MIRCERA Solution for injection Ref.[9292] Active ingredients: Epoetin beta

Treatment with MIRCERA 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 adult 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. MIRCERA should be administered either subcutaneously or intravenously in order to increase haemoglobin to not greater than 12 g/dl (7.45 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. Haemoglobin variability should be addressed through dose management, with consideration for the haemoglobin target range of 10 g/dl (6.21 mmol/l) to 12 g/dl (7.45 mmol/l). A sustained haemoglobin level of greater than 12 g/dl (7.45 mmol/l) should be avoided; guidance for appropriate dose adjustment for when haemoglobin values exceeding 12 g/dl (7.45 mmol/l) are observed are described below.

A rise in haemoglobin of greater than 2 g/dl (1.24 mmol/l) over a four-week period should be avoided. If it occurs, appropriate dose adjustment should be made as provided.

Patients should be monitored closely to ensure that the lowest approved effective dose of MIRCERA is used to provide adequate control of the symptoms of anaemia whilst maintaining a haemoglobin concentration below or at 12 g/dl (7.45 mmol/l).

Caution should be exercised with escalation of MIRCERA doses in patients with chronic renal failure. In patients with a poor haemoglobin response to MIRCERA, alternative explanations for the poor response should be considered (see section 4.4 and 5.1).

It is recommended that haemoglobin is monitored every two weeks until stabilized and periodically thereafter.

Patients not currently treated with an erythropoiesis stimulating agent (ESA)

In order to increase haemoglobin levels to greater than 10 g/dl (6.21 mmol/l), the recommended starting dose in 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.

The dose may be increased by approximately 25% of the previous dose if the rate of rise in haemoglobin is less than 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 haemoglobin level is obtained.

If the rate of rise in haemoglobin is greater than 2 g/dl (1.24 mmol/l) in one month or if the haemoglobin level is increasing and approaching 12 g/dl (7.45 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. After dose interruption a haemoglobin 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.

Patients treated once every two weeks whose haemoglobin concentration is above 10 g/dl (6.21 mmol/l) may receive MIRCERA administered once-monthly using the dose equal to twice the previous once-every-two-week dose.

Patients currently treated with an ESA

Patients currently treated with an ESA 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 as described in Table 1. The first injection should start at the next scheduled dose of the previously administered darbepoetin alfa or epoetin.

Table 1. MIRCERA starting doses:

If a dose adjustment is required to maintain the target haemoglobin concentration above 10 g/dl (6.21 mmol/l), the monthly dose may be increased by approximately 25%.

If the rate of rise in haemoglobin is greater than 2 g/dl (1.24 mmol/l) over a month or if the haemoglobin level is increasing and approaching 12 g/dl (7.45 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. After dose interruption a haemoglobin 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.

Since the treatment experience is limited in patients on peritoneal dialysis, regular haemoglobin monitoring and strict adherence to dose adjustment guidance are recommended in these patients.

Treatment interruption

Treatment with MIRCERA is normally long-term. However, it can be interrupted at any time, if necessary.

Missed dose

If one dose of MIRCERA is missed, the missed dose is to be administered as soon as possible and administration of MIRCERA is to be restarted at the prescribed dosing frequency.

Patients with hepatic impairment

No adjustments of the starting dose nor of the dose modification rules are required in patients with hepatic impairment (see section 5.2).

Elderly population

In clinical studies 24% of patients treated with MIRCERA were aged 65 to 74 years, while 20% were aged 75 years and over. No dose adjustment is required in patients aged 65 years or older.

Paediatric population

MIRCERA is not recommended for use in children and adolescents below 18 years due to a lack of safety and efficacy data.

Method of administration

MIRCERA should be administered either subcutaneously or intravenously. It can be injected subcutaneously in the abdomen, arm or thigh. All three injection sites are equally suitable. For instructions on the administration of the medicinal product, see section 6.6.

The therapeutic range of MIRCERA is wide. Individual responsiveness must be considered when treatment is initiated. Overdose can result in manifestations of an exaggerated pharmacodynamic effect, e.g. excessive erythropoiesis. In case of excessive haemoglobin levels, treatment with MIRCERA should be temporarily discontinued (see section 4.2). If clinically indicated, phlebotomy may be performed.

Shelf life: 3 years.

Store in a refrigerator (2°C–8°C).

Do not freeze.

Keep the pre-filled syringe in the outer carton in order to protect from light.

The end-user may remove the medicinal product from refrigeration for storage at a room temperature not above 30°C for one single period of 1 month. Once removed from the refrigerator the medicinal product must be used within this period.

Pre-filled syringe (type I glass) with laminated plunger stopper (bromobutyl rubber) and tip cap (bromobutyl rubber) and a needle 27G1/2.

Prefilled syringes 30, 40, 50, 60, 75, 100, 120, 150, 200 and 250 micrograms contain 0.3 ml solution.

Pre-filled syringe 360 micrograms contains 0.6 ml solution.

Prefilled syringes 30, 50, 75 micrograms are available in pack size of 1 or 3 pre-filled syringe(s).

Prefilled syringes 40, 60, 100, 120, 150, 200, 250 and 360 micrograms are available in pack size of 1 pre-filled syringe.

Not all pack sizes may be marketed.

The pre-filled syringe is ready for use. The sterile pre-filled syringe does not contain any preservative and is to be used for a single injection only. Only one dose should be administered per syringe. Only solutions which are clear, colourless to slightly yellowish and free of visible particles must be injected.

Do not shake.

Allow the pre-filled syringe to reach room temperature before injecting.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.