MIRCERA 120 micrograms/0.3 ml SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

Introduction

Leaflet:information for the user

MIRCERA

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

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

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

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

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

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

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

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

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

methoxy polyethylene glycol-epoetin beta

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed to you only, 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 side effects, ask your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What MIRCERA is and what it is used for
2. What you need to know before taking MIRCERA
3. How to use MIRCERA
4. Possible side effects
5. Storage of MIRCERA
6. Contents of the pack and further information

1. What MIRCERA is and what it is used for

Your doctor has prescribed this medicine because you have anemia caused by chronic kidney disease. This anemia is associated with typical symptoms such as fatigue, weakness, and shortness of breath. This means you have very few red blood cells and your hemoglobin level is too low (your body 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 been stabilized with the previous ESA.

MIRCERA is a medicine obtained by genetic engineering. Like the natural hormone erythropoietin, MIRCERA increases the number of red blood cells and the hemoglobin level in the blood.

2. What you need to know before taking MIRCERA

Do not use MIRCERA

• if you are allergic to methoxy polyethylene glycol-epoetin beta or to any of the other components of this medicine (listed in section 6)
• if you have uncontrolled high blood pressure

Warnings and precautions

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

The safety and efficacy of MIRCERA treatment in pediatric patients have only been established in patients whose hemoglobin level has been previously stabilized with an 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, a reduction or cessation of red blood cell production) 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 are receiving interferon and ribavirin, you should discuss this with your doctor, as the combination of ESAs with interferon and ribavirin can lead to 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 are also a cancer patient, you should be aware that ESAs may have a negative impact on your disease. You should discuss other options for treating anemia with your doctor.
• It is not known whether MIRCERA has a different effect in patients with hemoglobinopathies (disorders associated with abnormal hemoglobin levels), with current or past bleeding, with seizures, or in those with a high platelet count in the blood. If you have any of these conditions, your doctor will discuss them with you and treat you with caution.
• Healthy individuals should not use MIRCERA. Its use can lead to a level of hemoglobin that is too high and cause heart or blood vessel problems that can be life-threatening.

During treatment with MIRCERA

• If you are a patient with chronic kidney disease, and in particular 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 start 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 through 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.
• Tell your doctor if you feel tired, weak, or short of breath, as this may mean that your treatment with MIRCERA 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. They should be stabilized with maintenance ESA treatment before switching to MIRCERA and may or may not be receiving dialysis.

Ask your doctor, pharmacist, or nurse before administering this medicine if you or your child is under 18 years of age.

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

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

SJS/TEN can initially appear as red, circular patches or spots, often with central blisters on the trunk. Ulcers in the mouth, throat, nose, genitals, and eyes (eye irritation and swelling) may also appear. These severe skin reactions are often preceded by fever or flu-like symptoms. The skin rash can progress to widespread skin peeling and potentially life-threatening complications.

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

Using MIRCERA with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

No interaction studies have been performed. There is no evidence that MIRCERA interacts with other medicines.

Using MIRCERA with food and drinks

Food and drinks do not affect MIRCERA.

Pregnancy, breastfeeding, and fertility

Ask your doctor or pharmacist before using any medicine.

No studies have been performed with MIRCERA in pregnant or breastfeeding women.

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

Tell 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 any evidence of altering fertility in animals. The potential risk in humans is unknown.

Driving and using machines

MIRCERA does not affect your ability to drive or use machines.

Important information about some of the ingredients of MIRCERA

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

3. How to use MIRCERA

Follow the instructions for administration of this medicine exactly as indicated by your doctor. If you are unsure, ask your doctor or pharmacist again.

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

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

Treatment with MIRCERA should be started under the supervision of a healthcare professional. The following injections can be administered by a healthcare professional or, once you have been taught, the adult patient can inject MIRCERA themselves. Children and adolescents under 18 years of age should not self-inject MIRCERA; administration should be performed by a healthcare professional or a trained adult caregiver. (Follow the instructions at the end of the leaflet on how to use the MIRCERA pre-filled syringe 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 see how your anemia is responding to treatment.

• If you are an adult who is 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 in 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 the 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 in a single injection, under the skin or into a vein. Once the 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 medicine with MIRCERA. Your doctor will decide whether to treat you with MIRCERA administered in a single injection once a month. Your doctor will calculate your initial dose of MIRCERA based on your previous medicine's last dose. The first dose of MIRCERA will be administered on the day your previous medicine's 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

Tell your doctor or pharmacist if you use a higher dose of MIRCERA than you should, as you may need to have 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 stop treatment with MIRCERA

Treatment with MIRCERA is usually long-term. However, it can be interrupted at any time if your doctor decides to do so.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The frequency of possible side effects is listed below:

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

Uncommon side effects (may affect up to 1 in 100 patients) are:

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

Rare side effects (may affect up to 1 in 1,000 patients) are:

• hypertensive encephalopathy (very high blood pressure that can cause headache, especially sudden and severe migraine-like headache, confusion, speech disturbance, seizures, or convulsions)
• pulmonary embolism
• maculopapular rash (redness of the skin that can include pimples or pustules)
• flushing with warmth
• hypersensitivity (severe allergic reaction that can cause unusual sounds when breathing or difficulty breathing, swelling of the tongue, face, or throat, or swelling around the injection site, or make you feel dizzy, faint, or cause you to fall)

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

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

Hypersensitivity reactions, including cases of anaphylactic reaction and severe skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been observed with the administration of epoetins. These reactions can appear as red, circular patches or spots, often 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 medical attention immediately. See also section 2.

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

In some patients treated with ESAs, including MIRCERA, a disease called pure red cell aplasia (PRCA, a reduction or cessation of red blood cell production) has been observed due to the presence of anti-erythropoietin antibodies.

Reporting of side effects

If you experience any side effects, ask your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of MIRCERA

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

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

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

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

You can take the MIRCERA pre-filled syringe out of the refrigerator and store it at room temperature, never above 30°C, for a single period of one month. During this period, you cannot return MIRCERA to the refrigerator before use. Once you have taken the medicine out of the refrigerator, you must use it within this one-month period.

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

Medicines should not be disposed of via wastewater or household waste.

Ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Container Contents and Additional Information

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 injectable preparations.

Appearance of the Product and Container Contents

MIRCERA is an injectable solution in a pre-filled syringe.

Clear to slightly yellowish solution without visible particles.

MIRCERA is presented in pre-filled syringes with a laminated piston and a protector 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 30, 50, 75 microgram/0.3 ml doses. Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu/.

IMPORTANT INFORMATION

? Use MIRCERA pre-filled syringe only if it has been prescribed for you.

? Read the packaging and make sure 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 with care.

? 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, whitish, or contain particles.

? Never attempt to disassemble the syringe.

? Never throw or handle the syringe by the plunger.

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

? Do not ingestthe medication from the syringe.

? Do not injectthrough clothing.

? Do notreuse or re-sterilize the syringe or needle.

? Pre-filled syringes are not designed to administer partial doses.

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

STORAGE

Keep the pre-filled syringe, needle, andcontainer for disposal of sharp objectsout 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 medication to freeze, and protect the medication and needle from light. Keep the syringe and needle in a dry place.

MATERIALS Included in the Packaging (Figure A):

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

Figure A

MATERIALS Not Included in the Packaging (Figure B):

Figure B

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

Step 4: Attach the Needle to the Syringe