This is indicated for the treatment of anemia associated with chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis.

Methoxy polyethylene glycol-epoetin beta is a chemically synthesized continuous erythropoietin receptor activator. Methoxy polyethylene glycol-epoetin beta differs from erythropoietin through integration of an amide bond between either the N-terminal amino group or the ε-amino group of lysine (predominantly Lys52 and Lys45) and methoxy polyethylene glycol butanoic acid. This results in a molecular weight of approximately 60,000 daltons for methoxy polyethylene glycol-epoetin beta, with the PEG moiety having an approximate molecular weight of 30,000 daltons.

In contrast to erythropoietin, methoxy polyethylene glycol-epoetin beta shows different activity at the receptor level, characterized by slower association to and faster dissociation from the receptor, reduced specific activity in vitro with increased activity in vivo, and an increased half-life. These pharmacological properties allow a once-monthly dosing regimen in patients.

Methoxy polyethylene glycol-epoetin beta stimulates erythropoiesis by interacting with the erythropoietin receptor on progenitor cells in the bone marrow. As the primary growth factor for erythroid development, natural erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. In response to hypoxia, erythropoietin interacts with erythroid progenitor cells to increase red blood cell production.

This preparation is administered less frequently than other erythropoiesis stimulating agents (ESAs) due to the longer elimination half-life. Treatment with this preparation has to be initiated under the supervision of a healthcare professional.

Treatment of anemic patients with chronic kidney disease:

• The solution can be administered subcutaneously (s.c.) or intravenously (i.v.), according to clinical preference.
• This preparation can be injected subcutaneously in the abdomen, arm or thigh. All three injection sites are equally suitable for subcutaneous injection with this preparation.
• It is recommended that hemoglobin is monitored every two weeks until stabilized, and periodically thereafter.

Patients currently not treated with an Erythropoiesis Stimulating Agent:

• Patients not on dialysis – In order to increase the hemoglobin to greater than 11 g/dl (6.83 mmol/L), the recommended starting dose is 1.2 microgram/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 microgram/kg body weight may be administered once every two weeks as a single IV or SC injection.
• Patients on dialysis – In order to increase the hemoglobin to greater than 11 g/dl (6.83 mmol/L), the recommended starting dose of 0.6 microgram/kg body weight may be administered once every two weeks as a single IV or SC injection.
• The dose of this preparation may be increased by approximately 25 to 50% of the previous dose if the rate of rise in hemoglobin is less than 1.0 g/dl (0.621 mmol/L) over a month. Further increases of approximately 25 to 50% may be made at monthly intervals until the individual target hemoglobin level is obtained.
• If the rate of rise in hemoglobin is greater than 2 g/dl (1.24 mmol/L) in one month, the dose is to be reduced by approximately 25 to 50%. If the hemoglobin level exceeds 13 g/dl (8.07 mmol/L), therapy is to be interrupted until the hemoglobin level falls below 13 g/dl and then restarted with approximately 50% of the previously administered dose. For regions where the upper limit of hemoglobin level has been set at 12 g/dl, dose adjustments of 25% should be considered. After dose interruption a hemoglobin decrease of approximately 0.35 g/dl per week is expected.
• Patients treated once every two weeks whose hemoglobin concentration is above 11 g/dl (6.83 mmol/L) may receive this preparation administered once monthly using a dose equal to twice the previous once-every-two-weeks dose. Dose adjustments should not be made more often than once a month.

Patients currently treated with an Erythropoiesis Stimulating Agent: Patients currently treated with an ESA can be converted to this preparation administered once a month or, if desired, once every two weeks as a single i.v. or s.c. injection. The starting dose of this preparation is based on the calculated previously given weekly dose of darbepoetin alfa or epoetin at the time of substitution as described in Tables 1 and 2 below. The first injection of this preparation should be administered at the next scheduled dose of the previously administered darbepoetin alfa or epoetin.

No interaction studies have been performed. Clinical data do not indicate any interaction of Methoxy Polyethylene Glycol Epoetin Beta with other medicinal products. The effect of concomitant drugs on the pharmacokinetics and pharmacodynamics of Methoxy Polyethylene Glycol Epoetin Beta was evaluated using a population analysis approach. There was no evidence of an effect of concomitant medications on its pharmacokinetics or pharmacodynamics.

Methoxy Polyethylene Glycol Epoetin Beta is contraindicated in patients with:

• Uncontrolled hypertension.
• Known hypersensitivity to the active substance or any of the excipients.

Adverse reactions include hypertension, vascular access thrombosis, headache, hypersensitivity reactions, hypertensive encephalopathy, and maculo-papular rash (including serious reactions).

Pregnancy: There are no adequate data on the use of this preparation in pregnant women. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/fetal development, parturition, or postnatal development. Caution should be exercised when prescribing to pregnant women.

Nursing Mothers: It is unknown whether methoxy polyethylene glycol-epoetin beta is excreted in human breast milk. Animal studies have shown excretion in maternal milk. A decision should be made whether to continue or discontinue breastfeeding or therapy, considering the benefit to the child and the mother.

Supplementary iron therapy is recommended for all patients with serum ferritin below 100 µg/L or transferrin saturation below 20%. Iron status should be assessed before and during treatment to ensure effective erythropoiesis.

Lack of effect: Common causes of poor response to ESAs include iron deficiency and inflammatory disorders. Other conditions include chronic blood loss, bone marrow fibrosis, severe aluminium overload in renal failure, folic acid or vitamin B12 deficiency, and hemolysis. If these are excluded and there is sudden hemoglobin drop with reticulocytopenia and anti-erythropoietin antibodies, Pure Red Cell Aplasia (PRCA) should be considered. If PRCA is confirmed, treatment must be discontinued and patients should not switch to another ESA.

PRCA: PRCA associated with anti-erythropoietin antibodies has been reported with ESAs including this preparation. These antibodies cross-react with all ESAs; therefore, patients with confirmed or suspected antibodies should not be switched.

Blood pressure monitoring: Blood pressure may increase during treatment. It must be controlled before and during therapy. If hypertension is difficult to control, the dose should be reduced or withheld.

Pediatric use: Not recommended for patients under 18 years due to lack of safety and efficacy data.

Elderly: No dose adjustment is required in patients aged 65 years or older.

Hepatic impairment: No dose adjustment is required in any degree of hepatic impairment.

The therapeutic range is wide and individual response must be considered. Overdose may lead to exaggerated pharmacodynamic effects such as excessive erythropoiesis. In case of high hemoglobin levels, the drug should be temporarily withheld. If necessary, phlebotomy may be performed.

Drugs for haemolytic, hypoplastic & renal anemia

Do not use after the expiry date. Store in a refrigerator at 2°C–8°C. Keep the pre-filled syringe in the outer carton to protect from light. Do not freeze. The product may be kept at room temperature (not above 30°C) for a single period of up to 1 month after removal from refrigeration and must be used within this time.