Consumer medicine information

NeoRecormon

Epoetin beta

BRAND INFORMATION

Brand name

NeoRecormon

Active ingredient

Epoetin beta

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using NeoRecormon.

SUMMARY CMI

NeoRecormon®

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.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using NeoRecormon?

NeoRecormon contains the active ingredient epoetin beta. NeoRecormon is used to treat anaemia caused by chronic kidney disease. Anaemia is caused by a lack of red blood cells or haemoglobin which transports oxygen in the blood.

For more information, see Section 1. Why am I using NeoRecormon? in the full CMI.

2. What should I know before I use NeoRecormon?

Do not use if you have ever had an allergic reaction to NeoRecormon 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 NeoRecormon? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with NeoRecormon and affect how it works.

For more information, see Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use NeoRecormon?

  • Your doctor will tell you how much and how often to inject NeoRecormon according to your individual needs.
  • NeoRecormon can be given by your doctor or nurse. Alternatively your doctor, nurse or pharmacist may teach you or your carer how to inject NeoRecormon.

More instructions can be found in Section 4. How do I use NeoRecormon? in the full CMI.

5. What should I know while using NeoRecormon?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using NeoRecormon.
  • If you have blood pressure problems it is important to follow all your doctor's instructions to control your blood pressure, including any changes to your diet, while using NeoRecormon.
Things you should not do
  • Do not stop using this medicine suddenly
  • Do not let yourself run out of medicine over the weekend or on holidays.
  • Do not switch to any other brands of epoetin without consulting your doctor.
Driving or using machines
  • Be careful driving or operating machinery until you know how NeoRecormon affects you. NeoRecormon is not expected to affect your ability to drive a car or operate machinery.
Looking after your medicine
  • Store NeoRecormon pre-filled syringes in the fridge at 2 to 8°C. Do not freeze. Keep NeoRecormon in its carton, in the fridge, until it is time to use it.
  • You can use NeoRecormon if it has been left out of the fridge for no longer than 3 days (a single period only) at room temperature (up to 25°C).

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

6. Are there any side effects?

When you are using NeoRecormon, you can have some serious side effects. Serious side effects include: stabbing, migraine-like headache, chest pain, shortness of breath, double vision, dizziness, feeling lightheaded or tingling of extremities, swelling, pain, tenderness, warmth or discolouration of one leg or arm or along a vein in your leg or arm, sudden shortness of breath, chest pain, palpitations or coughing up blood, sudden trouble walking, speaking seeing or understanding what someone is saying, sudden onset of wheezing or difficulty breathing, swollen tongue, face or throat, severe skin reactions, hives, blisters or rash that may cover your whole body.

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.

WARNING FOR CANCER PATIENTS: use of medicines such as NeoRecormon which stimulate red blood cell production for anaemia in patients with cancer has been associated with increased risk of death in some studies. Your doctor should only use NeoRecormon to treat your anaemia if it is caused by chemotherapy and only when blood transfusion is not an appropriate treatment option.



FULL CMI

NeoRecormon®

Active ingredient(s): epoetin beta [recombinant human erythropoietin]

Consumer Medicine Information (CMI)

This leaflet provides important information about using NeoRecormon. 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 NeoRecormon.

Where to find information in this leaflet:

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

1. Why am I using NeoRecormon?

NeoRecormon contains the active ingredient epoetin beta (pronounced ee-poe-tin bee-ta). Epoetin beta is also known as recombinant human erythropoietin (pronounced ee-rith-roe-poy-tin). NeoRecormon 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, NeoRecormon works by increasing the number of red blood cells and the haemoglobin level in your blood. Anaemia is caused by a lack of red blood cells or haemoglobin which transport oxygen in the blood. If you have anaemia, your body's tissues might not receive enough oxygen.

NeoRecormon is used to treat anaemia caused by chronic kidney disease.

NeoRecormon may also be used:

  • If you are planning to have major surgery and you are going to have your own blood collected for use during the surgery.
  • To prevent anaemia in premature babies.
  • If you have anaemia after being treated with chemotherapy for cancer and you can't have a blood transfusion.

Your doctor, however, may have prescribed NeoRecormon for another reason.

2. What should I know before I use NeoRecormon?

Warnings

Do not use NeoRecormon if:

  • you are allergic to NeoRecormon, or any of the ingredients listed at the end of this leaflet. Always check the ingredients to make sure you can use this medicine.
  • you have high blood pressure that is not well controlled.
  • you are donating your own blood before surgery, and:
    - you have had a heart attack or stroke in the month before your treatment, or
    - you have new or increasing chest pain, or
    - you are at risk of blood clots in the veins (deep vein thrombosis) or if you have had clots before.

If any of these apply or might apply to you, tell your doctor at once.

Do not misuse NeoRecormon. Misuse by healthy people may lead to an excessive increase in the number of red blood cells in the blood. Such an increase may cause life-threatening effects on the heart and blood vessels.

Check with your doctor if you:

  • take any medicines for any other condition
  • have or have had any other health problems especially the following:
    - blood clotting conditions such as heart attack or deep vein thrombosis
    - bleeding conditions including stroke
    - cancer
    - epilepsy
    - you have had problems with another erythropoietin-type medicine
    - liver disease
    - you or your baby has severe phenylketonuria (a genetic metabolic disease). NeoRecormon contains phenylalanine as an inactive ingredient and you should consult your doctor about the risks.
    - you have been diagnosed with Pure Red Cell Aplasia (your bone marrow cannot produce enough red blood cells)
    - you had a severe cutaneous adverse reaction (serious skin reaction) after previous treatment with an erythropoietin product, include NeoRecormon
    - any other illness or health problems.
  • are using NeoRecormon for donating your own blood before surgery and you weigh less than 50 kg.

If you have high blood pressure - it is important to follow all your doctor's instructions to control your blood pressure, including any changes to your diet. Contact your doctor immediately or go to the nearest emergency centre if you get a sudden stabbing migraine headache as this can mean your blood pressure is very high and you could need urgent medical attention.

If NeoRecormon does not work properly or if you have abnormal blood test results, your doctor may decide to perform further testing. Your doctor might adjust or tell you to stop using this medicine.

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.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Your doctor will discuss the risks and benefits of using NeoRecormon if you are breast-feeding.

Use in children

  • NeoRecormon should not be used in infants (below 2 years of age) or in children who have certain conditions. Your doctor will determine whether NeoRecormon is appropriate and what the starting dose should be.

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.

4. How do I use NeoRecormon?

When and how much to use

  • The dosage of NeoRecormon is expressed in international units (IU). Your doctor will tell you how much and how often to inject NeoRecormon according to your individual needs.
  • If necessary, depending on your response to treatment, your dose may be changed by your doctor. The recommended subcutaneous starting dose is 60 IU/kg/week and the maximum dose is 1200 IU/kg/week.
  • Your doctor will keep track of your response to NeoRecormon by asking questions and doing tests such as taking your blood pressure or taking blood.
  • Do not exceed or change the dose recommended by your doctor.
  • Your treatment period could range from a few weeks up to a lifetime, depending on your illness.
  • Your doctor will tell you how often to use this medicine.
  • Injecting NeoRecormon at the same time of the day will have the best effect. It will also help you remember your injections.
  • Follow your doctor's instructions exactly on when to inject NeoRecormon.

How to inject NeoRecormon

NeoRecormon can be administered by subcutaneous (under the skin) or intravenous (into the vein) injection. Your doctor will decide which way is right for you.

NeoRecormon can be given by your doctor or nurse.

Alternatively your doctor, nurse or pharmacist may teach you or your carer how to inject NeoRecormon. Do not inject yourself with NeoRecormon unless you have received training.

Follow all directions given to you by your doctor, nurse or pharmacist carefully. Those directions may differ from the information contained in this leaflet.

Intravenous administration

Only a health professional should administer NeoRecormon intravenously.

Subcutaneous administration

It is recommended that the first dose of NeoRecormon be administered by a doctor or nurse.

Your doctor may discuss whether it would be more convenient for you to receive your injections at home, in which case you or a family member would be instructed on how to give the injection properly. This is a simple procedure and many patients prefer it.

If your doctor has directed you to use NeoRecormon by subcutaneous injection, please follow the instructions below.

You should read these directions from beginning to end before starting your injection. Follow these instructions carefully. Consult your doctor if you require further instructions.

Preparing to self-inject

Before you begin

  1. Find a clean, comfortable area.
  2. Gather all the medicinal supplies you will need:
  • an alcohol swab.
  • some cotton wool or a dry sterile pad.
  • a sharps disposal bin.
  1. Take the carton with the syringe and needle out of the fridge and check that the carton has not been damaged and the expiry date (EXP) has not passed. Do not use if the expiration date has passed or if the carton appears tampered with.
  2. Inspect the syringe and needle closely. Check that the liquid has no discolouration, cloudiness or particles. The liquid should look clear and colourless. Do not use the syringe if the liquid is cloudy, discoloured or has particles.
  3. Leave the syringe out of the fridge on a clean flat surface for 30 minutes so it can warm up on its own to room temperature before use. Leave the needle cap on while it warms up.
  • If the syringe does not reach room temperature, this could cause the injection to feel uncomfortable and make it hard to push the plunger.
  • Do not speed up the warming process in any way, and do not put the syringe in a microwave or in warm water.

Preparing the syringe and needle

  1. Wash your hands thoroughly.
  2. Remove the protective covering from the needle packaging.
  3. Remove the rubber cap from the end of the syringe.

  1. Push the needle firmly onto the syringe while gently twisting.
  2. Pull the needle shield straight off the needle.
  3. If you notice any air bubbles in the syringe, hold the syringe with the needle facing upwards, lightly tap the syringe to bring the air bubbles to the top. You may need to gently push the plunger in slightly to push air out of the syringe.

  1. Check the dose of medication your doctor has prescribed. You may need to gently push the plunger to push out some medication to get the dose your doctor has prescribed.
  2. If you need to put the syringe (with the needle attached) down, make sure the plastic guard covers the needle and place on a clean flat surface.
  3. The syringe is now ready for use.

Choosing the injection site

  1. Choose an injection site in the lower part of your stomach area below the belly button or the top of your thigh.

  1. Do not inject within a 5 cm area directly around your belly button
  2. Change injection sites with each injection to prevent soreness in one spot.
  3. Never inject into moles, scars, bruises or areas where the skin is tender, red, hard, swollen or not intact
  4. Never inject NeoRecormon into a muscle or vein.

Preparing the injection site

  1. Clean the injection site with an alcohol swab and let the skin dry (10 seconds). Do not fan, blow on or touch the cleaned area before giving the injection

  1. Remove the protective needle guard from the end of the syringe and hold the syringe with the needle facing upwards. Use the syringe within 5 minutes of removing the cap; otherwise, the needle may clog.
  2. Grab your skin at the injection site firmly between your thumb and forefinger to elevate your skin.

Injecting the medicine

  1. Hold the syringe at a 45 to 90 degree angle to your skin.
  2. Insert the needle in one quick motion with the bevel (flat edge) facing upwards.
  3. Slowly push the plunger all the way down.
  4. Once all the liquid has left the syringe, pull out the needle at the same angle at which you put it in.
  5. Do not recap the needle.
  6. If you notice slight bleeding, gently press over the injection site with some cotton wool or a dry sterile pad. Do not rub the injection site.

Remember: Most people can learn to give themselves a subcutaneous injection, but if you experience difficulty, please do not be afraid to ask for help and advice from your doctor, nurse or pharmacist.

Cleaning up after your injection

  1. The needle and syringe must be used ONCE only.
  2. Dispose of the needle and syringe into a sharps container immediately after injection.
  3. Do not replace the needle cover.
  4. NEVER place used needles and syringes into your normal household waste bin.

If you are not sure how to dispose of the needles and syringes, consult your doctor, nurse or pharmacist on how to properly dispose of the syringes and needles.

If you forget to use NeoRecormon

NeoRecormon should be used regularly at the same time of each dosing day. If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose you missed.

Because NeoRecormon is administered over prolonged periods, occasional missed doses are not expected to have a significant effect on your treatment.

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

If you have trouble remembering when to use your medicine, ask your pharmacist for some hints.

If you use too much NeoRecormon

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

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26) for Australia and National Poisons Centre (by calling 0800 764 766) for New Zealand, 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.

5. What should I know while using NeoRecormon?

Things you should do

Use NeoRecormon exactly as your doctor has prescribed.

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

Do not take any other medicines, whether they require a prescription or not, without first telling your doctor or pharmacist that you are using NeoRecormon.

If you have blood pressure problems it is important to follow all your doctor's instructions to control your blood pressure, including any changes to your diet, while using NeoRecormon.

Most people's blood iron levels decrease when using NeoRecormon. Almost all patients will need to be treated with iron supplements.

Tell your doctor if you become pregnant while using NeoRecormon.

Tell your doctor if, for any reason, you have not used NeoRecormon exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Be sure to keep all of your appointments with your doctor so that your progress can be checked. Your doctor will keep track of your response to NeoRecormon by asking questions and doing tests such as taking your blood pressure or taking blood.

Call your doctor straight away if you:

  • have a sudden, migraine-like headache
  • have a severe skin reaction

Remind any doctor, dentist or pharmacist you visit that you are using NeoRecormon.

Things you should not do

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

Driving or using machines

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

NeoRecormon is not expected to affect your ability to drive a car or operate machinery.

Looking after your medicine

  • Store NeoRecormon pre-filled syringes in the fridge at 2 to 8°C. Do not freeze.
  • Always keep NeoRecormon in its carton, in the fridge, until it is time to use it. This will protect NeoRecormon from being affected by light. If you take the pre-filled syringes out of the pack they may not keep well.
  • You can use NeoRecormon if it has been left out of the fridge for no longer than 3 days (a single period only) at room temperature (up to 25°C).
  • An appropriate container on the top shelf of a fridge is a good place to store NeoRecormon.

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

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink (or any other place where there is high humidity), or
  • in the car or on window sills (heat and dampness can destroy some medicines).

Keep it where young children cannot reach it.

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 in a puncture proof container as instructed by your doctor, nurse or pharmacist.

Never put the used syringe/needle in your normal household garbage.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

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
Bleeding-related:
  • bleeding or bruising more easily
Swelling related:
  • swelling of the arms, feet or legs
Injection site related:
  • stinging or swelling around the injection area
Infection:
  • chest or throat infection, difficulty breathing, cough
Urinary:
  • pain with urination or increased urgency and/or frequency of urination.
Flu-like symptoms:
  • You may experience flu-like symptoms (very rare) particularly when starting treatment. These include fever, chills, headaches, pain in the limbs, bone pain and/or generally feeling unwell. These reactions are usually mild to moderate and go away within a few hours or days.
General:
  • feeling tired or lacking energy, looking pale; this may be due to changes in your blood iron levels. Your doctor may prescribe an iron supplement for you
  • headache
  • weakness
  • nausea and vomiting
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Headache related:
  • stabbing, migraine-like headache
Heart symptoms:
  • cardiac (heart) symptoms such as chest pain, shortness of breath, double vision, dizziness, feeling lightheaded or tingling of extremities (fingers and toes).
Swelling related:
  • swelling, pain, tenderness, warmth or discolouration of one leg or arm or along a vein in your leg or arm
Breathing related:
  • sudden shortness of breath, chest pain, palpitations or coughing up blood
  • sudden onset of wheezing or difficulty breathing, swollen tongue, face or throat
Coordination:
  • sudden trouble walking, speaking, seeing or understanding what someone is saying
Skin related:
  • severe skin reactions, hives, blisters or rash that may cover your whole body
Allergic reaction related:
  • A severe allergic reaction (very rare) can occur, especially just after an injection. This must be treated at once. Symptoms of an allergic reaction include swelling, itching, rash or breathing difficulties.
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 or in New Zealand to the Centre of Adverse Reactions Monitoring (CARM) online at nzphvc.otago.ac.nz/consumer-reporting. 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 NeoRecormon contains

Active ingredient
(main ingredient)		epoetin beta (recombinant human erythropoietin)
Other ingredients
(inactive ingredients)		urea
sodium chloride
monobasic sodium phosphate
dibasic sodium phosphate dodecahydrate
calcium chloride dihydrate
polysorbate 20
glycine
leucine
isoleucine
threonine
glutamic acid
phenylalanine
Potential allergensNeoRecormon contains phenylalanine as an inactive ingredient and you should consult your doctor about the risks.

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

What NeoRecormon looks like

NeoRecormon solution for injection is contained in a disposable glass syringe. The solution is clear and colourless. A stainless steel needle is also supplied with the syringe to allow for subcutaneous injection.

NeoRecormon pre-filled syringes are available in the following strengths (syringe plungers and packaging are coloured as indicated below to easily identify the strength):

  • 2000 IU/0.3 mL (orange),
  • 3000 IU/0.3 mL (blue),
  • 4000 IU/0.3 mL (red),
  • 5000 IU/0.3 mL (grey),
  • 6000 IU/0.3 mL (green)#,
  • 10000 IU/0.6 mL (purple).

# Not available in New Zealand

Each pre-filled syringe pack contains 6 pre-filled syringes containing solution for injection and 6 needles.

Australian Registration Numbers:

2000 IU/0.3 mL: AUST R 104262

3000 IU/0.3 mL: AUST R 104263

4000 IU/0.3 mL: AUST R 104264

5000 IU/0.3 mL: AUST R 104265

6000 IU/0.3 mL: AUST R 104266

10000 IU/0.6 mL: AUST R 104267

Who distributes NeoRecormon

Distributed in Australia by:

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

Distributed in NZ by:

Roche Products (New Zealand) Limited
PO Box 109113, Newmarket Auckland 1149
NEW ZEALAND

Medical enquiries: 0800 276 243

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

This leaflet was prepared in July 2023.

Published by MIMS September 2023

BRAND INFORMATION

Brand name

NeoRecormon

Active ingredient

Epoetin beta

Schedule

S4

 

1 Name of Medicine

Epoetin beta.

2 Qualitative and Quantitative Composition

NeoRecormon 2000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.3 mL solution for injection contains 2000 international units (IU) epoetin beta.

NeoRecormon 3000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.3 mL solution for injection contains 3000 international units (IU) epoetin beta.

NeoRecormon 4000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.3 mL solution for injection contains 4000 international units (IU) epoetin beta.

NeoRecormon 5000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.3 mL solution for injection contains 5000 international units (IU) epoetin beta.

NeoRecormon 6000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.3 mL solution for injection contains 6000 international units (IU) epoetin beta.

NeoRecormon 10,000 IU solution for injection in pre-filled syringe.

One pre-filled syringe with 0.6 mL solution for injection contains 10,000 international units (IU) epoetin beta.
NeoRecormon (epoetin beta (rch)) is a sterile, purified, stable recombinant human erythropoietin concentrate produced from genetically engineered Chinese hamster ovary (CHO) cells containing a cloned human erythropoietin gene.
The active ingredient, epoetin beta (rch), is a highly purified glycoprotein, identical in amino acid sequence to endogenous erythropoietin, with a mean molecular weight of approximately 30 kDa. Epoetin beta (rch) is ≥ 98% pure, with no detectable cell line residues.

Excipients with known effect.

Phenylalanine; sodium.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Colourless, clear to slightly opalescent solution.

4 Clinical Particulars

4.1 Therapeutic Indications

NeoRecormon is indicated:
for the treatment of anaemia associated with chronic kidney disease (CKD) in patients on dialysis and symptomatic patients not yet undergoing dialysis;
to increase the yield of autologous blood from patients in a pre-donation programme initiated to avoid the use of homologous blood;
for the prevention of anaemia of prematurity in infants with a birth weight of 750 g to 1500 g and a gestational age of less than 34 weeks;
for the treatment of anaemia in patients with non-myeloid malignancies, where anaemia develops as a result of concomitantly administered chemotherapy, and where blood transfusion is not considered appropriate.

4.2 Dose and Method of Administration

Dosage.

General.

Important.

Use the lowest dose of NeoRecormon that will gradually increase the haemoglobin concentration. NeoRecormon dosing regimens are different for each of the indications described in this section.
It is recommended that the first dose of NeoRecormon be administered under the supervision of a healthcare professional.

Treatment of anaemia in patients with chronic kidney disease.

NeoRecormon may be administered by either intravenous or subcutaneous injection, however, subcutaneous should be considered where feasible since lower doses are required. Generally, the subcutaneous maintenance dose is approximately 20-35% lower than the intravenous maintenance dose. In the case of intravenous administration, the solution should be injected over approximately 2 minutes (e.g. in haemodialysis patients via the arteriovenous fistula at the end of dialysis). For non-haemodialysis patients, subcutaneous administration is preferred in order to avoid puncture of peripheral veins.
The recommended haemoglobin target is 100-120 g/L. The target haemoglobin should be determined individually in the presence of hypertension or existing cardiovascular, cerebrovascular or peripheral vascular diseases. It is recommended that haemoglobin is monitored at regular intervals until stabilised and periodically thereafter (see Section 4.4 Special Warnings and Precautions for Use).
Treatment with NeoRecormon is divided into two stages:
1. Correction phase.

Subcutaneous administration.

The recommended starting dose is 60 IU/kg body weight/week, administered as a single weekly injection or in up to 7 divided doses. The dose may be increased every 4 weeks by 60 IU/kg body weight/week if the haemoglobin increase is not adequate (Hb < 1.5 g/L per week).

Intravenous administration.

The initial dose is 120 IU/kg body weight/week, administered in 3 divided doses. The dose may be raised after 4 weeks to 240 IU/kg body weight/week. If further increments are needed they should be at 60 IU/kg body weight/week, at monthly intervals.
2. Maintenance phase. To maintain haemoglobin between 100-120 g/L the dose is initially reduced to half of the previously administered amount.
In the case of subcutaneous administration, the weekly dose can be given as a single injection or in up to 7 divided doses. Patients who are stable on a once weekly dosing regimen may be switched to once every 2 weeks administration. In this case dose increases may be necessary.

Dose adjustment.

Increases in dose should not be made more frequently than once a month. The dose for each patient should be adjusted so that the haemoglobin concentration does not exceed 120 g/L. If the haemoglobin is increasing and approaching 120 g/L, the dose should be reduced by approximately 25-50%. If the haemoglobin continues to increase, the dose should be temporarily withheld until the haemoglobin begins to decrease, at which point therapy should be re-initiated at a dose approximately 25-50% 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 25-50%.
The maximum dose should not exceed 720 IU/kg body weight/week.
NeoRecormon is normally a lifelong therapy. It can, however, be interrupted if necessary, at any time. Data on the once weekly dosing schedule are based on clinical studies with a treatment duration of 24 weeks.

Special populations.

Paediatric populations.

The results of clinical studies in children and adolescents have shown that on average, the younger the patient, the higher the NeoRecormon dose required. Nevertheless, the recommended dosing schedule should be followed as the individual response cannot be predicted.

Treatment for increasing the amount of autologous blood.

The dose may be administered by either intravenous or subcutaneous injection. In the case of intravenous administration, the solution should be injected over approximately 2 minutes.
The dose for autologous blood donation prior to elective surgery is 400-1600 IU/kg body weight/week IV or 300-1200 IU/kg body weight/week SC, administered in 2 divided doses, for a maximum of 4 weeks.
If the patient's PCV ≥ 33% or Hb > 110 g/L, NeoRecormon may be administered at the end of the blood donation. Patients with pre-existing cardiac diseases should be monitored carefully (see Section 4.4 Special Warnings and Precautions for Use).
The dose must be determined for each patient as a function of the required amount of pre-donated blood and the endogenous red cell reserve.
The required amount of pre-donated blood depends on the anticipated blood loss, the physical condition of the patient and use, if any, of blood conserving procedures. This amount should be that quantity which is expected to be sufficient to avoid homologous blood transfusions. The required amount of pre-donated blood is expressed in units whereby one unit in the nomogram is equivalent to 180 mL red cells.
The ability to donate blood depends predominantly on the patient's blood volume and baseline PCV. Both variables determine the endogenous red cell reserve, which can be calculated according to the following formula (see Equation 1):
The indication for NeoRecormon treatment and, if given, the single dose should be determined from the required amount of pre-donated blood and the endogenous red cell reserves according to Figures 1 and 2.
The single dose, as determined in Figures 1 and 2, is administered twice weekly over 4 weeks. The maximum dose should not exceed 1600 IU/kg body weight/week for IV and 1200 IU/kg body weight/week for SC administration.

Prevention of anaemia of prematurity.

The solution is administered subcutaneously at a dose of 750 IU/kg body weight/week administered in 3 divided doses.
NeoRecormon treatment should be commenced as early as possible, preferably by day 3 of life. Premature infants who have already been transfused prior to NeoRecormon treatment are not likely to benefit as much as non-transfused infants. The treatment should last for 6 weeks.

Treatment of anaemia in patients with non-myeloid malignancies.

NeoRecormon treatment should not be commenced unless the haemoglobin falls below 100-110 g/L. The recommended initial dose is 450 IU/kg body weight/week, administered subcutaneously as a single weekly injection or in 3 to 7 divided doses. If after 4 weeks, a patient does not show a satisfactory response in terms of haemoglobin values, then the dose should be doubled. The therapy should be continued up to 4 weeks after the end of chemotherapy. The maximum dose should not exceed 900 IU/kg body weight/week.
If haemoglobin falls by more than 10 g/L in the next cycle of chemotherapy despite concomitant NeoRecormon therapy, further administration may not be effective.
Rapid increases in haemoglobin concentrations or the use of erythropoietin in subjects with normal haemoglobin concentrations may result in an increased risk of thrombotic adverse events (see Section 4.4 Special Warnings and Precautions for Use). Therefore, a rise > 10 g/L per fortnight or haemoglobin concentration > 120 g/L should be avoided. If the haemoglobin concentration is rising by more than 10 g/L per fortnight, reduce the NeoRecormon dose by approximately 25%. If the haemoglobin concentration exceeds 120 g/L, discontinue NeoRecormon until it falls below 120 g/L and then restart NeoRecormon at a dose 25% below the previous dose. It is recommended that haemoglobin is monitored at regular intervals until stabilised and periodically thereafter (see Section 4.4 Special Warnings and Precautions for Use).

Method of administration.

Remove the cap from the syringe and affix the needle provided. Only solutions which are clear or slightly opalescent, colourless and practically free of visible particles should be injected. NeoRecormon pre-filled syringes are sterile but do not contain preservatives.
Product is for single use in one patient only.

4.3 Contraindications

NeoRecormon is contraindicated in patients with:
poorly controlled hypertension;
known hypersensitivity to the active substance or any of the excipients.
In the indication "increasing the yield of autologous blood" NeoRecormon must not be used in patients who, in the month preceding treatment, have suffered a myocardial infarction or stroke, patients with unstable angina pectoris, or patients who are at risk of deep venous thrombosis such as those with a history of venous thromboembolic disease.

4.4 Special Warnings and Precautions for Use

General.

In order to improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded in the patient medical record. Substitution by any other biological medicinal product requires the consent of the prescribing physician.
NeoRecormon should be used with caution in the presence of refractory anaemia with excess blasts in transformation, thrombocytosis, and chronic liver failure.
NeoRecormon contains phenylalanine as an excipient therefore this should be taken into consideration in patients affected with severe forms of phenylketonuria.
Anaphylactoid reactions have been observed in isolated cases. Rarely, skin reactions such as rash, pruritus, urticaria or injection site reactions may occur, however in controlled clinical studies, no increased incidences of hypersensitivity reactions were found. It is recommended that the first dose be administered under medical supervision.
The indication of nephrosclerotic patients not yet undergoing dialysis should be defined individually as a possible acceleration of progression of renal failure cannot be ruled out with certainty.
In dialysis patients, an increase in heparin dose is frequently required during the course of NeoRecormon therapy as a result of increased haemoglobin. Occlusion of the dialysis system is possible if heparinisation is not optimum. Shunt thrombosis may occur, especially in patients who have a tendency to hypotension or whose arteriovenous fistulae exhibit complications (e.g. stenoses, aneurysms). Early shunt revision and thrombosis prophylaxis by administration of acetylsalicylic acid, for example, is recommended in these patients.
Misuse by healthy persons may lead to an excessive increase in haemoglobin. This may be associated with life-threatening complications to the cardiovascular system (see Cardiovascular and thrombotic events/ increased mortality).

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 Erythropoiesis Stimulating Agents (ESAs) such as NeoRecormon.
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.
To reduce cardiovascular risks, use the lowest dose of NeoRecormon 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).
The use of NeoRecormon during an autologous blood pre-donation programme must be balanced against the reported increased risk of thromboembolic events. Patients in an autologous blood pre-donation programme prior to surgery, including orthopaedic surgery, who have been treated with NeoRecormon, had a higher incidence of thromboembolic events (6.7%), compared with placebo-treated patients (3.4%).

Growth factor potential/ increased tumour progression.

NeoRecormon, like other ESAs, is a growth factor that primarily stimulates red blood cell production. As with all growth factors, there is a theoretical concern that ESAs 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 survival in patients with metastatic breast cancer receiving chemotherapy when administered to a target haemoglobin of > 120 g/L.

Use in cancer patients.

A study comparing another ESA (epoetin alfa) with placebo in cancer patients with anaemia who were not being treated with chemotherapy demonstrated no benefit in terms of reduced transfusion requirements. In addition, there were an increased number of deaths in the active group (26% vs. 20%). NeoRecormon should only be used to treat cancer patients with anaemia where the anaemia has arisen as a result of concomitantly administered chemotherapy.

Hypertension.

Patients with uncontrolled hypertension should not be treated with NeoRecormon; blood pressure should be controlled adequately before initiation of therapy. Blood pressure may rise during treatment of anaemia with NeoRecormon. Hypertensive encephalopathy and seizures have been observed. They require the immediate attention of a physician and intensive medical care. Particular attention should be paid to sudden stabbing migraine-like headaches as a possible warning sign.
Special care should be taken to closely monitor and control blood pressure in patients treated with NeoRecormon. During NeoRecormon therapy, patients should be advised of the importance of compliance with anti-hypertensive therapy and dietary restrictions. If blood pressure is difficult to control after initiation of appropriate measures, the dose of NeoRecormon 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 NeoRecormon. 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 NeoRecormon. If anti-erythropoietin antibody-mediated PRCA develops whilst on NeoRecormon, therapy with NeoRecormon must be discontinued and patients should not be switched to another ESA.

Seizures.

ESAs should be used with caution in patients with epilepsy. Convulsions have been reported in patients with CKD receiving NeoRecormon.

Lack of effect.

The most common reasons for an incomplete response to ESAs are iron deficiency and chronic inflammation (e.g. access infections, surgical inflammation, AIDS, SLE). The following conditions may also compromise the effectiveness of ESA therapy: chronic blood loss, bone marrow fibrosis, severe aluminium overload due to treatment of renal failure, folic acid or vitamin B12 deficiencies, and haemolysis. If all the conditions mentioned 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 NeoRecormon must be discontinued and patients should not be switched to another ESA (see Pure red cell aplasia (PRCA) above).

Evaluation of iron status.

In order to ensure effective erythropoiesis, iron status should be evaluated for all patients before and during treatment, as the majority of patients will eventually need supplemental iron. As per CARI (Caring for Australasians with Renal Impairment) Guidelines, supplemental iron therapy is recommended for all CKD patients whose serum ferritin falls below 100 nanogram/mL or transferrin saturation below 20%.
In premature infants, oral Fe2+ should begin as soon as possible (by day 14 of life at the latest) at a dose of 2 mg/day. If serum ferritin falls below 100 nanogram/mL or if there are other signs of iron deficiency, the Fe2+ dose should be increased to 5-10 mg/day.

Autologous pre-donation.

For the use of NeoRecormon in an autologous pre-donation programme, the official guidelines on principles of blood donation must be considered. In particular:
only patients with a PCV ≥ 33% or Hb ≥ 110 g/L should donate;
special care should be taken with patients whose weight is below 50 kg;
the single blood volume drawn should not exceed approximately 12% of the patient's estimated blood volume.
When the scheduled major elective surgery requires a large volume of blood (4 or more units of blood for females or 5 or more units for males) treatment should only be given to patients with no iron deficiency and if blood conserving procedures are not available or insufficient. Treatment should be reserved for patients in whom it is considered of particular importance to avoid homologous blood transfusion taking into consideration the risk/benefit assessment for homologous transfusions.

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, NeoRecormon 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 NeoRecormon, treatment with NeoRecormon must not be restarted in this patient at any time.

Use in premature infants.

Prognostic factors for successful results are infant birth weight and baseline haematocrit (Hct). Infants with both a birth weight > 1100 g and baseline Hct > 45% benefited most. No success was achieved in those infants with both a birth weight < 1100 g and baseline Hct < 45%.
Lack of efficacy in terms of success rate (i.e. failure to maintain PCV permanently > 32% without blood transfusion) was observed in infants with lower birth weight, i.e. < 1100 g. Nevertheless, in this subgroup, 8 of the 33 infants on epoetin beta (rch) but only 2 of the 29 in the control group completed the study without needing transfusions.

Paediatric use.

Clinical trials have been performed in children and adolescents with anaemia due to chronic kidney disease (CKD) and in neonates for prevention of anaemia due to prematurity. For CKD, NeoRecormon should not be used in infants (i.e. below 2 years of age). NeoRecormon is not indicated for paediatric patients to increase autologous blood yield; nor for anaemic paediatric patients with non-myeloid malignancies receiving chemotherapy.

Use in the elderly.

No dedicated studies in elderly patients have been performed. A large proportion of elderly patients were included in clinical trials with NeoRecormon, however, a need for special dose adjustments in the elderly population has not been studied.

Effects on laboratory tests.

Platelet counts.

There may be a moderate dose-dependent rise in the platelet count, within the normal range, during treatment with NeoRecormon, especially after intravenous administration. This regresses during continued therapy. Development of thrombocytosis is very rare. It is recommended that the platelet count is regularly monitored during the first eight weeks of therapy. In autologous blood donation, treatment with NeoRecormon should be discontinued if platelets rise above the normal range or increase by more than 150 x 109/L.

Potassium and phosphate levels.

Serum potassium and phosphate concentrations should be monitored regularly during NeoRecormon therapy. Potassium elevation has been reported in a few uraemic patients receiving NeoRecormon although causality has not been established. If an elevated or rising potassium level is observed, then consideration should be given to ceasing NeoRecormon administration until the level has been corrected.
Transient increases in serum phosphate levels have been observed in isolated cases in CKD patients.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Clinical results to date do not indicate any interaction with other substances.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No fertility studies have been conducted in humans. However, epoetin beta (rch) at doses of up to 640 U/kg/day SC did not affect fertility in rats.
(Category B3)
Epoetin beta (rch) was not teratogenic in rats and rabbits at doses of up to 3000 IU/kg/day IV when administered during the period of organogenesis. Epoetin beta (rch) caused post-implantation loss and decreased foetal weight in animals dosed prior to mating right through gestation at doses of 160 U/kg/day SC and above. Kinked tails were observed in rat pups and foetuses (from 160 U/kg SC upwards). These effects are thought to be related to the pharmacodynamic action of the drug.
All safety information with regards to exposure of NeoRecormon during pregnancy have been gained from post marketing experience. A review of the available postmarketing data does not show evidence of a causal association between harmful effects with respect to pregnancy, embryonal/foetal development or postnatal development and treatment with NeoRecormon. However, in the absence of clinical study data, caution should be exercised when prescribing to pregnant women.
 Postnatal observations of the live offspring (F1 generation) of female rats treated with epoetin beta (rch) during gestation and lactation revealed no effect of epoetin beta (rch) at doses up to 1280 U/kg SC. There were, however, decreases in body weight gain, eyelid opening, and delayed testicular descent and vaginal opening in the F1 foetuses at doses of 320 IU/kg SC and above.
Only limited experience in human lactation has been gained. Endogenous erythropoietin is excreted into breast milk but it is not known whether it is absorbed by the neonatal gastrointestinal tract in functional form. A decision on whether to continue or discontinue breast-feeding or to continue or discontinue therapy with NeoRecormon should be made taking into account the benefit of breast-feeding to the child and the benefit of NeoRecormon therapy to the woman.

4.7 Effects on Ability to Drive and Use Machines

No effects on ability to drive or use machines have been observed.

4.8 Adverse Effects (Undesirable Effects)

Anaemic patients with chronic kidney disease (CKD).

The most frequent adverse drug reactions (common 1-10%), in particular during the early treatment phase with NeoRecormon are hypertensive events. Increases in blood pressure can occur in normotensive patients or can be an aggravation of existing hypertension (see Section 4.4 Special Warnings and Precautions for Use).
From controlled clinical trials in 490 patients (244 epoetin beta (rch), 246 control) the following adverse reactions were reported in > 5% of patients (see Table 1).

Cardiovascular system.

Common (> 1%): headache. Uncommon (0.1 ≤ 1%): hypertensive crisis with encephalopathy-like symptoms (e.g. headaches and confused state, sensorimotor disorders - such as speech disturbance or impaired gait - up to tonoclonic seizures).

Blood.

Common (> 1%): decrease of ferritin values and transferrin saturation. Uncommon (0.1 ≤ 1%): vascular access thromboses in hypotensive patients or those with vascular access complications, increase in platelet count. Very rare (< 0.01%): thrombocytosis, transient increase in potassium and phosphate.

Increasing the amount of autologous blood.

From clinical trials in 458 patients (341 epoetin beta (rch), 117 control) the following adverse reactions were reported in > 5% of patients (see Table 2).

Anaemia of prematurity.

From clinical trials in 404 patients (213 epoetin beta (rch), 191 control) the following adverse reactions were reported in > 5% of patients (see Table 3).

Anaemia in patients with non-myeloid malignancies.

Hypertensive events are common (1-10%) adverse drug reactions, in particular during the early phase of treatment.
In some patients, a fall in serum iron parameters is observed.
Clinical studies have shown a higher frequency of thromboembolic events in cancer patients treated with NeoRecormon compared to untreated controls or placebo. In patients treated with NeoRecormon, this incidence is 7% compared to 4% in controls (both "common"); this is not associated with any increase in thromboembolic mortality compared with controls.
From clinical trials in 335 patients (198 epoetin beta (rch), 137 control) the following adverse reactions were reported in > 5% of patients with solid tumours (see Table 4).
From clinical trials in 343 patients (170 epoetin beta (rch), 173 control) the following adverse reactions were reported in > 5% of patients with haematological tumours (MM, NHL, CLL) (see Table 5).
In general, adverse reactions reported in clinical trials of patients with cancer receiving chemotherapy were consistent with the underlying disease and the treatment with chemotherapy.

All indications.

Skin.

Rarely (0.01-0.1%): skin reactions such as rash, pruritus, urticaria, or injection site reactions.

Other.

Very rare (< 0.01%): anaphylactoid reactions.
In very rare cases (< 0.01%) particularly when starting treatment, flu-like symptoms such as fever, chills, headaches, pain in the limbs, malaise and/or bone pain have been reported. These reactions were mild to moderate in nature and subsided after a couple of hours or days.

Post-marketing experience.

The following adverse drug reactions have been identified from postmarketing experience with NeoRecormon (Table 6). Adverse drug reactions are listed according to system organ classes in MedDRA and the corresponding frequency category estimation for each adverse drug reaction is based on the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), unknown (cannot be estimated from the available data).

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 margin of NeoRecormon is very wide. Even at very high serum levels, no symptoms of poisoning have been observed.
Overdose can result in manifestations of an exaggerated pharmacodynamic effect e.g. excessive erythropoiesis, which may be associated with life-threatening complications to the cardiovascular system. In cases of excessive haemoglobin levels, NeoRecormon should be temporarily withheld (see Section 4.2 Dose and Method of Administration). 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

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antianemic, ATC code: B03XA01.

Mechanism of action.

Epoetin beta is a glycoprotein that stimulates the proliferation and differentiation processes of the erythroid stem cell compartment and also has a stimulatory effect on the proliferation and maturation compartment of the erythron. Epoetin beta therefore leads to an increase in haemoglobin formation and an associated acceleration of cell maturation with reduction in the cell cycle time. A further effect of epoetin beta is the acceleration of reticulocyte maturation and an increase in the release of reticulocytes into the bloodstream.

Clinical trials.

The therapeutic efficacy of epoetin beta (rch) has been evaluated in renal anaemia, autologous blood donation prior to elective surgery, the prevention of renal anaemia in premature infants and the treatment of anaemia in patients with non-myeloid malignancies.

Anaemic patients with chronic kidney disease (CKD).

Adult patients with renal anaemia on haemodialysis, peritoneal dialysis or not yet undergoing dialysis (predialysis) and uraemic children were studied.
Increases in reticulocyte count and haematocrit were observed from the first and second week respectively. With the recommended dose regimens, an increase in haematocrit of approximately 0.5%-1.0% per week is to be expected. The time to reach a target haematocrit was dependent on the baseline haematocrit and on the dose of epoetin beta (rch) used. The target haematocrit was reached by most patients after 12 weeks. The need for regular transfusions was abolished much earlier, usually after 4 weeks of therapy. Considerable improvements in physical performance and well-being were reported in most patients treated with epoetin beta (rch). Overall the therapeutic effects were fairly similar, irrespective of whether patients were on haemodialysis, peritoneal dialysis or not yet undergoing dialysis (pre-dialysis patients). The maintenance doses required were approximately 25%-30% lower if epoetin beta (rch) was given subcutaneously rather than intravenously.
In children response rates were age-dependent. Younger patients required more time and higher doses to reach target haematocrit. Most children reached the target haematocrit after 3 months and transfusions were abolished after 1 month if high enough doses were given. Although the response in children was age-dependent, the recommendations for the starting doses are the same for adults and children.
A summary of pivotal trials conducted in anaemic CKD patients is shown in Table 7.
Haemoglobin levels were effectively maintained in CKD patients switched from two or three times weekly to once weekly subcutaneous epoetin beta (rch) administration, and in patients switched from once weekly to once every two weeks administration.

Autologous pre-donation.

Treatment is indicated in patients with moderate anaemia [packed cell volume (PCV) approximately 33%-39% (Hb approx. 110-130 g/L) no iron deficiency] if blood conserving procedures are not available or insufficient either:
when the scheduled major elective surgery requires a large volume of blood (4 or more units for females or 5 or more units for males); or
when the period necessary to obtain the required volume of blood is too short.
The efficacy of epoetin beta (rch) in an autologous blood donation programme was demonstrated by the gain in red cell volume available at the time of surgery. The period of anaemia after blood donation was shortened and, postoperatively, haematocrit values moved towards initial values much more rapidly in epoetin beta (rch) than in placebo patients. The effective doses ranged between 200-800 IU/kg twice weekly IV and 150-600 IU/kg twice weekly SC.
Individual dose recommendations for epoetin beta (rch) in this indication are necessary and can be calculated from the nomograms taking into account the endogenous red cell reserve, the amount of autologous blood required and the sex of the patient. The nomograms also determine if the patient could donate a sufficient amount of blood even without NeoRecormon treatment. See Table 8.

Anaemia of prematurity.

The effectiveness of epoetin beta (rch) in the prevention of anaemia of prematurity was shown with a higher percentage of infants not needing transfusions in the epoetin beta (rch) group as compared with the untreated control group. In addition, the blood volumes transfused and the number of transfusions were lower in epoetin beta (rch) treated infants.
The success rates (haematocrit permanently > 32% without transfusions) were significantly higher in the epoetin beta (rch) group than in the control group. However, there are certain prognostic factors for successful results. Whereas infants with birth weight > 1100 g and baseline haematocrit > 45% benefited most, no success was achieved in those with both a birth weight < 1100 g and a baseline haematocrit < 45%. See Table 9.

Anaemia in patients with non-myeloid malignancies.

The effectiveness of epoetin beta (rch) was established in patients with solid tumours and lymphoid malignancies. In patients with solid tumours, epoetin beta (rch) was shown to increase haemoglobin levels or reduce the development of anaemia induced by chemotherapy and significantly reduce the need for blood transfusions. In patients with lymphoid malignancies, epoetin beta (rch) was shown to increase haemoglobin levels and significantly reduce the need for blood transfusion. Response rate (defined as an increase of 20 g/L from baseline without need for transfusion in the preceding 6 weeks) was significantly greater in epoetin beta (rch) treated patients than placebo and median time to first response was significantly shorter in the epoetin beta (rch) treated groups. For the patients who showed a response to treatment, the improvement in haematological parameters was associated with a statistically significant corresponding improvement in the patients' self-assessment of their quality of life.
Clinical studies have shown the efficacy of epoetin beta (rch) administered once weekly is similar to that of the thrice weekly regimen (see Table 10).

5.2 Pharmacokinetic Properties

Absorption.

Subcutaneous administration of epoetin beta (rch) results in variable rates of absorption with average maximal concentrations being reached between 12 and 28 hours after dosing.
The bioavailability of subcutaneously administered epoetin beta (rch) is between 23% and 42% as compared with intravenous administration. Slightly higher bioavailability occurs on repeated subcutaneous administration.

Distribution.

The distribution volume of epoetin beta (rch) administered intravenously corresponds to 1-2 times the plasma volume.

Excretion.

The half-life of intravenously administered epoetin beta (rch) is between 4 and 12 hours. The protracted absorption of subcutaneously administered epoetin beta (rch) results in an apparent terminal half-life of between 13 and 28 hours.

5.3 Preclinical Safety Data

Genotoxicity.

Epoetin beta (rch) did not reveal any genotoxic potential in a series of assays for gene mutations (Ames test, Chinese hamster lung cells) or chromosomal damage (human lymphocytes in vitro, mouse micronucleus test in vivo).

Carcinogenicity.

Since epoetin beta is a human protein and as such is immunogenic for other species, conventional 2-year carcinogenicity studies have not been undertaken in rodents. A carcinogenicity study with homologous erythropoietin in mice did not reveal any signs of proliferative or tumourigenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

Urea, Sodium chloride, Monobasic sodium phosphate, Dibasic sodium phosphate dodecahydrate, Calcium chloride dihydrate, Polysorbate 20, Glycine, Leucine, Isoleucine, Threonine, Glutamic acid, Phenylalanine.

6.2 Incompatibilities

In the absence of compatibility studies, NeoRecormon should not be mixed with other medicinal 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

NeoRecormon must not be used after the expiry date.
Store continuously in the refrigerator at 2°C to 8°C. Do not freeze. Protect from light.
The pre-filled syringes are for single use in one patient only. Discard any residue. For ambulatory use, the product may be removed from refrigerated storage (2°C to 8°C) for one single period of up to a maximum of 3 days at room temperature (up to 25°C).

6.5 Nature and Contents of Container

Pre-filled syringe (Type I glass) with a tip cap and a plunger stopper.

NeoRecormon 2000 IU, NeoRecormon 3000 IU, NeoRecormon 4000 IU, NeoRecormon 5000 IU and NeoRecormon 6000 IU solution for injection in pre-filled syringe.

Each pre-filled syringe contains 0.3 mL solution and is available in a pack of 6.

NeoRecormon 10,000 IU solution for injection in pre-filled syringe.

Each pre-filled syringe contains 0.6 mL solution and is available in a pack of 6.

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.

Disposal of syringes/sharps.

The following points should be strictly adhered to regarding the use and disposal of the pre-filled syringe and medicinal sharps:
needles and syringes should never be reused;
place all used needles and syringes into a sharps container (puncture-proof disposable container);
keep this container out of the reach of children;
avoid placing used sharps containers in the household waste;
dispose of the full container according to local requirements or as instructed by your healthcare provider.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

122312-54-3.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes