Mircera 120 micrograms/0.3 ml solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

MIRCERA

30 micrograms/0.3 ml solution for injection in pre-filled syringe

50 micrograms/0.3 ml solution for injection in pre-filled syringe

75 micrograms/0.3 ml solution for injection in pre-filled syringe

100 micrograms/0.3 ml solution for injection in pre-filled syringe

120 micrograms/0.3 ml solution for injection in pre-filled syringe

150 micrograms/0.3 ml solution for injection in pre-filled syringe

200 micrograms/0.3 ml solution for injection in pre-filled syringe

250 micrograms/0.3 ml solution for injection in pre-filled syringe

360 micrograms/0.6 ml solution for injection in pre-filled syringe

methoxy polyethylene glycol-epoetin beta

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience adverse effects, consult your doctor, even if they are adverse effects 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 using MIRCERA
3. How to use MIRCERA
4. Possible side effects
5. How to store MIRCERA
6. Contents of the pack and other information

1. What MIRCERA is and what it is used for

You have been 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 that you have too few red blood cells and your hemoglobin level is too low (possibly meaning that the tissues of your body are not 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 up to under 18 years of age) who are receiving maintenance therapy with an erythropoiesis-stimulating agent (ESA), after hemoglobin levels have been stabilized with prior ESA therapy.

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

2. What you need to know before using MIRCERA

Do not use MIRCERA

• if you are allergic to methoxy polyethylene glycol-epoetin beta or any of the other components of this medicine (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 for 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 levels have previously been stabilized with treatment using an erythropoiesis-stimulating agent (ESA).

Before starting MIRCERA treatment

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

If you are a patient with hepatitis C receiving interferon and ribavirin, you should discuss this with your doctor, because combining ESAs with interferon and ribavirin may lead to loss of response and, in rare cases, the development of PRCA, which is 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 you also have cancer, you should be aware that ESAs might have a negative impact on your condition. You should discuss other treatment options for 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 episodes, with seizures, or in those with a high platelet count in blood. If you have any of these conditions, your doctor will discuss them with you and treat you with caution.
• Healthy individuals must not use MIRCERA. Its use may cause hemoglobin levels to become too high and lead to heart or blood vessel problems, which could be life-threatening.

During treatment with MIRCERA

• If you are a patient with chronic renal failure, and particularly if you do not respond adequately to MIRCERA, your doctor will monitor your MIRCERA dose, as repeatedly increasing the dose when not responding to treatment may increase the risk of heart or blood vessel problems, and could 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 your iron levels in blood before and during treatment with MIRCERA. If levels are too low, your doctor may prescribe additional treatment.
• Your doctor will monitor your blood pressure before and during treatment with MIRCERA. If your blood pressure is high and cannot be controlled either by appropriate medication or by a special diet, your doctor will interrupt or reduce your MIRCERA treatment.
• Your doctor will ensure that your hemoglobin level does not exceed a certain value. High hemoglobin levels may increase the risk of serious heart or blood vessel problems, which may increase the risk of thrombosis, including pulmonary embolism, myocardial infarction, stroke, and death.
• Inform your doctor if you feel tired, weak, or short of breath, as this may indicate that your MIRCERA treatment is not effective. Your doctor will check for other causes of anemia and may perform blood tests or examine your bone marrow. If you develop PRCA, your MIRCERA treatment will be stopped. You will not receive another ESA, and your doctor will treat this condition.

Children and adolescents

MIRCERA can be used to treat children and adolescents aged 3 months to under 18 years with anemia associated with chronic kidney disease. They must be stabilized on maintenance ESA therapy before switching to MIRCERA and may or may not be receiving dialysis.

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

Exercise special caution with other medicines that stimulate red blood cell production: MIRCERA is one of the agents that stimulate red blood cell production, similar to the human protein erythropoietin. Your doctor must always record the exact product you are using.

Serious cutaneous adverse 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 macules or circular red rash lesions, often with central blisters on the trunk. Ulcers may also appear in the mouth, throat, nose, genitals, and eyes (eye irritation and swelling). These severe skin rashes are often preceded by fever or flu-like symptoms. The skin rash may progress to widespread skin peeling and potentially life-threatening complications.

If you develop 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

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

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

Using MIRCERA with food and drink

Food and drink do not affect MIRCERA.

Pregnancy, breast-feeding, and fertility

Consult your doctor or pharmacist before using any medicine.

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

Inform your doctor if you are pregnant, think you may be pregnant, or 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 affecting 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 components of MIRCERA

This medicine contains less than 1 mmol (23 mg) of sodium per ml; this is essentially “sodium-free”.

3. How to use MIRCERA

Follow exactly the administration instructions for this medicine given by your doctor. If in doubt, consult your doctor or pharmacist again.

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

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

Treatment with MIRCERA should be initiated under the supervision of a healthcare professional. Subsequent injections may be given by a healthcare professional or, once trained, by the adult patient self-administering MIRCERA. Children and adolescents under 18 years of age must not self-inject MIRCERA; administration must 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 into 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, by evaluating your hemoglobin level, monitor 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 monthly as a single subcutaneous injection. Alternatively, your doctor may decide to administer an initial dose of MIRCERA of 0.6 micrograms per kilogram of body weight, given once every two weeks subcutaneously or intravenously. Once anemia has been corrected, your doctor may adjust the dosing regimen to once monthly.

If you are on dialysis, the recommended initial dose is 0.6 micrograms per kilogram of body weight, administered once every two weeks as a single injection either subcutaneously or intravenously. Once anemia has been corrected, your doctor may adjust the dosing regimen to once monthly.

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

• If you are currently being treated with another ESA

Your doctor may switch your current medication to MIRCERA. Your doctor will decide whether to treat you with MIRCERA administered as a single injection once monthly. Your doctor will calculate your initial MIRCERA dose based on the last dose of your previous medication. The first dose of MIRCERA will be administered on the day your previous medication was scheduled.

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

If you use more MIRCERA than you should

Inform your doctor or pharmacist if you have used too high a dose of MIRCERA, as blood tests may be needed and interruption of treatment may be required.

If you forget to use MIRCERA

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

If you stop using MIRCERA

Treatment with MIRCERA is usually long-term. However, it may be interrupted at any time as directed by your doctor.

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 at the vascular access site (blood clots at the dialysis access site)
• thrombocytopenia
• thrombosis

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

• hypertensive encephalopathy (very high blood pressure which may cause headache, especially sudden, sharp, migraine-like headache, confusion, speech disturbances, seizures or convulsions)
• pulmonary embolism
• maculopapular rash (a skin reaction with redness that may include pimples or spots)
• flushing with warmth
• hypersensitivity (a severe allergic reaction which may cause unusual breathing sounds 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 collapse)

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

During clinical trials, patients experienced a slight decrease in platelet count in blood. Cases of platelet counts below normal levels (thrombocytopenia) have been reported during the post-marketing period.

Hypersensitivity reactions have been observed, including cases of anaphylactic reaction and severe skin rashes such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis, following administration of epoetins. These reactions may appear as red, circular patches or spots, often with central blisters on the trunk, skin peeling, and ulcers in the mouth, throat, nose, genital area, 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 also section 2.

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

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

Reporting of side effects

If you experience any type of side effect, talk to your doctor, pharmacist, or nurse, even if it is a possible side effect not listed in this leaflet. You can also report them directly through 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. Storage of 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 refers to the last day of the month indicated.

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

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

The pre-filled syringe of MIRCERA may be removed from the refrigerator and stored at room temperature, not exceeding 30 °C, for a single period of one month. During this period, once MIRCERA has been stored at room temperature not exceeding 30 °C, it must not be returned to the refrigerator before use. Once the medicine has been removed from the refrigerator, it must be used within that 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 any unused containers and medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of MIRCERA

• The active substance 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 injections.

Nature of the product and contents of the container

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

Clear, colourless to slightly yellowish solution, free from visible particles.

MIRCERA is supplied in pre-filled syringes with a laminated plunger and a needle 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 administration of partial doses. MIRCERA is available, for all strengths, in packs of 1 and also in packs of 3 for the 30, 50, 75 microgram/0.3 ml strengths.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:
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 regarding this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

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

IMPORTANT INFORMATION

• Use MIRCERA pre-filled syringe only if this medication has been prescribed for you.
• Check the packaging and make sure you have the dose prescribed by your doctor.
• Do not use MIRCERA if the syringe, needle, box, or plastic tray containing the syringe appears damaged.
• The needle is fragile; handle it with care.
• Do not touch the activation protectors (see Figure A), as this may damage the syringe and render it unusable.
• Do not use the syringe if the solution is cloudy, whitish, or contains particles.
• Never attempt to disassemble the syringe.
• Never push or handle the syringe by the plunger.
• Do not remove the needle cap until you are ready to administer the injection.
• Do not ingest the medication from the syringe.
• Do not inject through clothing.
• Do not reuse or re-sterilize the syringe or needle.
• Pre-filled syringes are not designed to deliver partial doses.
• Keep the syringe, needle, and supplies out of the reach of children.

STORAGE

Keep the pre-filled syringe, needle, and sharps disposal container out of the reach of children.

Store the syringe and needle in their original packaging until ready for use.

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

Do not allow 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):

• One pre-filled syringe containing MIRCERA
• One injection needle

MATERIALS NOT included in the package (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

Step 7: Dispose of the used syringe with the needle

Place used syringes into a sharps disposal container.

• Do not attempt to recap the needle.
• Do not reuse or resterilize the syringe and/or needle.
• Do not dispose of the used syringe with the needle in household trash.
• Dispose of used syringes in a sharps disposal container and/or according to regulations established by health authorities.
• Dispose of the full sharps disposal container.