NeoRecormon 10000 IU solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

NeoRecormon 500 IU

NeoRecormon 2,000 IU

NeoRecormon 3,000 IU

NeoRecormon 4,000 IU

NeoRecormon 5,000 IU

NeoRecormon 6,000 IU

NeoRecormon 10,000 IU

NeoRecormon 20,000 IU

NeoRecormon 30,000 IU

solution for injection in pre-filled syringe

epoetin beta

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What NeoRecormon is and what it is used for
2. What you need to know before using NeoRecormon
3. How to use NeoRecormon
4. Possible side effects
5. How to store NeoRecormon
6. Contents of the pack and other information

1. What NeoRecormon is and what it is used for

NeoRecormon is a clear, colourless solution for injection under the skin (subcutaneously) or into the vein (intravenously). It contains epoetin beta, a hormone that stimulates the production of red blood cells. Epoetin beta is produced by advanced genetic technology and works in exactly the same way as natural human erythropoietin hormone.

You should consult your doctor if you worsen or do not improve.

NeoRecormon is indicated for:

• Treatment of symptomatic anemia caused by chronic kidney disease (renal anemia) in patients undergoing dialysis or not yet undergoing dialysis.
• Prevention of anemia in premature infants (with a birth weight of 750 to 1,500 g and a gestational age of less than 34 weeks).
• Treatment of anemia with related symptoms in adult patients with cancer receiving chemotherapy.
• Treatment of individuals donating their own blood prior to undergoing surgery. Epoetin beta injections will increase the amount of blood that can be collected from your body before the operation, to be given back to you during or after surgery (this is an autologous transfusion).

2. What you need to know before using NeoRecormon

Do not use NeoRecormon:

• if you are allergic to epoetin beta or to any of the other ingredients of this medicine (listed in section 6)
• if you have blood pressure problems that cannot be controlled
• if you are donating your own blood before undergoing surgery and:
• you have had a myocardial infarction or stroke within the month prior to treatment
• you have unstable angina – new or worsening chest pain
• you are at risk of developing blood clots in the veins (deep vein thrombosis) – e.g. if you have previously had blood clots.

If you experience or may develop any of these conditions, tell your doctor immediately.

Warnings and precautions

Talk to your doctor before starting NeoRecormon

• If your baby requires treatment with NeoRecormon, your baby will be closely monitored for possible eye effects
• if your anemia does not improve with epoetin treatment
• if you have low levels of certain B vitamins (folic acid or vitamin B12)
• if you have high levels of aluminium in your blood
• if your platelet count is high
• if you have chronic liver disease
• if you have epilepsy
• if you have developed anti-erythropoietin antibodies and pure red cell aplasia (reduced or absent production of red blood cells) during prior exposure to any erythropoietic agent. In this case, you must not switch to NeoRecormon.

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

Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been observed with administration of epoetins.

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

If you develop a severe skin rash or any of these other skin symptoms, stop taking NeoRecormon and contact your doctor or seek immediate medical attention.

Special warning

During treatment with NeoRecormon

If you are a patient with chronic kidney disease, and particularly if you do not respond adequately to NeoRecormon, your doctor will monitor your NeoRecormon dose, as repeatedly increasing the dose of NeoRecormon when not responding to treatment may increase the risk of heart or blood vessel problems, and could increase the risk of myocardial infarction, stroke, and death.

If you are a cancer patient, you should know that NeoRecormon can act as a growth factor for blood cells and, under certain circumstances, may have a negative effect on cancer. Depending on your individual situation, a blood transfusion may be preferable. Please discuss this with your doctor.

If you are a nephrosclerotic patient not yet on dialysis, your doctor will decide whether treatment is appropriate for you. This is because a possible acceleration of renal failure cannot be definitively ruled out.

Your doctor may perform regular blood tests to monitor:

• your potassium levels. If you have high or increasing potassium levels, your doctor should reconsider your treatment
• your platelet count. During treatment with epoetin, the number of platelets may increase slightly to moderately, which may cause changes in blood coagulation.

If you are a patient with renal impairment undergoing hemodialysis, your doctor should adjust your heparin dose. This will prevent blockage of the tubes in the dialysis system.

If you are a patient with renal impairment undergoing hemodialysis and at risk of shunt thrombosis, clots (thrombosis) may form in your shunt (the vessel used to connect to the dialysis system). Your doctor may prescribe acetylsalicylic acid or modify the shunt.

If you are donating your own blood prior to surgery, your doctor will need to:

• check that you are eligible to donate blood, especially if your weight is less than 50 kg
• confirm that you have sufficient red blood cell levels (haemoglobin of at least 11 g/dl)
• ensure that no more than 12% of your total blood volume is removed at one time.

Do not misuse NeoRecormon:

Inappropriate use of NeoRecormon by healthy individuals may lead to an increase in blood cells and, consequently, thickening of the blood, which may result in life-threatening cardiac or vascular complications.

Use of NeoRecormon with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription.

Pregnancy, breast-feeding and fertility

Adequate experience with NeoRecormon in women during pregnancy and breast-feeding has not been obtained. Consult your doctor or pharmacist before taking any medicine.

NeoRecormon has not shown evidence of impaired fertility in animals. The potential risk in humans is unknown.

Driving and using machines

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

NeoRecormon contains phenylalanine

This medicine contains phenylalanine. It may be harmful for people with phenylketonuria.

If you have phenylketonuria, consult your doctor about treatment with NeoRecormon.

NeoRecormon contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; hence, it is essentially “sodium-free”.

NeoRecormon contains polysorbate

This medicine contains polysorbate 20 (0.034 mg/syringe of nominal volume 0.3 ml and 0.063 mg/syringe of nominal volume 0.6 ml). Polysorbates may cause allergic reactions. Consult your doctor if you have known allergies.

3. How to use NeoRecormon

Always use this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

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

If you do not respond adequately to NeoRecormon, your doctor will check your dose and inform you whether a dose adjustment is needed.

Treatment must be initiated under the supervision of a physician.

Other injections will be administered by your doctor or, after proper training, you may self-inject NeoRecormon (see instructions at the end of this leaflet).

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

Your doctor will perform periodic blood tests to monitor your response to treatment by measuring your hemoglobin levels.

NeoRecormon dosage

The dose of NeoRecormon depends on the severity of your condition, the route of administration (subcutaneous or intravenous), and your body weight. Your doctor will calculate the appropriate dose for you.

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

If you do not respond adequately to NeoRecormon, your doctor will monitor your dose and inform you whether a dose adjustment is necessary.

• Symptomatic anemia due to chronic renal disease

Injections are administered subcutaneously or intravenously. If the solution is administered intravenously, it must be injected over approximately 2 minutes, e.g., in hemodialysis patients via the arteriovenous fistula at the end of dialysis.

Non-hemodialyzed patients will normally receive subcutaneous administration.

Treatment with NeoRecormon consists of two phases:

1. Correction of anemia

Initial subcutaneous dose: 20 IU per injection per kg body weight, administered three times per week.

After 4 weeks, your doctor will perform tests and may increase your dose to 40 IU/kg per injection, administered three times per week. Your doctor may continue to increase your dose at monthly intervals if necessary.

The weekly dose may be divided into daily doses.

Initial intravenous dose: 40 IU per injection per kg body weight, administered three times per week.

After 4 weeks, your doctor will perform tests and, if the response to treatment is insufficient, may increase your dose to 80 IU/kg per injection, administered three times per week. Your doctor may continue to increase the dose at monthly intervals if necessary.

For both types of injection, the maximum dose should not exceed 720 IU per kg body weight per week.

2. Maintenance of red blood cell levels

Maintenance dose: Once your red blood cells reach an acceptable level, the dose is reduced to half the dose used to correct anemia. The weekly dose may be administered once weekly or divided into three or seven doses per week. If your red blood cell levels remain stable on a once-weekly regimen, administration may be changed to once every two weeks. In this case, a dose increase may be necessary.

Your doctor may adjust your dose every one or two weeks until your individual maintenance dose is established.

Children will start treatment following the same guidelines. In clinical trials, children generally required higher doses of NeoRecormon (the smaller the child, the higher the dose).

Treatment with NeoRecormon is usually long-term. However, it may be interrupted at any time if necessary.

• Anemia in premature infants

Injections are administered subcutaneously.

Initial dose: 250 IU per kg body weight, administered three times per week.

Preterm infants who have already received a blood transfusion prior to starting NeoRecormon treatment are less likely to benefit compared to non-transfused preterm infants.

The recommended duration of treatment is 6 weeks.

• Adults with symptomatic anemia due to cancer receiving chemotherapy

Injections are administered subcutaneously.

Your doctor may initiate NeoRecormon treatment if your hemoglobin level is ≤10 g/dl. After starting treatment, your doctor will maintain your hemoglobin level between 10 and 12 g/dl.

Initial weekly dose: 30,000 IU. This dose may be given as a single weekly injection or divided into 3 to 7 weekly injections. Your doctor will take regular blood samples. Based on the test results, your doctor may increase or reduce your dose or discontinue treatment. Hemoglobin levels should not exceed 12 g/dl.

Treatment should continue for up to 4 weeks after completion of chemotherapy.

Maximum dose: Must not exceed 60,000 IU per week.

• Patients donating their own blood prior to surgery

Injections are administered intravenously over approximately 2 minutes, or subcutaneously.

The NeoRecormon dose will depend on your condition, red blood cell levels, and the amount of blood you will donate before surgery.

The dose calculated by your doctor is administered twice weekly for 4 weeks. You will receive NeoRecormon at the end of each blood donation.

Maximum dose:

• for intravenous injection: 1,600 IU per kg body weight per week
• for subcutaneous injections: 1,200 IU per kg body weight per week

If you inject too much NeoRecormon

Do not increase the dose beyond what your doctor has prescribed. If you think you have injected more NeoRecormon than you should, contact your doctor. It is unlikely to be serious. Even at high blood levels, symptoms of poisoning have not been observed.

If you forget to use NeoRecormon

If you miss an injection or administer too little, inform your doctor.

Do not administer a double dose to make up for missed doses.

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

4. Possible adverse effects

Like all medicines, this medicine can have adverse effects, although not everyone will experience them.

Adverse effects that may affect any patient

• Low iron levels in the blood occur in most patients (very common: may affect more than 1 in 10 people). Almost all patients must be treated with iron supplements during treatment with NeoRecormon.
• Allergic or skin reactions such as rash or urticaria, or reactions at the injection site have rarely occurred (may affect up to 1 in 1,000 people).
• Severe allergic reactions have very rarely occurred (may affect up to 1 in 10,000 people), especially after injection. These must be treated immediately. If you experience wheezing or difficulty breathing; swelling of the tongue, face, throat, or around the injection site; dizziness or fainting; or if you collapse, call your doctor immediately.
• Very rarely (may affect up to 1 in 10,000 people), people experience flu-like symptoms, especially when starting treatment. These symptoms include fever, chills, headache, limb pain, bone pain, and/or general malaise. These reactions were usually mild or moderate and disappeared within hours or days.
• Serious skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed with epoetin administration. These reactions may appear as red, target-like macules or circular spots, often 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 NeoRecormon and contact your doctor or seek immediate medical attention if you experience these symptoms. See also section 2.

Adverse effects in patients with chronic kidney disease (renal anemia)

• The most common adverse effects (very common: may affect more than 1 in 10 people) are increases in blood pressure, worsening of existing high blood pressure, and headaches. Your doctor should treat high blood pressure with appropriate medication or temporarily interrupt treatment with NeoRecormon.
• If you have headaches, especially sudden, sharp, migraine-type headaches, confusion, speech disturbances, unsteadiness when walking, seizures, or convulsions, contact your doctor immediately. These may be symptoms of extremely high blood pressure (hypertensive crisis), even if your blood pressure is usually normal or low. This condition requires immediate treatment.
• If you have low blood pressure or vascular access complications, you may develop thrombosis of the vascular access (a blood clot in the vessel used to connect to the dialysis system).
• Very rarely (may affect up to 1 in 10,000 people), patients may develop elevated levels of potassium or phosphate in the blood. These can be treated by your doctor.
• Pure red cell aplasia (PRCA) caused by neutralizing antibodies has been observed during treatment with erythropoietin, including some isolated cases during treatment with NeoRecormon. PRCA means that the body stops or reduces the production of red blood cells. This leads to severe anemia, symptoms of which include unusual fatigue and lack of energy. If your body produces neutralizing antibodies, your doctor will discontinue therapy with NeoRecormon and determine the best way to manage your anemia.

Additional adverse effects in adults with cancer receiving chemotherapy

• Occasionally, increased blood pressure and headaches may occur. Your doctor may treat high blood pressure with medication.
• An increased incidence of blood clots has been observed.

Additional adverse effects in patients donating their own blood prior to surgery

• A slight increase in the incidence of blood clots has been observed.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is an adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of NeoRecormon

• Keep this medicine out of the sight and reach of children.
• Do not use NeoRecormon after the expiry date stated on the carton and label. The expiry date is the last day of the month indicated.
• Store in a refrigerator (between 2°C – 8°C).
• The syringe may be kept outside the refrigerator for a single period of up to 3 days at room temperature (not above 25°C).
• Keep the pre-filled syringe in the outer packaging to protect it from light.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of NeoRecormon

• The active substance is epoetin beta. 1 pre-filled syringe contains 500, 2,000, 3,000, 4,000, 5,000, 6,000, 10,000, 20,000 or 30,000 IU (international units) of epoetin beta in 0.3 ml or 0.6 ml of solution.
• The other components are:

urea, sodium chloride, polysorbate 20, disodium phosphate dodecahydrate, monosodium phosphate dihydrate, calcium chloride dihydrate, glycine, L-leucine, L-isoleucine, L-threonine, L-glutamic acid and L-phenylalanine, and water for injections. (See section 2 "NeoRecormon contains phenylalanine and sodium").

Appearance of NeoRecormon and contents of the pack

NeoRecormon is a solution in a pre-filled syringe for injection.

The solution is colourless and ranges from transparent to slightly opalescent.

NeoRecormon 500 IU, 2,000 IU, 3,000 IU, 4,000 IU, 5,000 IU and 6,000 IU: each pre-filled syringe contains 0.3 ml of solution.

NeoRecormon 10,000 IU, 20,000 IU and 30,000 IU: each pre-filled syringe contains 0.6 ml of solution.

NeoRecormon is available in the following pack sizes:

NeoRecormon 500 IU

1 pre-filled syringe with 1 needle (30G1/2) or

6 pre-filled syringes with 6 needles (30G1/2).

NeoRecormon 2,000 IU, 3,000 IU, 4,000 IU, 5,000 IU, 6,000 IU, 10,000 IU and 20,000 IU

1 pre-filled syringe with 1 needle (27G1/2) or

6 pre-filled syringes with 6 needles (27G1/2).

NeoRecormon 30,000 IU

1 pre-filled syringe with 1 needle (27G1/2) or

4 pre-filled syringes with 4 needles (27G1/2).

Only some pack sizes may be marketed.

Marketing Authorization Holder

Roche Registration GmbH

Emil-Barell-Strasse 1

79639 Grenzach-Wyhlen

Germany

Manufacturer

Roche Pharma AG

Emil-Barell-Strasse 1

D-79639 Grenzach-Wyhlen

Germany

For further information on this medicine, please contact the local representative of the Marketing Authorization Holder:

Czech Republic Roche s. r. o. Tel.: +420 - 2 20382111	Hungary Roche (Magyarország) Kft. Tel.: +36 - 1 279 4500
Denmark Roche Pharmaceuticals A/S Tel.: +45 - 36 39 99 99	Malta (See Ireland)
Germany Roche Pharma AG Tel.: +49 (0) 7624 140	Netherlands Roche Nederland B.V. Tel.: +31 (0) 348 438050
Estonia Roche Eesti OÜ Tel.: + 372 - 6 177 380	Norway Roche Norge AS Tel.: +47 - 22 78 90 00
Greece Roche (Hellas) A.E. Tel.: +30 210 61 66 100	Austria Roche Austria GmbH Tel.: +43 (0) 1 27739
Spain Roche Farma S.A. Tel.: +34 - 91 324 81 00	Poland Roche Polska Sp.z o.o. Tel.: +48 - 22 345 18 88
France Roche Tel: +33 (0) 1 47 61 40 00	Portugal Roche Farmacêutica Química, Lda Tel.: +351 - 21 425 70 00
Croatia Roche d.o.o. Tel.: +385 1 4722 333	Romania Roche România S.R.L. Tel.: +40 21 206 47 01
Ireland Roche Products (Ireland) Ltd. Tel.: +353 (0) 1 469 0700	Slovenia Roche farmacevtska družba d.o.o. Tel.: +386 - 1 360 26 00
Iceland Roche Pharmaceuticals A/S c/o Icepharma hf Sími: +354 540 8000	Slovakia Roche Slovensko, s.r.o. Tel.: +421 - 2 52638201
Italy Roche S.p.A. Tel.: +39 - 039 2471	Finland Roche Oy Puh/Tel: +358 (0) 10 554 500
Cyprus G.A. Stamatīs & Sia Ltd. Tel.: +357 - 22 76 62 76	Sweden Roche AB Tel.: +46 (0) 8 726 1200
Latvia Roche Latvija SIA Tel.: +371 - 6 7039831

Date of the most recent review of this leaflet<{MM/AAAA}> <{month YYYY}>

Other sources of information

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

NeoRecormon pre-filled syringe

Instructions for use

The following instructions explain how to administer an injection of NeoRecormon. Make sure you read, understand, and follow these instructions for use as well as the package leaflet before injecting NeoRecormon. Your healthcare professional will show you how to properly prepare and inject NeoRecormon before you use it for the first time.

Do not self-inject unless you have received training. Consult your healthcare professional if you require further training.

Always follow all instructions in these guidelines, as they may differ from your previous experiences. These instructions will minimize risks such as accidental needlestick injury and prevent incorrect use.

NeoRecormon can be administered in 2 ways; your doctor will decide which method is appropriate for you:

• Intravenous administration (into a vein or venous access), to be performed only by healthcare professionals.
• Subcutaneous administration (under the skin).

Before starting to use

• Do not remove the needle cap until you are ready to inject NeoRecormon.
• Do not attempt to remove the syringe at any time.
• Do not reuse the same syringe.
• Do not use if the syringe has been dropped or is damaged.
• Do not leave the syringe unattended.
• Keep the syringe, needle, and sharps disposal container out of the reach of children.
• If you have any questions, contact your healthcare professional.

Storage instructions

• Store the syringe(s) and unused needles in the original packaging and keep them refrigerated between 2 °C and 8 °C.
• Keep the syringe and needle away from direct sunlight.
• Do not freeze.
• Do not use if the syringe has been frozen.
• Always keep the syringe and needle dry.

Materials needed to administer the injection

Included in the packaging:

• NeoRecormon pre-filled syringe(s).

• Injection needle(s) (27G or 30G) (depending on the prescribed dose of the medicine) with safety shield (used for preparation, dose adjustment, and injection of the medicine).

Note: Each NeoRecormon package contains 1 syringe / 1 needle, 4 syringes / 4 needles, or 6 syringes / 6 needles.

• Instructions for use and package leaflet.

Not included in the packaging:

• 1 alcohol swab.
• 1 dry sterile gauze pad.
• 1 puncture-resistant container or sharps disposal container for the safe disposal of the rubber cap, needle cap, and used syringe.

Preparation for injection

1. Find a well-lit, clean, flat working surface.

• Remove the carton containing the syringe(s) and needle(s) from the refrigerator.

1. Check the packaging, perforations on the front, and the seal. Also check the expiration date.

• Do not use if the expiration date has passed, or if the packaging appears tampered with. In this case, proceed to step 20 and contact your healthcare professional.
• Do not use if the perforations or seal are broken. In this case, go to step 20 and contact your healthcare professional.

1. Open the packaging by pushing through the perforation around the seal.

2. Remove one syringe from the carton and one needle from the needle box. Handle the syringe carefully. Always hold the syringe as shown in the image below.

• Do not turn the carton upside down to remove the syringe.
• Do not handle the syringe by holding the plunger or the needle cap.

Note: If you have a multipack, return the carton containing the remaining syringe(s) and needle(s) to the refrigerator.

1. Carefully inspect the syringe and needle.

• Check that the syringe and needle are not damaged. Do not use the syringe if it has been dropped or if any part appears damaged.
• Verify the expiration date on the syringe and needle. Do not use the syringe or needle if the expiration date has passed.
• Check the liquid in the syringe. The liquid should be clear and colorless. Do not use the syringe if the liquid is cloudy, discolored, or contains particles.

1. Place the syringe on a clean, flat surface.

• Leave it aside for 30 minutes to allow it to reach room temperature. Keep the needle cap on during this time.
• Do not accelerate the warming process in any way, and do not place the syringe in a microwave or warm water.

Note: If the syringe does not reach room temperature, this may make the injection uncomfortable and make it difficult to push the plunger.

1. Attach the needle to the syringe.

• Remove the needle from its ampoule.
• Remove the rubber cap from the end of the syringe (A).
• Immediately dispose of the rubber cap in a puncture-resistant or sharps disposal container.
• Do not touch the tip of the syringe.
• Do not push or pull the plunger.
• Hold the syringe by the barrel and push the needle onto the syringe (B).
• Gently twist until fully secured (C).

A)

B)

C)

1. Place the syringe on a clean, flat surface until ready for use.

2. Wash your hands with soap and water.

3. Choose an injection site:

• Recommended injection sites are the upper thigh or the lower abdomen below the navel. Do not inject within the 5 cm (2 inches) area directly around your navel.
• Choose a different injection site for each new injection.
• Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard, or not intact.
• Do not inject into a vein or muscle.

1. Clean the injection site with an alcohol swab and allow it to air dry for 10 seconds.

• Do not blow on or fan the cleaned area.
• Do not touch the injection site again before administering the injection.

Subcutaneous injection administration

1. Slide the safety shield of the needle away from the syringe barrel.

1. Firmly hold the syringe and carefully remove the needle cap from the syringe. Use the syringe within 5 minutes after removing the cap; otherwise, the needle may become clogged.

• Do not hold the plunger while removing the needle cap.
• Do not touch the needle after removing the cap.
• Do not recap the needle.
• Do not straighten the needle if it is bent or damaged.

Immediately dispose of the needle cap in a sharps disposal container.

1. Hold the syringe with the needle pointing upward. Remove large air bubbles by gently tapping the syringe barrel with your fingers until the air bubbles rise to the top. Then slowly push the plunger upward to expel the air bubbles from the syringe.

1. Adjust the prescribed dose by slowly pushing the plunger.

1. Pinch the selected injection site and insert the needle completely at an angle of 45° to 90° with a quick, firm motion.

• Do not touch the plunger while inserting the needle into the skin.
• Do not insert the needle through clothing.

Once the needle is inserted, release the pinch and firmly hold the syringe in place.

1. Slowly inject the prescribed dose by gently pushing the plunger to the end.

• Remove the needle and syringe from the injection site at the same angle as insertion.

After the injection

1. There may be slight bleeding at the injection site. You may press a dry sterile gauze pad over the site. Do not rub the injection site.

• If needed, you may cover the injection site with a small bandage.
• In case of contact with the medication, wash the affected area with water.

1. Slide the safety shield forward 90°, away from the syringe barrel (A).

Holding the syringe in one hand, press the safety shield firmly and quickly against a flat surface until you hear a "click" (B).

• If you do not hear a click, ensure that the needle is fully covered by the safety shield.
• Always keep your fingers behind the safety shield and away from the needle.

A)

B)

1. Immediately place the used syringe in a sharps disposal container after use.

• Do not attempt to remove the used injection needle from the used syringe.
• Do not recap the used injection needle with the cap.
• Do not throw the syringe in your household trash.

Important: Always keep the sharps disposal container out of the reach of children.

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Instructions for intravenous injection, intended for healthcare professionals only

The following instructions explain how to administer an intravenous injection of NeoRecormon. Make sure you read, understand, and follow the Instructions for use as well as the package leaflet before injecting NeoRecormon.

Intravenous injection administration (for healthcare professionals only).

Preparation for injection: follow steps 1 to 9 of subcutaneous injection (above).

1. Select a vein. Change the vein with each injection to prevent localized pain.

• Do not inject into a red or swollen area.
• Do not inject into a muscle.

Clean the skin over the vein with an alcohol swab and allow it to dry.

• Do not blow on or fan the cleaned area.
• Do not touch the injection site again before administering the injection.

1. Prepare the syringe and needle: follow steps 12 to 15 of subcutaneous injection (above).

2. Insert the needle into the vein.

• Do not hold or push the plunger while inserting the needle.
  1. Slowly inject the prescribed dose by gently pushing the plunger to the end. Remove the needle and syringe from the injection site at the same angle as insertion.

After the injection, follow steps 18 to 20 of subcutaneous injection (above).

Administering intravenous injection through an injection port (for healthcare professionals only).
Preparation for injection: follow steps 1 to 9 of subcutaneous injection (above).

1. Clean the skin at the injection site with an alcohol swab and allow it to dry.

Clean the injection site according to the device provider's instructions.

• Do not blow on or fan the cleaned area.
• Do not touch the injection site again before administering the injection.

1. Prepare the syringe and needle: follow steps 12 to 15 of subcutaneous injection (above).

2. Insert the needle into the injection site (follow the venous access device provider's instructions).

• Do not hold or push the plunger while inserting the needle.

1. Slowly inject the prescribed dose by gently pushing the plunger to the end. Remove the needle and syringe from the injection port at the same angle as insertion.

After the injection, follow steps 18 to 20 of subcutaneous injection (above).