MIRCERA

Active material: Methoxy polyethylene glycol-epoetin beta
When ATH: B03XA03
CCF: The stimulator of erythropoiesis
ICD-10 codes (testimony): D63
When CSF: 19.01.02.02
Manufacturer: F.Hoffmann-La Roche Ltd. (Switzerland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

The solution for I / O and p / to the introduction in the form of a transparent, a colorless or slightly yellowish liquid.

Excipients: L-methionine, Sodium sulfate anhydrous, sodium dïgïdrofosfata monohydrate, mannitol, poloxamer 188, diluted hydrochloric acid or sodium hydroxide solution, water d / and.

0.3 ml – ampin (1) complete with needle (1 PC.) – packings Valium planimetric (1) – packs cardboard.

The solution for I / O and p / to the introduction in the form of a transparent, a colorless or slightly yellowish liquid.

Excipients: L-methionine, Sodium sulfate anhydrous, sodium dïgïdrofosfata monohydrate, mannitol, poloxamer 188, diluted hydrochloric acid or sodium hydroxide solution, water d / and.

0.6 ml – ampin (1) complete with needle (1 PC.) – packings Valium planimetric (1) – packs cardboard.

The solution for I / O and p / to the introduction in the form of a transparent, a colorless or slightly yellowish liquid.

Excipients: L-methionine, Sodium sulfate anhydrous, sodium dïgïdrofosfata monohydrate, mannitol, poloxamer 188, diluted hydrochloric acid or sodium hydroxide solution, water d / and.

1 ml – colorless glass vials (1) – packs cardboard.

Pharmacological action

Stimulator of hematopoiesis. Mircera^® – chemically synthesized a new class of continuous erythropoietin receptor activator action. Methoxypolyethylene glycol-epoetin beta is a covalent conjugate of a protein, produced by recombinant DNA, and linear methoxypolyethylene (PEG). Methoxypolyethylene glycol-epoetin beta differs from erythropoietin presence of an amide bond between the N-terminal amino or ε-amino group of lysine, preferably Lys⁵² and Lys⁴⁵ , and metoksipolietilenglikolbutanovoy acid. The molecular weight of methoxy polyethylene glycol-epoetin beta is about 60 kDa, including 30 kDa molecular weight PEG.

Mircera^® It has distinct from erythropoietin activity at the receptor level and is characterized by a long association with the receptor and faster dissociation from the receptor, decrease of specific activity in vitro and enhanced activity in vivo, as well as increasing T_1/2, that allows you to enter MIRCERA^® 1 once a month.

Mircera^® It stimulates erythropoiesis in interaction with the erythropoietin receptor on progenitor cells of the bone marrow.

In 97.5% patients with chronic kidney disease, not on dialysis, Mircera for the treatment of^® marked correction of anemia. In 93.3% patients with chronic kidney disease, dialysis, Mircera for the treatment of^® marked correction of anemia. Patients, dialysis, when translating from treatment with epoetin or darbepoetin alfa therapy MIRCERA^® remains stable target hemoglobin level.

Pharmacokinetics

Absorption and distribution

After p / to the introduction of the time to reach C_max serum methoxypolyethylene glycol-epoetin beta – 72 no.

The absolute bioavailability of methoxy polyethylene glycol-epoetin beta in patients, dialysis, and patients, not on dialysis, is 62% and 54%, respectively.

V_d is 5 l and is not dependent on the dose of.

The introduction of methoxy polyethylene glycol-epoetin beta 1 once every 4 week does not lead to significant accumulation of the drug, cumulation coefficient is equal to 1.03 when administered 1 once every 4 week and 1.12 – when administered 1 once every 2 of the week

Deduction

After the on / in the MIRCERA^® T_1/2 in 15-20 times longer, than when administered recombinant human erythropoietin. T_1/2 methoxy polyethylene glycol-epoetin beta in the / in the introduction of 134 no (or 5.6 d), when s / to – 139 no (or 5.8 d), total clearance – 0.494 ml / h / kg.

Clearance methoxypolyethylene glycol-epoetin beta does not depend on the dose.

Pharmacokinetics in special patient groups

Duration of treatment does not affect the clearance, V_d and bioavailability of methoxy polyethylene glycol-epoetin beta.

There were no differences in the pharmacokinetics of the drug in patients, receiving and not receiving dialysis. Hemodialysis does not affect the pharmacokinetics of methoxy polyethylene glycol-epoetin beta.

The pharmacokinetics of methoxy polyethylene glycol-epoetin beta in patients with severe hepatic impairment and healthy subjects did not differ.

Pharmacokinetics, pharmacodynamics and tolerability of the local places do not depend on s / c injection of the drug (shoulder, front of the thigh, anterior abdominal wall).

No initial dose adjustment is required methoxy polyethylene glycol-epoetin beta according to race, sex and age of the patient.

Testimony

- Anemia in chronic renal failure (classification NKF K / DOQI – in chronic kidney disease).

Dosage regimen

Given a longer T_1/2 active substance, Mircera^® can be administered less frequently, than other erythropoiesis-stimulating.

Treatment with MIRCERA^® should begin only under the supervision of a specialist.

The drug can be administered as a n / a, and / in.

N / a drug is introduced only in the shoulder area, anterior thigh or abdominal wall.

The content of hemoglobin should be monitored 1 every two weeks until stable, and periodically after stabilization.

Patients, not receiving erythropoiesis stimulator now

The recommended starting dose: 0.6 ug / kg / or sc / k 1 once every 2 of the week, target hemoglobin >110 g / l (6.83 mmol / l).

The dose of MIRCERA^® can be increased by 25-50% from previous, If after a month increase in hemoglobin is less than 10 g / l (0.621 mmol / l). Further increase of a dose of about 25-50% may be carried out at intervals 1 once a month until the individual target hemoglobin content.

The dose of MIRCERA^® to reduce 25-50% from previous, If the increase in hemoglobin after one month is over 20 g / l (1.24 mmol / l). If the hemoglobin exceeds 130 g / l (8.07 mmol / l), the therapy should be interrupted until the hemoglobin less 130 g / l (8.07 mmol / l) and then resume, dose 50% from previous. When the target value of hemoglobin 120 g / l dose is changed to 25%.

After discontinuation of therapy hemoglobin is reduced by about 3.5 g / l (0.22 mmol / l) in Week.

Correction of the dose is carried out no more 1 once a month.

Patients, receiving erythropoiesis-stimulating now

Patients, receiving other erythropoiesis-stimulating, can be translated into therapy MIRCERA^® an administration regime 1 once a month or 1 once every 2 week n / a or /. Initial dose dependent weekly dose previously administered drug – darbepoetin alfa or epoetin (alpha or beta) (Tables 1 and 2). The first injection of MIRCERA^® spend a day next scheduled injection formerly used darbepoetin alfa or epoetin (alpha or beta).

Table 1. Go with epoetin (alpha or beta)

Table 2. Go to darbepoetin alfa

If the maintenance of Hb levels above 110 g / l (6.83 mmol / l) Dosage adjustment, the monthly dose may be changed to 25%.

The dose of MIRCERA^® to reduce 25-50% from previous, If after a month increase in hemoglobin is greater than 20 g / l (1.24 mmol / l). If the hemoglobin exceeds 130 g / l (8.07 mmol / l), the therapy should be interrupted until the hemoglobin decrease to less than 130 g / l (8.07 mmol / l) and then resume, dose 50% from previous.

At the target level of hemoglobin 120 g / l dose is changed to 25%.

After discontinuation of therapy hemoglobin is reduced by about 3.5 g / l (0.22 mmol / l) in Week.

Correction of the dose is carried out no more 1 once a month.

Break in treatment

Treatment of anemia, incl. and therapy with MIRCERA^®, usually long. But if necessary, therapy with MIRCERA^® It can be interrupted at any time.

Propushtennaya dose

Missed a single injection of MIRCERA^® you must enter as soon as possible and then inject the drug with the prescribed dosing frequency.

In patients with hepatic failure of any severity It does not require correction of the dose.

In elderly patients (senior 65 years) It does not require correction of the initial dose.

How to use solution

Mircera solution^® sterile and contains no preservatives. The following shall apply only to clear, colorless or slightly yellowish solution, containing no visible impurities. Before the introduction of the solution was brought to room temperature.

Injection tube can be stored for 1 months at room temperature not exceeding 25 ° C and must be used within this month.

The bottle can be stored for 7 days at room temperature not exceeding 25 ° C and must be used during these 7 days.

Unused solution should be discarded. Each vial or syringe-tube can be used only once. Do not shake.

Side effect

Determination of the frequency of adverse reactions: often (≥1 / 100 and <1/10), rarely (≥1 / 1000 <1/100), rarely (≥1/10 000 and <1/1000).

Adverse reactions observed in approximately 6% patients, receiving MIRCERA^®, common – arterial hypertension.

The following are the side effects of mild or moderate severity, common in patients, treated with MIRCERA^®.

Cardio-vascular system: often – arterial hypertension; rarely - shunt thrombosis.

CNS: seldom - a headache, rarely – hypertensive encephalopathy.

Allergic reactions: rarely – hypersensitivity reactions.

Dermatological reactions: very rarely - maculo-papular rash.

From the hematopoietic system: in 7.5% patients, treated with MIRCERA^®, and 4.4 % patients, treated with stimulants other erythropoiesis, nablyudalasy thrombocytopenia (platelet count < 100 000/l).

Contraindications

- Uncontrolled hypertension;

- Children up to age 18 years (Safety and efficacy have not been established);

- Hypersensitivity to the drug.

FROM caution It should be used during pregnancy, during breastfeeding, when hemoglobinopathies, epilepsy, thrombocytosis (platelet count over 500 000/l), because the safety and efficacy of MIRCERA^® for these groups are not well understood.

Pregnancy and lactation

The safety and efficacy of MIRCERA^® during pregnancy and breastfeeding are not well understood. The drug should be prescribed only, if the expected benefit to the mother outweighs the potential risk to the fetus or child.

Unknown, Whether or methoxy polyethylene glycol-epoetin beta in breast milk in humans.

IN experimental studies Animal MIRCERA^® It has no direct or indirect adverse effects on pregnancy, embryonic / fetal development, birth or postnatal development. Displaying, that methoxy polyethylene glycol-epoetin beta is excreted in breast milk.

Cautions

Before and during treatment with MIRCERA^® necessary to eliminate iron deficiency.

Additional iron therapy recommended, if the content of serum ferritin below 100 ug / L or the transferrin iron saturation below 20%.

Lack of effect: the most frequent causes of an incomplete response to treatment facilities, stimulates erythropoiesis, is iron deficiency, inflammation, Chronic blood loss, fibrosis of the bone marrow, a sharp increase in the concentration of aluminum, due to hemodialysis, deficiency of folic acid or vitamin B₁₂, gemoliz. If all of the excluded state and the patient has a sudden drop of hemoglobin, reticulocytopenia and have antibodies to erythropoietin, necessary to carry out a study of the bone marrow to avoid partial red cell aplasia (PKKA). With the development of Mircera therapy PKKA^® It must be stopped and patients should not be translated into other erythropoiesis-stimulating therapy.

Reported cases of PKKA, induced antibodies eritropoetonu, during therapy with erythropoiesis stimulators. Antibodies have cross reaction with all stimulators of erythropoiesis. It should not be translated into therapy MIRCERA^® patients with confirmed the presence of antibodies to erythropoietin or their suspected presence.

Arterial hypertension: before and during treatment with MIRCERA^®, As with other erythropoiesis-stimulating, necessary to control blood pressure. If blood pressure can not be controlled with medication, necessary to reduce the dose or suspend treatment Mircera^®.

Effect on tumor growth: Mircera^®, Like other drugs, stimulating erythropoiesis, It is a growth factor, which primarily stimulates the formation of erythrocytes. Erythropoietin receptors may be present on the surface of various tumor cells. Maybe, that means, stimulating erythropoiesis, can stimulate the growth of any type of malignancy. In clinical studies,, where Epoetin used in patients with various malignant tumors, incl. Head and Neck, Breast, there was an increase in mortality, reasons which are unclear.

Effects on ability to drive and operate machinery

Studies on the effect of the drug on the ability to drive and use machines have not been conducted. Based on the mechanism of action and safety profile, Mircera^® It does not affect the ability of such activities.

Overdose

The maximum tolerated dose in patients not determined. Chance of excessive pharmacodynamic response, ie. excessive erythropoiesis. At a high level of hemoglobin to temporarily interrupt treatment Mircera^®. If necessary, it can be carried phlebotomy.

Drug Interactions

Research on the interaction with other drugs has not been. The resulting data to date have not revealed any interaction of Mircera^® with other drugs.

When the population analysis showed no evidence of the influence of other drugs on the pharmacokinetics and pharmacodynamics of MIRCERA^®.

Pharmaceutical interaction

Do not mix methoxy polyethylene glycol-epoetin beta with other drugs or injection solution.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.