Index of drugs

Treatment of symptomatic anemia associated with chronic kidney disease.

One 0.3 ml pre-filled syringe contains 30 μg, 50 μg, 75 μg, 100 μg, 120 μg, 150 μg or 200 μg of methoxy polyethylene glycol-epoetin beta.

A drug that stimulates erythropoiesis. Methoxy polyethylene glycol-epoetin beta stimulates erythropoiesis by interacting with the erythropoietin receptor in bone marrow stem cells. In contrast to epoetin, it is an activator of the erythropoietin receptor with a continuous action, exhibiting different effects at the receptor level. This effect is characterized by slower binding to the receptor and faster release from the connection with the receptor, reduced internal activityin vitro with increased internal activityin vivo and prolonged half-life. After subcutaneous administration of the preparation to non-dialyzed patients with anemia in the course of chronic kidney disease (CKD) C_max methoxy polyethylene glycol-epoetin beta in the serum was observed 95 h after the administration; the bioavailability was 54%; T_0,5 - 142 h. After subcutaneous dialysis preparation to patients with CKD C_max observed 72 h after administration; bioavailability was 62%; T_0,5 - 139 h. Following intravenous administration of the dialyzed preparation to patients with CKD, the total systemic clearance was 0.494 ml / h / kg; T_0,5 was 134 h. Hemodialysis has no effect on the pharmacokinetics of the drug.

Hypersensitivity to the active substance or to any of the excipients. Uncontrolled overpressure.

The safety and efficacy of the drug in indications other than anemia in the course of chronic kidney disease, including anemia in cancer patients, have not been established. Iron management should be monitored in all patients before and during treatment. Iron supplementation is recommended in all patients with serum ferritin <100 μg / l or transferrin saturation <20%. In the case of a lack of reaction to the treatment, the typical causes of non-response to treatment (eg iron deficiency, folic acid, vitamin B) should be excluded.₁₂, co-existing infections, inflammation, injuries, latent blood loss, haemolysis, severe aluminum intoxication, concomitant haematological diseases or bone marrow fibrosis) and determine the number of reticulocytes. If the cause is not identified and the patient shows a rapid decrease in hemoglobin levels associated with reticulocytopenia and the presence of antibodies to erythropoietin, a bone marrow biopsy should be considered for the diagnosis of the Red Cell Aplasia (PRCA). If PRCA is diagnosed, treatment with the preparation should be stopped immediately, no other erythropoiesis stimulating agents should be administered. Patients suspected or confirmed with erythropoietin antibodies should not receive the preparation. In patients with hepatitis C, treated with Interferon, Ribavirin and epoetin, cases of PRCA have been reported (epoetins are not approved for the treatment of anemia associated with hepatitis C). Due to the increased risk of death and severe cardiovascular or cerebrovascular events, patients with chronic kidney disease should not be maintained hemoglobin> 12 g / dl (7.5 mmol / l). There were no significant benefits associated with the use of epoetins if hemoglobin levels were above the value necessary to control the symptoms of anemia and to avoid blood transfusions. The safety and efficacy of the preparation have not been established in patients with hemoglobinopathies, convulsions, bleeding or recent bleeding requiring transfusion, platelet count> 500 x 10⁹/ l - caution should be exercised when using the drug in these groups of patients. Blood pressure should be monitored before and during treatment.If you have difficulty in maintaining your blood pressure, despite using pharmacological therapy or a diet, reduce the dose or discontinue the medicine. As with all growth factors, there is a risk that erythropoiesis stimulants can stimulate the growth of various types of cancer - two controlled clinical trials in which epoetins have been administered to patients with various types of cancer, including head and neck cancers and breast cancer, showed an unexplained increase in mortality.

There are no clinical data on the use of methoxy polyethylene glycol-epoetin beta during pregnancy. Animal studies do not indicate direct harmful effects to the pregnancy, embryonal or fetal development, parturition or development of the newborn, but indicate a reversible reduction in fetal body weight. Caution should be exercised when prescribing to pregnant women. It is not known whether methoxy polyethylene glycol-epoetin beta is excreted in human milk. The decision to continue or terminate breastfeeding or to continue or discontinue treatment should be made taking into account the benefits of breastfeeding for the child and the benefits of using the product for the mother.

Common: hypertension. Uncommon: headache, thrombosis of vascular access. Rarely: hypertensive encephalopathy, maculopapular rash, hot flushes, hypersensitivity reactions. Not known: anaphylactic reactions, thrombosis (including pulmonary embolism), thrombocytopenia, selective red cell aplasia (PRCA), Stevens-Johnson syndrome, toxic epidermal necrolysis. Impact may occur.

Subcutaneously in the stomach, arm or thigh or intravenously. Subcutaneous administration is preferred in patients who are not hemodialyzed to avoid puncturing peripheral veins. It is recommended to check hemoglobin every 2 weeks until a stable concentration is obtained and then periodically. Due to interindividual variability, individual patients may occasionally observe fluctuations in Hb levels, which should be counteracted by dose correction, taking into account the target Hb concentrations: 10 g / dl (6.21 mmol / l) -12 g / dl (7.45 mmol / l). Avoid maintaining Hb> 12 g / dl (7.45 mmol / l) and increase Hb by more than 2 g / dl (1.24 mmol / l) over 4 weeks. Patients should be carefully monitored to ensure that the lowest dose of the preparation is used to ensure adequate control of the symptoms of anemia. Caution should be exercised when increasing the dose in patients with chronic renal failure, because cumulative high doses of epoetin may be associated with increased mortality, severe cardiovascular and cerebrovascular events. Patients with an insufficient level of hemoglobin during treatment with epoetins may need to consider other factors affecting their poor response.Patients untreated with erythropoiesis stimulating agent (ESA). In order to increase the level of hemoglobin to above 10 g / dl (6.21 mmol / l), the recommended initial dose in non-dialysis patients is 1.2 μg / kg, given once a month as a single subcutaneous injection. Alternatively, an initial dose of 0.6 μg / kg may be used in patients undergoing or not on dialysis, given at 2-week intervals as a single intravenous or subcutaneous injection. The dose can be increased by about 25% of the previous dose if the increase in Hb over one month is <1 g / dl (0.621 mmol / l). Further dose increases of approx. 25% can be made on a monthly basis until reaching the target Hb concentration. If the increase in Hb is greater than 2 g / dl (1.24 mmol / l) per month or if the Hb concentration increases and reaches 12 g / dl (7.45 mmol / l), the dose should be reduced by approx. 25%. If the Hb level continues to increase, treatment should be discontinued until the Hb concentration begins to decrease. At this point, treatment should be resumed, starting with a 25% lower dose than the one previously administered. After discontinuation of treatment, the Hb concentration may be expected to decrease at a rate of 0.35 g / dl (0.22 mmol / l) per week. Adjustment of the dose should not take place more than once a month.If the patient's Hb> 10 g / dl (6.21 mmol / l) is achieved, the product may be given once a month at a dose equivalent to two doses given previously at 2-week intervals.Patients receiving erythropoiesis stimulating agents (ESA). Patients receiving erythropoiesis can be switched to methoxy polyethylene glycol-epoetin beta given once a month as a single intravenous or subcutaneous injection. The starting dose of methoxy polyethylene glycol-epoetin beta, administered once a month, should be calculated on the basis of a previously administered intravenous or subcutaneous weekly dose of darbepoetin alfa or epoetin at the time of drug replacement: <40 μg / wk. darbepoetin alfa or <8,000 IU / s epoetin corresponds to 120 μg / month. methoxy polyethylene glycol-epoetin beta; 40-80 μg / week darbepoetin alfa or 8,000-16000 IU / s epoetin corresponds to 200 μg / month. methoxy polyethylene glycol-epoetin beta; > 80 μg / week darbepoetin alfa or> 16000 IU / s epoetin corresponds to 360 μg / month. methoxy polyethylene glycol-epoetin beta. The first injection should be done according to the date of the Next scheduled dose of darbepoetin alfa or epoetin. If a dose adjustment is necessary to maintain the target Hb> 10 g / dl (6.21 mmol / l), the monthly dose may be increased by approximately 25%. If the increase in Hb is greater than 2 g / dl (1.24 mmol / l) per month or if the Hb concentration increases and reaches 12 g / dl (7.45 mmol / l), the dose should be reduced by approx. 25%. If the Hb level continues to increase, treatment should be discontinued until the Hb concentration begins to decrease. At this point, treatment should be resumed, starting with a 25% lower dose than the one previously administered. After discontinuation of therapy, a reduction in Hb levels at a rate of 0.35 g / dl (0.22 mmol / l) per week is expected. Adjustment of the dose should not take place more than once a month.Skip the dose. If one dose is missed, the missed dose should be administered as soon as possible. The administration of subsequent doses should be resumed from this moment with a fixed frequency.Discontinuation of the drug. If necessary, treatment can be interrupted at any time.Special groups of patients. There is no need to change the dosage in elderly patients or patients with hepatic impairment. Clinical experience in patients on peritoneal dialysis is limited - caution should be exercised (regular monitoring of hemoglobin). The use in children and adolescents <18 years is not recommended due to lack of data on safety and efficacy.