Consumer medicine information

Mircera

Methoxy polyethylene glycol-epoetin beta

BRAND INFORMATION

Brand name

Mircera

Active ingredient

Methoxy polyethylene glycol-epoetin beta

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mircera.

SUMMARY CMI

Mircera®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Mircera?

Mircera contains the active ingredient methoxy polyethylene glycol-epoetin beta. Mircera is used to treat anaemia caused by chronic kidney disease (kidney failure).
For more information, see Section 1. Why am I using Mircera? in the full CMI.

2. What should I know before I use Mircera?

Do not use if you have ever had an allergic reaction to Mircera or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.
For more information, see Section 2. What should I know before I use Mircera? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Mircera and affect how it works. Tell your doctor or pharmacist if you are taking any medicines, including any that you can get without a prescription or if you are unsure about any medicine.
A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Mircera?

Treatment with Mircera must be started under the supervision of a healthcare professional.
Further injections can be given by a healthcare professional or, after you have been trained, you can inject Mircera under the skin yourself (see instructions "How to self-inject Mircera".)
Mircera can be injected under the skin on the abdomen, arm or thigh or into a vein. Your doctor will decide which is best for you. More instructions can be found in Section 4. How do I use Mircera? in the full CMI.

5. What should I know while using Mircera?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit or tell the surgeon or anaesthetist if you are going to have surgery that you are using Mircera.
  • Tell your doctor if you feel unusually tired, weak (lack of energy) or have shortness of breath as this could mean your Mircera treatment is not effective.
Things you should not do
  • Do not stop using this medicine or change the dose without first checking with your doctor.
  • Do not let yourself run out of Mircera over the weekend or on holidays.
Driving or using machines
  • Mircera is not expected to affect your ability to drive a car or operate machinery. However, be careful driving or operating machinery until you know how Mircera affects you.
Looking after your medicine
  • Store in the fridge (2°C to 8°C). Do not freeze. Do not shake. Store in outer carton to protect from light
  • You may remove an individual dose of Mircera from the fridge and store it at room temperature (not above 30°C) for one month and on one occasion only.

For more information, see Section 5. What should I know while using Mircera? in the full CMI.

6. Are there any side effects?

Common side effects include: back or join pain, muscle spasms, changes in blood pressure, ringing in ears, vision problems, diarrhoea, constipation, nausea, vomiting, stomach pain, indigestion, sore throat or nose, fever, cough, shortness of breath, difficulty sleeping, pain with urination, swelling of ankles, feet or hands, feel tired, itching, hot flushes. Serious side effects include blood clots in your dialysis access, bleeding or bruising more easily, chest pain, feeling of tightness in chest, headache, red skin reaction. These side effects require medical attention.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Mircera® (Pronounced "meer-seh-ra")

Active ingredient(s): methoxy polyethylene glycol-epoetin beta


Consumer Medicine Information (CMI)

This leaflet provides important information about using Mircera. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Mircera.

Where to find information in this leaflet:

1. Why am I using Mircera?
2. What should I know before I use Mircera?
3. What if I am taking other medicines?
4. How do I use Mircera?
5. What should I know while using Mircera?
6. Are there any side effects?
7. Product details

1. Why am I using Mircera?

Mircera contains the active ingredient methoxy polyethylene glycol-epoetin beta. Mircera is used to treat anaemia caused by chronic kidney disease (kidney failure).

Anaemia is a condition caused by low levels of red blood cells, resulting in low haemoglobin, a protein that transports oxygen in the blood. Consequently your body's tissues might not receive enough oxygen. Symptoms may include tiredness, weakness and shortness of breath.

Mircera belongs to a group of medicines known as hormones. The kidneys produce the natural hormone erythropoietin, which stimulates the production of red blood cells in the bone marrow and spleen.

Like erythropoietin, Mircera works by increasing the number of red blood cells and the haemoglobin level in your blood. It will reduce your need for blood transfusions. Compared to other erythropoietin medicines, Mircera can stay in your body longer, therefore requiring fewer injections for your treatment.

Mircera is used to treat anaemia caused by chronic kidney disease. It has not been shown that Mircera can be used to treat anaemia caused by other diseases.

Your doctor, however, may have prescribed Mircera for another purpose.

Ask your doctor if you have any questions about why Mircera has been prescribed for you.

Mircera is not addictive.

This medicine is available only with a doctor's prescription.

2. What should I know before I use Mircera?

Warnings

Do not use Mircera if:

  • you are allergic to methoxy polyethylene glycol-epoetin beta, any other similar medicines (i.e. containing erythropoetin) or any of the ingredients listed at the end of this leaflet.
    - Some of the symptoms of an allergic reaction may include: shortness of breath, wheezing or difficulty breathing, swelling of the face, lips, tongue or other parts of the body, rash, itching or gives on the skin.
    - Always check the ingredients to make sure you can use this medicine.
  • You have high blood pressure that is not well controlled.
  • The package is torn or shows signs of tampering.
  • The expiry date (EXP) printed on the pack has passed.
    If you take this medicine after the expiry date has passed, it may not work as well.
  • You are not sure if you should be using Mircera, talk to your doctor.
  • You are healthy or have not been prescribed Mircera. Using it can lead to too high haemoglobin levels and cause problems with the heart or blood vessels that may be life-threatening.
  • Do not give Mircera to children or adolescents under the age of 18 years.
    The safety and effectiveness of Mircera have not been established in these patients.

Check with your doctor if you:

  • have any of the following medical conditions:
    - Disorders associated with abnormal haemoglobin (haemoglobinopathies);
    - Blood clotting diseases, which mean you bleed or bruise more easily;
    - High blood pressure - it is important to follow your doctor's instructions to control your blood pressure, including taking blood pressure medicines and changes to your diet;
    - Cancer;
    - Epilepsy or seizures;
    - Any other illness or health problems. A number of conditions such as vitamin deficiencies may affect how well you respond to Mircera;
  • Have any allergies to any other medicines, foods, preservatives or dyes.
  • Plan to have surgery.
  • take any medicines for any other condition
  • Have not told your doctor about any of the above, tell them before you start using Mircera.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

  • Mircera is not generally recommended for use in pregnant women unless the benefits of treatment outweigh the risk to the unborn baby.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

  • It is not known whether Mircera passes into breast milk. Your doctor will discuss the risks and benefits of using Mircera if you are breast-feeding.

Blood and Blood Pressure

  • Your doctor will check the amount of iron in your blood before and during your Mircera treatment. If the amount is too low your doctor may recommend you take iron supplements.
  • Your doctor will check your blood pressure before and during your Mircera treatment. It is important to follow your doctor's instructions to control your blood pressure, including taking blood pressure medicines and changes to your diet. If your blood pressure cannot be controlled your doctor may stop your Mircera treatment or reduce the dose.
  • A condition called pure red cell aplasia (stopped or reduced production of red blood cells due to your body producing antibodies against erythropoietin) has been observed in some patients treated with erythropoietin products including Mircera. If your doctor suspects or confirms that you have these antibodies in your blood you must not be treated with Mircera.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may be affected by Mircera, or may affect how well it works. You may need to use different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while using Mircera.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Mircera.

4. How do I use Mircera?

Use Mircera exactly as your doctor has prescribed.

Treatment with Mircera must be started under the supervision of a healthcare professional.

Further injections can be given by a healthcare professional or, after you have been trained, you can inject Mircera under the skin yourself (see instructions "How to self-inject Mircera".)

Mircera can be injected under the skin on the abdomen, arm or thigh or into a vein. Your doctor will decide which is best for you.

Your doctor will carry out regular blood tests that monitor your haemoglobin levels and making sure they do not exceed a certain level. High haemoglobin levels could put you at risk of heart or blood vessel problems which could increase the risk of death. If necessary, your dose may be changed by your doctor during therapy according to your response.

If you have not been treated with an erythropoietin medicine

If you are not currently on dialysis, the recommended starting dose of Mircera is 1.2 micrograms for every kilogram of your body weight once per month or if you prefer 0.6 micrograms for every kilogram of your body weight once every 2 weeks.

If you are currently on dialysis, the recommended starting dose of Mircera is 0.6 micrograms for every kilogram of your body weight once every 2 weeks.

Your haemoglobin level should be tested regularly. Depending on the result, your doctor may increase or decrease your Mircera dose. Dose changes should not be made more often than once a month.

Once your anaemia is corrected, your doctor may change your injection to once a month.

If you are already being treated with an erythropoietin medicine

Your doctor may replace your current medicine with Mircera.

Your doctor will calculate your Mircera starting dose based on the last dose of your previous medicine. The first Mircera dose will be given on the planned injection day of your previous medicine. Mircera will be given as a single injection once a month (or if you prefer, once every two weeks).

Your haemoglobin level should be tested regularly. Depending on the result, your doctor may increase or decrease your Mircera dose, or temporarily stop treatment. Dose changes should not be made more often than once a month.

Treatment with Mircera is normally long-term. It can however, be stopped on the advice of your doctor at any time. Continue using Mircera until your doctor tells you to stop.

When to use Mircera

  • Mircera should be used as a single injection once a month (or if you prefer, once every two weeks) depending on your body weight.

How to self-inject Mircera

Your doctor may discuss with you whether it would be more convenient for you to inject Mircera yourself at home. This is a simple procedure and many patients prefer it. Always use Mircera exactly as your doctor has told you. Check with your doctor or nurse if you are unsure.

The Mircera pre-filled syringe is ready for use and can be injected by yourself either under the skin (on the abdomen, arm or thigh) or if you are on haemodialysis, through the haemodialysis vascular access according to your doctor's advice.

Each pre-filled syringe is to be used for a single injection only. Do not mix Mircera solution with other injectable medicines.

Setting up for an injection

Before you begin

  1. Find a clean, comfortable area
  2. Gather all the supplies you will need;

Included in the pack:

  • A Mircera pre-filled safety syringe and a separate needle.

Not included in the pack:

  • Cleansing alcohol swabs.
  • Cotton wool or dry sterile pad.
  • A sharps (puncture proof) disposal container.
  1. Remove an individual dose of Mircera from the fridge and allow it to reach room temperature. This should take about 30 minutes. Do not warm up the syringe in any other way.

Do not shake the pre-filled syringe. If the solution has been shaken and appears foamy, do not use it (shaking Mircera or exposing it to light may damage the medicine).

Check the expiration date stated on the outer carton and pre-filled syringe label after 'EXP' to make sure that it has not expired. The expiry date refers to the last day of that month. Do not use Mircera after the expiry date.

Preparing the Mircera pre-filled syringe and needle for injection

  1. Wash your hands with soap and water. Cleanliness is vital during the injection procedure.
  2. Take the pre-filled syringe and needle out of the blister packaging.

  1. Only use if the solution is clear, colourless (slightly yellow in colour is acceptable) and there are no visible particles.
  2. Grasp the needle shield (C) firmly in both hands. Remove the plastic cap (B), twist then pull.

DO NOT REMOVE THE NEEDLE SHEILD (C). DO NOT TOUCH THE PLUNGER ROD (E) OR FINGER RESTS (F) AT THIS TIME. Doing so will release the needle guard (G) and you will be unable to inject your dose of Mircera.

  1. Remove the rubber cap (D) from the syringe (bend and pull).

  1. Attach the needle with needle shield (A and C) to the syringe (H) by pushing firmly together.

  1. Remove the needle shield (C) and prepare for injection.

To remove air bubbles from the pre-filled syringe, hold the syringe with the needle pointing up. Tap the syringe gently to bring any bubbles to the top.

Push the plunger up slowly to remove all air, as shown to you by a healthcare professional.

Injecting the solution

If your doctor has advised you to inject Mircera into a vein (e.g. through the haemodialysis vascular access) please administer your dose as shown by your healthcare professional.

If you have been advised to inject Mircera under your skin please follow the subsequent instructions step by step.

  1. Select the injection site on the outer upper arm, abdomen (away from your navel or waistline) or thigh as shown below. The back of the upper arm is not a recommended site for self-injection. Use this injection site only if you inject someone else.

You should use a different injection site each time you administer an injection, at least three centimetres from the area you used for the previous injection. Do not inject areas that could be irritated by a belt or waistband.

Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard or not intact.

  1. Clean the skin where the injection is to be made with a cleansing alcohol swab. Wait for the area to dry.

  1. Hold the syringe firmly with one hand and pull off the needle shield (C) with the other hand. Throw away the needle shield in the puncture-resistant or sharps container.
Do not touch the needle or let it touch any surface, as the needle may become contaminated and may cause injury if touched.

You may see a drop of liquid at the end of the needle. This is normal.

  1. With one hand, pinch a fold of loose skin. Insert the needle into the pinched skin, using a quick “dart like” motion, as shown by your healthcare professional.

  1. Slowly press the plunger rod (E) with your thumb while holding the finger rests (F), until the full dose has been given.
Do not release the plunger rod (E).

Removing the needle

  1. Take the needle out of the skin without releasing the plunger rod (E).

  1. Once removed, release the plunger rod (E) allowing the needle to retract into the needle guard (G).

  1. Press the injection site with cotton wool or a dry sterile pad for several seconds. Do not massage the injection site.

  1. Dispose of the syringe with the needle (protected in the needle guard (G)) in a puncture-proof (sharps) container as instructed by your doctor, nurse or pharmacist.

Never put the used syringe in your normal household garbage or recycling.

If you forget to use Mircera

Mircera should be used regularly at the same time as prescribed. If you miss your dose at the usual time, administer the missed dose as soon as you remember and speak to your doctor about when to take the next dose.

If you use too much Mircera

Please contact your doctor or pharmacist if you used too much Mircera as it may be necessary to perform some blood tests and stop your treatment temporarily.

If you think that you have used too much Mircera, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Keep these telephone numbers handy.

If you are not sure what to do, contact your doctor or pharmacist.

5. What should I know while using Mircera?

Things you should do

If you are about to start any new medicine, remind your doctor and pharmacist that you are using Mircera.

Tell all doctors, dentists, and pharmacists who are treating you that you are using Mircera.

If you are going to have surgery, tell the surgeon or anaesthetist that you are using Mircera.

It may affect other medicines used during surgery.

Tell your doctor if you become pregnant while using Mircera.

Tell your doctor if, for any reason, you have not used your medicine exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Tell your doctor if you feel that Mircera is not helping your condition.

Medicines do not always help every patient.

Be sure to keep all of your appointments with your doctor so that your progress can be checked.

Call your doctor straight away if you:

Remind any doctor, dentist or pharmacist you visit that you are taking Mircera.

Things you should not do

  • Do not stop using Mircera or change the dose without first checking with your doctor.
  • Do not let yourself run out of Mircera over the weekend or on holidays.
  • Do not give Mircera to anyone else even if they have the same condition as you.
  • Do not use Mircera to treat any other complaints unless your doctor tells you to.

Blood and Blood Pressure monitoring

  • Tell your doctor that you are using Mircera if you are having any blood tests.

Most patients' blood iron levels decrease when on erythropoietin therapy and you may need to be treated with iron supplements.

  • If you have blood pressure problems it is important to follow your doctor's instructions to control your blood pressure, including taking blood pressure medicines and changes to your diet while using Mircera.
  • Tell your doctor if you feel unusually tired, weak (lack of energy) or have shortness of breath as this could mean your Mircera treatment 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 pure red cell aplasia your Mircera treatment will be discontinued. You will not receive another erythropoietin and your doctor will determine the best course of action to treat your anaemia.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Mircera affects you.

However, Mircera is not expected to affect your ability to drive a car or operate machinery.

Looking after your medicine

  • Store in the fridge (2°C to 8°C). Do not freeze. Do not shake.
  • Do not use a pre-filled syringe that has been frozen and do not expose it to temperatures above 30°C.
  • Keep the pre-filled syringe in the outer carton in order to protect from light.
  • Once dispensed, take Mircera home and place in the fridge as soon as possible.
  • You may then remove an individual dose of Mircera from the fridge and store it at room temperature (not above 30°C) for one month and on one occasion only. Once you have stored Mircera at room temperature (not above 30°C) you must not put Mircera back in the fridge. Once you have removed Mircera from the fridge you must use it within one month even if it has not passed the expiry date.
  • Keep Mircera where young children cannot reach it.

Follow the instructions in the carton on how to take care of your medicine properly.

When to discard your medicine

The syringe is intended for single use only and must be thrown away after the injection. Dispose of the syringe with the needle (protected in the needle guard) in a puncture proof container as instructed by your doctor, nurse or pharmacist.

Never put the used syringe in your normal household garbage.

Getting rid of any unwanted medicine

If your doctor tells you to stop using Mircera, or the pre-filled syringe has passed its expiry date, ask your pharmacist what to do with any medicine that is left over.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Stomach/digestion/bowel/bladder related:
  • Diarrhoea or constipation
  • Pain with urination or increased need to urinate
  • Nausea (feeling sick) or vomiting
  • Stomach pain or indigestion
Nose/throat/breathing related:
  • Sore throat or nose
  • Cough or shortness of breath
Skin related:
  • Itching
  • Hot flushes
Blood pressure related:
  • High blood pressure symptoms include headache, dizziness, confusion, ringing in the ears (tinnitis) and vision problems
  • Low blood pressure symptoms include dizziness or light headedness
General body related:
  • Swelling of the ankles, feet or hands
  • Back or joint pain or muscle spasms
  • Fever
  • Difficulty sleeping
  • Fatigue or unusual weakness, looking pale
Speak to your doctor if you have any of these less serious side effects and they worry you.
This list includes the more common side effects of Mircera. They are usually mild and short-lived.

Serious side effects

Serious side effectsWhat to do
Blood related:
  • Blood clots in your dialysis access.
  • Bleeding or bruising more easily.
General symptoms:
  • Chest pain, feeling of tightness, pressure or heaviness in the chest.
  • Headache.
  • Red skin reaction that can include pimples or spots.
The above list includes serious side effects that may require medical attention. Serious side effects are uncommon.
Tell your doctor as soon as possible if you notice any of those listed.
Blood pressure related:
  • Worsening of existing high blood pressure. Symptoms may include headache, especially sudden, stabbing, migraine-like headache, confusion, speech disturbances, fits or convulsions.
Allergic/skin related:
  • Allergic reaction. Symptoms may include shortness of breath, wheezing or breathing difficulties, swelling of the face, lips, tongue or other parts of the body, rash, itching or hives on the skin.
  • Blisters on your skin, especially severe blisters and bleeding in the lips, eyes, mouth, nose and genitals.
  • Severe skin reactions or rash that may cover your whole body.
  • Feeling unusually tired, weak (lack energy) or have shortness of breath.
The above list includes very serious side effects that may require urgent medical attention or hospitalisation. These side effects are rare.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems.

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Mircera contains

Active ingredient
(main ingredient)
Methoxy polyethylene glycol-epoetin beta
Other ingredients
(inactive ingredients)
Monobasic sodium phosphate monohydrate
Sodium sulfate
Mannitol
Methionine
Poloxamer
Water for injections
Potential allergensNIL

Mircera is lactose and gluten free.

Do not take this medicine if you are allergic to any of these ingredients.

What Mircera looks like

Mircera solution for injection is slightly yellow to colourless and clear (no visible particles).

Mircera is available as a pack containing one single use prefilled syringe and a 27 gauge ½ inch needle The syringe plungers and packaging are coloured to easily identify the strength as follows:

30 mcg/0.3 mL (aqua)

50 mcg/0.3 mL (yellow)

75 mcg/0.3 mL (red)

100 mcg/0.3 mL (turquoise)

120 mcg/0.3 mL (lime)

200 mcg/0.3 mL (purple)

360 mcg/0.6 mL (salmon)

Australian Registration Numbers

30 mcg/0.3 mL AUST R 153810

50 mcg/0.3 mL AUST R 153813

75 mcg/0.3 mL AUST R 153801

100 mcg/0.3 mL AUST R 153806

120 mcg/0.3 mL AUST R 153807

200 mcg/0.3 mL AUST R 153805

360 mcg/0.6 mL AUST R 153804

Who distributes Mircera

Mircera is distributed in Australia by:

Roche Products Pty Limited.
ABN 70 000 132 865
Level 8, 30 - 34 Hickson Road
Sydney NSW 2000
Medical enquiries: 1800 233 950

Please check with your pharmacist for the latest Consumer Medicine Information.

This leaflet was prepared in November 2023.

Published by MIMS January 2024

BRAND INFORMATION

Brand name

Mircera

Active ingredient

Methoxy polyethylene glycol-epoetin beta

Schedule

S4

 

1 Name of Medicine

Methoxy polyethylene glycol-epoetin beta.

2 Qualitative and Quantitative Composition

Mircera 30 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 50 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 75 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 100 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 120 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 150 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 200 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 250 micrograms/0.3 mL solution for injection in pre-filled syringe.
Mircera 360 micrograms/0.6 mL solution for injection in pre-filled syringe.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Solution for injection in pre-filled syringe.
The solution is clear and colourless to slightly yellowish and the pH is 6.2.

4 Clinical Particulars

4.1 Therapeutic Indications

Mircera is indicated for the treatment of anaemia associated with chronic kidney disease (CKD).

4.2 Dose and Method of Administration

Dosage.

General. Use the lowest dose of Mircera that will gradually increase the haemoglobin concentration. Mircera is administered less frequently than Aranesp, Eprex and NeoRecormon due to the longer elimination half-life.
Treatment with Mircera is to be initiated under the supervision of a healthcare professional.
Treatment of anaemic patients with chronic kidney disease. The solution can be administered by subcutaneous (SC) or intravenous (IV) injection, according to clinical preference. Mircera can be injected SC in the abdomen, arm or thigh. All three injection sites are equally suitable for SC injection with Mircera.
Patients being changed from SC to IV administration of Mircera (or vice-versa) should have their haemoglobin levels monitored to ensure that the haemoglobin concentration stays within the desired target of 100 and 120 g/L. Patients should be monitored closely to ensure that the lowest effective dose of Mircera is used to provide adequate control of the symptoms of anaemia.
Patients not currently treated with an erythropoiesis stimulating agent (ESA).

Patients not on dialysis.

The recommended starting dose is 1.2 microgram/kg body weight administered once every month as a single SC injection. Alternatively, a starting dose of 0.6 microgram/kg body weight may be administered once every two weeks as a single IV or SC injection.

Patients on dialysis.

The recommended starting dose of 0.6 microgram/kg body weight may be administered once every two weeks as a single IV or SC injection.
It is recommended that haemoglobin is monitored every two weeks until stabilised, and periodically thereafter (see Section 4.4 Special Warnings and Precautions for Use).
The dose of Mircera may be increased by approximately 25% of the previous dose if the rate of rise in haemoglobin is less than 10 g/L over a month. Further increases of approximately 25% may be made at monthly intervals until the individual target haemoglobin level is obtained.
Dose adjustments should not be made more frequently than once a month. The dose for each patient should be adjusted so that the haemoglobin level does not exceed 120 g/L. If the rate of rise in haemoglobin is greater than 20 g/L in one month or the haemoglobin level is increasing and approaching 120 g/L, the Mircera dose should be reduced by approximately 25%.
If the haemoglobin level continues to increase following dose reduction, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If the haemoglobin increases by more than 10 g/L in any 2 week period, the dose should be decreased by approximately 25%. After dose interruption, a haemoglobin decrease of approximately 3.5 g/L per week is expected.
Patients treated once every two weeks whose target haemoglobin has been reached may receive Mircera administered once monthly using the dose equal to twice the previous fortnightly dose.
Patients currently treated with an erythropoiesis stimulating agent (ESA). When converting from epoetin or darbepoetin alfa, Mircera can be administered once monthly or, if desired, once every two weeks as a single IV or SC injection. The starting dose of Mircera is calculated based on the previously given ESA weekly dose at the time of conversion, as described in Table 1. The two-weekly dose should be approximately half the once monthly dose. The first injection of Mircera should be administered at the next scheduled dose of the previously administered darbepoetin alfa or epoetin.
It is recommended that haemoglobin is monitored every month until stabilised, and periodically thereafter (see Section 4.4 Special Warnings and Precautions for Use).
If a dose adjustment is required to maintain the target haemoglobin concentration between 100 - 120 g/L, the monthly dose may be adjusted by approximately 25%.
Dose adjustments should not be made more frequently than once a month. The dose for each patient should be adjusted so that the haemoglobin level does not exceed 120 g/L. If the haemoglobin is increasing and approaching 120 g/L, the dose should be reduced by approximately 25%. If the haemoglobin continues to increase following dose reduction, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose. If the haemoglobin increases by more than 10 g/L in any 2 week period, the dose should be decreased by approximately 25%. After dose interruption, a haemoglobin decrease of approximately 3.5 g/L per week is expected.

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 should be administered as soon as possible and administration of Mircera restarted at the prescribed dosing frequency.

Dosage adjustment.

Hepatic impairment.

No adjustments of the starting dose or dose modification rules are required in patients with any degree of hepatic impairment.

4.3 Contraindications

Mircera is contraindicated in patients with: uncontrolled hypertension; known hypersensitivity to the active substance or any of the excipients.

4.4 Special Warnings and Precautions for Use

Serious allergic reactions including pruritus and rash, have been reported in patients treated with Mircera. If a serious allergic or anaphylactic reaction occurs due to Mircera, treatment should be immediately discontinued and appropriate therapy should be administered.

Cardiovascular and thrombotic events/ increased mortality.

Cardiovascular and thrombotic events such as myocardial ischaemia and infarction, cerebrovascular haemorrhage and infarction, transient ischaemic attacks, deep venous thrombosis, arterial thrombosis, pulmonary emboli, retinal thrombosis and haemodialysis graft occlusion have been reported in patients receiving ESAs.
In controlled clinical trials, ESAs increased the risk for death in oncology patients and for serious cardiovascular events in oncology and CKD patients when administered to target a haemoglobin of > 120 g/L. There was an increased risk of serious arterial and venous thromboembolic events, including myocardial infarction, stroke, congestive heart failure and haemodialysis graft occlusion. A rate of haemoglobin rise of > 10 g/L over 2 weeks may also contribute to these risks.
ESAs also increased the risk of thrombosis in patients undergoing orthopaedic procedures or coronary artery bypass.
The safety and efficacy of Mircera have not been established in patients with anaemia due to cancer chemotherapy or in the peri-surgical setting.
To reduce cardiovascular risks, use the lowest dose of Mircera that will gradually increase the haemoglobin concentration. The haemoglobin concentration should not exceed 120 g/L and the rate of haemoglobin increase should not exceed 10 g/L in a 2 week period. Haemoglobin levels should be checked at regular intervals and dosages adjusted (see Section 4.2 Dose and Method of Administration).

Growth factor potential/ increased tumour progression.

Mircera, like other ESAs, is a growth factor that primarily stimulates red blood cell (RBC) production. As with all growth factors, there is a theoretical concern that epoetins could act as a growth factor for any type of malignancy. ESAs, when administered to target haemoglobin of > 120 g/L, shortened the time to tumour progression in patients with advanced head and neck cancer receiving radiation therapy. ESAs also shortened the time to tumour progression and/or survival in patients with breast cancer, cervical cancer, lymphoid malignancy or non-small cell lung cancer when administered to a target haemoglobin ≥ 120 g/L. Although the target haemoglobin was ≥ 120 g/L, the risk of accelerated tumour progression and shortened survival has not been excluded when ESAs are used to target haemoglobin < 120 g/L.
ESAs have been associated with an increased risk of thrombosis (see Section 4.4 Special Warnings and Precautions for Use) and accelerated tumour progression. Mircera is not indicated for the treatment of anaemia in patients with cancer.

Hypertension.

Patients with uncontrolled hypertension should not be treated with Mircera; blood pressure should be adequately controlled before initiation of therapy. Blood pressure may rise during treatment of anaemia with Mircera as with other ESAs. Hypertensive encephalopathy and seizures have been observed in patients treated with Mircera as with other ESAs.
Special care should be taken to closely monitor and control blood pressure in patients treated with Mircera. During Mircera therapy, patients should be advised of the importance of compliance with antihypertensive therapy and dietary restrictions. If blood pressure is difficult to control after initiation of appropriate measures, the dose of Mircera should be reduced or temporarily withheld until haemoglobin begins to decrease (see Section 4.2 Dose and Method of Administration).

Pure red cell aplasia (PRCA).

PRCA caused by neutralising anti-erythropoietin antibodies has been reported in association with ESA therapy including Mircera. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients suspected or confirmed to have neutralising antibodies to erythropoietin should not be switched to Mircera. If anti-erythropoietin antibody-mediated PRCA develops whilst on Mircera, therapy with Mircera must be discontinued and patients should not be switched to another ESA.

Seizures.

ESAs should be used with caution in patients with epilepsy.

Severe cutaneous adverse reactions.

Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with epoetin treatment. More severe cases have been observed with long acting epoetins.
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, Mircera should be withdrawn immediately and an alternative treatment considered.
If the patient has developed a severe cutaneous skin reaction such as SJS or TEN due to the use of Mircera, treatment with Mircera must not be restarted in this patient at any time.

General.

The safety and efficacy of Mircera therapy have not been established in patients with haemoglobinopathies or with a platelet level greater than 500 x 109/L. Therefore, caution should be used in these patients.
Supplementary iron therapy is recommended for all patients with serum ferritin values below 100 microgram/L or whose transferrin saturation is below 20%, as per Caring for Australasians with Renal Impairment (CARI) Guidelines. To ensure effective erythropoiesis, iron status should be evaluated for all patients prior to, and during treatment.
A lack of response or failure to maintain haemoglobin response with Mircera within the recommended dose range should prompt a search for causative factors. Deficiencies of iron, folic acid, and vitamin B12 should be excluded or corrected. The following conditions may also compromise the effectiveness of ESA therapy: chronic blood loss, bone marrow fibrosis, haemolysis, and severe aluminium overload due to treatment of renal failure. If all these conditions are excluded and the patient has a sudden drop of haemoglobin associated with reticulocytopenia and anti-erythropoietin antibodies, examination of the bone marrow for the diagnosis of PRCA should be considered. If PRCA is diagnosed, therapy with Mircera must be discontinued and patients should not be switched to another ESA.
Misuse by non-anaemic persons may lead to an excessive increase in haemoglobin. This may be associated with life threatening complications of the cardiovascular system.

Paediatric use.

Mircera is not recommended for use in patients aged less than 18 years due to a lack of data on safety and efficacy.

Use in the elderly.

Of the 1789 CKD patients treated with Mircera in clinical trials, 24% were aged 65 to 74 years, while 20% were aged 75 years and over. Based on population analyses, no adjustment of the starting dose is required in patients aged 65 years or older.

Effects on laboratory tests.

See Section 4.8 Adverse Effects (Undesirable Effects).

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed. The results from clinical trials do not indicate any interaction of Mircera with other medicinal products. There was no indication of an effect of concomitant medications on the pharmacokinetics and pharmacodynamics of Mircera using a population analysis approach.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

When Mircera was administered subcutaneously to male and female rats prior to, and during mating, at 6 times the clinical systemic exposure, based on AUC values, fertility, and sperm count and motility were not affected.
(Category B3)
Methoxy polyethylene glycol-epoetin beta crossed the rat placenta and was distributed to foetal tissues, particularly the reproductive organs, spleen and kidneys. A reduction in foetal weights occurred in rats and rabbits at systemic exposures 1 to 3 times clinical exposure, with an increase in reversible developmental delays, such as incomplete ossification, in both species. In rabbits there was an increase in the incidence of flat ribs at 29 times the clinical systemic exposure (based on AUC values). All doses tested in both species caused exaggerated pharmacodynamic effects in dams. Post-implantation loss was increased in rabbits and sometimes in rats. Mircera should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
It is unknown whether Mircera is excreted in human breast milk. Methoxy polyethylene glycol-epoetin beta was excreted into the milk of rats. Mircera treatment of lactating rats was associated with some adverse effects on the offspring, which included reduced pup bodyweight gain, developmental delay, slightly increased pup mortality, increased incidence of pale livers and/or lungs and an increase in the incidence of abdominal distension post weaning. A decision on whether to discontinue breast-feeding or therapy with Mircera should be made taking into account the benefit of Mircera therapy to the woman and the potential risks to the child.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, no effects are expected based on the mechanism of action and the known safety profile of Mircera.

4.8 Adverse Effects (Undesirable Effects)

Clinical trials.

The safety database for Mircera (based on data from the completed phase II and III studies and long-term follow-up information from safety extension studies) comprised of 2737 CKD patients, where 1789 were treated with Mircera and 948 with another ESA.
Based on the results of 1789 patients, approximately 8% of patients treated with Mircera experienced adverse reactions. The most frequently reported adverse reaction was hypertension.
Adverse events (irrespective of causal relationship) with ≥ 5% incidence in patients treated with Mircera or a reference drug (epoetin or darbepoetin alfa) are presented in Table 2.
The adverse event of thrombocytopenia was reported in 0.8% of Mircera treated patients and 0.5% of patients receiving epoetin or darbepoetin alfa, irrespective of causal relationship. However, the incidence of platelet count less than 100 x 109/L was considerably higher in both treatment groups (see Section 4.4 Special Warnings and Precautions for Use).

Platelet count and thrombocytopenia.

During treatment with Mircera, a slight decrease (median 5.7%) in platelet counts, remaining within the normal range, was observed in clinical studies. The decline was observed after the first dose and there was a partial recovery over the course of the studies.
A platelet count below 100 x 109/L was observed in 9.0% of patients treated with Mircera and 6.2% of patients treated with other ESAs.
Some of the adverse events reported are typically associated with CKD, or recognised complications of dialysis, and may not necessarily be attributable to Mircera therapy.
The following descriptors are used to describe the frequency of adverse reactions attributed to treatment with Mircera in controlled clinical trials:
Common (≥ 1/100 and < 1/10), Uncommon (≥ 1/1,000 and < 1/100), and Rare (≥ 1/10,000 and < 1/1,000).

Vascular disorders.

Common: hypertension; rare: hot flush.

Injury, poisoning and procedural complications.

Uncommon: vascular access thrombosis.

Immune system disorders.

Rare: hypersensitivity, anaphylactic reaction (not known).

Nervous system disorders.

Uncommon: headache; rare: hypertensive encephalopathy.

Skin and subcutaneous tissue disorders.

Rare: rash (maculo-papular, serious).
All other events attributed to Mircera were reported with rare frequency and were of mild to moderate severity in the majority of patients. These events were consistent with co-morbidities known in the population.

Post-marketing experience.

Neutralising anti-erythropoietin antibody-mediated pure red cell aplasia (AEAB-PRCA) associated with Mircera therapy has been reported during post marketing experience (see Section 4.4 Special Warnings and Precautions for Use). Stevens-Johnson syndrome/ toxic epidermal necrolysis has been reported.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

The therapeutic range of Mircera is wide and individual response to therapy must be considered when Mircera treatment is initiated. Overdose can result in manifestations of an exaggerated pharmacodynamic effect, e.g. excessive erythropoiesis. In case of excessive haemoglobin levels, Mircera should be temporarily withheld. If clinically indicated, phlebotomy may be performed.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: Other antianemic preparations, ATC code: B03XA03.

5.1 Pharmacodynamic Properties

Mechanism of action.

Mircera shows different activity to recombinant erythropoietin at the receptor level. It is characterised by slower association to the receptor and slightly faster dissociation, resulting in a lower affinity for the receptor. This lower affinity may result in less receptor-mediated endocytosis and contribute together with reduced subsequent lysosomal degradation and/or increased recycling to the slower elimination. Mircera thus has a longer half-life than erythropoietin which enables Mircera to be administered in a once monthly dosing regimen.
Erythropoietin is a growth factor for erythroid development. It is produced in the kidney and released into the bloodstream in response to hypoxia, interacting with erythroid progenitor cells to increase red blood cell production. Production of endogenous erythropoietin is impaired in patients with chronic kidney disease (CKD), and erythropoietin deficiency is the primary cause of their anaemia.
The onset of haemoglobin increase (defined as an increase > 4 g/L from baseline) is observed in CKD patients after 7 to 15 days following a single dose of Mircera.

Clinical trials.

Chronic kidney disease anaemia. Mircera has been evaluated in patients not currently treated with an ESA (including patients on dialysis and not on dialysis) and those currently treated with an ESA.

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

See Table 3.
The change in haemoglobin levels (from baseline) observed in these clinical trials demonstrated Mircera to be clinically non-inferior to darbepoetin alfa (p < 0.0001). The time to haemoglobin response was longer with Mircera than the comparator. For the ARCTOS and AMICUS trials the observed median dose of Mircera (once every two weeks) was 0.6 microgram/kg.
A lower proportion of patients treated with Mircera experienced a haemoglobin level greater than 130 g/L during the first 8 weeks of treatment compared to the reference arms in the AMICUS and ARCTOS studies (7.5% in the Mircera group compared to 17.8% for epoetin alfa or beta and 34% in the darbepoetin alfa arm compared to 11.4% for Mircera). The corresponding proportions of patients experiencing a haemoglobin level greater than 120 g/L during the first 8 weeks of treatment in the CORDATUS study were 25.8% in the Mircera group and 47.7% in the darbepoetin alfa group.

Patients currently treated with an erythropoiesis stimulating agent (ESA).

CKD patients currently receiving an ESA were randomised to stay on their current treatment or switched to Mircera to maintain stable haemoglobin levels. For patients randomised to receive Mircera (either once every two weeks or once every four weeks) the initial dose was determined based on the patient's previous weekly ESA dose. (See Table 4.)
The results from these studies demonstrated the ability of Mircera to maintain haemoglobin concentrations within the study target range of 110 - 130 g/L.
The most frequently reported adverse effect in clinical trials (both comparators and Mircera) was hypertension (see Section 4.4 Special Warnings and Precautions for Use).

Other clinical trials.

In a randomised, placebo-controlled, single-blind, three-way crossover study, pain scores after SC injection with Mircera were similar to placebo and significantly less compared to other ESAs.

5.2 Pharmacokinetic Properties

The pharmacokinetics of Mircera was studied in healthy volunteers and in anaemic CKD patients, including patients on dialysis and not on dialysis.
A comparison of serum concentrations of Mircera measured before and after haemodialysis in 41 CKD patients showed that haemodialysis had no effect on Mircera serum concentrations in vivo.
The results of a study in 42 healthy volunteers indicated that the site of subcutaneous (SC) injection (abdomen, arm or thigh) had no clinically relevant effect on the pharmacokinetics, pharmacodynamics, or local tolerability of Mircera. Based on these results, all three sites are considered suitable for SC injection with Mircera.
An analysis in 126 CKD patients showed no pharmacokinetic difference between patients on dialysis and patients not on dialysis.
Multiple dosing in CKD patients was found to have no effect on the clearance, volume of distribution and bioavailability of Mircera.

Absorption.

Following SC administration in CKD patients, the maximum serum concentrations of Mircera were observed 72 hours (median value) after administration in dialysis patients and 95 hours after administration in patients not on dialysis. The absolute bioavailability of Mircera after SC administration was 62% and 54%, in dialysis patients and patients not on dialysis, respectively.
A study in 400 CKD patients showed that the volume of distribution of Mircera is approximately 5 L.
After administration every 4 weeks in CKD patients, there was virtually no accumulation of Mircera, as demonstrated by a ratio of accumulation of 1.03. After administration every 2 weeks, the ratio of accumulation in serum was 1.12.

Excretion.

The pharmacokinetic and the pharmacological properties of Mircera allow for monthly administration due to the longer elimination half-life. The elimination half-life after intravenous (IV) administration of Mircera is 15 to 20 times longer compared to recombinant human erythropoietin.
Following IV administration in CKD patients, the observed terminal elimination half-life (t1/2) for Mircera was 134 hours, and the total systemic clearance was 0.494 mL/hr/kg. Following SC administration the t1/2 was 139 hours in dialysis patients and 142 hours in patients not on dialysis.
Data on methoxy polyethylene glycol-epoetin beta metabolism in animals is not available. In rat, both unchanged methoxy polyethylene glycol-epoetin beta (about 1% of administered dose) and polyethylene glycol-like material were found in urine. In humans, it is unknown whether a significant proportion of methoxy polyethylene glycol-epoetin beta is catabolised. In clinical trials with healthy volunteers, unchanged methoxy polyethylene glycol-epoetin beta was not detected in the urine. Due to its high molecular weight, renal excretion of methoxy polyethylene glycol-epoetin beta would not be expected.

Pharmacokinetics in special populations.

Population analyses evaluated the potential effects of demographic characteristics on the pharmacokinetics of Mircera. Results of these analyses showed that no dose adjustments are necessary for age, gender, or race.
From a single dose study, it was shown that following IV administration, the pharmacokinetics of Mircera are similar in patients with severe hepatic impairment compared to healthy subjects.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of Mircera has not been evaluated.

Carcinogenicity.

The carcinogenic potential of Mircera has not been evaluated in long-term animal studies. As with all growth factors, there is a concern that ESAs could stimulate the growth of any type of malignancy (see Section 4.4 Special Warnings and Precautions for Use).

6 Pharmaceutical Particulars

6.1 List of Excipients

Monobasic sodium phosphate monohydrate, sodium sulfate, mannitol, methionine, poloxamer, water for injections.

6.2 Incompatibilities

Mircera should not be mixed with other products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Mircera must not be used after the expiry date.
Store continuously in the refrigerator at 2°C to 8°C. Do not freeze. Do not shake. Protect from light.
The prefilled syringes contain no antimicrobial preservative and are for single-use in one patient only. Discard any residue.
The end user may remove Mircera from refrigeration (2°C to 8°C) for storage at room temperature (up to 30°C) for one single period of 1 month. Once removed from the fridge, the product must be used within 1 month and not returned to the fridge for storage.
Allow the product to reach room temperature before injecting.

6.5 Nature and Contents of Container

Mircera is supplied in a pack containing one single-use prefilled syringe and a 27 gauge, ½ inch needle. Each prefilled syringe is equipped with a needle guard that covers the needle during disposal to reduce the risk of needle stick injury after application.
Mircera is available in the following strengths and plungers are colour coded for easy identification as indicated in Table 5.

6.6 Special Precautions for Disposal

The release of medicines into the environment should be minimised. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Unused or expired medicine should be returned to a pharmacy for disposal.

6.7 Physicochemical Properties

Chemical structure.


Mircera (methoxy polyethylene glycol-epoetin beta) is a chemically synthesised Erythropoiesis Stimulating Agent (ESA) with a much longer half-life than erythropoietin.
It is produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cells and differs from erythropoietin through the integration of an amide bond between either the N-terminal amino group or the epsilon-amino group of lysine, predominantly Lys52 and Lys45 and methoxy polyethylene glycol butanoic acid. This results in a molecular weight of approximately 60 kilodaltons with the polyethylene glycol-moiety having an approximate molecular weight of 30 kilodaltons. The dosage strength in micrograms indicates the quantity of the protein moiety of the methoxy polyethylene glycol-epoetin beta molecule without consideration of glycosylation.

CAS number.

677324-53-7.

7 Medicine Schedule (Poisons Standard)

S4. Prescription only medicine.

Summary Table of Changes