MIRCERA 100 micrograms/0.3 ml SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE

2. What you need to know before you start using MIRCERA

Do not use MIRCERA

• if you are allergic to methoxy polyethylene glycol-epoetin beta or any of the other ingredients 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 anaemia in patients with cancer.

The safety and efficacy of MIRCERA treatment in paediatric patients have only been established in patients whose haemoglobin level has been stabilised previously 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 failure of the bone marrow to produce red blood cells) has been observed due to the presence of antibodies against erythropoietin.
• 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 anaemia. ESAs are not approved for the treatment of anaemia associated with hepatitis C.

• If you are a patient with chronic kidney disease and anaemia, treated with an ESA, and you 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 anaemia with your doctor.
• It is not known whether MIRCERA has a different effect in patients with haemoglobinopathies (disorders associated with abnormal haemoglobin levels), with bleeding, or 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 haemoglobin 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 heart attack, stroke, and death.
• Your doctor may start treatment with MIRCERA if your haemoglobin level is 10 g/dl (6.21 mmol/l) or less. After starting treatment, your doctor will keep your haemoglobin 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 by medication or by a special diet, your doctor will stop your treatment with MIRCERA or reduce the dose.
• Your doctor will check that your haemoglobin level does not exceed a certain value. A high haemoglobin level can increase the risk of serious heart or blood vessel problems, which can increase the risk of blood clots, including pulmonary embolism, heart attack, 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 anaemia and may perform blood tests or examine your bone marrow. If you have developed PRCA, your treatment with MIRCERA will be stopped. 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 anaemia associated with chronic kidney disease. They should be stabilised with maintenance ESA treatment before switching to MIRCERA and may or may not be receiving dialysis.

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

Be careful with other medicines that stimulate the production of red blood cells:MIRCERA is one of the agents that stimulate the production of red blood cells, as does 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 may initially appear as red, circular patches or spots, often with central blisters on the trunk. Ulcers in the mouth, throat, nose, genitals, and eyes (irritation and swelling of the eyes) may also appear. These severe skin reactions are often preceded by fever or flu-like symptoms. The skin reaction may progress to widespread 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 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 taking 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 breastfeeding or stop treatment with MIRCERA.

MIRCERA has not shown any effect on fertility in animal studies. 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 prescribed 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 anaemia.

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 trained, you can inject MIRCERA yourself. Children and adolescents under 18 years of age should not inject MIRCERA themselves; 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 haemoglobin level to see how your anaemia 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 your anaemia 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 your anaemia has been corrected, your doctor may modify the dosage to once a month.

Your doctor may increase or decrease your dose or temporarily stop your treatment to adjust your haemoglobin 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. The first dose of MIRCERA will be administered on the day your previous medicine was scheduled to be injected.

Your doctor may increase or decrease your dose or temporarily stop your treatment to adjust your haemoglobin 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 your treatment may need to be stopped.

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 stopped at any time if your doctor decides to do so.

If you have any further questions on 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 people) is high blood pressure.

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

• hypertensive encephalopathy (very high blood pressure that can cause headache, especially sudden and severe headache, confusion, speech disturbance, seizures, or convulsions)
• pulmonary embolism
• maculopapular rash (redness of the skin that can include pimples or spots)
• 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 tell 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 failure of the bone marrow to produce red blood cells) has been observed due to the presence of antibodies against erythropoietin.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing MIRCERA

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

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

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 (not above 30°C) for a single period of one month. During this period, you cannot put MIRCERA back in 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 clear, colourless to slightly yellowish, and free from visible particles.

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

Ask your pharmacist how to dispose of medicines no longer required. 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 Authorisation 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 from the local representative of the marketing authorisation 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 you have been prescribed this medication.

? 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 PACKAGE (Figure A):

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

Figure A

MATERIALS NOT INCLUDED IN THE PACKAGE (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