Эпоратио - instructions for use, doses, side effects, contraindications

Active substanceEpoetin thetaEpoetin theta

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Teva Pharmaceutical Enterprises Co., Ltd. Israel

Dosage form: & nbspsolution for intravenous and subcutaneous administration

Composition:

Syringe 0,5 ml. Active substance: epoetin theta 1000 ME (2000 ME, 3000 ME, 4000 ME, 5000 ME); Excipients: 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.

Syringe 1 ml. Active substance: epoetin theta 10000 ME (20000 ME, 30000 ME); Excipients: sodium dihydrogen phosphate dihydrate 3,12 mg, sodium chloride 3,92 mg, polysorbate-20 0.30 mg, trometamol (Tris) 8.48 mg, hydrochloric acid (6 M) 9.70 μl, water for injection up to 1 ml.

Description:A clear, colorless solution.

Pharmacotherapeutic group:Erythropoiesis Stimulant

ATX: & nbsp

B.03.X.A.01 Erythropoietin

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 mitosis-stimulating 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 chronic renal failure (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 the erythropoietin deficiency and the 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 gender.

Bioavailability of epoetin in the subcutaneous (sc) injection - 31% of the bioavailability index for intravenous (IV) administration. The time to reach the maximum concentration of epoetin in the blood plasma is 10-14 hours.

In patients with chronic renal insufficiency (CRF), after the administration of 40 IU / kg, the final half-life (T1 / 2) is higher than after the IV introduction,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 found.

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

The volume of distribution is approximately equal to the volume of circulating blood.

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 found.

Pharmacokinetics in special clinical cases.

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

Indications:

- Treatment of anemia associated with CRF, including in patients on hemodialysis.

- Treatment of anemia in patients with non-myeloid tumors receiving chemotherapy (only s / c injection).

Contraindications:

Hypersensitivity to epoetin theta or one of the componentspreparation; pregnancy; the period of breastfeeding; true erythrocyte aplasia (IETA); uncontrolled arterial hypertension; insufficiency of liver function, sickle-cell anemia, age over 75; anemia in patients with malignant tumors who are not receiving chemotherapy and radiation therapy; Anemia with a hemoglobin concentration (Hb) more than 12 g / dL (7.45 mmol / l) in patients with malignant tumors receiving chemotherapy and radiation therapy; age younger than 18 years (no experience with the drug).

Carefully:Cardiovascular diseases, including diseases of the vessels of the brain and peripheral vessels; patients with a risk of thrombosis and thromboembolism.

Pregnancy and lactation:

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

Dosing and Administration:

Treatment is carried out under the supervision of a doctor.

In / in a slow introduction for 2 minutes and a / c slow injection into the abdomen, shoulder or thigh area. 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 can not 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 goal of treatment is to increase the concentration of hemoglobin. The effectiveness of therapy depends on an adequately selected individual treatment regimen. Since it is impossible to predict the individual response to treatment with the Ecopothio drug, the concentration of hemoglobin 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, including in patients on hemodialysis

A / c and iv introduction. Patients who do not receive hemodialysis, preferably sc, are introduced to avoid repeated punctures of the 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 the Hb concentration is increased to more than 12 g / dl (7.45 mmol / L), the dose of the preparation of Epororio is reduced by 25-50%.

It is recommended that the concentration of Hb be monitored every two weeks before and after stabilization is achieved. If the concentration of Hb continues to increase, 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, including arterial hypertension, diseases of cerebral vessels and peripheral vessels, 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 the concentration of Hb

S / o introduction: 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 hemoglobin is reached.

IV introduction: initial dose is 40 IU / kg 3 times a week. In addition, the dose is increased 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 IV and IV administration should not exceed 700 IU / kg per week.

The stage of stabilizing the concentration of Hb

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 administration: the total weekly dose is administered concomitantly or divided by a dose of 3 injections per week.

IV introduction: 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 the mode of administration.

The maximum dose for IV and IV administration should not exceed 700 IU / kg per week.

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

Only s / c introduction.

The initial dose is 20,000 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 60,000 IU per week.

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 make sure that you have everything you need for an injection: a filled syringe with Ecoporio, a cotton swab moistened with alcohol, a piece of gauze dressing or a sterile gauze swab,Puncture-resistant container for used syringes.

What you should do before injecting 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. Do not use the drug if the date of the last day indicated on the label of the month has expired.

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

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

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

7. Connect the needle to the syringe (see Figure 3). The cap protecting the needle, do not remove it yet.

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 warm the preparation with any other method (for example, do not heat it in a microwave oven or in hot water).

9. Do not remove Protective cap from the needle if you are not yet ready to inject.

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

11. Wash your hands thoroughly.

How to prepare for an injection

Before the injection of the drug, you need to do the following:

1. 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 or press the plunger.

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

3. There is a scale on the syringe barrel.Push the plunger to the unit (ME) of the scale corresponding to the dose of Ecoporio prescribed by your doctor.

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

5. 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;

- stomach, with the exception of the umbilical region (see areas shaded in gray in Figure 5).

There may be an introduction to the back and side of the shoulder if someone helps you to make an injection (see the areas shaded in gray in Figure 6). It is preferable to change the injection site each time to avoid the risk of developing pain in the same area.

How to make an injection

1. Disinfect the area of the skin at the injection site with a cotton swab dipped in alcohol, and gently gather the skin into the fold with the thumb and index finger, without squeezing it (see Figure 7).

2. Fully insert the needle under the skin. The angle between the syringe and the skin should not be too sharp (at least 45 ° C, see figure 8).

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

4. Slowly and uniformly inject the drug solution under the skin, holding the fold.

5. After the administration of the drug, remove the needle and release the skin.

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

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

What you should do before injecting the drug, with a SurGuard2 needle with a needle safety device.

1. Take one blister of the drug from the fridge.

2. Open the blister and remove the filled syringe and the blister with the needle. Do not pull the pre-filled syringe past the piston or protective cap.

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

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

5. Open the blister and remove the SurGuard2 needle with the needle safety device, as shown in figure 1.

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

7. Connect the needle to the syringe (see Figure 3). The cap protecting the needle, do not remove it yet.

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 warm the preparation with any other method (for example, do not heat it in a microwave oven or in hot water).

9. Do not remove Protective cap from the needle if you are 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) are laid out so that you can reach them easily.

11. Wash your hands thoroughly.

How to prepare for an injection

Before the injection of the drug, you need to do

1. Leave the protective device from the SurGuard2 needle in the direction of the syringe barrel (see Fig.Figure 4).

2. 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 5.

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

4. There is a scale on the syringe barrel. Push the plunger to the unit (ME) of the scale corresponding to the dose of Ecoporio prescribed by your doctor.

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

6. 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 areas shaded in gray in Figure 6).

It is possible to insert a posterior or lateral surface of the shoulder if someone helps you to make an injection (see the areas shaded in gray in Figure 7).It is preferable to change the injection site each time to avoid the risk of developing pain in the same area.

How to make an injection

1. Disinfect the area of the skin at the injection site with a cotton swab dipped in alcohol and gently gather the skin into the fold with the thumb and index finger, without squeezing it (see Figure 8).

2. 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 ° C, see figure 9).

3. Slowly and uniformly inject the drug solution under the skin, holding the fold (see Figure 10).

4. After the administration of the drug, remove the needle and release the skin. Leave the SurGuard2 needle in a safe position by quickly lowering the protective device until it clicks (see Figures 11 and 12).

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

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

Side effects:

Side effects are classified according to frequency in accordance with the recommendations of the World Health Organization: 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.

From the side 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); rarely - thrombocytosis, thromboembolic disorders, IETA.

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

From the central nervous system: often a headache.

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

From the musculoskeletal and articular tissues: often - arthralgia.

Other: often - the flu-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.

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: With polycythemia, therapy with the drug Eporatio is stopped. When need to conduct phlebotomy.

Interaction:

The data obtained to date have not revealed any interaction of epoetin with other drugs.

To avoid incompatibility or reduce the activity of the drug, you should not mix epoetin theta with other medicinal products or injectable solutions.

Special instructions:

For all patients with serum ferritin values less than 100 μg / 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 as the basis for the search for other etiopathogenetic factors of anemia development.Therefore, before the start of treatment, it is necessary to eliminate 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, hemolytic erythrocytes, aluminum intoxication, latent hematologic disorders or bone marrow fibrosis.

In the case of exclusion of the most common causes of the absence of an erythropoietic reaction, if a patient exhibits a sharp decrease in the concentration of Hb, associated with reticulocytopenia, it is necessary to determine the anti-erythropoietin antibodies and the bone marrow examination for a differential diagnosis with IETA, which is an indication for discontinuing treatment with the drug Eporatio. Cases when IECA was caused by the neutralizing effect of anti-erythropoietin 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 (BP), 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 impairment, gait disturbance) and associated complications (convulsions) 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 Ecoporio. With the stabilization and successful control of blood pressure, therapy with Ecoporio 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 the therapy with the drug Ecoporio. In addition, deaths were more frequent in this group of patients compared to younger patients.

Anemia, associated with CRF, including in patients on hemodialysis

The possibility of using the drug Ecoporothy in patients with nephrosclerosis who have not undergone dialysis should be determined individually, because the possible accelerated development of renal failure can not 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 must not exceed the upper limit of the concentration of Hb, recommended in the section "Method of administration and dose".In clinical studies, there was an increased mortality and serious cardiovascular complications, when epoetins were administered to patients with a concentration of Hb 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 trials, the use of epoetins in patients with anemia associated with cancer has not demonstrated an increase in overall survival or a reduction in the risk of tumor progression. According to controlled clinical studies, the use of epoetin can lead to:

- - to reduce the time to tumor progression in patients with head and neck cancer receiving radiation therapy, 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 up 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.

Effect on the ability to drive transp. cf. and fur:The drug Ecoporio does not significantly affect the ability to drive vehicles and perform potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and subcutaneous injection.

Packaging:

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 Luer type (type I glass according to Eur.Pharm.) With a chlorobutyl rubber piston sealant and a bromobutyl rubber cap complete with a sterile needle with a Luer adapter (the needle is in a plastic container) or with a sterile needle SurGuard2 with the needle safety device (the needle is in the blister).

1 syringe and 1 needle are placed in a sealed PVC / PET / PE blister.

For 6 blisters together with instructions for use in a cardboard bundle. The first opening is controlled 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 one-time use of the Luer type (glass I of the type according to Eur. Pharm.) With the sealant of the chlorobutyl rubber piston and the bromobutyl rubber cap supplied with a sterile needle with Luer adapter (the needle is in a plastic container) or with a sterile needle SurGuard2 with the needle safety device (the needle is in the blister).

1 syringe and 1 needle are placed in a sealed PVC / PET / PE blister.

For 1, 4 or 6 blisters together with instructions for use in a cardboard bundle. The first opening is controlled by two protective stickers on a cardboard bundle.

Storage conditions:

Store at a temperature of 2 to 8 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003157

Date of registration:31.08.2015

Expiration Date:31.08.2020

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

MERCKLE, GmbH Germany