Methoxy polyethylene glycol-epoetin beta

Mircera is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia associated with chronic kidney disease (CKD) in: • adult patients on dialysis and adult patients not on dialysis. • pediatric patients 3 months to 17 years of age on dialysis or not on dialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA. Limitations of Use Mircera is not indicated and is not recommended for use: • In the treatment of anemia due to cancer chemotherapy. • As a substitute for RBC transfusions in patients who require immediate correction of anemia. Mircera has not been shown to improve quality of life, fatigue, or patient well-being.

Mircera is an erythropoietin receptor activator with greater activity in vivo as well as increased half-life, in contrast to erythropoietin. A primary growth factor for erythroid development, erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. In responding to hypoxia, erythropoietin interacts with erythroid progenitor cells to increase red cell production. Production of endogenous erythropoietin is impaired in patients with CKD and erythropoietin deficiency is the primary cause of their anemia.

Mircera is administered by subcutaneous or intravenous injection. Adult Patients • Initial Treatment: (patients not currently treated with an ESA): • CKD patients on dialysis: 0.6 mcg/kg body weight administered once every two weeks. • CKD patients not on dialysis: 1.2 mcg/kg body weight administered once every month as a single subcutaneous injection. Alternatively, a starting dose of 0.6 mcg/kg body weight may be administered once every two weeks as a single intravenous or subcutaneous injection. • Conversion from Another ESA: • Dosed once monthly or once every two weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion. Pediatric Patients • Conversion from another ESA: dosed once every 4 weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion.

Mircera is contraindicated in patients with: • Uncontrolled hypertension • Pure red cell aplasia (PRCA) that begins after treatment with Mircera or other erythropoietin protein drugs • History of serious or severe allergic reactions to Mircera (e.g., anaphylactic reactions, angioedema, bronchospasm, skin rash, and urticaria). • Uncontrolled hypertension. • Pure red cell aplasia (PRCA) that begins after treatment with Mircera or other erythropoietin protein drugs. • History of serious allergic reactions to Mircera, including anaphylaxis.

WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS and TUMOR PROGRESSION OR RECURRENCE WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS and TUMOR PROGRESSION OR RECURRENCE Chronic Kidney Disease: • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. • Hypertension: Control hypertension prior to initiating and during treatment with Mircera. • Seizures: Seizures have occurred in CKD patients participating in Mircera clinical studies. Increase monitoring of these patients for changes in seizure frequency or premonitory symptoms. • PRCA: If severe anemia and low reticulocyte count develop during Mircera treatment, withhold Mircera and evaluate for PRCA.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: • Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism • Increased Mortality and/or Tumor Progression in Patients with Cancer • Hypertension • Seizures • Pure Red Cell Aplasia • Serious Allergic Reactions • Severe Cutaneous Reactions The most common adverse reactions (≥ 10%) are hypertension, diarrhea, nasopharyngitis.

Store Mircera refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake. The end-user may store the product at room temperature up to 25°C (77°F) in the original carton up to 30 days.