Methoxy polyethylene glycol-epoetin beta
When ATH: B03XA03
Methoxy polyethylene glycol-epoetin beta – Pharmacological action
Stimulator of hematopoiesis. Methoxy polyethylene glycol-epoetin beta – chemically synthesized a new class 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, predominantly 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.
Methoxypolyethylene glycol-epoetin beta 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, and increased T1 / 2 of, that allows you to enter methoxy polyethylene glycol-epoetin beta 1 once a month.
Methoxypolyethylene glycol-epoetin beta 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, for the treatment of methoxy polyethylene glycol-epoetin beta is marked correction of anemia. In 93.3% patients with chronic kidney disease, dialysis, during therapy marked correction of anemia. Patients, dialysis, when translating from treatment with epoetin or darbepoetin alfa therapy methoxy polyethylene glycol-epoetin beta remains stable target hemoglobin level.
Methoxy polyethylene glycol-epoetin beta – Pharmacokinetics
Absorption and distribution
After p / to the introduction of time to reach Cmax in serum methoxy polyethylene 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.
Vd 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 methoxy polyethylene glycol-epoetin beta T1 / 2 15-20 times longer, than when administered recombinant human erythropoietin. T1 / 2 of 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, Vd and bioavailability methoxypolyethylene 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.
Methoxy polyethylene glycol-epoetin beta – Testimony
Anemia of chronic renal failure (classification NKF K / DOQI – in chronic kidney disease).
Methoxy polyethylene glycol-epoetin beta – Dosage regimen
Given a longer T1 / 2 of the active substance, Methoxy polyethylene glycol-epoetin beta may be administered less frequently, than other erythropoiesis-stimulating.
Drug treatment should be started 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).
Dose-methoxy epoetin beta 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.
Dose-methoxy epoetin beta is reduced by 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 methoxy polyethylene glycol-epoetin beta to 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 the drug is carried out on the day of the next scheduled injection formerly used darbepoetin alfa or epoetin (alpha or beta).
If the maintenance of Hb levels above 110 g / l (6.83 mmol / l) Dosage adjustment, the monthly dose may be changed to 25%.
Dose-methoxy epoetin beta is reduced by 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 methoxy polyethylene glycol-epoetin beta, usually long. But if necessary, drug therapy can be interrupted at any time.
Propushtennaya dose
Missed single injection methoxy polyethylene glycol-epoetin beta is necessary to enter as soon as possible and then inject the drug with the prescribed dosing frequency.
Patients with hepatic insufficiency of any severity does not require correction of the dose.
Elderly patients (senior 65 years) It does not require correction of the initial dose.
Methoxy polyethylene glycol-epoetin beta – 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 methoxy polyethylene glycol-epoetin beta, common – arterial hypertension.
The following are the side effects of mild or moderate severity, common in patients, receiving methoxy polyethylene glycol-epoetin beta.
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 methoxy polyethylene glycol-epoetin beta, and 4.4 % patients, treated with stimulants other erythropoiesis, nablyudalasy thrombocytopenia (platelet count < 100 000/l).
Methoxy polyethylene glycol-epoetin beta – Contraindications
Uncontrolled hypertension;
Children up to age 18 years (Safety and efficacy have not been established);
Hypersensitivity to the drug.
Caution should be used during pregnancy, during breastfeeding, when hemoglobinopathies, epilepsy, thrombocytosis (platelet count over 500 000/l), because the safety and efficacy of methoxy polyethylene glycol-epoetin beta for these groups are not well understood.
Methoxy polyethylene glycol-epoetin beta – Pregnancy and lactation
The safety and efficacy MMetoksipolietilenglikol-epoetin beta during gestation and lactation 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 animal studies, methoxy polyethylene glycol-epoetin beta 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.
Methoxy polyethylene glycol-epoetin beta – Cautions
Before and during treatment with methoxy polyethylene glycol-epoetin beta is necessary to eliminate iron deficiency.
Additional iron therapy is 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 therapy PKKA methoxy polyethylene glycol-epoetin beta should be discontinued 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 methoxy polyethylene glycol-epoetin beta in patients with a confirmed presence of antibodies to erythropoietin or suspicion of their presence.
Arterial hypertension: before and during treatment with epoetin beta-methoxy, 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 methoxy-epoetin beta.
Effect on tumor growth: Methoxy polyethylene glycol-epoetin beta, 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, Methoxypolyethylene glycol-epoetin beta does not affect the ability of such activities.
Methoxy polyethylene glycol-epoetin beta – Overdose
The maximum tolerated dose in patients not determined. Chance of excessive pharmacodynamic response, ie. excessive erythropoiesis. At a high level of hemoglobin necessary to temporarily interrupt therapy methoxy-epoetin beta. If necessary, it can be carried phlebotomy.
Methoxy polyethylene glycol-epoetin beta – Drug Interactions
Research on the interaction with other drugs has not been. The obtained data so far did not reveal any interaction methoxypolyethylene glycol-epoetin beta with other drugs.
When the population analysis showed no evidence of the influence of other drugs on the pharmacokinetics and pharmacodynamics of methoxy polyethylene glycol-epoetin beta.
Pharmaceutical interaction
Do not mix methoxy polyethylene glycol-epoetin beta with other drugs or injection solution.
