Silapo - patient leaflet, side effects, dosage

1. What Silapo is and what it is used for

Silapo contains the active substance epoetin zeta – a protein, that stimulates the bone marrow to produce more red blood cells, which carry haemoglobin (a substance that transports oxygen). Epoetin zeta is a copy of the human protein erythropoietin (ee-rith-roe-po-eh-tin) and acts in the same way.

• Silapo is used to treat symptomatic anaemia caused by kidney disease

• – in children on haemodialysis

• – in adults on haemodialysis or peritoneal dialysis

• – in severely anaemic adults not yet undergoing dialysis

If you have kidney disease, you may be short of red blood cells if your kidney does not produce enough erythropoietin (necessary for red cell production). Silapo is prescribed to stimulate your bone marrow to produce more red blood cells.

• Silapo is used to treat anaemia in adults receiving chemotherapy for solid tumours,

malignant lymphoma or multiple myeloma (bone marrow cancer) who may have a need for a blood transfusion. Silapo can reduce the need for a blood transfusion in these patients.

• Silapo is used in moderately anaemic adults who donate some of their blood before

surgery, so that it can be given back to them during or after the operation. Because Silapo stimulates the production of red blood cells, doctors can take more blood from these people.

• Silapo is used in moderately anaemic adults about to have major orthopaedic surgery

(for example hip or knee replacement operations ), to reduce the potential need for blood transfusions.

• Silapo is used to treat anaemia in adults with a bone marrow disorder that causes a severe

disruption in the creation of blood cells (myelodysplastic syndromes). Silapo can reduce the need for a blood transfusion.

2. What you need to know before you use Silapo

Do not use Silapo

• If you are allergic to epoetin zeta or any of the other ingredients of this medicine (listed in

section 6).

• If you have been diagnosed with Pure Red Cell Aplasia (the bone marrow cannot produce

enough red blood cells) after previous treatment with any product that stimulates red blood cell production (including Silapo). See section 4.

• If you have high blood pressure not properly controlled with medicines
• To stimulate the production of your red blood cells (so that doctors can take more blood from

you) if you cannot have transfusions with your own blood during or after surgery.

• If you are due to have major elective orthopaedic surgery (such as hip or knee surgery), and

you:

• – have severe heart disease

• – have severe disorders of the veins and arteries

• – have recently had a heart attack or stroke

• – can’t take medicines to thin the blood

Silapo may not be suitable for you. Please discuss with your doctor. While on Silapo, some people need medicines to reduce the risk of blood clots. If you can’t take medicines that prevent blood clotting, you must not have Silapo.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Silapo.

Silapo and other products that stimulate red cell production may increase the risk of developing blood clots in all patients. This risk may be higher if you have other risk factors for developing blood clots (for example, if you have had a blood clot in the past or are overweight, have diabetes, have heart disease or you are off your feet for a long time because of surgery or illness). Please tell your doctor about any of these things. Your doctor will help you to decide if Silapo is suitable for you.

Talk to your doctor if any of the following apply to you. You may still be able to use Silapo, but discuss it with your doctor first.

• If you know you suffer, or have suffered, from:

• - high blood pressure

• - epileptic seizures or fits

• - liver disease

• - anaemia from other causes

• - porphyria (a rare blood disorder)

• If you are a patient with chronic renal failure, and particularly if you do not respond properly

to Silapo, your doctor will check your dose of Silapo because repeatedly increasing your dose of

Silapo if you are not responding to treatment may increase the risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.

• If you are a cancer patient be aware that products that stimulate red blood cell production (like

Silapo) may act as a growth factor and therefore in theory may affect the progression of your cancer. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

• If you are a cancer patient, be aware that use of Silapo may be associated with shorter survival

and a higher death rate in head and neck, and metastatic breast cancer patients who are receiving chemotherapy.

• Serious skin reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal

necrolysis (TEN) have been reported in association with epoetin treatment.

SJS/TEN can appear initially as reddish target-like spots or circular patches often with central blisters on the trunk. Also, ulcers of mouth, throat, nose, genitals and eyes (red and swollen eyes) can occur. These serious skin rashes are often preceded by fever and/or flu-like symptoms. The rashes may progress to widespread peeling of the skin and life-threatening complications.

If you develop a serious rash or another of these skin symptoms, stop taking Silapo and contact your doctor or seek medical attention immediately.

Take special care with other products that stimulate red blood cell production:

Silapo is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional will always record the exact product you are using.

If you are given a product in this group other than Silapo during your treatment, speak to your doctor or pharmacist before using it.

Other medicines and Silapo

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

If you are taking a medicine called ciclosporin (used e.g. after kidney transplants), your doctor may order blood tests to check the level of ciclosporin while you are taking Silapo.

Iron supplements and other blood stimulants may increase the effectiveness of Silapo. Your doctor will decide if it is right for you to take them.

If you visit a hospital, clinic or family doctor , tell them you are having Silapo treatment. It may affect other treatments or test results.

Pregnancy, breast-feeding and fertility

It is important to tell your doctor if any of the following apply to you. You may still be able to use Silapo, but discuss it with your doctor first.

• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a

baby, ask your doctor or pharmacist for advice before taking this medicine.

No data on the effects of Silapo on fertility are available.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed.

Silapo contains phenylalanine

This medicine contains up to 0.5 mg phenylalanine in each dosage unit. Phenylalanine may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

Silapo contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say essentially ‘sodium-free’.

3. How to use Silapo

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

Your doctor has carried out blood tests and decided you need Silapo.

Silapo may be given by injection:

• Either into a vein or a tube that goes into a vein (intravenously)
• Or under the skin (subcutaneously).

Your doctor will decide how Silapo will be injected. Usually the injections will be given to you by a doctor, nurse or other health care professional. Some people, depending on why they need Silapo treatment, may later learn how to inject themselves under the skin: see Instructions on how to inject Silapo yourself.

Silapo should not be used:

• after the expiry date on the label and outer carton
• if you know, or think that it may have been accidentally frozen, or
• if there has been a refrigerator failure.

The dose of Silapo you receive is based on your bodyweight in kilograms. The cause of your anaemia is also a factor in your doctor deciding the correct dose.

Your doctor will monitor your blood pressure regularly while you are using Silapo.

People with kidney disease

• Your doctor will maintain your haemoglobin level between 10 and 12 g/dL as a high

haemoglobin level may increase the risk of blood clots and death. In children the haemoglobin level should be maintained between 9.5 and 11 g/dL.

• The recommended starting dose of Silapo for adults and children is 50 Internatio­nal Units

(IU) per kilogram (/kg) of body weight given three times a week.

• For patients on peritoneal dialysis Silapo may be given twice a week.
• For adults and children Silapo is given as an injection either into a vein (intravenously) or a tube

that goes into a vein. When this access (via a vein or tube) is not readily available, your doctor may decide that Silapo should be injected under the skin (subcutaneously). This includes patients on dialysis and patients not yet on dialysis.

• Your doctor will order regular blood tests to see how your anaemia is responding and may

adjust the dose, usually no more frequently than every four weeks. A rise in haemoglobin of greater than 2 g/dL over a four week period should be avoided.

• Once your anaemia has been corrected, your doctor will continue to check your blood regularly.

Your Silapo dose and frequency of administration may be further adjusted to maintain your response to treatment. Your doctor will use the lowest effective dose to control the symptoms of your anemia.

• If you do not respond adequately to Silapo, your doctor will check your dose and will inform

you if you need to change doses of Silapo.

• If you are on a more extended dosing interval (greater than once weekly) of Silapo, you may not

maintain adequate haemoglobin levels and you may require an increase in Silapo dose or frequency of administration.

• You may be given iron supplements before and during Silapo treatment to make it more

effective.

• If you are having dialysis treatment when you begin treatment with Silapo, your dialysis regime

may need to be adjusted. Your doctor will decide this.

Adults on chemotherapy

• Your doctor may initiate treatment with Silapo if your haemoglobin is 10 g/dL or less.
• Your doctor will maintain your haemoglobin level between 10 and 12 g/dL as a high

haemoglobin level may increase the risk of blood clots and death.

• The recommended starting dose is either 150 IU per kilogram bodyweight three times a week

or 450 IU per kilogram bodyweight once a week.

• Silapo is given by injection under the skin.
• Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia

responds to Silapo treatment.

• You may be given iron supplements before and during Silapo treatment to make it more

effective.

• You will usually continue Silapo treatment for one month after the end of chemotherapy.

Adults donating their own blood

• The recommended dose is 600 IU per kilogram bodyweight twice a week.
• Silapo is given by injection into a vein immediately after you have donated blood for 3 weeks

before your surgery.

• You may be given iron supplements before and during Silapo treatment to make it more

effective.

Adults scheduled for major orthopaedic surgery

• The recommended dose is 600 IU per kilogram bodyweight once a week.
• Silapo is given by injection under the skin each week for three weeks before surgery and on the

day of surgery.

• If there is a medical need to reduce the time before your operation, you will be given a daily

dose of 300 IU/kg for up to ten days before surgery, on the day of surgery and for four days immediately afterwards.

• If blood tests show your haemoglobin is too high before the operation, the treatment will be

stopped.

• You may be given iron supplements before and during Silapo treatment to make it more

effective.

Adults with myelodysplastic syndrome

• Your doctor may initiate treatment with Silapo if your haemoglobin is 10 g/dL or less. The aim

of treatment is to maintain your haemoglobin level between 10 and 12 g/dL as a higher haemoglobin level may increase the risk of blood clots and death.

• Silapo is given by injection under the skin.
• The starting dose is 450 IU per kilogram bodyweight once a week.
• Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia

responds to Silapo treatment.

Instructions on how to inject Silapo yourself

When treatment starts, Silapo is usually injected by medical or nursing staff. Later, your doctor may suggest that you or your caregiver learn how to inject Silapo under the skin (subcutaneously ) yourself.

• Do not attempt to inject yourself unless you have been trained to do so by your doctor or

nurse.

• Always use Silapo exactly as instructed by your doctor or nurse.
• Only use Silapo if it has been stored correctly – see section 5, How to Store Silapo.
• Before use, leave the Silapo syringe to stand until it reaches room temperature. This

usually takes between 15 and 30 minutes.

Only take one dose of Silapo from each syringe.

If Silapo is injected under the skin (subcutaneously), the amount injected is not normally more than one millilitre (1 mL) in a single injection.

Silapo is given alone and not mixed with other liquids for injection.

Do not shake Silapo syringes. Prolonged vigorous shaking may damage the product. If the product has been shaken vigorously, don’t use it.

How to inject yourself using a pre-filled syringe:

• Take a syringe out of the refrigerator. The liquid needs to come to room temperature. Do not

remove the syringe’s needle cover while allowing it to reach room temperature.

• Check the syringe, to make sure it is the right dose, has not passed its expiry date, is not

damaged, and the liquid is clear and not frozen.

• Choose an injection site. Good sites are the top of the thigh and around the tummy (abdomen)

but away from the navel. Vary the site from day to day.

• Wash your hands. Use an antiseptic swab on the injection site, to disinfect it.
• Hold the pre-filled syringe by the body of the syringe with the covered needle pointing upward.
• Do not hold by the plunger head, plunger or needle cover.
• Do not pull back on the plunger at any time.
• Do not remove the needle cover from the pre-filled syringe until you are ready to inject Silapo.
• Take the needle cover off the syringe by holding the barrel and pulling the needle cover off

carefully without twisting it. Don’t push the plunger, touch the needle or shake the syringe.

• Pinch a fold of skin between your thumb and index finger. Don’t squeeze it.
• Push the needle in fully. Your doctor or nurse may have shown you how to do this.
• Push the plunger with your thumb as far as it will go to inject the entire amount of liquid. Push

it slowly and evenly, keeping the skin fold pinched.

• When the plunger is pushed as far as it will go, take out the needle and let go of the skin.
• When the needle is pulled out of your skin, there may be a little bleeding at the injection site.

This is normal. You can press an antiseptic swab over the injection site for a few seconds after the injection.

• Dispose of your used syringe in a sharps container. Do not try to replace the needle cover.
• Never put used syringes into your normal household waste bin.

How to inject yourself using a pre-filled syringe:

Your pre-filled syringe has a passive needle guard device attached to it in order to protect you from needle stick injury.

• Take a syringe out of the refrigerator. The liquid needs to come to room temperature. Do not

remove the syringe’s needle cover while allowing it to reach room temperature.

• Check the syringe, to make sure it is the right dose, has not passed its expiry date, is not

damaged, and the liquid is clear and not frozen.

• Choose an injection site. Good sites are the top of the thigh and around the tummy (abdomen)

but away from the navel. Vary the site from day to day.

• Wash your hands. Use an antiseptic swab on the injection site, to disinfect it.
• Hold the pre-filled syringe by the body of the syringe with the covered needle pointing upward.
• Do not hold by the plunger head, plunger or needle cover.
• Do not pull back on the plunger at any time.
• Do not remove the needle cover from the pre-filled syringe until you are ready to inject Silapo.
• Take the needle cover off the syringe by holding the barrel and pulling the needle cover off

carefully without twisting it. Don’t push the plunger, touch the needle or shake the syringe.

• Pinch a fold of skin between your thumb and index finger. Don’t squeeze it.
• Push the needle in fully. Your doctor or nurse may have shown you how to do this.
• Depress the plunger while grasping the finger flange until the entire dose has been given. The

needle guard will NOT activate unless the ENTIRE dose has been given.

• When the plunger is pushed as far as it will go, take out the needle and let go of the skin.
• Let go of the plunger and allow the syringe to move up until the entire needle is guarded and

locks into place.

• When the needle is pulled out of your skin, there may be a little bleeding at the injection site.

This is normal. You can press an antiseptic swab over the injection site for a few seconds after the injection.

• Dispose of your used syringe in a sharps container. Do not try to replace the needle cover.
• Never put used syringes into your normal household waste bin.

If you use more Silapo than you should

Tell the doctor or nurse immediately if you think too much Silapo has been injected. Side effects from an overdose of Silapo are unlikely.

If you forget to use Silapo

Make the next injection as soon as you remember. If you are within a day of your next injection, forget the missed one and carry on with your normal schedule. Do not double up the injections to make up for a forgotten dose.

If you are a patient with hepatitis C and you receive interferon and ribavirin

You should discuss this with your doctor because a combination of Silapo with interferon and ribavirin has led to a loss of effect and development of a condition called pure red cell aplasia (PRCA), a severe form of anaemia, in rare cases. Silapo is not approved in the management of anaemia associated with hepatitis C.

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

4. Possible side effects

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

Tell your doctor or nurse immediately if you notice any of the effects in this list.

Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in association with epoetin treatment. These can appear as reddish target-like macules or circular patches often with central blisters on the trunk, skin peeling, ulcers of mouth, throat, nose, genitals and eyes and can be preceded by fever and flu-like symptoms. Stop using Silapo if you develop these symptoms and contact your doctor or seek medical attention immediately. See also section 2.

Very common: may affect more than 1 in 10 people

• Diarrhoea
• Feeling sick in your stomach
• Vomiting
• Fever
• Respiratory tract congestion, such as stuffy nose and sore throat, has been reported in patients

with kidney disease not yet on dialysis.

Common: may affect up to 1 in 10 people

• Increased blood pressure. Headaches, particularly sudden, stabbing migraine-like headaches,

feeling confused or having fits may be signs of a sudden increase in blood pressure. This requires urgent treatment. Raised blood pressure may require treatment with medicines (or adjustment to any medicines you already take for high blood pressure).

• Blood clots (including deep vein thrombosis and embolism) that may require urgent treatment.

You may have chest pain, breathlessness, and painful swelling and redness, usually in the leg as symptoms.

• Cough
• Skin rashes, which may result from an allergic reaction
• Bone or muscle pain
• Flu-like symptoms, such as headache, aches and pains in the joints, feeling of weakness, chills,

tiredness and dizziness. These may be more common at the start of treatment. If you have these symptoms during injection into the vein, a slower delivery of the injection may help to avoid them in the future.

• Redness, burning and pain at the site of injection
• Swelling of the ankles, feet or fingers
• Arm or leg pain

Uncommon: may affect up to 1 in 100 people

• High levels of blood potassium which can cause abnormal heart rhythm (this is a very common

side effect in patients on dialysis).

• Fits
• Nose or airway congestion
• Allergic reaction
• Hives

Rare: may affect up to 1 in 1 000 people

• Symptoms of pure red cell aplasia (PRCA)

PRCA means the bone marrow does not make enough red blood cells. PRCA causes sudden and severe anaemia. The symptoms are: – unusual tiredness,

• - feeling dizzy,

• - breathlessness.

PRCA has been very rarely reported mostly in patients with kidney disease after months to years of treatment with Silapo and other products that stimulate red blood cell production.

• An increase in levels of small blood cells (called platelets), which are normally involved in the

formation of a blood clot may occur, particularly when starting treatment. Your doctor will check on this.

• Severe allergic reaction that may include:

• – a swollen face, lips, mouth, tongue or throat

• – difficulty swallowing or breathing

• – itchy rash (hives).

• Problem with the blood that may cause pain, dark coloured urine or increased sensitivity of the

skin to sunlight (porphyria).

If you are receiving haemodialysis:

• Blood clots (thrombosis) may form in your dialysis shunt. This is more likely if you have low

blood pressure or if your fistula has complications.

• Blood clots may also form in your haemodialysis system. Your doctor may decide to increase

your heparin dose during dialysis.

Tell your doctor or nurse immediately if you are aware of any of these effects, or if you notice any other effects while you are receiving treatment with Silapo.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Silapo

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

Do not use this medicine after the expiry date which is stated on the box and on the label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C – 8 °C). You may take Silapo out of the refrigerator and keep it at room temperature (up to 25 °C) for no longer than 3 days. Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25 °C) it must either be used within 3 days or disposed of.

Do not freeze or shake.

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

Do not use this medicine if you notice that the seal is broken or if the liquid is coloured or you can see particles floating in it. In the event of either being observed, discard the medicinal product.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Silapo contains

• — The active substance is epoetin zeta (produced by recombinant DNA technology in Chinese Hamster Ovary (CHO) cell line).

What Silapo looks like and contents of the pack

Silapo is presented as a clear and colourless solution for injection in a pre-filled syringe with a fixed injection needle.

The pre-filled syringes contain between 0.3 and 1 mL solution, depending on the content of epoetin zeta (see “What Silapo contains”).

One pack contains 1, 4 or 6 pre-filled syringes with or without a needle guard device.

Marketing Authorisation Holder

STADA Arzneimittel AG

Stadastrasse 2–18

D-61118 Bad Vilbel

Germany

Manufacturer

STADA Arzneimittel AG

Stadastrasse 2–18

D-61118 Bad Vilbel

Germany

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

STADAPHARM GmbH

StadastraBe 2–18

D-61118 Bad Vilbel

Tel: +49 (0) 6101 603–0

Fax: +49 (0) 6101 603–3888

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

Detailed information on this medicine is available on the European Medicines Agency web site:.

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