Instruction for use: Eporatio

Dosage form: Solution for intravenous and subcutaneous administration

Active substance:Epoetinum theta

ATX

B03XA01 Erythropoietin

The nosological classification (ICD-10)

D63.0 Anemia in neoplasm: Anemia in chronic diseases; Anemia due to radiation damage; Radiation anemia; Anemia in patients with solid tumors; Pernicious anemia

D63.8 Anemia in other chronic diseases classified elsewhere: Anemia in chronic diseases; Anemia in immunological disorders; Anemia in peptic ulcer; Anemia in kidney diseases; Anemia with HIV treatment; Anemia in the background of chronic renal failure; Anemia in patients with myeloma; Symptomatic anemia; Symptomatic anemia of renal genesis; Anemia in HIV-infected patients; Renal anemia

Z49.1 Aids that include extracorporeal dialysis: hemodialysis; Chronic hemodialysis; Extracorporeal circulation; Thrombosis of hemodialysis shunt

Z51.1 Chemotherapy for neoplasm: Cystitis hemorrhagic, caused by cytostatics; Urotoxicity of cytostatics

Composition

Solution for intravenous and subcutaneous injection 1 syringe 0.5 ml

active substance: Epoetin of theta 1000 ME (2000 ME, 3000 ME, 4000 ME, 5000 ME)

Auxiliary substances: sodium dihydrogen phosphate dihydrate - 1.56 mg; Sodium chloride - 1,96 mg; Polysorbate 20 - 0.15 mg, trometamol (Tris) - 4.24 mg; Hydrochloric acid (6 M) - 4.85 μl; Water for injection - up to 0.5 ml

Solution for intravenous and subcutaneous injection of 1 ml syringe

active substance: Epoetin of theta 10000 ME (20000 ME, 30000 ME)

Auxiliary substances: sodium dihydrogen phosphate dihydrate - 3,12 mg; Sodium chloride - 3.92 mg; Polysorbate 20 - 0.3 mg; Trometamol (Tris) - 8.48 mg; Hydrochloric acid (6M) - 9.70 μl; Water for injection - up to 1 ml

Description of dosage form

Clear colorless solution.

Pharmachologic effect

Mode of action - Erythropoietic.

Pharmacodynamics

Human erythropoietin is an endogenous glycoprotein hormone, which is the main regulator of erythropoiesis through specific interactions with erythropoietin receptors on erythroid marrow precursor cells. It acts as a mitostimulating factor and a differentiating hormone.

The production of erythropoietin primarily occurs and is regulated by the kidney in response to changes in oxygen concentration in tissues. In patients with CRF, endogenous erythropoietin production is disrupted and the main cause of anemia is erythropoietin deficiency. In patients with malignant neoplasms receiving chemotherapy, the etiology of anemia is multifactorial. In such patients, the cause of anemia is both a deficiency of erythropoietin and a reduced response of erythroid progenitor cells to endogenous erythropoietin.

The epoetin of theta is identical in its amino acid sequence and similar in its carbohydrate composition (glycosylation) to endogenous human erythropoietin.

Pharmacokinetics

The pharmacokinetics of epoetin a theta has been studied in healthy volunteers, in patients with CRF and in patients with oncological diseases receiving chemotherapy.

The pharmacokinetics of epoetin theta does not depend on age or sex.

Bioavailability of epoetin a theta with SC the introduction - 31% of the bioavailability index with the IV introduction. The time to achieve Cmax epoetin a theta in blood plasma is 10-14 h.

In patients with chronic renal failure after 40 mg IU / kg, the final T1 / 2 is higher than after intravenous administration, an average of 25 hours after a single dose and 34 hours in a stable state after repeated doses 3 times a week. The effect of accumulation of epoetin theta was not detected.

In patients with oncological diseases receiving chemotherapy, after repeated administration of 20000 ME epoetin theta once a week, T1 / 2 - 29 hours after the first dose and 28 hours with repeated application. The effect of accumulation of epoetin theta was not detected.

Vd is approximately equal to bcc.

In patients with chronic hemodialysis CRF, T1 / 2 epoetin theta is 6 hours after a single dose and 4 hours after repeated iv injection of epoetin theta 40 IU / kg 3 times a week. The effect of accumulation of epoetin theta was not detected.

Special clinical cases. The pharmacokinetics of epoetin a theta in patients with hepatic insufficiency has not been studied.

Indications of the Eporatio

Treatment of anemia associated with chronic renal failure, incl. In patients on hemodialysis;

Treatment of anemia in patients with non-myelogenous tumors receiving chemotherapy (only SC administration).

Contraindications

Hypersensitivity to epoetin theta or one of the components of the drug;

True erythrocyte aplasia (IETA);

Uncontrolled arterial hypertension;

Insufficiency of liver function;

Sickle-cell anemia;

Age over 75 years;

Anemia in patients with malignant tumors who are not receiving chemotherapy and radiation therapy;

Anemia at a Hb concentration of more than 12 g / dL (7.45 mmol / L) in patients with malignant tumors receiving chemotherapy and radiation therapy;

pregnancy;

The period of breastfeeding;

Age younger than 18 years (no experience with the drug).

With caution: cardiovascular diseases, incl. Diseases of the vessels of the brain and peripheral vessels; Patients with a risk of developing thrombosis and thromboembolism.

Application in pregnancy and breastfeeding

Information on the efficacy and safety of the use of the drug Eporatio in pregnancy and during breastfeeding are absent.

Side effects

Side effects are classified according to frequency according to WHO recommendations: very often - not less than 10%; Often - not less than 1%, but less than 10%; Infrequently - not less than 0,1%, but less than 1%; Rarely - not less than 0.01%, but less than 0.1%; Very rarely - less than 0.01%, including single messages.

On the part of the blood and lymphatic system: often - shunt thrombosis (can occur mainly in patients who are prone to hypotension or in the presence of complications of arteriovenous fistula: stenosis or aneurysm); Very rarely - thrombocytosis, thromboembolic disorders, IETA.

From the immune system: often - skin rash, itching, hives: very rarely - anaphylactoid reactions.

From the side of the central nervous system: often - a headache.

From the CVS: often - the emergence or strengthening of the existing arterial hypertension, hypertensive crisis with the phenomena of encephalopathy (headaches, confusion, sensory and motor disturbances up to tonic-clonic seizures).

From the musculoskeletal and articular tissues: often - arthralgia.

Other: often - influenza-like syndrome (especially at the beginning of therapy), the symptoms of which are usually mild or moderate and disappear after a few hours or days, incl. Fever, chills, headache, pain in the extremities or bones, general malaise.

Interaction

The data obtained so far have not revealed any interaction of epoetin with other drugs.

To avoid incompatibility or decrease in drug activity, epoetinethate should not be mixed with other medications or injectable solutions.

Dosing and Administration

Treatment is carried out under the supervision of a doctor.

IV a slow introduction for 2 minutes and SC slow injection into the abdomen, shoulder or thigh. It is necessary to change the injection site regularly for injections to avoid the development of local reactions.

Before use, make sure that the syringe is usable, filled with a clear solution and has no suspended visible particles. The solution for injection cannot be shaken. Before use, the injection solution should reach room temperature. If the drug Eporatio is substituted for another preparation of epoetin, then it is necessary to maintain the same method of administration. The aim of treatment is to increase the concentration of Hb. The effectiveness of therapy depends on an adequately selected individual treatment regimen. Since it is not possible to predict the individual response to treatment with the drug Eporatio, the concentration of Hb can be controlled by changing the dose of the drug Eporatio, keeping it at least 10 g / dL (6.21 mmol / L) but not more than 12 g / dl (7, 45 mmol / L).

Treatment of anemia associated with CRF, incl. In patients on hemodialysis

SC and IV introduction. Patients who do not receive hemodialysis, preferably SC injection, to avoid repeated punctures of peripheral veins. Patients on hemodialysis - through the arteriovenous shunt at the end of the dialysis session.

If the concentration of Hb is increased by more than 2 g / dl (1.24 mmol / L) for 4 weeks or an increase in Hb concentration of more than 12 g / dl (7.45 mmol / L), the dose of the preparation of Epororio is reduced by 25-50%.

It is recommended to monitor the concentration of Hb every 2 weeks before and after stabilization has been achieved. If the Hb concentration continues to increase, then the therapy is interrupted until the Hb concentration begins to decrease, after which the therapy is resumed at a dose equal to approximately 25% of the initial dose. With concomitant cardiovascular diseases, incl. Arterial hypertension, cerebrovascular disease and peripheral vascular disease, the increase in Hb concentration and the target Hb concentration should be determined individually for each patient, taking into account the clinical picture.

The stage of correction of Hb concentration.

SC: the initial dose is 20 IU / kg 3 times a week. In case of insufficient increase in Hb concentration (less than 1 g / dL (0.62 mmol / L) for 4 weeks), the dose is increased to 40 IU / kg 3 times a week every 4 weeks. If necessary, additionally increase the dose of the drug Eporatio by 25% from the previous dose at an interval of 1 month until the individual target concentration of Hb is reached.

IV: the initial dose is 40 IU / kg 3 times a week. In addition, the dose is increased after 4 weeks to 80 IU / kg 3 times a week. If necessary, the dose is increased by 25% from the previous dose at an interval of 1 month. The maximum dose for p / to and / in the introduction should not exceed 700 IU / kg / week.

Stage of stabilization of Hb concentration. The maintenance dose is adjusted to maintain an individual target Hb concentration of at least 10 g / dL (6.21 mmol / L), but not more than 12 g / dL (7.45 mmol / L). If necessary, the dose adjustment is changed by approximately 25%.

SC: the total weekly dose is given at a time or divided by a dose of 3 injections during the week.

IV: with the stability of the concentration of Hb, the total weekly dose is divided into 3 injections during a week or 2 injections during a week.

When changing the mode of administration, it is necessary to monitor the concentration of Hb and, if necessary, adjust the dose and mode of administration.

The maximum dose for SC and IV the introduction should not exceed 700 IU / kg / week.

Treatment of anemia in patients with non-myeloid tumors receiving chemotherapy.

Only SC introduction. The initial dose is 20000 IU once a week. If the concentration of Hb increases by 1 g / dL (0.62 mmol / L) for 4 weeks, therapy is continued at the initial dose. In case of insufficient increase in Hb concentration (less than 1 g / dL (0.62 mmol / L) for 4 weeks), the dose is increased to 40,000 IU. If after 4 weeks the increase in Hb concentration is still insufficient, consider the possibility of increasing the total weekly dose to 60,000 ME. The maximum dose should not exceed 60000 ME / wk.

If, after 12 weeks of therapy, there is no increase in Hb concentration by at least 1 g / dL (0.62 mmol / L), evaluate the effectiveness of treatment with the drug Ecopartio and, if necessary, discontinue treatment.

If the increase in Hb concentration exceeds 2 g / dl (1.24 mmol / L) for 4 weeks or the Hb concentration exceeds 12 g / dl (7.45 mmol / L), then the dose is reduced by 25-50%. If the Hb concentration is more than 13 g / dl (8.07 mmol / L), then the therapy is interrupted until the Hb concentration drops to 12 g / dL (7.45 mmol / L) or lower, after which the therapy is resumed at Dose of approximately 25% of the initial dose.

Therapy with the drug Eporatio should last up to 4 weeks after the end of chemotherapy.

Recommendations for the use of the drug

First you need to make sure that the patient has everything you need for an injection: a filled syringe with an Ecoporio preparation, a cotton swab dampened with alcohol, a piece of gauze dressing or a sterile gauze swab, a puncture resistant container for used syringes.

What the patient should do before the injection of the drug

1. Take one blister with the drug Ecoporio from the refrigerator.

2. Open the blister and remove the filled syringe and the container with the needle. Do not pull the filled syringe behind the piston or protective cap.

3. Check the expiration date on the label of the filled syringe (Good to :). Do not use the drug if the date of the last day indicated on the label of the month has expired.

4. Evaluate the appearance of the drug Eporatio. It must be a clear and colorless liquid. Do not use the drug if there are particles in it or when the solution is cloudy.

5. At the end of the container with the needle there is a cap, open the marked seal / label and remove the cap (see picture 1).

Picture 1.

6. Remove the protective cap from the filled syringe (see picture 2).

Picture 2.

7. Connect the needle to the syringe (see picture 3). A cap that protects the needle until removed.

Picture 3.

8. For a more comfortable injection procedure, leave the filled syringe for 30 minutes to warm to room temperature (no higher than 25 ° C) or carefully, hold the syringe in your hand for several minutes. Do not heat the preparation with any other method (for example, do not heat it in a microwave oven or in hot water).

9. Do not remove the protective cap from the needle if the patient is not yet ready to inject.

10. Choose a comfortable, well-lit place. The materials needed for the injection (a filled syringe with the preparation of Ecoporio, a cotton swab dampened with alcohol, a piece of gauze dressing or a sterile gauze swab and a puncture-resistant container) are spread out so that the patient can reach them easily.

11. Wash hands thoroughly.

How to prepare for an injection

Prior to the injection of the drug, the patient needs to do the following:

12. Take the syringe and carefully remove the protective cap from the needle, avoiding rotation. The cap should be pulled along the axis of the syringe, as shown in Figure 4. Do not touch the needle and do not press the plunger.

Picture 4.

13. There may be a small amount of air bubbles in the filled syringe. If air bubbles are present, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. By directing the syringe upward, remove air from the syringe, by slowly pressing the piston in the upward direction.

14. There is a scale on the syringe barrel. Press the plunger to the unit (ME) scale corresponding to the dose of Ecoporio prescribed for the patient by the doctor.

15. Recheck the correctness of the set dose of Ecoporio according to the scale of the syringe.

16. Now the filled syringe is ready for use.

Selecting a site for injection

The most suitable places for injections are the following areas:

- the upper part of the thigh;

- the abdomen, except for the umbilical region (see the areas shaded in gray in picture 5).

Picture 5.

There may be an introduction to the back and side of the shoulder, if someone helps the patient to do the injection (see the areas shaded in gray in picture 6). Preferably change injection sites each time in order to avoid the risk of pain in the same area.

Picture 6.

How to make an injection

17. Disinfect the area of the skin at the injection site with a cotton swab dipped in alcohol and gently fold the skin into the fold with the thumb and forefinger without squeezing it (see picture 7).

Picture 7.

18. Fully insert the needle, protected by a nozzle, under the skin. The angle between the syringe and the skin should not be too sharp (at least 45 °, see picture 8). The protective nozzle on the needle will be retracted when the needle is inserted under the skin.

Picture 8.

19. Slightly pull the plunger to ensure that the blood vessel has not been punctured. If the patient sees blood in the syringe, remove the needle and re-enter it elsewhere.

20. Slowly and evenly apply the drug solution under the skin, holding the fold (see picture 9).

Picture 9.

21. After the injection, remove the needle and release the skin. The needle will again be protected with a nozzle and automatically closed so that the patient cannot accidentally inject itself (see picture 10).

Picture 10.

22. Press the injection site with a piece of gauze dressing or a sterile gauze pad and hold for a few seconds.

23. Use a syringe for only one injection. Do not use the remaining solution in the syringe preparation Eporatio.

Overdose

Symptoms: The therapeutic index of the drug is very wide, but one should take into account the individual response to therapy at the beginning of treatment. An excessive pharmacodynamic response is possible, i.e. Polycythemia with life-threatening cardiovascular complications.

Treatment: polycythemia therapy with the drug Eporatio stop. If necessary, conduct a phlebotomy.

Special instructions

For all patients with serum ferritin values less than 100 mkg / l or with transferrin saturation less than 20%, additional iron therapy is recommended. To ensure effective erythrocytopoiesis, the iron content of each patient should be carefully evaluated before and during therapy. Absence of effect in therapy with the drug Eporatio should be considered the basis for the search for other etiopathogenetic factors of the development of anemia. Therefore, before the start of treatment, it is necessary to exclude the deficiency of cyanocobalamin and folic acid, which can reduce the effectiveness of epoetins.

The erythropoietic reaction can also be weakened by intercurrent infections, inflammatory processes or trauma, hidden blood loss, hemolysis of erythrocytes, aluminum intoxication, latent hematologic disorders or bone marrow fibrosis.

In the case of the elimination of the most common causes of the absence of an erythropoietic reaction, if the patient is found to have a sharp decrease in the concentration of Hb associated with reticulocytopenia, a definition of antierythropoietin antibodies should be made and a bone marrow examination for a differential diagnosis with IETA, which is an indication of discontinuation of treatment with Eporatio. Cases where IECA was caused by the neutralizing effect of anti-EPSO antibodies are described in connection with the use of therapy with the drug Eporatio. It has been shown that these antibodies cross-react with all epoetins, so patients with suspicion or confirmation of the presence of neutralizing antibodies should not use the drug Eporatio.

When therapy with the drug Eporatio in patients can increase blood pressure, especially at the initial stage of treatment. BP should be monitored before and during therapy to avoid acute complications such as hypertensive crisis with symptoms of encephalopathy (headache, confusion, speech disorders, gait disturbance) and associated complications (seizures) that may also occur in patients Both with normal and low blood pressure. Particular attention should be paid to a sudden acute migraine-like headache as a possible warning signal.

Increased blood pressure may require treatment with antihypertensive drugs or increase their dose. If blood pressure remains high, it may be necessary to temporarily stop therapy with Eporatio. With the stabilization and successful control of blood pressure, therapy with Eporatio should be started anew in a reduced dose.

The erroneous use of the drug Eporatio in healthy people can lead to an excessive increase in the concentration of Hb and hematocrit, which can lead to life-threatening cardiovascular complications. Due to limited clinical experience, the efficacy and safety of the Ecoporothy drug have not been established in patients with impaired hepatic function or homozygous sickle cell anemia.

In clinical studies in patients over the age of 75, there was a higher incidence of serious and severe adverse events, regardless of the causal relationship with therapy with the drug Ecoporio. In addition, deaths were more frequent in this group of patients compared to younger patients.

Anemia associated with CRF, incl. In patients on hemodialysis. The possibility of using the drug Eporatio in patients with nephrosclerosis who have not undergone dialysis should be determined individually, since the possible accelerated development of renal failure cannot be ruled out. During hemodialysis, patients taking the drug Eporatio may need to increase the dose of anticoagulant to prevent thrombosis of the arteriovenous shunt.

In patients with CRF, the concentration of Hb in the stabilization phase should not exceed the upper limit of the Hb concentration recommended in the "Application and dose" section. In clinical studies, increased mortality and serious cardiovascular complications were observed when epoetins were administered to patients with a Hb concentration of more than 12 g / dL (7.45 mmol / L).

Anemia in patients with non-myeloid tumors receiving chemotherapy. Erythropoietins are growth factors that mainly stimulate the production of red blood cells. Receptors to erythropoietin can be expressed on the surface of various tumor cells. As with any growth factor, there is a suggestion that erythropoietins are capable of stimulating the growth of any type of malignancy.

In a number of controlled clinical studies, the use of epoetins in patients with anemia associated with cancer has not demonstrated an increase in overall survival or a decrease in the risk of tumor progression.

According to controlled clinical studies, the use of epoetin can lead to:

- to shorten the time to tumor progression in patients with head and neck cancer receiving radiotherapy, while achieving a target Hb concentration of more than 14 g / dl (8.69 mmol / L);

- to a reduction in overall survival and an increase in the number of deaths associated with disease progression within 4 months from the start of treatment in patients with metastatic breast cancer receiving chemotherapy while achieving a target Hb concentration of 12 to 14 g / dl (from 7, 45 to 8.69 mmol / L);

- to an increased risk of death in patients with active malignancy not receiving chemotherapy and radiation therapy, while achieving a target Hb concentration of 12 g / dl (7.45 mmol / L). The drug is unsuitable for use in these patients.

Based on the above, in some clinical situations, blood transfusion is preferable for the treatment of anemia in patients with oncological diseases. The solution for the use of recombinant erythropoietins should be based on an estimate of the ratio of expected benefit to the possible risk for a particular patient, in which a specific clinical picture should be taken into account.

Influence on the ability to drive vehicles and mechanisms. The drug Eporatio does not significantly affect the ability to drive vehicles and perform potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Release form

Solution for intravenous and subcutaneous injection.

For dosages of 1000 IU / 0.5 ml, 2000 IU / 0.5 ml, 3000 IU / 0.5 ml, 4000 IU / 0.5 ml, 5000 IU / 0.5 ml: 0.5 ml of the preparation in a glass Graduated syringe of one-time use of Luer type (glass type I according to Eur. Pharm.) With a sealant of chlorobutyl rubber piston and bromobutyl rubber cap complete with sterile needle with Luer adapter (needle is in a plastic container) or with sterile SurGuard2 needle with safety device The needle is in the blister). 1 syringe and 1 needle are placed in a sealed PVC / PET / PE blister. At 6 bl. Placed in a cardboard box. Control of the first opening is provided by two protective stickers on a cardboard bundle.

For dosages of 10,000 IU / ml, 20,000 IU / ml, 30,000 IU / mL: 1 ml of the drug in a glass graduated syringe of the Luer type (type I glass according to Eur. Pharm.) With a chlorobutyl rubber piston sealant and a bromobutyl rubber cap in Complete with a sterile needle with a Luer adapter (the needle is in a plastic container) or with a sterile SurGuard2 needle with a safety device (the needle is in the blister). 1 syringe and 1 needle are placed in a sealed PVC / PET / PE blister. By 1, 4 or 6 bl. Are placed in a cardboard box. Control of the first opening is provided by two protective stickers on a cardboard bundle.

Manufacturer

Merkle GmbH, Ludwig-Merkle-Strasse 3, 89143 Blaubeuren, Germany.

Legal entity in whose name the RU is issued: Teva Pharmaceutical Enterprises Ltd., Israel.

Claims of consumers should be sent to the address: 119049, Moscow

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Eporatio

At a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life of the drug Eporatio

2 years.

Do not use after the expiry date printed on the package.