MIRCERA

Treatment has to be initiated under the supervision of a physician experienced in the management of patients with renal impairment. Posology Treatment of symptomatic anaemia in chronic kidney disease patients Anaemia symptoms and sequelae may vary with age, gender, and overall burden of disease; a physician’s evaluation of the individual patient’s clinical course and condition is necessary.

45 mmol/l). Subcutaneous use is preferable in patients who are not receiving haemodialysis to avoid puncture of peripheral veins. Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed.

45 mmol/l). 45 mmol/l) are observed are described below. 62 mmol/l) in paediatric patients over a four-week period should be avoided. If it occurs, appropriate dose adjustment should be made as provided. 45 mmol/l). Caution should be exercised with escalation of treatment doses in patients with chronic renal failure.

1). 4). 2 microgram/kg body weight, administered once every month as a single subcutaneous injection. 6 microgram/kg bodyweight may be administered once every two weeks as a single intravenous or subcutaneous injection in patients on dialysis or not on dialysis.

621 mmol/l) over a month. Further increases of approximately 25% may be made at monthly intervals until the individual target haemoglobin level is obtained. 45 mmol/l), the dose is to be reduced by approximately 25%. If the haemoglobin level continues to increase, therapy should be interrupted until the haemoglobin level begins to decrease, at which point therapy should be restarted at a dose approximately 25% below the previously administered dose.

22 mmol/l) per week is expected. Dose adjustments should not be made more frequently than once a month. 21 mmol/l) may receive methoxy polyethylene glycol-epoetin beta administered once-monthly using the dose equal to twice the previous once-every-two-week dose.

Adult patients currently treated with an ESA:

Patients currently treated with an ESA can be switched to methoxy polyethylene glycol-epoetin beta administered once a month as a single intravenous or subcutaneous injection. The starting dose of methoxy polyethylene glycol-epoetin beta is based on the calculated previous weekly dose of darbepoetin alfa or epoetin at the time of substitution as described in Table 1.

(a) Summary of the safety profile The safety data base from clinical trials comprised 3,042 CKD adult patients, including 1,939 adult patients treated with methoxy polyethylene glycol-epoetin beta and 1,103 with another ESA. Approximately 6% of adult patients treated with methoxy polyethylene glycol-epoetin beta are expected to experience adverse reactions.

The most frequent reported adverse reaction was hypertension (common). (b) Tabulated list of adverse reactions Adverse reactions in Table 3 are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

8 gb-spc-mircera-clean-240111-pfs Table 3: Adverse reactions attributed to the treatment with methoxy polyethylene glycol- epoetin beta in CKD adult patients. Adverse reactions observed only during post-marketing are marked (*). System organ class Frequency Adverse reaction Uncommon Thrombocytopenia*Blood and lymphatic system disorders Not known Pure red cell aplasia* Rare Hypersensitivity Immune system disorders Not known Anaphylactic reaction* Uncommon Headache Nervous system disorders Rare Hypertensive encephalopathy Common Hypertension Uncommon Thrombosis* Rare Hot flush Vascular disorders Rare Pulmonary embolism* Rare Rash, maculopapular Skin and subcutaneous disorders Not known Stevens-Johnson syndrome / toxic epidermal necrolysis* Injury, poisoning and procedural complications Uncommon Vascular access site thrombosis (c) Description of selected adverse reactions Adult population Cases of thrombocytopenia have been reported from post-marketing setting.

A slight decrease in platelet counts remaining within the normal range was observed in clinical studies. Platelet counts below 100 x 109/l were observed in 7% of adult patients treated with methoxy polyethylene glycol-epoetin beta and 4% of adult patients treated with other ESAs during clinical development.

The safety and efficacy of methoxy polyethylene glycol-epoetin beta therapy in other indications, including anaemia in patients with cancer, has not been established. Caution should be exercised with escalation of methoxy polyethylene glycol-epoetin beta doses in patients with chronic renal failure since high cumulative epoetin doses may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events.

1).

Paediatric population:

Paediatric patients, especially children <1 year of age, should be carefully evaluated before switching from another ESA treatment and the haemoglobin level should be stabilised prior to switching. Following ESA conversion, it is recommended that haemoglobin is monitored every 4 weeks.

If the current ESA dose is <9 microgram/week of darbepoetin alfa or <2,000 IU/week of epoetin, the patient should not be switched to methoxy polyethylene glycol-epoetin beta, as the lowest available pre-filled syringe dose strength is 30 micrograms.

Administration of partial doses with pre-filled syringes is not recommended. Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 microgram/l or with transferrin saturation below 20%. To ensure effective erythropoiesis, iron status has to be evaluated for all patients prior to and during treatment.

Failure to respond to treatment should prompt for a search for causative factors. Deficiencies of iron, folic acid or vitamin B12 reduce the effectiveness of ESAs and should therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases, or bone marrow fibrosis may also compromise the erythropoietic response.

A reticulocyte count should be considered as part of the evaluation. If all the conditions mentioned are excluded and the patient has a sudden drop of haemoglobin associated with reticulocytopenia and anti-erythropoietin antibodies, examination of the bone marrow for the diagnosis of Pure Red Cell Aplasia (PRCA) should be considered.

1. Uncontrolled hypertension.