Mircera
Mircera: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Mircera
ATX code: B03XA03
Active ingredient: methoxypolyethylene glycol-epoetin beta (Methoxipolyethylenglycol-epoetin beta)
Manufacturer: F. Hoffmann-La Roche Ltd. (F. Hoffmann-La Roche, Ltd.) (Switzerland); Roche Diagnostics, GmbH (Germany)
Description and photo update: 2019-09-07
Prices in pharmacies: from 4050 rubles.
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Mircera is an antianemic agent, a stimulant of erythropoiesis.
Release form and composition
Mircera is produced in the form of a solution for intravenous (i / v) and subcutaneous (s / c) administration: a colorless or slightly yellow transparent liquid (1 ml each in a colorless glass bottle, sealed with a butyl rubber lid, crimped with an aluminum cap, and a closed plastic lid, in a cardboard box 1 bottle; 0.3 or 0.6 ml each in a syringe tube, the body of which is made of glass, the piston is made of plastic with a butyl rubber stopper, laminated with fluoropolymer, the piston handle has the Roche logo; in protective transparent plastic container with a spring 1 syringe tube, in a hermetically sealed plastic container 1 sterile injection needle; in a hermetically sealed blister strip 1 syringe tube with a container with a needle, in a cardboard box 1 pack Each pack also contains instructions for the use of Mircera).
Composition of the preparation:
- active substance for 1 bottle of 1 ml: methoxypolyethylene glycol-epoetin beta - 50, 100, 200, 300, 400, 600 or 1000 mcg;
- active substance per 1 syringe tube with a volume of 0.3 ml: methoxypolyethylene glycol-epoetin beta - 30, 40, 50, 60, 75, 100, 120, 150, 200 or 250 μg;
- active substance per 1 syringe tube with a volume of 0.6 ml - 360, 400, 600 or 800 μg;
- additional components: sodium sulfate anhydrous, mannitol, L-methionine, sodium dihydrogen phosphate monohydrate, diluted hydrochloric acid or sodium hydroxide solution (qs to pH 6.2), water for injection, poloxamer 188.
Pharmacological properties
Pharmacodynamics
Mircera is a chemically synthesized representative of a new class, a long-acting erythropoietin receptor activator. Methoxypolyethylene glycol-epoetin beta, the active ingredient of the drug is a covalent conjugate of linear methoxypolyethylene glycol (PEG) and a protein, which is produced by recombinant DNA. Unlike erythropoietin, methoxypolyethylene glycol-epoetin beta has an amide bond between methoxypolyethylene glycolbutanoic acid and the N-terminal amino group or ε-amino group of lysine, mainly Lys 52 and Lys 45. The molecular weight of methoxypolyethylene glycol-epoetin beta is approximately 60 kDa, of which 30 kDa is the molecular weight of PEG.
The synthesized substance is characterized by such features as different from erythropoietin activity at the receptor level, prolonged association with the receptor and faster dissociation from the receptor, weakened specific activity in vitro and increased activity in vivo, as well as an extended half-life (T 1/2), which makes it possible to administer the drug once a month.
Mircera accelerates erythropoiesis by interacting with erythropoietin receptors located on bone marrow progenitor cells. Natural erythropoietin, the main growth factor required for the maturation of red blood cells, is produced by the kidneys and is released into the bloodstream in response to hypoxia. Erythropoietin interacts with erythrocyte precursor cells and causes an increase in erythrocyte formation.
During therapy with Mircera, 97.5% of patients with chronic kidney disease (CKD) who were not on dialysis, as well as 93.3% of patients with CKD on dialysis, had anemia correction. In patients receiving dialysis treatment, when switching from therapy with epoetin or darbepoetin alfa to therapy with Mircera, a stable target hemoglobin (Hb) level is maintained.
In studies in the group using Mircera as a maintenance drug once a month, the proportion of CKD patients on hemodialysis with a positive response to treatment was significantly higher compared with the maintenance group with darbepoetin alfa, once a month (p <0.0001).
Pharmacokinetics
After intravenous administration of Mircera, T 1/2 is 15–20 times longer than with the introduction of recombinant human erythropoietin. In the course of research, the pharmacokinetic parameters of the drug were studied in healthy volunteers and in patients with anemia and CKD, receiving and not receiving dialysis treatment. It was found that the volume of distribution (Vd) and the clearance of methoxypolyethylene glycol-epoetin beta in the presence of CKD are independent of the dose.
Pharmacokinetic parameters of the drug were studied in patients with CKD after a single dose of the drug at 9 and 19 or 21 weeks. It was found that repeated administration has no effect on V d, clearance and bioavailability of the active substance. The use of methoxypolyethylene glycol-epoetin beta in patients with CKD once every 4 weeks did not cause a significant accumulation of the agent, the cumulation coefficient was 1.03. When administered once every 2 weeks, the cumulation coefficient slightly increased to 1.12.
According to the results of a comparison of the levels of methoxypolyethylene glycol-epoetin beta before and after hemodialysis in serum in patients with CKD, hemodialysis does not affect the pharmacokinetics of the drug.
Local tolerance, pharmacodynamics and pharmacokinetics of the active substance do not depend on the site of subcutaneous administration (anterior abdominal wall, shoulder or anterior thigh), as evidenced by the results of a study with healthy volunteers.
The time to reach serum C max of methoxypolyethylene glycol-epoetin beta after SC administration was 72 hours in patients with CKD on dialysis and 95 hours in those not on dialysis. The absolute bioavailability of the active substance in patients receiving and in patients not receiving dialysis treatment was 62 and 54%, respectively. In patients with CKD V d is equal to 5 liters.
With the on / in the introduction of T 1/2 of the drug 134 hours (or 5.6 days), the full systemic clearance is 0.494 ml / h / kg. With subcutaneous administration, T 1/2 in patients on dialysis was 139 hours, in patients not requiring dialysis - 142 hours.
There is no need to adjust the starting dose of Mircera for race, gender and age.
Indications for use
The use of Mircera is recommended for the treatment of anemia associated with chronic renal failure [code N18 according to the classification of the International Association of Nephrologists (NKF K / DOQI) - CKD].
Contraindications
Absolute:
- age up to 18 years;
- uncontrolled arterial hypertension;
- hypersensitivity to any component of the drug.
Relative (Mircera should be used with extreme caution, since its safety and effectiveness for these groups have not been sufficiently studied):
- pregnancy and lactation;
- epilepsy;
- hemoglobinopathy;
- thrombocytosis (platelet count is above 500 × 10 9 / l).
Mircera, instructions for use: method and dosage
Mircera solution is intended for subcutaneous and intravenous administration.
Due to the longer half-life of the drug, it should be used less frequently than other stimulants of erythropoiesis. It is necessary to start using the drug only under the supervision of a specialist.
The solution for s / c and i / v injections is sterile and does not include preservatives. You can enter only a colorless or pale yellow transparent solution, without visible impurities. If the product has been stored in the refrigerator, it should be brought to room temperature before injection.
Mircera in a syringe tube can be stored for 1 month at a temperature not exceeding 30 ° C, it should be applied during this month. The drug in a vial can be stored for 7 days at a temperature not exceeding 25 ° C, and used during this period. Each syringe tube or bottle can only be used once. Do not shake the drug. Dispose of unused solution.
The Hb level is required to be determined once every 14 days before stabilization and occasionally after stabilization.
Treatment of patients not currently receiving an erythropoiesis stimulant
Patients who do not use drugs to stimulate erythropoiesis at the time of initiation of therapy are recommended to use Mircera at an initial dose of IV or SC 1 time in 14 days at 0.6 μg / kg, target Hb> 110 g / L (6.83 mmol / L), or in an alternative regimen (for patients not on dialysis treatment) - sc once a month at 1.2 μg / kg, target Hb> 110 g / L (6.83 mmol / L) …
If a month after the start of the course, the increase in Hb is less than 10 g / l (0.621 mmol / l), the dose of Mircera can be increased by 25-50% from the previous one. The subsequent dose increase by approximately 25-50% can be carried out no more than 1 time per month, until the individual level of the target Hb is reached.
If after 1 month the increase in Hb is more than 20 g / l (1.24 mmol / l), the dose of the drug can be reduced by 25-50% of the previously received one. If the Hb level exceeds 130 g / l (8.07 mmol / l), it is necessary to interrupt the use of the drug until the Hb drops below 130 g / l and then start using Mircera again at a dose of 50% of the previous one. If the target Hb content is 120 g / l, the dose should be changed by 25%.
After completion of treatment, Hb decreases by an average of 3.5 g / L (0.22 mmol / L) in 7 days. If it is revealed that the level of the target Hb exceeds 110 g / l (6.83 mmol / l) when receiving Mircera therapy once every 14 days, it is allowed to transfer the patient to an antianemic agent once a month at a dose that is 2 times higher than previously used … The dose of the drug should be adjusted no more than 1 time per month.
Treatment of patients currently receiving an erythropoiesis stimulant
If patients receive another drug that stimulates erythropoiesis, they can switch to the use of Mircera s / c or i / v, adhering to the administration regimen once every 14 days or once a month. The initial dose in this case is set taking into account the weekly dose of the previously administered drug: darbepoetin alfa - mcg at 7 days; epoetin alpha / beta - units of action (U) in 7 days. The first injection of Mircera is carried out on the day of the next scheduled injection of the previously used drug.
Switching to injections of Mircera solution from injections of darbepoetin alfa and epoetin (alpha or beta). The previous weekly doses of darbepoetin alfa (μg / 7 days) / epoetin (U / 7 days) and the initial doses of Mircera are indicated - once / month (μg / month) / once every 14 days (μg / 14 days):
- less than 40 / less than 8000: 120/60;
- 40-80 / 8000-16000: 200/100;
- over 80 / over 16,000: 360/180.
If a dose change is required to maintain the target Hb concentration above 110 g / L (6.83 mmol / L), the monthly dose can be adjusted by 25%.
If after 1 month the increase in the Hb content is more than 20 g / l (1.24 mmol / l), the dose of Mircera should be reduced by 25-50% from the previous one. If Hb reaches values exceeding 130 g / L (8.07 mmol / L), it is required to interrupt therapy until the Hb level falls below 130 g / L (8.07 mmol / L), after which the drug should be resumed at a dose of 50 % from the previous one.
With a target Hb level of 120 g / l, the dose of Mircera is changed by 25%. After completion of the course, Hb decreases by approximately 3.5 g / L (0.22 mmol / L) in 7 days. The dose of the drug is adjusted no more than 1 time per month.
Therapy for anemia, including the use of Mircera, is usually carried out for a long time, however, if necessary, treatment with the drug can be interrupted at any time.
If one of the injections has been missed, it should be carried out as soon as possible and then Mircera should be used as usual.
Technique for preparing and conducting injection with a syringe tube
Step-by-step instructions for preparing a syringe tube for the injection procedure:
- Remove from the cardboard box, without removing the protective film, a blister strip transparent packaging with a syringe tube and a container with a needle.
- Wash hands well with warm water and soap.
- Remove the protective film from the cell packaging and take out the syringe tube and the plastic container with the needle.
- While holding the needle container, separate the cap by rotating it clockwise, and then remove it from the top of the needle container.
- While holding the syringe tube, bend and pull the rubber tip, removing it from the syringe.
- Holding a transparent container with a needle, firmly insert the needle into the syringe tube.
Preparation and administration of the injection:
- Choose one of the recommended areas for subcutaneous injection: the outer surface of the shoulder, the anterior surface of the mid-thigh, the anterior abdominal wall, except for the area around the navel. The solution should not be injected into the tissues of scars, birthmarks, hematomas or the navel, into areas with seals and / or disorders after previous injections. It is required to alternate the injection sites each time, avoiding areas that may possibly be irritated due to exposure to a belt or waistband.
- Treat the skin at the injection site with a tampon soaked in alcohol, wait until the skin dries.
- Gently holding the syringe tube without pressing the plunger, carefully remove the transparent container from the needle.
- At the site of the intended injection, collect the skin with two fingers and insert the needle at a right angle into the formed skin fold.
- Smoothly pressing the plunger of the syringe tube, slowly introduce the entire solution. Continue to push down on the plunger until the needle is removed from the skin.
- Remove the needle from the skin after the entire dose has been injected without releasing the plunger of the syringe tube. After the piston is released, the safety device will release and cover the needle.
- Press the injection site with a cotton swab. If necessary, tape the injection site with a plaster.
Side effects
During treatment with the drug, approximately 6% of patients receiving Mircera may develop adverse reactions, the most common of which is arterial hypertension.
Disorders caused by the use of Mircera and recorded during clinical trials in patients with CKD:
- immune system: extremely rare - hypersensitivity reactions;
- nervous system: rarely - headache; extremely rare - hypertensive encephalopathy;
- cardiovascular system: often - arterial hypertension; extremely rare - hot flashes;
- poisoning, injuries and complications of procedures: rarely - shunt thrombosis;
- skin and its appendages: extremely rare - maculopapular rash;
- changes in laboratory parameters: thrombocytopenia (platelet count <100 × 10 9 / l), was observed in 7.5% of patients using methoxypolyethylene glycol-epoetin beta, and in 4.4% of those receiving treatment with other stimulants of erythropoiesis.
Other disorders associated with Mircera's treatment were rare and were mild to moderate in most cases.
Overdose
The maximum tolerated dose of methoxypolyethylene glycol-epoetin beta has not been established. An overdose symptom may be an increased pharmacodynamic response, i.e. excessive erythropoiesis.
Against the background of high Hb levels, it is necessary to temporarily stop using Mircera. If necessary, phlebotomy can be prescribed.
special instructions
Before starting the course and during the use of an antianemic agent, it is necessary to exclude iron deficiency. If the serum ferritin level in the blood is less than 100 μg / L or the saturation of transferrin with iron is less than 20%, additional iron therapy is recommended.
The most common reasons for an incomplete response to treatment with stimulants of erythropoiesis include the following factors: chronic blood loss, inflammation, deficiency of iron, vitamin B 12 or folic acid, bone marrow fibrosis, hemodialysis-induced sharp increase in aluminum concentration, hemolysis. If all of these conditions are excluded and a sudden decrease in the Hb content, reticulocytopenia, and antibodies to erythropoietin are detected, a bone marrow examination is necessary to exclude partial red cell aplasia (PCA). When confirming the diagnosis of PKKA, it is required to discontinue treatment with Mircera, and also one should not switch to therapy with other drugs that stimulate erythropoiesis.
There have been reports of cases of PCAA, caused by antibodies to erythropoietin, against the background of the use of stimulants of erythropoiesis. It has been found that antibodies cross-react with all drugs that stimulate erythropoiesis. As a result, patients who have identified antibodies to erythropoietin or are suspected of having them should not be transferred to Mircera therapy.
Before using the drug and during the period of therapy, it is necessary to monitor blood pressure (BP). If it cannot be controlled with medication, it is necessary to reduce the dose of methoxypolyethylene glycol-epoetin beta or temporarily abandon drug therapy.
Mircera, like other drugs that activate erythropoiesis, refers to growth factors that mainly stimulate the production of erythrocytes. Erythropoietin receptors can be found on the surface of various tumor cells. It is assumed that drugs that stimulate erythropoiesis, like other growth factors, are capable of stimulating the growth of any type of malignant neoplasm. When using epoetins in patients with various malignant tumors (breast, head, neck), there was an increase in mortality, the causes of which are not clear.
Influence on the ability to drive vehicles and complex mechanisms
The effect of an antianemic agent on the ability to drive vehicles and other complex, potentially dangerous moving machinery has not been studied. Given the safety profile and mechanism of action of Mircera, it is assumed that the antianemic agent does not have such effectiveness.
Application during pregnancy and lactation
The efficacy and safety of using Mircera in pregnant women has not been sufficiently studied.
According to the results of studies carried out on animals, the drug does not have a direct / indirect negative effect on the course of pregnancy, embryonic / fetal development, childbirth or postnatal development. When prescribing an antianemic agent, pregnant women need to be especially careful.
It is not known whether methoxypolyethylene glycol-epoetin beta is excreted in breast milk in women, but it has been established that it passes into human milk in animals. The question of stopping breastfeeding or discontinuing treatment should be decided on the basis of the importance of therapy to the mother and breastfeeding to the baby.
In the course of preclinical studies in animals, no negative effects of Mircera on fertility were found.
Pediatric use
In patients under 18 years of age, Mircera therapy is contraindicated, since the safety and efficacy of using the drug in patients of this age group has not been sufficiently studied.
With impaired renal function
In patients receiving and not receiving dialysis, there are no differences in the pharmacokinetics of the drug.
For violations of liver function
In healthy volunteers and in patients with severe hepatic insufficiency, no differences in the pharmacokinetics of Mircera were found. In the presence of liver failure of any severity, individual selection of the initial dose and correction of the dosage regimen is not required.
Use in the elderly
Elderly patients aged 65 years and older do not need to change the initial dose of Mircera.
Drug interactions
The interaction of methoxypolyethylene glycol-epoetin beta with other drugs has not been studied. In accordance with the data obtained to date, no interactions of Mircera with other medicinal substances / agents have been identified, and there have been no signs of the effect of the latter on the pharmacodynamics and pharmacokinetics of Mircera.
It is not recommended to mix Mircera with other injectable solutions or medicines.
Analogs
Mircera's counterparts are Aranesp, Binocrit, Eprex, Erythropoietin, Erythrostim, Vero-epoetin, Bestim, etc.
Terms and conditions of storage
Store in a place protected from light, out of reach of children, at a temperature of 2–8 ° C, without freezing.
The shelf life of the solution in vials is 1 year, in syringe tubes - 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription
Reviews about Mircera
In the few reviews of Mircera, they most often indicate the effectiveness of the drug in the treatment of anemia in patients with chronic kidney disease. Many of them, being on dialysis, emphasized that due to the action of the drug, they were able to reach Hb levels approaching 130 g / l. The advantages of the drug also include a convenient dosing regimen, no need to adjust the initial dose for elderly patients and patients with impaired liver function.
The disadvantages of Mircera are its high cost and the development of adverse reactions, mainly increased blood pressure.
The price of Mircera in pharmacies
The price of Mircera, solution for intravenous and subcutaneous administration, for 1 set (syringe tube + sterile needle), can be:
- dosage 50 mcg / 0.3 ml - 2800 rubles;
- dosage 75 mcg / 0.3 ml - 4800 rubles;
- dosage 100 mcg / 0.3 ml - 7000 rubles;
- dosage 150 mcg / 0.3 ml - 14,300 rubles.
Mircera: prices in online pharmacies
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Drug name Price Pharmacy |
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Mircera 50 μg solution for intravenous and subcutaneous administration 0.3 ml 1 pc. 4050 RUB Buy |
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Mircera 75 μg / 0.3 ml solution for intravenous and subcutaneous administration 0.3 ml 1 pc. RUB 4100 Buy |
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Mircera 100 μg / 0.3 ml solution for intravenous and subcutaneous administration 0.3 ml 1 pc. RUB 5100 Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
