Expiration date: 06/2025

Composition and form of issue:

Solution for intravenous and subcutaneous injection 1 syringe

epoetin alpha 1000 IU, 2000 IU, 4000 IU or 10000 IU

auxiliary substances: Polysorbate 80 sodium chloride sodium hydrogen phosphate dihydrate sodium dihydrogen phosphate dihydrate glycine water for injections 

in 0, 5 ml (1000 and 2000 IU), 0, 4 ml (4000 IU) and 1 ml (10000 IU) syringes are equipped with A protecs™ needle protection device to prevent injury by the needle after its use in a contour cell package 3 syringes in a carton pack 2 packages.

Solution for intravenous and subcutaneous injection 1 syringe

epoetin alpha recombinant 20000 IU or 40000 IU

auxiliary substances: Polysorbate 80 sodium chloride sodium hydrogen phosphate dihydrate sodium dihydrogen phosphate dihydrate glycine water for injections to 1 ml 

in 0, 5 (20,000 IU) or 1 ml (40,000 IU) syringes, the syringes are provided with a PROTECS™ needle protection device to prevent the needle from being injured after it is used in a contour cell package 1 2 3 syringes in a carton pack 1 (containing 1 syringe) or 2 (containing 2 or 3 syringes) packages.

Description of dosage form:

Clear, colorless solution.

Description of the pharmacological action:

Epoetin alpha is a purified glycoprotein that stimulates erythropoiesis and influences the division and differentiation of precursor cells. It is produced by mammalian cells with a built-in gene encoding the synthesis of human erythropoietin. The biological properties of epoetin Alfa is not different from that of human erythropoietin.

The protein fraction is about 58% of the molecular weight and consists of 165 amino acids. Four hydrocarbon chains are attached to the protein by three N-glycoside bonds and one O-glycoside bond. The molecular weight of erythropoietin is approximately 32000-40000 Dalton.

After administration of the drug, the number of red blood cells, reticulocytes, hemoglobin level and absorption rate 59Fe increase. On the culture of bone marrow cells shown that epoetin alpha selectively stimulates erythropoiesis, without affecting leucopoiesis.

T1/2 at / in the introduction of 5-6 hours, regardless of the severity of the disease. The volume of distribution is approximately equal to the plasma volume. The concentration of the drug in the blood serum with n / to the introduction is much lower than in/in the introduction. The level of the drug in the blood serum increases slowly and reaches a maximum of 12-18 hours after the n/a administration. T1/2 when s/to the introduction is approximately 24 h. the drug Bioavailability when s/to the introduction — about 25%.

Epoetin Alfa has minimal ability to induce the formation of antibodies.

No Carcinogenicity studies have been conducted.

Epoetin alpha does not cause mutations in bacterial genes (Ames test), chromosomal aberrations in mammalian cells, and mutations of hgprt genes.

In one study, revealed no differences in the incidence of bone marrow fibrosis in patients who were on dialysis and receiving epoetin Alfa for 3 years, and that of similar patients not receiving epoetin Alfa.

The teratogenicity of the drug in humans has not been studied, in rats and rabbits teratogenic effects epoetin alpha was not detected.

Indications:

Common for all dosages:

• anemia in cancer patients with non-myeloid tumors (for prevention and treatment)
  
• as part of the pre-hospital program before extensive surgery in patients with hematocrit levels of 33-39%, to facilitate the collection of autologous blood and reduce the risk associated with the use of allogeneic hemotransfusions, if the expected need for blood transfusion exceeds the amount that can be obtained by autologous collection without the use of epoetin alpha
  
• before an extensive surgery with expected blood loss 900-1800 ml (2-4 units) to adult patients without anemia or with mild to moderate anemia (hemoglobin level 100-130 g/l) to reduce the need for allogeneic hemotransfusions and facilitate the recovery of erythropoiesis.
  

For the solution for I / o and p/to the introduction of 1000, 2000, 4000 and 10000 IU (optional):

• anemia associated with chronic renal failure in adults and children, including patients on hemo-or peritoneal dialysis
  
• anemia in HIV-infected patients receiving zidovudine therapy with endogenous erythropoietin level less than 500 IU / ml.
  

For solution for I / o and p / C administration of 20,000 and 40,000 IU (optional):

• Anemia in patients with malignant lymphoma or multiple myeloma (prevention and treatment).
  

Contraindications:

• hypersensitivity to the drug components
  
• uncontrolled hypertension
  
• patients with severe coronary, carotid, cerebral and peripheral vascular pathologies, including those who have recently had a myocardial infarction or acute cerebrovascular accident (as part of a pre-hospital blood collection program prior to extensive surgery)
  
• pregnancy
  
• lactation
  
• patients, for any reason, are not able to receive adequate preventive antithrombotic therapy
  
• patients with partial red cell aplasia, receiving therapy with any erythropoietin (contraindicated use of Eprex and all other erythropoietins).
  

With caution:

• epilepsy (including epilepsy in anamnesis)
  
• thrombocytosis
  
• thrombosis (history)
  
• obliterating peripheral vascular disease and other vascular lesions
  
• gout
  
• sickle cell anemia
  
• iron-, B12 - or folate-deficient state
  
• CHD
  
• diagnosed porphyria in patients with liver failure (see " Special instructions»)
  
• a sharp decrease in the effectiveness of erythropoietin therapy in patients with chronic renal failure (see " Special instructions»)
  
• partial red cell aplasia (see Special instructions»)
  
• malignant neoplasms of the bone marrow (see "Special instructions").
  

Use during pregnancy and breast-feeding:

The use of Eprex during pregnancy and lactation is possible if the potential benefit of its use exceeds the possible risk to the fetus or newborn.

Data on teratogenic action of alpha epoetina the person does not have. Unknown, selects whether the drug in breast milk, therefore, in the treatment Eprex need to stop breastfeeding.

Side effect:

Mainly at the beginning of treatment may occur flu-like syndrome: dizziness, drowsiness, fever, headache, joint and muscle pain, weakness.

The most common side effect: dose-dependent increase in blood PRESSURE or deterioration of existing hypertension (most often in patients with chronic renal failure).

When using epoetina alpha may develop hypersensitivity and allergic reactions (skin rash, eczema, urticaria, itching).

Rarely there is the appearance of hypertensive crises (malignant hypertension), symptoms of encephalopathy (headache, confusion) and generalized tonic-clonic seizures, even in patients who had normal blood PRESSURE before the treatment of epoethine alpha thrombocytosis of shunt thrombosis in patients on hemodialysis, especially with a tendency to arterial hypotension or having complications from the arteriovenous fistula (stenosis, aneurysm, etc.) serious complications, associated with respiratory disorders or with a decrease in the pressure of immune reactions to the drug administration of hypertensive processes, such as myocardial ischemia, myocardial infarction, stroke, transient ischemic disorder, deep vein thrombosis, arterial thrombosis, pulmonary embolism, aneurysms, retinal thrombosis and blockage in the artificial kidney system.

In some cases, it is possible to develop angioedema and anaphylactic reaction.

In rare cases, patients with chronic renal failure treated with erythropoietin within a few months or years, may develop partial red cell aplasia (erythroblastopenia) (see "Special instructions").

Also, in rare cases, partial red cell aplasia was observed in patients with hepatitis C, receiving therapy with interferon and ribavirin, while the appointment of erythropoiesis stimulants. Erythropoiesis stimulants are not indicated for the treatment of anemia associated with hepatitis C.

In some cases, patients had local reactions: hyperemia, burning, weak or moderate soreness at the site of administration of the drug (more often with n/a).

Drug interaction:

Data on the interaction epoetin Alfa with other drugs no. However, it is possible to influence the concentration of cyclosporine with simultaneous application, therefore requires additional control of the level of cyclosporine with its subsequent correction.

You can not breed and pour the drug from the original into any other container, you can not enter Eprex in a mixture with other drugs.

Method of application and doses:

intravenous, subcutaneous

Before use, you should carefully inspect the solution for visible particles or color changes. The drug should not be shaken, because it can lead to denaturation of glycoprotein and loss of drug activity. Eprex does not contain preservatives, so individual packaging is designed for single use.

In / in the introduction of. The duration of injection is at least 1-5 minutes slower introduction is preferable for patients who have flu-like symptoms noted on the drug. Patients who are on hemodialysis, injection of the drug is made through a needle in the fistula at the end of the dialysis procedure.

Do not administer the drug in the form of/infusion or mix it with other drugs.

To wash the connecting tubes, as well as to ensure a satisfactory introduction of the drug into the circulation system after injection of Eprex, 10 ml of isotonic sodium chloride solution is administered (only for the solution for I/o and p/C administration of 1000, 2000, 4000 and 10000 IU).

P/to the injections. The maximum volume of one n / a injection should not exceed 1 ml, if necessary, the introduction of large volumes should use several points of administration. The drug is administered under the skin of the shoulder, thigh, anterior abdominal wall.

When changing the method of administration of the drug is administered in the same dose, then the dose is adjusted if necessary (to achieve the same therapeutic effect in subcutaneous administration requires a dose of 20-30% less than/in the introduction) (only for the solution for I/o and n/a 1000, 2000, 4000 and 10000 IU).

Patients with oncological diseases — n/a.

The optimal hemoglobin content should be 120 g / l for men and women and should not be exceeded.

Eprex may be prescribed to patients with symptomatic anemia, for the prevention of anemia in patients receiving chemotherapy and having an initial low hemoglobin content during the first course of chemotherapy (for example, a decrease in hemoglobin content by 10-20 g/l with an initial 110-130 g/l or a decrease of more than 20 g/l with an initial hemoglobin content of more than 130 g/l).

The initial dose for the prevention or treatment of anemia should be 150 IU / kg body weight 3 times a week n / C. alternatively, the initial dose may be 450 IU / kg (for the solution for I/o and p/C administration of 1000, 2000, 4000 and 10000 IU) and 40000 IU (for the solution for I/o and p / C administration of 20,000 and 40,000 IU) 1 time a week n / K.

If after 4 weeks of treatment, the hemoglobin content increased and is not less than 10 g/l, or the number of reticulocytes increased by more than 40 000 CL/µl above the initial dose, the Eprex remains the same — 150 IU/kg body weight 3 times a week or 450 IU/kg (for a solution for I/V and p/K administration of 1000, 2000, 4000 and 10000 IU) or 40000 IU (for a solution for I/V and p / K administration of 20,000 and 40,000 IU) once a week.

If, after 4 weeks of treatment, the increase in hemoglobin is less than 10 g/l and the increase in the number of reticulocytes is less than 40,000 CL/µl compared to the initial, then during the next 4 weeks the dose is increased to 300 IU/kg body weight 3 times a week (for all dosages) or 60000 IU 1 time a week (for a solution for I/V and p / C administration of 20,000 and 40,000 IU — additionally).

If after an additional 4 weeks of treatment at a dose of Eprex 300 IU/kg body weight 3 times a week (for all dosages) or 60000 IU 1 time a week (for a solution for I/o and p/to the introduction of 20,000 and 40,000 IU — additionally), hemoglobin increased and is not less than 10 g/l or the number of reticulocytes increased by more than 40,000 CL / µl, then maintain the existing dose of Eprex.

If after 4 weeks of treatment at a dose of 300 IU / kg of body weight (for all dosages) or 60,000 (for a solution for I/V and p/K administration of 20,000 and 40,000 IU — additionally) hemoglobin increases by less than 10 g/l and an increase in the number of reticulocytes is less than 40 000 CL/µl compared to the original, treatment should be discontinued.

In case of an increase in hemoglobin by more than 20 g/l for 1 month or reaching hemoglobin 120 g/l dose should be reduced by 25%. If hemoglobin exceeds 120 g/l, it is necessary to suspend treatment until it is reduced below 120 g / l and then continue administration of Eprex at a dose of 25% below the original.

Therapy with Eprex should be continued for 1 month after the end of chemotherapy.

Serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with Eprex. If necessary, an additional intake of iron is prescribed.

Adult patients participating in the program of autologous blood collection before surgical procedures — IV.

Epoetin alpha should be administered at the end of the blood collection procedure.

Before the appointment of Eprex, all contraindications to the collection of autologous blood should be taken into account. Before surgery, Eprex should be prescribed 2 times a week for 3 weeks. At each visit to the doctor, a portion of blood is taken from the patient (if hematocrit &ge33% and/or hemoglobin level &ge110 g/l) and stored for autologous transfusion. The recommended dose of Eprex is 600 IU/kg / 2 times a week.

Serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with Eprex. If necessary, an additional intake of iron is prescribed.

In the presence of anemia, its cause should be established before the start of therapy with Eprex. It is necessary in the shortest possible time to ensure adequate intake of iron into the body, prescribing oral iron preparation at a dose of 200 mg/day (based on the elementary iron) and to maintain the intake of iron at this level throughout the course of therapy.

Patients in pre-and postoperative period, not participating in the program of autologous blood collection, - p/C.

It is recommended to use the drug at a dose of 600 IU / kg per week for 3 weeks prior to surgery (21, 14 and 7 days before surgery), and on the day of surgery. If necessary, when it is necessary to reduce the preoperative period for medical reasons, Eprex can be prescribed daily at a dose of 300 IU/kg for 10 days before surgery, on the day of surgery and for 4 days after surgery. If the hemoglobin level in the preoperative period reaches 150 g/l and above, the use of epoetin should be discontinued.

Before therapy epoetinom alpha is necessary to ensure that no patients of iron deficiency.

All patients should receive an adequate amount of iron (orally at a dose of 200 mg / day — based on basic iron) throughout the course of treatment. If possible, you should provide additional ingestion of iron before the treatment with Eprex to ensure adequate depot of iron in the body of the patient.

Solution for the on/in and s/to the introduction of the 1000, 2000, 4000 and 10000 IU (optional)

Patients with chronic renal insufficiency-I/V, p/K. I / V administration of the drug preferably for patients on hemodialysis. Patients with chronic renal failure who are not receiving dialysis or are on peritoneal dialysis, the drug can be administered p / C.

The optimal level of hemoglobin for adult patients is 100-120 g/l, for children — 95-110 g / l.

In the presence of patients with concomitant clinically expressed IHD or chronic heart failure, the supported hemoglobin level should not exceed the upper limit of the optimal value.

Dose is 50 IU/kg. In the process of selecting the dose of Eprex is increased if the hemoglobin level increases of less than 10 g/l/month.

Adult patients on hemodialysis-in / in (preferably).

Treatment is divided into 2 phases — phase correction of anemia and maintenance phase.

The phase of correction of anemia

Eprex is introduced at the rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks) at 25 IU/kg 3 times a week to achieve optimal hemoglobin levels.

Supporting phase

The usual dose to maintain optimal hemoglobin levels is 30-100 IU / kg 3 times a week. The available data suggest that patients with severe anemia (hemoglobin level — less than 60 g/l) require a large maintenance dose.

Adult patients on peritoneal dialysis-I/V, p / C.

The phase of correction of anemia

The drug is administered at a rate of 50 IU / kg 2 times a week. If necessary, the dose can be gradually increased (no more than 1 time in 4 weeks) by 25 IU/kg 2 times a week to achieve optimal hemoglobin levels.

Supporting phase.

The usual dose to maintain optimal hemoglobin level is 25-50 IU / kg 2 times a week.

Adult patients with chronic renal failure who are not receiving dialysis, in/in, n/a.

The phase of correction of anemia

Eprex is introduced at the rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks ) at 25 IU/kg 3 times a week to achieve optimal hemoglobin levels.

Supporting phase

The usual dose to maintain optimal hemoglobin levels is 17-33 IU / kg 3 times a week.

Children who are on hemodialysis, regardless of age-IV.

The phase of correction of anemia

Eprex is introduced at the rate of 50 IU / kg 3 times a week. If necessary, the dose can be increased (not more than 1 time in 4 weeks) at 25 IU/kg 3 times a week to achieve optimal hemoglobin levels.

Supporting phase

Usually children with body weight under 30 kg require a large maintenance dose than adults and children weighing more than 30 kg. In clinical studies after 6-month therapy with Eprex were installed following maintenance doses epoetin alpha:

Body weight, kg	Dose of the drug in IU / kg 3 times a week
	Conventional supporting	Median
<10	75-150	100
10-30	60-150	75
>30	30-100	33

The available data suggest that patients with severe anemia (hemoglobin level — less than 68 g/l) require a higher maintenance dose than patients with less severe anemia.

HIV-infected patients receiving zidovudine therapy

It is recommended to determine the initial level of endogenous erythropoietin in blood serum before treatment with Eprex. Studies have shown that at the level of erythropoietin more than 500 IU/ml, the effect of Eprex therapy is unlikely.

Phase correction of anemia-p/C or b / V.

The drug is prescribed at a dose of 100 IU / kg 3 times a week for 8 weeks. If after 8 weeks of therapy could not achieve a satisfactory effect (for example, to reduce the need for blood transfusions or to increase the level of hemoglobin), the dose can be increased in stages (not more than 1 time in 4 weeks) at 50-100 IU/kg 3 times a week. If a satisfactory effect of Eprex therapy at a dose of 300 IU/kg 3 times a week could not be achieved, then the appearance of a response to further therapy in higher doses is unlikely.

Supporting phase

After achieving a satisfactory effect in the phase of correction of anemia, the maintenance dose should provide a level of hematocrit within 30-35%, depending on the change in the dose of zidovudine, the presence of concomitant infectious or inflammatory diseases. In hematocrit more than 40% should stop the introduction of Eprex to reduce hematocrit to 36%. When you resume therapy dose epoetin alpha should be reduced by 25% with subsequent adjustment to maintain the desired level of hematocrit.

The hemoglobin content in HIV-infected patients receiving zidovudine therapy should not exceed 120 g/l.

Serum ferritin level (or serum iron level) should be determined in all patients before and during treatment with Eprex. If necessary, an additional intake of iron is prescribed.

Overdose:

Symptoms: with an overdose of epoetin alpha, there are effects that reflect the extreme degree of severity of its pharmacological action.

Treatment: at very high levels of hemoglobin may use bloodletting.

Precautionary measures:

In patients with chronic renal insufficiency receiving Eprex as p/C injections, it is necessary to regularly monitor the effectiveness of therapy, defined as the absence or reduction of response to the administration of erythropoietin in patients who were previously susceptible to this therapy.

If a patient with chronic renal insufficiency has a sharp decrease in the effectiveness of erythropoietin therapy, defined as a decrease in hemoglobin by 10-20 g/l for 1 month with an increase in the need for transfusions, it is necessary to determine the number of reticulocytes and conduct a survey to identify one of the typical causes of resistance — iron deficiency, folic acid or vitamin B12, severe aluminum poisoning, concomitant infectious or inflammatory processes, bleeding, hemolysis.

If the number of reticulocytes less than 20,000 mm3 (less than 20,000 CL/µl or less than 0, 5%), the number of platelets and leukocytes in the normal, and no other causes of loss of efficiency, it is necessary to analyze the presence of antibodies to erythropoietin and bone marrow examination for the diagnosis of partial red cell aplasia.

If you suspect the diagnosis of partial red cell aplasia, should immediately stop treatment epoetinom alpha. Do not prescribe similar drugs in connection with the possibility of cross-reaction of antibodies to erythropoietin with other erythropoietins. According to the indications, appropriate therapy (blood transfusion) can be carried out.

Eprex should be used with great caution in patients with epileptic syndrome (including epilepsy in history), thrombocytosis, thrombosis (history), obliterating peripheral vascular diseases and other vascular lesions, gout, sickle cell anemia, iron, B12-or folio-deficiency States, IHD.

In rare cases, patients with hepatic insufficiency may experience an exacerbation of porphyria when using Eprex. In patients with diagnosed porphyria, the drug should be used with great caution.

Epoetin alpha, being a hematopoietic growth factor, can have a stimulating effect on some types of tumors, especially on malignant tumors of the bone marrow.

To reduce the risk of hypertension, the rate of increase in hemoglobin should be approximately 10 g/l (maximum 20 g/l) per 1 month.

For all patients receiving erythropoietin alpha, regular monitoring of hemoglobin levels 1 once a week to achieve stable levels and periodic monitoring in the future. At the initial level of hemoglobin 140 g/l in the pre - and postoperative period, hemoglobin level control is carried out more often.

Before and after the start of therapy with Eprex, it is necessary to adequately control blood PRESSURE. If it is impossible to reduce the pressure with antihypertensive drugs, Eprex therapy should be discontinued. It is necessary to pay special attention to the occurrence of unusual headaches or increased headaches.

Safety of Eprex in patients with impaired liver function has not been established. In these patients as a result of slowing of metabolism can be observed a more pronounced increase in erythropoiesis.

In the treatment of Eprex requires regular monitoring of platelet levels, especially during the first 8 weeks, as possible development of dose-relative increase in the number of platelets, which is normalized in the future without cancellation of therapy in rare cases, there is an absolute increase in the number of platelets.

Erythropoiesis stimulators are not necessarily equivalent to each other. Therefore, it should be emphasized that patients can be transferred from one erythropoiesis stimulator (e.g. Eprex) to another only with the permission of the attending physician.

Inadequate response to Eprex therapy occurs in iron deficiency, folic acid, vitamin B12, severe aluminum poisoning, associated infectious and inflammatory processes, injuries, hidden bleeding, hemolysis, bone marrow fibrosis of various etiology. Therefore, before starting Eprex therapy, it is necessary to assess the iron reserves in the body. Serum ferritin level should be regularly determined throughout the course of treatment. All patients with serum ferritin level less than 100 ng/ml are recommended to use oral iron preparations at a dose of 200-300 mg/day (children — 100-200 mg / day). Patients with chronic renal insufficiency with serum ferritin level less than 300 ng / ml are recommended to use oral iron preparations at a dose of 200-300 mg / day.

In patients with chronic renal failure, anemia correction can cause improved appetite and increased intake of potassium and protein, which may require the regulation of dialysis parameters to maintain urea, creatinine and potassium levels within normal limits.

Due to the increase in hematocrit during therapy with Eprex, patients on hemodialysis may require an increase in the dose of heparin, otherwise the occlusion of the dialysis system is possible.

In some patients with chronic renal insufficiency during treatment with Eprex, the resumption of menstruation was noted. The possibility of pregnancy and the need for contraceptive measures should be discussed with the patient before the start of therapy.

Regardless of the treatment with Eprex, surgical patients with concomitant cardiovascular diseases may experience thrombotic and vascular lesions as a result of repeated phlebotomies. Therefore, in such patients, the usual compensation of blood volume should be carried out according to the program of collection of autologous blood. Note that the preoperative increase of hemoglobin level in orthopaedic patients, regardless of therapy epoetinom alpha may serve as a predisposing factor to the development of thrombotic complications, require appropriate treatment. All patients who are scheduled for surgery should receive adequate preventive antithrombotic therapy.

Patients with hemoglobin level more than 150 g/l, application in pre - and postoperative period epoetin Alfa is not recommended.

In patients with chronic renal insufficiency and clinically expressed IHD or chronic heart failure, the upper limit of hemoglobin levels should not exceed 100-120 g/l — for adults and 95-110 g/l — for children.

Before and during treatment with Eprex, it is necessary to determine the serum iron level and serum ferritin level in all patients, if necessary, additional iron preparations are required.

It is necessary to exclude other possible causes of anemia before treatment with Eprex.

Due to the high risk of development of arterial hypertension at the beginning of therapy patients with chronic renal insufficiency should avoid such potentially dangerous activities as driving a car and working with technology (to determine the optimal maintenance dose of the drug).

The package intended for use may be stored at room temperature (not exceeding 25 °C) for no more than 7 consecutive days.

Special instruction:

Application note.

When n / to the introduction of Eprex, the amount of the drug is usually not more than 1 ml per single injection. It is not allowed to mix it with other solutions for injection.

It is not recommended to shake syringes or bottles with Eprex! Prolonged intense shaking may damage the drug. If the vial or syringe with the drug was subjected to strong shaking, its use is not recommended.

Instructions for self-injection using a pre-filled syringe with a protection device.

The syringes are equipped with A protecs™ needle protection device to prevent the needle from being injured after using the needle (there are instructions on the package).

1. Get the syringe out of the fridge. Bring the solution to room temperature, which is usually 15-30 minutes.

2. Check the syringe for the correct dosage, shelf life, no damage, as well as transparency and the temperature of the solution necessary for use.

3. Choose the injection site. The appropriate injection site is the upper thigh and anterior abdominal wall, except for the umbilical region. It should be daily alternate injection site.

4. Wash your hands. Treat the injection site with a swab with antiseptic for disinfection.

5. Remove the packaging from the syringe by grasping the housing and pulling the packaging without kinking. Do not press the piston, touch the needle or shake the syringe.

6. Collect the skin fold between the thumb and forefinger without pulling it.

7. Insert the needle the entire length.

8. Make sure that the needle is not in the lumen of the blood vessel, slightly pulling the piston over. If blood enters the syringe, remove the needle and try to repeat the injection elsewhere.

9. Without efforts and evenly, continuing to pinch the skin fold, push down on the plunger until it stops — for the introduction of the entire solution. The needle protection device will not activate unless a full dose is injected.

10. With the maximum possible pressure on the piston, remove the needle and straighten the skin fold.

11. Remove the thumb from the piston. Allow the needle to move up until it is completely closed with a protective nozzle.

12. Press the tampon with antiseptic to the injection site (after it is completed) for a few seconds.