Label: information for the user

Eporatio 1,000 UI/0.5 ml injectable solution in pre-filled syringe

Eporatio 2,000 UI/0.5 ml injectable solution in pre-filled syringe

Eporatio 3,000 UI/0.5 ml injectable solution in pre-filled syringe

Eporatio 4,000 UI/0.5 ml injectable solution in pre-filled syringe

Eporatio 5,000 UI/0.5 ml injectable solution in pre-filled syringe

Eporatio 10,000 UI/1 ml injectable solution in pre-filled syringe

Eporatio 20,000 UI/1 ml injectable solution in pre-filled syringe

Eporatio 30,000 UI/1 ml injectable solution in pre-filled syringe

Epoetin zeta (epoetin theta)

Read this label carefully before starting to use this medication, as it contains important information for you.

-Keep this label, as you may need to read it again.

-If you have any questions, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

-If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

1.What is Eporatio and how is it used

2.What you need to know before starting to use Eporatio

3.How to use Eporatio

4.Possible adverse effects

5.Storage of Eporatio

6.Contents of the package and additional information

7.Information for self-injection

What is Eporatio

Eporatio contains the active ingredient epoetina zeta (epoetin theta), which is almost identical to erythropoietin, a natural hormone produced by the body. Epoetina zeta (epoetin theta) is a protein produced by biotechnology.It functions exactly in the same way as erythropoietin. Erythropoietin is produced in the kidneys and stimulates the bone marrow to produce red blood cells. Red blood cells are very important for distributing oxygen throughout the body.

What is Eporatio used for

Eporatio is used for the symptomatic treatment of anemia and its symptoms (for example, fatigue, weakness, and shortness of breath). Anemia occurs when blood cells do not contain enough red blood cells. The treatment for anemia is administered to adult patients with chronic kidney disease or adult patients with non-myeloid cancer (cancer that does not originate in the bone marrow), who are receiving chemotherapy (medicines to treat cancer) at the same time.

No use Eporatio

-if you are allergic to epoetin zeta (epoetin theta), other epoetins, or any of the other components of this medication (listed in section6);

-if you have uncontrolled hypertension.

Warnings and precautions

General

This medication may not be recommended for the following patients. Please consult your doctor if you belong to any of these patient groups:

-patients with liver problems

-patients with pathological changes in their red blood cells (sickle cell anemia homozygous).

Before and during treatment with this medication, your blood pressure should be closely monitored. If your blood pressure increases, your doctor may give you medication to lower your blood pressure. If you are already being treated with medication to lower your blood pressure, your doctor may increase the dose. It may also be necessary to reduce the dose of Eporatio or interrupt treatment with Eporatio for a short period of time.

Seek medical attention immediately if you experience sudden, severe, migraine-type headache, confusion, speech alteration, gait deterioration, seizures, or convulsions. These may be signs of very high blood pressure, even if your blood pressure is normally normal or low. It is essential to treat simultaneously.

Your doctor will regularly perform blood tests to monitor various blood components and their levels. In addition, your iron levels in the blood should be monitored before and during treatment with this medication. If your iron levels are too low, your doctor may prescribe an iron medication.

If you feel tired and weak or experience fatigue, you should consult your doctor. These symptoms may indicate that treatment with this medication is ineffective. Your doctor will check that there are no other causes of anemia and may perform blood tests or a bone marrow examination.

The healthcare professional caring for you will record exactly the product you are using at all times. This may help provide more information about the safety of this medication.

Healthy individuals should not use Eporatio. Using this medication by healthy individuals may excessively increase certain blood parameters and cause heart or blood vessel problems, potentially putting your life at risk.

Severe skin reactions, such as Stevens-Johnson syndrome (SSJ) and toxic epidermal necrolysis (NET), have been observed with the administration of epoetins. SSJ/NET may initially appear as circular, red, target-like lesions on the trunk, often with central blisters. You may also experience ulcers in the mouth, throat, nose, genitals, and eyes (eye irritation and swelling). These severe skin reactions are often preceded by fever or flu-like symptoms. The skin reaction may progress to generalized skin peeling and potentially life-threatening complications. If you experience a severe skin reaction or any of these other skin symptoms, stop using Eporatio and seek medical attention immediately.

Anemia caused by chronic kidney disease

If you have chronic kidney disease, your doctor will monitor a specific blood parameter (hemoglobin) to ensure it does not exceed the defined threshold. If your blood parameters become too high, you may experience heart or blood vessel problems, increasing the risk of death.

If you have chronic kidney disease and do not respond adequately to Eporatio, your doctor will monitor your Eporatio dose, as repeated increases in the Eporatio dose if you are not responding to treatment may increase the risk of heart or blood vessel problems and may increase the risk of myocardial infarction, stroke, and death.

If you have renal vascular sclerosis but do not require dialysis treatment, your doctor will consider whether treatment is suitable for you. In this case, it cannot be ruled out with absolute certainty that the progression of renal function deterioration may be accelerated.

If you are on dialysis, medications that prevent blood clotting are used. If you are being treated with Eporatio, the dose of the anticoagulant medication may need to be increased. Otherwise, the increase in red blood cells may cause blockage of the arteriovenous fistula (a surgically created connection between an artery and a vein in patients on dialysis).

Anemia in cancer patients

If you are a cancer patient, you should know that this medication can act as a growth factor for blood cells and, in some cases, may have a negative impact on cancer. Depending on the individual situation, it may be preferable to receive a blood transfusion. Please discuss this with your doctor.

Children and adolescents

Do not administer this medication to children and adolescents under 18years, as there is no evidence to demonstrate the safety and efficacy of this medication in this age group.

Other medications and Eporatio

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

Pregnancy and breastfeeding

The use of Eporatio in pregnant women has not been investigated. It is essential to inform your doctor if you are pregnant, think you may be pregnant, or intend to become pregnant, as your doctor will decide whether it is advisable not to use this medication.

The active ingredient in this medication is unknown to pass into breast milk. Therefore, your doctor will decide whether it is advisable not to use this medication while breastfeeding.

Driving and operating machinery

This medication does not affect your ability to drive and operate machinery.

Eporatio contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per pre-filled syringe; this is, essentially “sodium-free”.

Your treatment with this medication will be initiated by an experienced doctor in the previously mentioned indications.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose is…

The dose of Eporatio (expressed in International Units or UI)will depend on your disease, your body weight, and the route of administration of the injection (subcutaneous injection under the skin or intravenous injection into a vein). Your doctor will indicate the correct dose for you.

Chronic renal failure anemia

Injections can be administered under the skin or into a vein. Patients undergoing hemodialysis, usually receive the injection at the end of dialysis via an arteriovenous fistula. Patients not undergoing dialysis treatment, usually receive the injection under the skin. Your doctor will regularly perform blood tests and adjust the dose or discontinue treatment if necessary. The blood hemoglobin values should not exceed a value of 12 g/dl (7.45 mmol/l). Your doctor will use the most effective dose to control the symptoms of anemia. If you do not respond adequately to Eporatio, your doctor will check your dose and inform you if it is necessary to change the doses of Eporatio.

The treatment with Eporatio is divided into two parts:

a) Anemia correction

The initial dose for subcutaneous injections is 20 UI per kg of body weight, administered 3 times a week. If necessary, your doctor will increase the dose at monthly intervals.

The initial dose for intravenous injections is 40 UI per kg of body weight, administered 3 times a week. If necessary, your doctor will increase the dose at monthly intervals.

b) Maintenance of red blood cell levels

Once an adequate number of red blood cells has been achieved, the required maintenance dose to maintain a constant level will be determined by your doctor.

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

In the case of intravenous injections, the dose can be adjusted to 2 injections per week.

If you modify the frequency of dose administration, a dose adjustment may be necessary.

The treatment with Eporatio is usually a long-term treatment.

The maximum dose should not exceed 700 UI per kg of body weight per week.

Cancer anemia

Subcutaneous injections. The injection will be administered once a week. The initial dose is 20,000 UI. Your doctor will regularly perform blood tests and adjust the dose or discontinue treatment if necessary. The blood hemoglobin values should not exceed a value of 12 g/dl (7.45 mmol/l). You will normally receive Eporatio for up to 1 month after completing chemotherapy.

The maximum dose should not exceed 60,000 UI.

How are the injections administered?

This medication is administered by injection using a preloaded syringe. The injection is administered either into a vein (intravenous injection) or into the tissue just below the skin (subcutaneous injection).

If you receive Eporatio treatment as a subcutaneous injection, your doctor may suggest that you learn to administer this medication to yourself. Your doctor or nurse will give you instructions on how to do it. Do not attempt to administer this medication to yourself without these instructions. Part of the information you need to use the preloaded syringe can be found at the end of this leaflet (see section,“7. Self-injection information”). However, for optimal treatment of your disease, close and constant cooperation with your doctor is required.

Each preloaded syringe is for single use only.

If you use more Eporatio than you should

Do not increase the dose prescribed by your doctor. If you think you have injected more Eporatio than you should, consult your doctor. It is unlikely to be serious. Even with very high blood levels, no symptoms of poisoning have been observed.

If you forget to use Eporatio

If you have forgotten an injection, or have injected very little, tell your doctor. Do not use a double dose to compensate for the missed doses.

If you interrupt treatment with Eporatio

Before interrupting treatment with this medication, consult your doctor.

If you have any other questions about the use of thismedication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects:

-Very high blood pressure:

Seek immediate medical attention if you experience sudden, severe headache, like a migraine, confusion, speech changes, gait disturbances, seizures, or convulsions. These may be signs of very high blood pressure (common in patients with chronic kidney failure, which can affect up to 1 in 10 people), even if your blood pressure is normally normal or low. It needs to be treated simultaneously.

-Allergic reactions:

Severe allergic reactions, such as skin rash, widespread itching, severe allergic reactions with weakness, low blood pressure, respiratory difficulty, and facial swelling (frequency unknown, cannot be estimated from available data), have been reported. If you think you have had this type of reaction, stop treatment with Eporatio and seek immediate medical help.

-Severe skin eruptions:
Severe skin eruptions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been observed with the administration of epoetins. These reactions may appear as red, circular patches or spots with central blisters on the trunk, skin peeling, and ulcers in the mouth, throat, nose, genitals, and eyes, and may be preceded by fever and flu-like symptoms. Stop using Eporatio if you experience these symptoms and contact your doctor or seek immediate medical attention. See also section 2.

You may experience the following additional side effects:

Frequent (may affect up to 1 in 10 people)

-Headache;

-High blood pressure;

-Flu-like symptoms, such as fever, chills, feeling weak, fatigue;

-Skin reactions, such as rash, itching, or reactions at the injection site.

Frequent in patients with chronic kidney failure (may affect up to 1 in 10 people)

-Blood clot in the arteriovenous fistula in patients on dialysis.

Frequent in patients with cancer (may affect up to 1 in 10 people)

-Joint pain.

Unknown frequency in patients with chronic kidney failure (cannot be estimated from available data)

-Aplastic pure red cell anemia (APCR) has been reported. APCR means that the body either fails to produce or reduces the production of red blood cells, which causes severe anemia. If your doctor suspects or confirms that you have this disease, you should not be treated with Eporatio or another epoetin.

Unknown frequency in patients with cancer (cannot be estimated from available data)

-Thromboembolic episodes, such as blood clots.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the outer box and on the pre-filled syringe after CAD. The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2°C and 8°C).

Do not freeze.

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

You can remove Eporatio from the refrigerator and store it at a temperature not exceeding 25°C for a period of up to 7 days without exceeding the expiration date. Once removed from the refrigerator, the medication must be used within that time frame or discarded.

Do not use this medication if you observe turbidity or particles inside.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. In this way, you will help protect the environment.

Composition of Eporatio

- The active principle is epoetin zeta (epoetin theta).

Eporatio 1,000 UI/0.5 ml: A pre-filled syringe contains 1,000 international units (UI) (8.3 micrograms) of epoetin zeta (epoetin theta) in 0.5 ml of injectable solution equivalent to 2,000 international units (UI) (16.7 micrograms) per ml.

Eporatio 2,000 UI/0.5 ml: A pre-filled syringe contains 2,000 international units (UI) (16.7 micrograms) of epoetin zeta (epoetin theta) in 0.5 ml of injectable solution equivalent to 4,000 international units (UI) (33.3 micrograms) per ml.

Eporatio 3,000 UI/0.5 ml: A pre-filled syringe contains 3,000 international units (UI) (25 micrograms) of epoetin zeta (epoetin theta) in 0.5 ml of injectable solution equivalent to 6,000 international units (UI) (50 micrograms) per ml.

Eporatio 4,000 UI/0.5 ml: A pre-filled syringe contains 4,000 international units (UI) (33.3 micrograms) of epoetin zeta (epoetin theta) in 0.5 ml of injectable solution equivalent to 8,000 international units (UI) (66.7 micrograms) per ml.

Eporatio 5,000 UI/0.5 ml: A pre-filled syringe contains 5,000 international units (UI) (41.7 micrograms) of epoetin zeta (epoetin theta) in 0.5 ml of injectable solution equivalent to 10,000 international units (UI) (83.3 micrograms) per ml.

Eporatio 10,000 UI/1 ml: A pre-filled syringe contains 10,000 international units (UI) (83.3 micrograms) of epoetin zeta (epoetin theta) in 1 ml of injectable solution equivalent to 10,000 international units (UI) (83.3 micrograms) per ml.

Eporatio 20,000 UI/1 ml: A pre-filled syringe contains 20,000 international units (UI) (166.7 micrograms) of epoetin zeta (epoetin theta) in 1 ml of injectable solution equivalent to 20,000 international units (UI) (166.7 micrograms) per ml.

Eporatio 30,000 UI/1 ml: A pre-filled syringe contains 30,000 international units (UI) (250 micrograms) of epoetin zeta (epoetin theta) in 1 ml of injectable solution equivalent to 30,000 international units (UI) (250 micrograms) per ml.

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

Aspect of the product and content of the packaging

Eporatio is a transparent and colorless injectable solution in a pre-filled syringe with a needle for injection.

Eporatio 1,000 UI/0.5 ml, Eporatio 2,000 UI/0.5 ml, Eporatio 3,000 UI/0.5 ml, Eporatio 4,000 UI/0.5 ml and Eporatio 5,000 UI/0.5 ml: Each pre-filled syringe contains 0.5 ml of solution.

Packaging of 6 pre-filled syringes; 6 pre-filled syringes with safety needle or 6 pre-filled syringes with safety device.

Eporatio 10,000 UI/1 ml, Eporatio 20,000 UI/1 ml and Eporatio 30,000 UI/1 ml: Each pre-filled syringe contains 1 ml of solution. Packaging of 1, 4 and 6 pre-filled syringes; 1, 4 and 6 pre-filled syringes with safety needle or 1, 4 and 6 pre-filled syringes with safety device.

It may only be marketed in some packaging sizes.

Holder of the marketing authorization

ratiopharm GmbH

Graf-Arco-Strasse 3

89079 Ulm

Germany

Responsible for manufacturing

Teva Biotech GmbH

Dornierstrasse 10

89079 Ulm

Germany

You can request more information about this medicine by contacting the local representative of the holder of the marketing authorization:

Last revision date of this leaflet:

The detailed information about this medicine is available on the website of the European Medicines Agency:

http://www.ema.europa.eu

7. Information for self-injection

This section contains information on how to administer Eporatio to yourself under the skin. It is essential that you do not attempt to administer an injection without having received the necessary instructions from your doctor or nurse. If you are unsure about being able to inject or have any doubts, consult your doctor or nurse.

How to administer Eporatio

It should be injected into the tissue just below the skin. This is known as subcutaneous injection.

Equipment needed for administration

To administer the injection under the skin, you will need:

- a pre-filled syringe of Eporatio,

- an alcohol swab,

- a sterile gauze or cotton ball,

- a sharps container (a plastic container provided by a hospital or pharmacy) to safely dispose of used syringes.

What to do before administering the injection

1. Remove a blister pack with a pre-filled syringe from the refrigerator.

2. Open the blister pack and remove the pre-filled syringe and needle from the pack. Do not grasp the syringe by the plunger or the cap of the syringe.

3. Check the expiration date on the label of the pre-filled syringe (CAD). Do not use it if the date is beyond the last day of the month shown.

4. Check the appearance of Eporatio. It should be a clear and colorless liquid. If there are particles inside or it is cloudy, do not use it.

5. There is a cap at the end of the needle. Break the safety seal and remove the cap (see image 1)

6. Remove the cap from the pre-filled syringe (see image 2)

7. Attach the needle to the syringe (see image 3). Do not remove the cap from the syringe yet.

8. To make the injection more comfortable, let the syringe sit for 30 minutes to reach room temperature (not above 25°C) or gently hold the syringe in your hands for a few minutes.

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

10. Find a comfortable and well-lit place. Place everything you need within reach (the pre-filled syringe of Eporatio, the alcohol swab, and a sterile gauze or cotton ball).

11. Wash your hands carefully.

2 3

How to prepare for self-administration of the Eporatio injection

Before administering the Eporatio injection to yourself, you must do the following:

1. Grasp the syringe and carefully remove the protective cover from the needle without tilting it. Separate it as indicated in the images 4. Do not touch the needle or the protective cover or push the plunger.

2. Small air bubbles may appear in the pre-filled syringe. If there are bubbles, gently tap the syringe with your fingers until the bubbles rise to the top of the syringe. With the syringe pointing upwards, remove all the air from the syringe by pushing the plunger slightly upwards.

3. The syringe has a scale on the body of the syringe. Push the plunger until the number (UI) on the syringe corresponds to the dose of Eporatio prescribed by your doctor.

4. Check again that the dose of Eporatio in the syringe is correct.

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

4 5

Where to put the injection

The most suitable places for the injection are:

- the upper part of the thighs,

- the abdomen, except the area around the navel (see the gray areas in image 6).

If someone is helping you to put the injection, you can also put it in the back and side of the arms (see the gray areas in image 7)

It is better to change the injection site every day to avoid the risk of pain in some areas.

6 7

How to inject

1. Disinfect the injection site using an alcohol swab and pinch the skin between your thumb and index finger, without squeezing (see image 8).

2. Insert the needle completely into the skin as indicated by your doctor or nurse. The angle between the syringe and the skin should not be too small (at least 45° see image 9).

3. Inject the liquid into the tissue slowly and regularly, keeping the skin pinched.

4. After injecting the liquid, remove the needle and pull it out of the skin.

5. Press the injection site with a sterile gauze or cotton ball for a few seconds.

6. Use only one syringe for one injection. Do not use any remaining Eporatio from the syringe.

8 9

Remember

If you have any problems, please seek help or advice from your doctor or nurse.

How to dispose of used syringes

- Do not put the protective cover back on used syringes.

- Deposit used syringes in a sharps container and keep this container out of sight and reach of children.

- Dispose of the sharps container according to the instructions of your doctor, pharmacist, or nurse.

- Never put used syringes in your household trash

7. Information for self-injection

This section contains information on how to administer Eporatio to yourself under the skin. It is essential that you do not attempt to administer an injection without having received the necessary instructions from your doctor or nurse. If you are unsure about being able to inject or have any doubts, consult your doctor or nurse.

How to administer Eporatio

It should be injected into the tissue just below the skin. This is known as subcutaneous injection.

Equipment needed for administration

To administer the injection under the skin, you will need:

- a pre-filled syringe of Eporatio,

- an alcohol swab,

- a sterile gauze or cotton ball.

What to do before administering the injection

1. Remove a blister pack with a pre-filled syringe from the refrigerator.

2. Open the blister pack and remove the pre-filled syringe and needle from the pack. Do not grasp the syringe by the plunger or the cap of the syringe.

3. Check the expiration date on the label of the pre-filled syringe (CAD). Do not use it if the date is beyond the last day of the month shown.

4. Check the appearance of Eporatio. It should be a clear and colorless liquid. If there are particles inside or it is cloudy, do not use it.

5. There is a cap at the end of the needle. Break the safety seal and remove the cap (see image 1)

6. Remove the cap from the pre-filled syringe (see image 2)

7. Attach the needle to the syringe (see image 3). Do not remove the cap from the syringe yet.

8. To make the injection more comfortable, let the syringe sit for 30 minutes to reach room temperature (not above 25°C) or gently hold the syringe in your hands for a few minutes.

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

10. Find a comfortable and well-lit place. Place everything you need within reach (the pre-filled syringe of Eporatio, the alcohol swab, and a sterile gauze or cotton ball).

11. Wash your hands carefully.

1 2 3

How to prepare for self-administration of the Eporatio injection

Before administering the Eporatio injection to yourself, you must do the following:

1. Grasp the syringe and carefully remove the protective cover from the needle without tilting it. Separate it as indicated in the images 4. The needle is surrounded by a retractable needle guard. Do not touch the needle or the needle guard or push the plunger (see image 5).

2. Small air bubbles may appear in the pre-filled syringe. If there are bubbles, gently tap the syringe with your fingers until the bubbles rise to the top of the syringe. With the syringe pointing upwards, remove all the air from the syringe by pushing the plunger slightly upwards.

3. The syringe has a scale on the body of the syringe. Push the plunger until the number (UI) on the syringe corresponds to the dose of Eporatio prescribed by your doctor.

4. Check again that the dose of Eporatio in the syringe is correct.

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

4 5

Where to put the injection

The most suitable places for the injection are:

- the upper part of the thighs,

- the abdomen, except the area around the navel (see the gray areas in image 6).

If someone is helping you to put the injection, you can also put it in the back and side of the arms (see the gray areas in image 7)

It is better to change the injection site every day to avoid the risk of pain in some areas.

6 7

How to inject

1. Disinfect the injection site using an alcohol swab and pinch the skin between your thumb and index finger, without squeezing (see image 8).

2. Insert the needle completely into the skin, without hesitation and with a continuous movement, as indicated by your doctor or nurse. The angle between the syringe and the skin should not be too small (at least 45° see image 9). The needle guard will retract completely when you insert the needle into the skin (see image 10).

3. Inject the liquid into the tissue slowly and regularly, keeping the skin pinched (see image 11).

4. After injecting the liquid, remove the needle and pull it out of the skin. The needle will be automatically protected and blocked so that you can safely dispose of it (see image 12),

5. Press the injection site with a sterile gauze or cotton ball for a few seconds.

6. Use only one syringe for one injection. Do not use any remaining Eporatio from the syringe.

8 9

10 11

12

Remember

If you have any problems, please seek help or advice from your doctor or nurse.

How to dispose of used syringes

The safety device prevents puncture injuries after use, so no special precautions are required for disposal. Dispose of the used syringes with a safety device according to the instructions of your doctor, pharmacist, or nurse.