Eporatio 10,000 IU/1 ml solution for injection in pre-filledsyringe

What Eporatio is

Eporatio contains the active substance epoetin theta, which is almost identical to erythropoietin, a natural hormone produced by your body. Epoetin theta is a protein produced by biotechnology in Chinese Hamster Ovary Cells. It works in exactly the same way as erythropoietin. Erythropoietin is produced in your kidneys and stimulates your bone marrow to produce red blood cells. Red blood cells are very important for distributing oxygen within your body.

What Eporatio is used for

Eporatio is used for the treatment of anaemia accompanied by symptoms. Anaemia occurs when your blood does not contain enough red blood cells and the symptoms may be fatigue, weakness and shortness of breath. Treatment for anaemia is given to adult patients with chronic renal failure or to some adult cancer patients who at the same time are receiving chemotherapy.

Do NOT use Eporatio

• if you are allergic (hypersensitive) to epoetin theta, another epoetin or any of the other ingredients of Eporatio;
• if you have high blood pressure that cannot be controlled.

Take special care with Eporatio

General
Eporatio may not be suitable for the following patients. Please speak with your doctor if you belong to one of these patient groups:

• patients with liver problems,
• patients with pathological changes in their red blood cells (homozygous sickle cell anaemia),
• patients under 18 years.

Your blood pressure needs to be checked closely before and during treatment with Eporatio. If your blood pressure rises, your doctor may give you medicines to reduce your blood pressure. If you are already taking a medicine to reduce your blood pressure, your doctor might increase the dosage. It may also be necessary to reduce your dose of Eporatio or to stop the treatment for a short period of time.

If you get headaches, especially sudden, stabbing, migraine-like headaches, confusion, speech disturbance, unsteady walking, fits or convulsions, tell your doctor IMMEDIATELY. These may be signs of severely elevated blood pressure, even if your blood pressure is usually normal or low. It needs to be treated at once.

Your doctor will carry out regular blood tests in order to monitor various blood components and their levels. In addition, the iron level in your blood will be checked before and during treatment with Eporatio. If your iron level is too low, your doctor may also prescribe you an iron preparation.

If you feel tired and weak or experience breathlessness, you must consult your doctor. These symptoms could indicate that your treatment with Eporatio is ineffective. Your doctor will check that you do not have other causes of anaemia and may perform blood tests or examine your bone marrow.

Healthy people should not use Eporatio. The use of Eporatio by healthy people can excessively increase certain blood parameters and in so doing cause problems with the heart or blood vessels that can be life threatening.

Anaemia caused by chronic renal failure
If you are a patient with chronic renal failure, your doctor will check that a particular blood parameter (haemoglobin) does not exceed a defined threshold. If this blood parameter becomes too high, heart or vascular problems might arise, increasing the risk of death.

If you have hardening of the blood vessels in your kidneys (nephrosclerosis) but do not need to undergo dialysis, your doctor will consider whether treatment is suitable for you. This is because one cannot rule out a possible acceleration of progression of kidney disease with absolute certainty.

During dialysis, medicines that prevent blood coagulation are used. If you are being treated with Eporatio, the dose of the anticoagulant medicine may have to be increased. Otherwise the increased number of red blood cells may cause blocking of the arterio-venous fistula (an artificial connection between an artery and a vein which is surgically prepared in dialysis patients).

Anaemia in cancer patients
If you are a cancer patient you should be aware that Eporatio may act as a blood cell growth factor and in some circumstances may have a negative impact on your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Eporatio has not been tested in pregnant women. It is important to tell your doctor if you are pregnant, think you may be pregnant or plan to get pregnant, as the doctor may decide that you should not use this medicine.

It is unknown whether the active substance in this medicine passes over to the breast milk. Therefore, your doctor may decide that you should not use this medicine if you are breast-feeding.

Driving and using machines
Eporatio has no or negligible influence on your ability to drive and use machines.

Important information about some of the ingredients of Eporatio

This medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, i.e. essentially ?sodium-free?.

Always use Eporatio exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The dosage is...

The dose of Eporatio (expressed in International Units or IU) depends on your disease condition, the way the injection is given (under the skin or into a vein) and your body weight. Your doctor will work out the right dose for you.

Anaemia caused by chronic renal failure
The injections are given under the skin or into a vein. Patients on haemodialysis will usually receive the injection at the end of dialysis via an arterio-venous fistula. Patients who do not have to undergo dialysis are usally given the injections under the skin. Your doctor will carry out blood tests regularly and adjust the dosage or suspend the treatment if necessary. The haemoglobin values in your blood should not exceed a value of 12 g/dl (7.45 mmol/l).

Treatment with Eporatio is divided into two stages:

a) Correcting the anaemia The initial dose for injections under the skin is 20 IU per kg of bodyweight, given 3 times per week. If necessary, your doctor will increase your dose at monthly intervals.

The initial dose for injections into veins is 40 IU per kg of bodyweight, given 3 times per week. If necessary, your doctor will increase your dose at monthly intervals.

b) Maintaining sufficient red blood cell levels Once an adequate number of red blood cells has been reached, the maintenance dose required to keep the number constant will be determined by your doctor.

In the case of injections under the skin, the weekly dose can be given either as 1 injection per week or as 3 divided injections per week.

In the case of injections into veins, your dosage may be switched to 2 injections weekly.

If the frequency of administration is changed, dose adjustments may be necessary.

Treatment with Eporatio is normally a long-term therapy.

The maximum dose should not exceed 700 IU per kg of bodyweight per week.

Anaemia in cancer patients
Injections are given under the skin. The injection will be given once-weekly. The initial dose is 20,000 IU. Your doctor will carry out blood tests regularly and adjust the dosage or suspend the treatment if necessary. The haemoglobin values in your blood should not exceed a value of 12 g/dl (7.45 mmol/l). You will usually receive Eporatio until 1 month after the end of chemotherapy.

The maximum dose should not exceed 60,000 IU.

How to administer Eporatio

This medicine is given as an injection using a pre-filled syringe. The injection is administered either into a vein (intravenous injection) or into the tissue just under the skin (subcutaneous injection).

If you are receiving Eporatio as an injection under the skin, your doctor may suggest that you learn how to inject yourself this medicine. Your doctor or nurse will give you instructions on how to do this. Do not attempt to self-administer Eporatio without this training. Some of the information required for using the pre-filled syringe can be found at the end of this package leaflet (see section ?INFORMATION FOR INJECTING YOURSELF?). Proper treatment of your disease, however, requires close and constant co-operation with your doctor.

Each pre-filled syringe is for single use only.

If you use more Eporatio than you should
Do not increase the dose your doctor has given you. If you think you have injected more Eporatio than you should, contact your doctor. It is unlikely to be serious. Even at very high blood levels, no symptoms of poisoning have been observed.

If you forget to use Eporatio
If you have missed an injection, or injected too little, talk to your doctor. Do not inject a double dose to make up for a forgotten dose.

If you stop using Eporatio

Before you stop usingEporatio, talk to your doctor.

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

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

These side effects can occur with the following frequencies very common common uncommon rare very rare not known affects more than 1 user in 10 affects 1 to 10 users in 100 affects 1 to 10 users in 1,000 affects 1 to 10 users in 10,000 affects less than 1 user in 10,000 frequency cannot be estimated from the available data.

Important side effects:

• Severely elevated blood pressure: If you get headaches, especially sudden, stabbing, migraine-like headaches, confusion, speech disturbance, unsteady walking, fits or convulsions, tell your doctor IMMEDIATELY. These may be signs of severely elevated blood pressure (common in patients with chronic renal failure), even if your blood pressure is usually normal or low. It needs to be treated at once.
• Allergic reactions: Allergic reactions such as skin rash, raised areas of the skin that itch and severe allergic reactions with weakness, drop in blood pressure, difficulty breathing and swelling of the face have been reported (frequency not known). If you think you are having this type of reaction, you must stop your Eporatio injection and get medical help IMMEDIATELY.

You may experience the following additional side effects:

• headache (common);
• high blood pressure (common);
• flu-like symptoms (common), such as fever, chills, feeling of weakness, tiredness;
• skin reactions (common), such as rash, itching or reactions around the injection site;
• joint pain (common in cancer patients);
• blood clot in the arterio-venous fistula in patients on dialysis (common in patients with chronic renal failure);
• thromboembolic events, e.g. increase in blood clots (frequency not known in patients with cancer);
• Cases of a condition called pure red cell aplasia (PRCA) have been reported very rarely in patients treated with other epoetins. PRCA means that the body has stopped or reduced the production of red blood cells which causes severe anaemia. If your doctor suspects or confirms that you have this condition, you must not be treated with Eporatio or another epoetin.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Eporatio after the expiry date which is stated on the outer carton and on the pre-filled syringe after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C ? 8 °C).

Do not freeze.

Keep the pre-filled syringe in the outer carton, in order to protect from light.

You may remove Eporatio from the refrigerator and store it not above 25 °C for a single period of up to 7 days without exceeding the expiry date. Once you have removed your medicine from the refrigerator you must use it within this period or it must be discarded.

Do not use Eporatio if you notice it is cloudy or there are particles in it.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Eporatio contains

• The active substance is epoetin theta . Eporatio 1,000 IU/0.5 ml: One pre-filled syringe contains 1,000 international units (IU) (8.3 micrograms) epoetin theta in 0.5 ml solution for injection corresponding to 2,000 international units (IU) (16.7 micrograms) per ml. Eporatio 2,000 IU/0.5 ml: One pre-filled syringe contains 2,000 international units (IU)

(16.7 micrograms) epoetin theta in 0.5 ml solution for injection corresponding to 4,000 international units (IU) (33.3 micrograms) per ml.
Eporatio 3,000 IU/0.5 ml: One pre-filled syringe contains 3,000 international units (IU) (25 micrograms) epoetin theta in 0.5 ml solution for injection corresponding to 6,000 international units (IU) (50 micrograms) per ml.
Eporatio 4,000 IU/0.5 ml: One pre-filled syringe contains 4,000 international units (IU) (33.3 micrograms) epoetin theta in 0.5 ml solution for injection corresponding to 8,000 international units (IU) (66.7 micrograms) per ml.
Eporatio 5,000 IU/0.5 ml: One pre-filled syringe contains 5,000 international units (IU) (41.7 micrograms) epoetin theta in 0.5 ml solution for injection corresponding to 10,000 international units (IU) (83.3 micrograms) per ml..
Eporatio 10,000 IU/1 ml: One pre-filled syringe contains 10,000 international units (IU) (83.3 micrograms) epoetin theta in 1 ml solution for injection corresponding to 10,000 international units (IU) (83.3 micrograms) per ml.
Eporatio 20,000 IU/1 ml: One pre-filled syringe contains 20,000 international units (IU) (166.7 micrograms) epoetin theta in 1 ml solution for injection corresponding to 20,000 international units (IU) (166.7 micrograms) per ml.
Eporatio 30,000 IU/1 ml: One pre-filled syringe contains 30,000 international units (IU) (250 micrograms) epoetin theta in 1 ml solution for injection corresponding to 30,000 international units (IU) (250 micrograms) per ml.

• The other ingredients are sodium dihydrogen phosphate dihydrate, sodium chloride, polysorbate 20, trometamol, hydrochloric acid (6 M) (for pH adjustment) and water for injections.

What Eporatio looks like and contents of the pack

Eporatio is a solution for injection in pre-filled syringe along with an injection needle.

Eporatio 1,000 IU/0.5 ml, Eporatio 2,000 IU/0.5 ml, Eporatio 3,000 IU/0.5 ml, Eporatio 4,000 IU/0.5 ml and Eporatio 5,000 IU/0.5 ml: Each pre-filled syringe contains 0.5 ml of solution. Packs of 6 pre-filled syringes with and without safety device.

Eporatio 10,000 IU/1 ml, Eporatio 20,000 IU/1 ml and Eporatio 30,000 IU/1 ml: Each pre-filled syringe contains 1 ml of solution. Packs of 1, 4 or 6 pre-filled syringes with and without safety device.

Not all pack sizes may be marketed.

Eporatio is a clear and colourless solution.

Marketing Authorisation Holderratiopharm GmbH
Graf-Arco-Straße 3
D-89079 Ulm
Germany
info@ratiopharm.de

Manufacturer

Merckle Biotec GmbH
Dornierstraße 10
D-89079 Ulm
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien ratiopharm Belgium S.A. TélTel 32 2 761 10 11 LuxembourgLuxemburg ratiopharm S.A. Luxemburg TélTel 35 2 40 37 27

ratiopharm GmbH, Te 49 731 402 02 Magyarország ratiopharm Hungária Kft. Tel 36 1 273 2730

eská republika ratiopharm CZ s.r.o. Tel 420 2 510 21 122 Malta ratiopharm GmbH, Il ermanja Tel 49 731 402 02

Danmark ratiopharm AS Tlf 45 45 46 06 60 Nederland ratiopharm Nederland bv Tel 31 23 7070 840

Deutschland ratiopharm GmbH Tel 49 731 402 02 Norge ratiopharm AS Tlf 47 66 77 55 90

Eesti ratiopharm Eesti büroo Tel 372 6838 006 Österreich ratiopharm Arzneimittel Vertriebs-GmbH Tel 43 1 97 007

ratiopharm GmbH, 49 731 402 02 Polska ratiopharm Polska Sp.z.o.o Tel 48 22 335 39 20

España ratiopharm España, S.A. Tel 34 91 567 29 70 Portugal ratiopharm, Comércio e Indústria de Produtos farmacêuticos Lda Tel 351 21 424 80 00

France Laboratoire ratiopharm S.A. Tél 33 1 42 07 97 04 România ratiopharm GmbH, Germania Tel 49 731 402 02

Ireland ratiopharm UK Ltd, United Kingdom Tel 44 239 238 6330 Slovenija ratiopharm GmbH, Nemija Tel 49 731 402 02

Ísland ratiopharm GmbH, skaland Sími 49 731 402 02 Slovenská republika ratiopharm Slovensko s.r.o. Tel 421 2 57 200 300

Italia ratiopharm Italia s.r.l. Tel 39 02 28 87 71 SuomiFinland ratiopharm Oy PuhTel 358 20 180 5900

ratiopharm GmbH, 49 731 402 02 Sverige ratiopharm AB Tel 46 42 37 0740

Latvija ratiopharm Latvijas prstvniecba Tel 371 67499110 United Kingdom ratiopharm UK Ltd Tel 44 239 238 6330

Lietuva
ratiopharm atstovas Lietuvoje
Tel: + 370 5 212 3295

This leaflet was last approved in {MM/YYYY}.

INFORMATION FOR INJECTING YOURSELF

This section contains information on how to give yourself an injection of Eporatio under the skin. It is important that you do not try to give yourself the injection unless you have received special training from your doctor or nurse. If you are not sure about giving yourself the injection or you have any questions, please ask your doctor or nurse for help.

How do I use Eporatio?

You will need to give yourself the injection into the tissue just under the skin. This is known as a subcutaneous injection.

Equipment that I need

To give yourself an injection into the tissue under the skin you will need:

• a pre-filled syringe of Eporatio,
• an alcohol wipe,
• a piece of gauze bandage or a sterile gauze swab,
• a puncture-proof container (plastic container provided by the hospital or pharmacy) so you can dispose of used syringes safely.

What should I do before my injection?

Eporatio is supplied in pre-filled syringes either with or without safety device. The following figures refer either to syringes without (Figures 2a, 3a, 4a) or with (Figures 2b, 3b, 4b, 9) safety device. The other figures (1, 5, 6, 7, 8) apply to both syringes. Your doctor or pharmacist can tell you which pre-filled syringe you have received.

1. Take one blister with an Eporatio pre-filled syringe out of the refrigerator.

2. Take the pre-filled syringe and the needle container out of the blister.

3. Check the expiry date on the pre-filled syringe label (EXP). Do not use it if the date has passed the last day of the month shown.

4. Check the appearance of Eporatio. It must be a clear and colourless liquid. If there are particles in it or if it is cloudy, you must not use it.

5. There is a cap at the end of the needle container. Break the labelled seal and remove the cap (see picture 1).

6. Remove the tip cap from the pre-filled syringe (see picture 2a for syringes without safety device and picture 2b for syringes with safety device).

7. Attach the needle to the syringe (see picture 3a for syringes without safety device and picture 3b for syringes with safety device). Do not remove the needle cover at this time.

8. For a more comfortable injection, let the pre-filled syringe stand for 30 minutes to reach room temperature or hold the pre-filled syringe gently in your hand for a few minutes. Do not warm Eporatio in any other way (for example, do not warm it in a microwave or in hot water).

9. Do not remove the needle cover from the syringe until you are ready to inject.

10. Wash your hands thoroughly.

11. Find a comfortable, well-lit place. Put everything you need where you can reach them (the Eporatio pre-filled syringe, an alcohol wipe, a piece of gauze bandage or a sterile gauze swab and the puncture-proof container).

2a Without safety device

2b With safety device

3a Without safety device

3b With safety device

How do I prepare my injection?

Before you give yourself an Eporatio injection, you must do the following:

1. Hold the syringe and gently remove the cover from the needle without twisting. Pull straight as shown in picture 4a for syringes without safety device and picture 4b for syringes with safety device. Do not touch the needle or push the plunger.

2. You may notice a small air bubble in the pre-filled syringe. If there are air bubbles present, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. With the syringe pointing upwards, expel all air from the syringe by pushing the plunger slowly upwards.

3. The syringe has a scale on the syringe barrel. Push the plunger up to the number (IU) on the syringe that matches the dose of Eporatio that your doctor prescribed.

4. Check again to make sure the correct dose of Eporatio is in the syringe.

5. You can now use the pre-filled syringe.

4a Without safety device

4b With safety device

Where should I give my injection?

The most suitable places to inject yourself are:

• the top of your thighs; and
• the abdomen, except for the area around the navel (see grey areas in picture 5).

If someone else is injecting you, they can also use the back of your arms (see grey areas in picture 6).

It is better to change the injection site every day to avoid the risk of soreness at any one site.

How do I give my injection?

1. Disinfect the injection site on the skin by using an alcohol wipe and pinch the skin between your thumb and forefinger, without squeezing it (see picture 7).

2. Put the needle fully into the skin as shown by your nurse or doctor. The angle between the syringe and skin should not be too narrow (? 45°, see picture 8).

3. Pull slightly on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, remove the needle and re-insert it in another place.

4. Inject the liquid into the tissue slowly and evenly, always keeping your skin pinched.

5. Syringe without safety device: After injecting the liquid, remove the needle and let go of your skin. Syringe with safety device: Do not release the plunger fully until after the full dose has been given. The entire needle will be removed automatically from the skin and safely guarded so that you can not prick yourself (see picture 9).

6. Press the injection site with a piece of gauze bandage or a sterile gauze swab for several seconds.

7. Only use each syringe for one injection. Do not use any Eporatio that is left in the syringe.

9 With safety device

Remember

If you have any problems, please do not be afraid to ask your doctor or nurse for help and advice.

Disposing of used syringes

• Do not put the cover back on used needles.
• Put used syringes into the puncture-proof container and keep this container out of the reach and sight of children.
• Dispose of the full puncture-proof container as instructed by your doctor, nurse or pharmacist.
• Never put the syringes that you have used into your normal household rubbish bin.