What is MIRCERA®?
MIRCERA® is a Continuous Erythropoetin Receptor Activator (C.E.R.A.) indicated for:
the treatment of symptomatic anaemia associated with chronic kidney disease (CKD) in adult patients.
the treatment of symptomatic anaemia associated with chronic kidney disease (CKD) in paediatric patients from 3 months to less than 18 years of age who are converting from another erythropoiesis stimulating agent (ESA) after their haemoglobin level was stabilised with the previous ESA.
Due to its different mode of action, MIRCERA® closely mimics the homeostatic maintenance of erythrocyte production under normal physiological conditions1 . This allows correction of anaemia and stable control of Haemoglobin (Hb) levels at extended, once monthly administration intervals.
1) Jarsch M et al. Pharmacology. 2008;81(1):63-9.
How to manage anaemia in patients with CKD
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.
MIRCERA® should be administered either subcutaneously or intravenously in order to increase Hb.
Due to intra-patient variability, occasional individual Hb values for a patient above and below the desired Hb level may be observed. Hb variability should be addressed through dose management, with consideration for the Hb target range of
10 g/dl to 12 g/dl (6.21 mmol/l - 7.45 mmol/l).
A sustained Hb level of greater than
12 g/dl (7.45 mmol/l) should be avoided.
2) Locatelli F, et al. Nephrol Dial Transplant 2013; 28:1346–1359.
How to change to MIRCERA® from other erythropoesis stimulating agents in adult patients
Adult patients currently treated with an Epoetin or Darbepoetin alfa can be switched to MIRCERA® administered once a month as a single intravenous or subcutaneous injection.
The starting dose of MIRCERA® is based on the calculated previous weekly dose of darbepoetin alfa or epoetin at the time of substitution. The first injection should start at the next scheduled dose of the previously administered darbepoetin alfa or epoetin.
| Previous weekly darbepoetin alfa intravenous or subcutaneous dose (microgram/week) | Previous weekly epoetin intravenous or subcutaneous dose (IU/week) | Monthly MIRCERA® intravenous or subcutaneous dose (microgram/once monthly) |
| <40 | <8000 | 120 |
| 40-80 | 8000 - 16000 | 200 |
| >80 | >16000 | 360 |
How to change to MIRCERA® from other erythropoesis stimulating agents in paediatric patients
Paediatric patients from the age of 3 months to less than 18 years, whose haemoglobin level has been stabilised by treatment with an erythropoiesis stimulating agent can be converted to MIRCERA administered once every 4 weeks as an IV or SC injection, but keeping the same administration route.
The starting dose of MIRCERA is calculated based on the total weekly ESA dose at the time of conversion.
| Previous weekly darbepoetin alfa dose (mcg/week) | Previous weekly epoetin dose (IU/week) | Every 4-week MIRCERA ® dose (mcg) |
| 9 - <12 | 2000 - <2700 | 30 |
| 12- <15 | 2700 - <3500 | 50 |
| 15 - <24 | 3500 - <5500 | 75 |
| 24 - <30 | 5500 - <6500 | 100 |
| 30 - <35 | 6500 - <8000 | 120 |
| 35 - <47 | 8000 - <10000 | 150 |
| 47- <60 | 10000 - <13000 | 200 |
| 60 - <90 | 13000 - <20000 | 250 |
| ~90 | ~20000 | 360 |
Pre-filled syringes are not designed for administration of partial doses. Due to the available dose strengths of pre-filled syringes, paediatric patients with an ESA dose of <9 microgram/week (darbepoetin alfa) or <2000 IU/week of epoetin, should not be switched to methoxy polyethylene glycol-epoetin beta.
If a dose adjustment is required to maintain the target haemoglobin concentration above 10 g/dl, the 4 weekly dose may be adjusted by approximately 25%.
If the rise in haemoglobin is greater than 1 g/dl (0.62 mmol/l) over 4 weeks or the haemoglobin level is increasing and approaching 12 g/dl (7.45 mmol/l), the MIRCERA dose is to be reduced by approximately 25%.
If the haemoglobin level continues to increase following dose reduction, therapy is to 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.
Dose adjustments should not be made more often than once every 4 weeks.
How to start treatment with MIRCERA® for correction of renal anemia in adult patients
The recommended starting dose in adult patients not on dialysis 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 bodyweight may be administered once every two weeks as a single intravenous or subcutaneous injection in patients on dialysis or not on dialysis.
How to maintain haemoglobin target of 10-12g/dl following anemia correction in adult patients
Use lowest approved dose of MIRCERA® to maintain Hb target range of 10–12 g/dl and avoid a sustained Hb level above 12 g/dl.
The dose may be increased by approximately 25% of the previous dose if the rate of rise in Hb is ≤1.0 g/dl (0.621 mmol/l) over a month. Further increases of approximately 25% may be made at monthly intervals until the individual target Hb level is obtained.
If the rate of rise in Hb is ≥2 g/dl (1.24 mmol/l) in one month or if the Hb level is ≥ 12 g/dl (7.45 mmol/l), the dose is to be reduced by approximately 25%.
If the Hb level continues to increase, therapy should be interrupted until the Hb level begins to decrease and restarted at a dose approximately 25% below the previously administered dose.
After dose interruption a Hb decrease of approximately
0.35 g/dl (0.22 mmol/l) per week is expected.
Dose adjustments should not be made more frequently than once a month.
How to use the MIRCERA® Pre-filled Syringe
Store in a refrigerator (2°C – 8°C). Once removed from the refrigerator MIRCERA® must be used within one month.
MIRCERA® Safety Information
Contraindications:
Hypersensitivity to any ingredient. Uncontrolled hypertension.
Precautions & Warnings:
Iron stores should be monitored and managed by iron supplementation. Failure to respond to treatment should be investigated: correct iron, folate or vitamin B12 deficiencies or search for other reasons. If sudden drop in Hb with reticulocytopenia and anti-erythropoietin antibodies (AEAB), examine bone marrow for the diagnosis of Pure Red Cell Aplasia (PRCA). Discontinue therapy if PRCA diagnosed and do not switch to another ESA. If patient has AEAB do not switch to MIRCERA®.
In clinical trials an increased risk of death and serious cardiovascular events was observed when ESAs were administered to target Hb >12 g/dl. Monitor blood pressure; if high blood pressure cannot be controlled by treatment or diet, reduce or withhold dose.
Caution in patients with haemoglobinopathies, seizures, severe liver disease, bleeding, recent bleeding requiring transfusion, platelets >500 x 109/l.
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long-acting epoetins.
ESAs may stimulate growth of any type of malignancy; MIRCERA® is not approved for the treatment of anaemia in patients with cancer. Epoetins are not approved in the management of anaemia associated with hepatitis C.
Misuse of MIRCERA® by healthy people may lead to an excessive increase in Hb. This may be associated with life-threatening cardiovascular complications.
Side effects:
Common: hypertension; uncommon: headache, vascular access thrombosis;
Rare: hypersensitivity, hot flush, rash, hypertensive encephalopathy;
Frequency not known: thrombocytopenia, pure red cell aplasia, anaphylactic reaction, thrombosis, pulmonary embolism, Steven-Johnson syndrome/ toxic epidermal necrolysis. During treatment a slight decrease in platelet counts remaining within the normal range was observed in clinical trials.
Adverse events should be reported to F. Hoffmann- La Roche Ltd.
