Label:information for the user

MIRCERA

30micrograms/0.3ml injectable solution in pre-filled syringe

50micrograms/0.3ml injectable solution in pre-filled syringe

75micrograms/0.3ml injectable solution in pre-filled syringe

100micrograms/0.3ml injectable solution in pre-filled syringe

120micrograms/0.3ml injectable solution in pre-filled syringe

150micrograms/0.3ml injectable solution in pre-filled syringe

200micrograms/0.3ml injectable solution in pre-filled syringe

250micrograms/0.3ml injectable solution in pre-filled syringe

360micrograms/0.6ml injectable solution in pre-filled syringe

methoxy-polyethylene glycol epoetin beta

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this label. See section 4.

1.What MIRCERA is and what it is used for

2.What you need to knowbeforestarting touse MIRCERA

3.How to use MIRCERA

4.Possible side effects

5.Storage of MIRCERA

6.Contents of the pack and additional information

Your doctor has prescribed this medication because you have anemia caused by chronic kidney disease that you have. This anemia is associated with typical symptoms such as fatigue, weakness, and a feeling of shortness of breath. This means that you have very few red blood cells and that your hemoglobin level is too low (your body's tissues may not be receiving enough oxygen).

MIRCERA is indicated only for the treatment of symptomatic anemia caused by chronic kidney disease in adult and pediatric patients (from 3 months to less than 18 years of age) who are receiving maintenance treatment with an erythropoiesis-stimulating agent (ESA) after their hemoglobin levels have stabilized with the previous ESA.

MIRCERA is a genetically engineered medication. Like the natural hormone erythropoietin, MIRCERA increases the number of red blood cells and the level of hemoglobin in the blood.

Do not use MIRCERA

• If you are allergic to methoxy-polyethylene glycol epoetin beta or any of the other components of this medication (listed in section 6)
• If you have high blood pressure that cannot be controlled

Warnings and precautions

The safety and efficacy of MIRCERA treatment have not been established in other indications, including anemia in cancer patients.

The safety and efficacy of MIRCERA treatment in pediatric patients have only been established in patients whose hemoglobin level has been stabilized previously through treatment with an erythropoiesis-stimulating agent (ESA).

Before starting treatment with MIRCERA

• In some patients treated with erythropoiesis-stimulating agents (ESAs), including MIRCERA, a disease called pure red cell aplasia (PRCA) has been observed due to the presence of anti-erythropoietin antibodies.
• If your doctor suspects or confirms that you have these antibodies in your blood, you should not be treated with MIRCERA.

If you are a patient with hepatitis C and receive interferon and ribavirin, you must inform your doctor, because a combination of ESAs with interferon and ribavirin results in a loss of effect and, in exceptional cases, the development of PRCA, a severe anemia. ESAs are not approved for the treatment of anemia associated with hepatitis C.

• If you are a patient with chronic kidney disease and anemia, treated with an ESA and also a cancer patient, you should be aware that ESAs may have a negative impact on your disease. You should discuss with your doctor other options for treating anemia.
• The safety and efficacy of MIRCERA in patients with hemoglobinopathies (diseases associated with an abnormal hemoglobin level), with current or past bleeding, with seizures, or with an elevated platelet count in the blood are unknown. If you suffer from any of these diseases, your doctor will discuss this with you and treat you with caution.
• Healthy individuals should not use MIRCERA. Its use can cause a hemoglobin level that is too high and lead to heart or blood vessel problems that can be life-threatening.

During treatment with MIRCERA

• If you are a patient with chronic kidney disease, and particularly if you do not respond adequately to MIRCERA, your doctor will monitor your MIRCERA dose, as repeated increases in the MIRCERA dose if you are not responding to treatment may increase the risk of heart or blood vessel problems, and may increase the risk of myocardial infarction, stroke, and death.
• Your doctor may initiate treatment with MIRCERA if your hemoglobin level is less than or equal to 10 g/dl (6.21 mmol/l). After starting treatment, your doctor will maintain your hemoglobin level between 10 and 12 g/dl (7.45 mmol/l).
• Your doctor will check the amount of iron in your blood before and during treatment with MIRCERA. If the amount is too low, your doctor may give you additional treatment.
• Your doctor will check your blood pressure before and during treatment with MIRCERA. If your blood pressure is high and cannot be controlled, either with medication or a special diet, your doctor will interrupt your treatment with MIRCERA or reduce the dose.
• Your doctor will check that your hemoglobin level does not exceed a certain value. A high hemoglobin level can increase the risk of serious heart or blood vessel problems, which can increase the risk of thrombosis, including pulmonary embolism, myocardial infarction, stroke, and death.
• Inform your doctor if you feel tired, weak, or have shortness of breath, as this may indicate that your MIRCERA treatment is not effective. Your doctor will check that you do not have other causes of anemia and may perform blood tests or examine your bone marrow. If you have developed PRCA, your treatment with MIRCERA will be interrupted. You will not receive another ESA, and your doctor will treat this disease.

Children and adolescents

MIRCERA can be used to treat children and adolescents, from 3 months to less than 18 years of age, with anemia associated with chronic kidney disease. You should be stabilized with ESA maintenance treatment before switching to MIRCERA, and you may or may not be receiving dialysis.

Consult your doctor, pharmacist, or nurse before this medication is administered to you or your child if you or your child are under 18 years of age.

Be especially careful with other medications that stimulate red blood cell production:MIRCERA is one of the erythropoiesis-stimulating agents, such as the human protein erythropoietin. Your doctor should always register the exact product you are using.

Severe skin reactions, such as Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (TEN), have been observed with the administration of epoetins.

SSJ/TEN may initially appear as circular, red macules or patches with central blisters on the trunk. They may also appear as ulcers in the mouth, throat, nose, genitals, and eyes (irritation and swelling of the eyes). These severe skin reactions are often preceded by fever or flu-like symptoms. The skin reaction may progress to generalized skin peeling and potentially life-threatening complications.

If you experience a severe skin reaction or any of these other skin symptoms, stop taking Mircera and seek medical attention immediately.

Use of MIRCERA with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

No interactions have been studied. There is no evidence that MIRCERA interacts with other medications.

Use of MIRCERA with food and drinks

Foods and beverages do not affect MIRCERA.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before using any medication.

No studies have been conducted on MIRCERA in pregnant women or breastfeeding women.

Inform your doctor if you are pregnant, if you think you may be pregnant, or if you plan to become pregnant. Your doctor will consider the best treatment for you during pregnancy.

Inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will advise you whether to stop or continue breastfeeding and whether to stop or continue your treatment.

MIRCERA has not shown evidence of altered fertility in animals. The potential risk in humans is unknown.

Driving and operating machinery

MIRCERA does not affect your ability to drive and operate machinery.

Important information about some of the components of MIRCERA

This medication contains less than 1 mmol (23 mg) of sodium per ml; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

Your doctor will use the most effective dose to control your anemia symptoms.

If you do not respond adequately to MIRCERA, your doctor will check your dose and inform you if you need to change the MIRCERA dose.

MIRCERA treatment should be initiated under the supervision of a healthcare professional. Subsequent injections can be administered by a healthcare professional or, once instructed, an adult patient can self-administer MIRCERA. Children and adolescents under 18 years of age should not self-administer MIRCERA; administration should be performed by a healthcare professional or an adult caregiver who has been trained. (Follow instructions at the end of the leaflet on how to use the pre-filled syringe of MIRCERA to administer an injection to yourself or another person).

MIRCERA can be injected under the skin in the abdomen, arm, or thigh, or into a vein. Your doctor will decide what is best for you.

Your doctor will perform regular blood tests and monitor your hemoglobin level to evaluate how your anemia is responding to treatment.

• If you are an adult not currently being treated with an ESA
• If you are not on dialysis, the recommended initial dose of MIRCERA is 1.2 micrograms per kilogram of body weight, administered once a month as a single injection under the skin. Alternatively, your doctor may decide to administer an initial dose of MIRCERA of 0.6 micrograms per kilogram of body weight. The dose is administered once every two weeks under the skin or into a vein. Once your anemia has been corrected, your doctor may modify the dosage to once a month.
• If you are on dialysis, the recommended initial dose is 0.6 micrograms per kilogram of body weight. The dose is administered once every two weeks as a single injection under the skin or into a vein. Once your anemia has been corrected, your doctor may modify the dosage to once a month.

Your doctor may increase or decrease your dose or temporarily interrupt your treatment to adjust your hemoglobin level to the appropriate level for you. Dose changes will not be made more frequently than once a month.

• If you are currently being treated with another ESA

Your doctor may replace your current medication with MIRCERA. Your doctor will decide if you will be treated with MIRCERA administered as a single injection once a month. Your doctor will calculate your initial dose of MIRCERA based on your last dose of your previous medication. The first dose of MIRCERA will be administered on the day your previous medication injection was scheduled.

Your doctor may increase or decrease your dose or temporarily interrupt your treatment to adjust your hemoglobin level to the appropriate level for you. Dose changes will not be made more frequently than once a month.

If you use more MIRCERA than you should

Inform your doctor or pharmacist if you use too much MIRCERA, as it may be necessary to perform blood tests and interrupt your treatment.

If you forget to use MIRCERA

If you forget a dose of MIRCERA, administer the dose as soon as you remember and ask your doctor when to administer the next doses.

If you interrupt MIRCERA treatment

MIRCERA treatment is usually long-term, but it can be interrupted at any time if your doctor indicates.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The frequency of possible side effects is listed below:

A frequent side effect (can affect up to 1 in 10 patients) is hypertension (high blood pressure).

The less common side effects (can affect up to 1 in 100 patients) are:

• headache
• thrombosis in the vascular access area (blood clots in the dialysis access) thrombocytopenia
• thrombosis

The rare side effects (can affect up to 1 in 1000 patients) are:

• hypertensive encephalopathy (very high blood pressure that can cause headache, especially migraine-type headache, sudden and stabbing, confusion, speech alteration, seizures, or convulsions).
• pulmonary embolism
• maculopapular eruption (skin reaction that can include redness, pimples, or acne)
• flushing with heat
• hypersensitivity (severe allergic reaction that can cause unusual breathing sounds or difficulty breathing, inflammation in the tongue, face, or throat, or swelling around the injection site, making you feel dizzy, faint, or causing a fall).

If you experience these symptoms, please inform your doctor immediately to receive treatment.

During clinical trials, patients presented a small decrease in platelet count in the blood. Cases of platelet count below the normal level (thrombocytopenia) have been reported in the post-marketing period.

Severe hypersensitivity reactions, including anaphylactic reactions and severe skin eruptions, such as Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis, have been observed with the administration of epoetins. These reactions can appear as red, circular patches with central blisters on the trunk, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Stop using Mircera if you experience these symptoms and contact your doctor or seek immediate medical attention. See section 2.

Like with other EPOs, cases of thrombosis, including pulmonary embolism, have been reported in the post-marketing period.

In some patients treated with EPOs, including MIRCERA, a disease called pure red cell aplasia (AEP, anemia due to the presence of anti-erythropoietin antibodies) has been observed.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet.You can also report them directly through thenational reporting system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use MIRCERA after the expiration date that appears on the carton and on the pre-filled syringe label after “EXP”. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C – 8 °C). Do not freeze.

Store the pre-filled syringe in the outer packaging to protect it from light.

You may remove the pre-filled syringe from MIRCERA from the refrigerator and store it at room temperature, never above 30 °C, for a single period of one month. During this period in which you have stored MIRCERA at room temperature never above 30 °C, you cannot return MIRCERA to the refrigerator before use. Once you have removed the medication from the refrigerator, you must use it within that one-month period.

Only inject transparent, colorless to slightly yellowish solutions that are free of visible particles.

Medicines should not be disposed of through drains or in the trash.

Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of MIRCERA

• The active ingredient is methoxy-polyethylene glycol epoetin beta. A pre-filled syringe contains: 30, 50, 75, 100, 120, 150, 200 or 250 micrograms in 0.3 ml and 360 micrograms in 0.6 ml.
• The other components are monosodium phosphate monohydrate, sodium sulfate, mannitol (E421), methionine, poloxamer 188 and water for injection.

Appearance of the product and contents of the pack

MIRCERA is a pre-filled syringe injectable solution.

Clear, colourless to slightly yellowish solution without visible particles.

MIRCERA is presented in pre-filled syringes with a laminated piston and a protective cap with a 27 G1/2 needle. Each pre-filled syringe contains 0.3 ml or 0.6 ml of solution.The pre-filled syringes are not designed for partial dose administration.MIRCERA is available, for all doses, in packs of 1 and also in packs of 3 for the doses of 30, 50, 75 micrograms/0.3 ml.Only some pack sizes may be marketed.

Marketing authorisation holder and responsible manufacturer

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of the summary of product characteristics:

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu/.

IMPORTANT INFORMATION

?Use only MIRCERA pre-filled syringe if you have been prescribed this medicinal product.

?Read the packaging and ensure you have the dose prescribed by your doctor.

?Do not useMIRCERA if the syringe, needle, box or plastic tray containing the syringe appears to be damaged.

• The needle is fragile, handle it carefully.

?Do not touchthe activation protectors (see Figure A) as this may damage the syringe and render it unusable.

?Do not usethe syringe if the contents are cloudy, white or contain particles.

?Never attempt to disassemble the syringe.

?Never throw or manipulate the syringe by the plunger.

?Do not removethe needle protective cap until you are ready to administer the injection.

?Do not ingestthe medicinal product from the syringe.

?Do not injectthrough clothing.

?Do not re-useor re-sterilise the syringe or needle.

?The pre-filled syringes are not designed for partial dose administration.

?Keep the syringe, needle and supplies out of the reach of children.

CONSERVATION

Keep the pre-filled syringe, needle and thesharps containerout of the reach of children.

Store the syringe and needle in their original packaging until the time of use.

Always store the syringe and needle in the refrigerator at a temperature of 2 – 8 ºC (35.6 - 46.4°F).

Do notallow the medicinal product to freeze, and protect the medicinal product and needle from light. Keep the syringe and needle in a dry place.

CONTENTS OF THE PACK (Figure A):

• A pre-filled syringe containing MIRCERA
• A needle for injection

Figure A

CONTENTS NOT INCLUDED IN THE PACK (Figure B):

Figure B

Place all the elements you need for an injection on a flat, clean and well-lit surface, such as a table.

Step 4: Place the needle in the syringe