blood collection and reduce the risks that exist due to the use of allogeneic hemotransfusions with a probable need for receiving transfused blood exceeding the volumes that can be obtained through an autologous collection method without the administration of α-epoetin;
• moderate or mild severity of anemia (hemoglobin index is> 10- 13 g / l) before performing an extensive surgical procedure for an adult, at which the average rate of blood loss is expected (2-4 IU of hemoglobin or 0.9-1.8 l of blood ). This is required to reduce the need for allogeneic hemotransfusions and to facilitate the recovery of erythropoiesis.

[1], [2]

Release form

The release of the medicinal element is made in the form of injection fluid - 0.5 ml of the substance per 1 ml (manufactured form 2000), 0.4 ml / 1 ml (form 4000) and 1 ml / 1 ml (form 10,000) inside a syringe equipped with a needle . Inside the pack contains 1 such syringe.

Pharmacodynamics

Erythropoietin is a glycoprotein that has a purified form that stimulates erythropoiesis. Amino acid structure of α-epoetin, created using 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 level; It contains 165 amino acids. 4 chains of carbohydrates are attached to the protein by means of 3 N-glycosidic and 1st O-glycosidic binder.

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 increase, the volume of reticulocytes with erythrocytes increases, as well as the absorption rate of the 59Fe element. In addition, α-epoetin selectively stimulates the processes of erythropoiesis, without affecting the performed leukopoiesis.

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

Pharmacokinetics

Intravenous injections.

Half-life after i / v injections of the drug in the range of 50-100 U / kg is approximately 4 hours. In people with kidney failure after applying the dosages of 50, 100 or 150 U / kg, this figure is about 5 hours. The half-life of drugs for a child is approximately 6 hours.

Subcutaneous injections.

Plasma drug values after s / c injection is much lower than when conducting / injections. Plasma parameters increase slowly, reaching the Cmax level for 12-18 hours after application.

Half-life after s / c injection is equal to almost 24 hours. The bioavailability of drugs with this method of administration is about 20%.

Dosing and administration

The drug is introduced in / in the way. If intravenous access is not possible, but there are strict indications, it is allowed to inject the solution subcutaneously.

The most commonly used general treatment regimens are:

• adults who have a renal failure of chronic nature - first, the drug is used in a portion of 50-100 IU / kg, 3 times a week, intravenously or subcutaneously. Further, a maintenance weekly dosage is used - a reduction in the portion by 25 IU / kg, when the necessary hemoglobin index is obtained;
• adults who do not undergo dialysis - first, subcutaneously or intravenously injected 50-100 IU / kg of substance, 3 times a week. Then, a supporting dose is applied 3 times a week - 17-33 IU / kg;
• Adults who are on hemodialysis - first, 50-100 IU / kg of medication is administered (s / c or v / v), 3 times a week. Later the maintenance dosage is used - 30-100 IU / kg, 3 times a week;
• adults who are on peritoneal dialysis - the initial dosage is 50 IU / kg; administered subcutaneously, 3 times a week;
• children on hemodialysis — first, 50 IU / kg of the drug are administered intravenously 3 times a week. The size of the maintenance dosage is 25-50 IU / kg, with 3 single intravenous administrations per week;
• people with oncology - at first it is required 3 times a week subcutaneous administration of 150 IU / kg of the drug. Later, the maintenance portion per week is doubled (if the monthly hemoglobin values increased by <10 g / l) or reduced by 25% (if this indicator increased by> 20 g / l);
• people with HIV who use zidovudine - the size of the initial portion 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 their operations, are administered intravenously at 600 IU / kg of substance, 2 times a week within the 21st day before performing the surgery procedure;
• people during the pre- and postoperative period who are not participants in the autologous program - 1 subcutaneous application of 600 IU / kg per week during the 21st day before surgery, and with it on the day of the procedure. In addition, a scheme can be used with daily administration of 300 IU / kg of the substance for 10 days before surgery, on the day of the operation, and another 4 days.

People with chronic stage of renal failure.

For such disorders, the drug is administered intravenously whenever possible.

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

In individuals with chronic renal failure, a clinical form of coronary artery disease or a heart failure that is stagnant, supporting hemoglobin values must remain below the upper limit of the indicated optimal hemoglobin index.

Before the introduction of Vepox, any patient needs to determine the values of ferritin (or serum indicator of iron).

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

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

Adults staying on hemodialysis procedures.

Such people medicine is introduced into / in the method. The process of therapy consists of 2 phases.

Correctional stage.

The introduction of 50 IU / kg of the drug 3 times a week, intravenously. If necessary, the dosage can be increased gradually (adjustment is carried out maximum 1-fold per month) by 25 IU / kg with 3-time use per week until the optimal hemoglobin value is obtained.

Supporting stage.

For a week it is recommended to enter within 75-300 IU / kg of the medicinal substance. Most often, a 1-fold portion used to maintain optimal hemoglobin values is 30-100 IU / kg with 3 single doses per week. Existing information allows us to conclude that people with severe anemia (hemoglobin level - <6 g / l) require an increased maintenance dosage (in comparison with people with less severe anemia).

Adults requiring peritoneal dialysis sessions.

In these cases, if possible, the drug is administered in / in the method. In case of unavailability of intravenous administration, it is required to determine the degree of benefit and risks in case of s / c administration of the substance (separately for each patient). Therapy consists of 2 phases.

Correctional stage.

The introduction of 50 IU / kg of the drug 2-fold per week.

Supporting stage.

Adjust the portion to maintain the desired hemoglobin value of 10-12 g / l (corresponds to 6.2-7.5 mmol / l), it is possible within 25-50 IU / kg, with 2-fold application for week (introduction of 2 equal portions of drugs).

Adults with kidney failure and not on dialysis.

People during the predialysis period, the drug is, if possible, used intravenously. With the unavailability of intravenous administration is required to analyze the benefits and risks of drug administration subcutaneously (individually for each patient). The therapeutic course consists of 2 stages.

Correctional stage.

It requires 3-fold administration of 50 IU / kg of drug per week. Later, if required, the portion is gradually increased by 25 IU / kg with 3 times a week, until the desired effect is obtained (correction is made gradually and over at least 1 month).

Supporting stage.

The portion size that supports the necessary hemoglobin index, which is in the range of 10-12 g / dl (corresponding to 6.2-7.5 mmol / l), is 17-33 IU / kg with 3-fold administration per week.

The maximum allowable size of a 1-fold portion is 200 IU / kg. You can enter it 3 times a week.

Children on hemodialysis procedures.

Correctional stage.

The introduction of 50 IU / kg of the drug is carried out 3 times a week. If necessary, the dosage can be increased in 2 phases (maximum 1-fold per month), by 25 IU / kg, with 3 single doses per week, until the optimal hemoglobin level is obtained.

Supporting stage.

For the most part, for children weighing less than 30 kg, a higher dosage is required than for a child weighing more than 30 kg and for an adult. In clinical tests after semi-annual therapy, the following maintenance portions of α-erythropoietin were identified:

• weight <10 kg - the average portion is 100 IU / kg, and supporting - in the range of 75-150 IU / kg;
• weight in the range of 10-30 kg - the average dosage is 75 IU / kg, supporting - 60-150 IU / kg;
• weight> 30 kg - the average dose is 33 IU / kg, supporting - 30-100 IU / kg.

The drug is administered 3 times a week.

Existing information suggests that people with extremely low initial hemoglobin values (<60 g / l or <4.25 mmol / l) may need a higher portion of Vepox to maintain the level of this substance than people with different values ( > 68 g / l or> 4.25 mmol / l).

For persons with cancer, the optimal hemoglobin value should be approximately 120 g / l.

The drug is allowed to apply in people with anemia of a symptomatic nature.

The drug can also be used in the prevention of anemia in patients undergoing chemotherapeutic procedures who had low initial hemoglobin values (<11 g / dL). In addition, it is assigned to people who have significantly decreased hemoglobin index during the 1st chemotherapeutic cycle (for example, a decrease of 10-20 g / l of hemoglobin level at initial values of 110-130 g / l, or a decrease of 20+ g / l, when the initial rate was more than 130 g / l).

The size of the initial portion for the prevention or treatment of anemia is 150 IU / kg, with subcutaneous administration 3 times a week. With an increase in hemoglobin values of less than 10 g / l for 1 month of therapy, it is required to double the portion (300 IU / kg). With an increase in hemoglobin indices of less than 1 g / dl after a 1-month application of this portion, it is concluded that the effect could not be achieved, and the treatment is canceled.

With an increase in hemoglobin of more than 2 g / dL per month, the portion is required to be reduced by approximately 25%. With an increase in hemoglobin values to more than 14 g / dl, the therapy must be canceled until this figure decreases to 12 g / dl, after which the medication is administered in portions reduced by 25% from the original dose.

It is necessary to periodically assess the need for continuation of treatment - for example, after the end of the chemotherapeutic course.

Before using the drug, as well as during therapy, the values of iron should be monitored and its additional intake should be ensured, if necessary. Also, before starting to use the medication, other possible factors for the development of anemia are required.

People with HIV who used zidovudine.

Before initiating therapy, prior to transfusion, it is necessary to determine the initial indicator of internal serum erythropoietin. The data from such tests show that if erythropoietin is above 500 IU / ml, the drug effect of  Vepox  will be extremely low.

Correctional stage.

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

With an unsatisfactory response to a 2-month treatment (for example, the need for blood transfusions could not be reduced, or the hemoglobin index did not increase), the dose of drugs is increased by 50-100 IU / kg with 3 single doses per week, during the 1st of the month. If the use of a dosage of 300 IU / kg also did not produce an effect, treatment can be canceled, because the probability of receiving a response to the introduction of higher doses is extremely small.

Supporting stage.

Upon reaching the desired result at the correction stage, the supporting portion is necessary to ensure hematocrit values within 30-35%, taking into account also some other factors (change in the portion of zidovudine, the presence of concomitant infections or inflammations). With a hematocrit of over 40%, the use of the drug should be discontinued until it decreases to 36%. After resuming treatment, the portion of Vepox is reduced by 25%, further adjusting it to maintain hematocrit values.

Ferritin index (or intra-serum values of iron) must be identified in all patients before and during therapy. If necessary, iron is introduced additionally. In addition, before starting therapy, it is necessary to exclude other possible factors for the occurrence of anemia.

Adults who are participants in an autologous program who will be operated on.

Before the introduction of drugs is required to take into account the existing contraindications for autologous blood collection program. Before the operation, the drug is administered 2 times a day for 14 days. During each visit, the doctor takes a portion of blood from the patient (at hematocrit values of 33-39% or hemoglobin values of 11 g / l), saving it for autologous transfusion.

The size of the recommended dose of medication is 600 IU / kg, with 2-fold use per week for the 21st day before the operation. Thanks to the use of α-epoetin, the likelihood of using homologous blood is reduced by 50% (compared to persons who do not use α-epoetin).

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

Serum iron levels should be determined in each patient before starting therapy. If iron deficiency is noted, take measures required to restore its values before starting an autologous program. If there is anemia, you need to determine its cause. It should be as fast as possible to ensure the supply of the required amount of iron (ingestion to an adult inside - 0.2 g of iron per day) and maintain it at this level throughout the entire therapeutic cycle.

Adults during the pre- and post-operative period (who are not participants in the autologous blood program).

The drug is administered s / c method.

The drug is used in portions, which is 600 IU / kg per week, for the 21st day before the operation (on the 21st, 14th, and 7th day), and in addition, on the day of the procedure.

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

All people who use Vepox need to be provided with the necessary amount of iron (oral administration of 0.2 g of iron per day) throughout the entire therapeutic cycle. If this is possible, it is necessary to provide an option with an additional intake of iron before starting treatment to ensure the necessary cumulation of this component.

[5], [6]

Use Vepox 4000 during pregnancy

The introduction of Vepox is allowed during lactation or pregnancy only in situations where the likely benefits of therapy are more expected than the risk of adverse effects on the fetus.

There is no information on whether α-epoetin passes into breast milk, which is why it should be used very carefully during lactation.

Contraindications

Main contraindications:

• erythrocytic aplasia of true character, which appears due to the use of erythropoietin;
• increased blood pressure values that cannot be controlled;
• the presence of strong sensitivity to the elements of the drug;
• You must also take into account all existing contraindications that are prescribed for an autologous program (for individuals receiving α-epoetin).

To people who will undergo elective surgery of the orthopedic type, while not being participants in the autologous program, α-epoetin is not prescribed in such cases:

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

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

[3]

Side effects Vepox 4000

At the initial stages of therapy, symptoms of a cold — feeling of drowsiness and lethargy, fever, dizziness, pain in muscles and joints, as well as headaches — may appear.

Thrombocytosis has sometimes been observed.

Certain people who used erythropoietin had thrombotic complications associated with the vessels, such as a heart attack or myocardial ischemia, cerebrovascular complications (stroke, cerebral hemorrhage, etc.), TIA, deep venous or arterial thrombosis, PELA, and hidromo-osteoarthrosis, etc. , aneurysms, and in addition occlusion affecting the dialysis system.

There is evidence of manifestations on the epidermis in the injection area (more often occur in the case of s / c injection, and not in / in). There is the appearance of moderate or mild pain around the injection area and redness of the skin.

Immune lesions after using Vepox are observed only occasionally. There is evidence of signs of intolerance and allergic symptoms; sometimes the development of anaphylactic manifestations and Quincke edema was recorded.

The appearance of erythrocytic aplasia of the true type (erythroblastopenia) was rarely noted - with months or many years of s / c administration of α-epoetin.

People with renal insufficiency.

When using α-epoetin, an increase in blood pressure values or a decrease in the course of hypertension already present in a patient, often depending on the size of the portion, is often observed. Mostly a similar reaction occurs in people with chronic renal failure.

Individuals developed hypertensive crises or encephalopathic manifestations (a feeling of confusion, severe headaches, etc.), as well as generalized seizures of tonic-clonic type. The most careful attention should be paid to the occurrence of sudden migraine attacks or headaches (they can be a warning signal). It is necessary to track blood pressure indicators from the very beginning of the use of the medicine.

Individuals who were on hemodialysis sessions (especially patients who have a tendency to develop hypotension or those who have complications associated with arteriovenous fistula (such as aneurysm, stenosis, etc.)) sometimes developed a shunt thrombosis.

Persons with cancer diseases.

Due to the likelihood of an increase in blood pressure when using α-epoetin, during therapy it is necessary to closely monitor hemoglobin values and blood pressure values.

People treated with erythropoietin, among which is α-epoetin, have experienced thrombotic complications.

Tests conducted on women with metastatic breast carcinoma, the purpose of which was to determine the degree of effectiveness of general treatment without adjusting for anemic conditions, revealed that overall mortality rates, as well as death rates, which are associated with the progression of pathology, and the situation with death resulting thromboembolism in the treatment of α-epoetin, were higher than similar values when compared with placebo.

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

Without being bound to the prescribed treatment with α-epoetin, complications of a vascular and thrombotic nature can develop in such people if there are any concomitant pathologies of the cardiovascular system and multiple phlebotomies.

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

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

People with stable hemoglobin values of> 13 g / dL (corresponding to 8.1 mmol / l) and requiring elective orthopedic surgery are subject to a significantly higher likelihood of complications of vascular or thrombotic type associated with treatment α - epoetin. Therefore, patients with such risk factors are prohibited from using Vepox.

 

[4]

Overdose

The drug has a significant range of therapeutic effects. Poisoning with α-epoetin leads to the appearance of signs that reflect the strong severity of the drug effect of the hormone.

With extremely high hemoglobin, phlebotomy can be used. After that, symptomatic measures are taken.

[7], [8]

Interactions with other drugs

Do not administer medication by IV infusion or mix with other medicinal substances.

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

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

[9], [10]

Storage conditions

Vepox is required to be kept in a dark and forbidden place. Do not freeze or shake the medicine bottle. Temperature marks - in the range of 2-8 ° C.

Shelf life

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

[11], [12]

Analogs

Analogues of the medication are substances such as Recormon, Erythrostim, Shanpoetin, Epoetin with Epobiocrin, as well as Epoetal and Eprex.