Aranesp ® Solution

Your doctor has given you ARANESP® (an anti-anaemic) to treat your anaemia. Anaemia is when your blood does not contain enough red blood cells and the symptoms may be fatigue, weakness and shortness of breath.

ARANESP® works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is produced in your kidneys and encourages your bone marrow to produce more red blood cells. The active substance of ARANESP® is darbepoetin alfa produced by gene-technology in Chinese Hamster Ovary Cells (CHO-K1).

If you have chronic renal failure ARANESP® is used to treat symptomatic anaemia that is associated with chronic renal failure (kidney failure) in adults and children. In kidney failure, the kidney does not produce enough of the natural hormone erythropoietin which can often cause anaemia. Because it will take your body some time to make more red blood cells, it will be about four weeks before you notice any effect. Your normal dialysis routine will not affect the ability of ARANESP® to treat your anaemia.

If you are receiving chemotherapy ARANESP® is used to treat symptomatic anaemia in adult cancer patients with non-bone marrow cancers (non-myeloid malignancies) who are receiving chemotherapy. One of the main side effects of chemotherapy is that it stops the bone marrow producing enough blood cells. Towards the end of your chemotherapy course, particularly if you have had a lot of chemotherapy, your red blood cell count may fall making you anaemic.

You should not use ARANESP®:

• if you are allergic to darbepoetin alfa or any of the other ingredients of ARANESP® (listed in section 6).
• if you have been diagnosed with high blood pressure which is not being controlled with other medicines prescribed by your doctor.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Aranesp. Please tell your doctor if you are suffering or have suffered from:

• high blood pressure which is being controlled with medicines prescribed by your doctor;
• sickle cell anaemia;
• epileptic fits (seizures);
• convulsions (fits or seizures);
• liver disease;
• significant lack of response to medicines used to treat anaemia;
• an allergy to latex (the needle cap on the pre-filled syringe contains a derivative of latex); or
• hepatitis C.

Special warnings

If you have symptoms which include unusual tiredness and a lack of energy this could mean you have pure red cell aplasia (PRCA), which has been reported in patients. PRCA means that the body has stopped or reduced the production of red blood cells which causes severe anaemia. If you experience these symptoms you should contact your doctor who will determine the best course of action to treat your anaemia.

Take special care with other products that stimulate red blood cell production: ARANESP® is one of a group of products that stimulate the production of red blood cells like the human protein erythropoietin does. Your healthcare professional should always record the exact product you are using.

If you are a patient with chronic renal failure, ARANESP® places you at a higher risk for death, problems of the heart (myocardial infarction) or blood vessels, stroke, blood clots (thrombosis) and tumour progression or recurrence. Particularly if you do not respond properly to ARANESP® your doctor will check your dose of ARANESP® repeatedly increasing your dose of ARANESP® if you are not responding to treatment.

Your doctor should try to keep your haemoglobin between 10 and 12 g/dl. Your doctor will check that your haemoglobin does not exceed a certain level, as high haemoglobin concentrations could put you at risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.

If you have symptoms which include severe headache, drowsiness, confusion, problems with your eyesight, nausea, vomiting or fits (seizures), it could mean that you have very high blood pressure. If you experience these symptoms you should contact your doctor.

If you are a ARANESP® acts as a blood cell growth factor and increases the risk of tumour progression or recurrence. You should not use ARANESP® if you are receiving chemotherapy that suppresses you bone marrow’s production of blood cells and platelets. Depending on your individual situation a blood transfusion may be preferable. Please discuss this with your doctor.

Misuse by healthy people can cause life-threatening problems with the heart or blood vessels.

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 ARANESP® and contact your doctor or seek medical attention immediately.

If you are undergoing surgery, blot clotting prevention is recommended as ARANESP® places you at higher risk of developing blood clots (deep vein thrombosis).

Other medicines and ARANESP®

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. Ciclosporin and tacrolimus (medicines which suppress the immune system) may be affected by the number of red cells in your blood. It is important to tell your doctor if you are taking either of these medicines.

Using ARANESP® with food and drink

Food and drink do not affect ARANESP®.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor, pharmacist or other healthcare professional for advice before taking this medicine. ARANESP® 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.

It is not known whether darbepoetin alfa is excreted in human milk. You must stop breast-feeding if you use ARANESP®.

Driving and using machines

ARANESP® should not affect your ability to drive or use machinery.

ARANESP® contains sodium ARANESP® contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium-free’.

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Following blood tests, your doctor has decided you need ARANESP® as your haemoglobin level is 10 g/dl or less. Your doctor will tell you how much and how often you must take ARANESP® in order to maintain a haemoglobin level between 10 and 12 g/dl. This may vary depending on whether you are an adult or a child.

Injecting ARANESP® yourself

Your doctor may decide that it is best for you or a carer to inject ARANESP®. Your doctor, nurse or pharmacist will show you how to inject yourself with a pre-filled syringe. Do not try to inject yourself if you have not been trained. Never inject ARANESP® into a vein yourself.

If you have chronic renal failure For all adult and paediatric patients ≥ 1 year of age with chronic renal failure, ARANESP® is given as a single injection, either under your skin (subcutaneous) or into a vein (intravenous). In order to correct your anaemia, your initial dose of ARANESP® per kilogram of your body weight will be either:

• 0.75 micrograms once every two weeks, or
• 0.45 micrograms once weekly

For adult patients not on dialysis, 1.5 micrograms/kg once monthly may also be used as the initial dose. For all adult and paediatric patients ≥ 1 year of age with chronic renal failure, once your anaemia is corrected you will continue to receive ARANESP® given as a single injection, either once a week or once every two weeks. For all adults and paediatric patients ≥ 11 years of age not on dialysis, ARANESP® could also be given as an injection once monthly. Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose once every four weeks as necessary in order to maintain long-term control of your anaemia. Your doctor will use the lowest effective dose to control the symptoms of your anaemia. If you do not respond adequately to ARANESP®, your doctor will check your dose and will inform you if you need to change doses of ARANESP®. Your blood pressure will also be checked regularly, particularly at the beginning of your treatment.

In some cases, your doctor may recommend that you take iron supplements. Your doctor may decide to change the way that your injection is given (either under the skin or into a vein). If this changes you will start on the same dose as you have been receiving and your doctor will take blood samples to make sure that your anaemia is still being managed correctly. If your doctor has decided to change your treatment from r-HuEPO (erythropoietin produced by gene-technology) to ARANESP®, they will choose whether you should receive your ARANESP® injection once weekly or once every two weeks. The route of injection is the same as with r-HuEPO but your doctor will tell you how much you should take, and when, and may adjust your dose if necessary. If you are receiving chemotherapy ARANESP® is given as a single injection, either once a week or once every three weeks, under your skin. In order to correct your anaemia, your initial dose will be:

• 500 micrograms once every three weeks (6.75 micrograms of ARANESP® per kilogram of your body weight), or
• 2.25 micrograms (once weekly) of ARANESP® per kilogram of your body weight.

Your doctor will take regular blood samples to measure how your anaemia is responding and may adjust your dose as necessary. Your treatment will continue until approximately four weeks after the end of your chemotherapy. Your doctor will tell you exactly when to stop taking ARANESP®.

In some cases, your doctor may recommend that you take iron supplements. If you use more ARANESP® than you should you could have serious problems if you use more ARANESP® than you need, such as very high blood pressure. You should contact your doctor, nurse or pharmacist if this does happen. If you feel unwell in any way you should contact your doctor, nurse or pharmacist immediately.

If you forget to use ARANESP® do not use a double dose to make up for a forgotten dose. If you have forgotten a dose of ARANESP®, you should contact your doctor to discuss when you should inject the next dose.

If you stop using ARANESP® if you want to stop using ARANESP® you should discuss it with your doctor first.

Like all medicines, ARANESP® can cause side effects, although not everybody gets them. The following side effects have been experienced by some patients taking ARANESP®:

Chronic renal failure patients

Very Common: may affect more than 1 in 10 people

• High blood pressure (hypertension)
• Allergic reactions

Common: may affect up to 1 in 10 people

• Stroke
• Pain around the area injected
• Rash and/or redness of the skin

Uncommon: may affect up to 1 in 100 people

• Blood clots (thrombosis)
• Convulsions (fits and seizures)
• Bruising and bleeding at the site of injection
• Blood clots in a dialysis access

Not known: frequency cannot be estimated from available data

• pure red cell aplasia (PRCA) – (anaemia, unusual tiredness, lack of energy)

Cancer patients

Very common: may affect more than 1 in 10 people

• Allergic reactions

Common: may affect up to 1 in 10 people

• High blood pressure (hypertension)
• Blood clots (thrombosis)
• Pain around the area injected
• Rash and/or redness of the skin
• Fluid retention (oedema)

Uncommon: may affect up to 1 in 100 people

• Convulsions (fits and seizures).
• Bruising and bleeding at the site of injection

All patients

Not known: frequency cannot be estimated from available data

• Serious allergic reactions which may include:
• Sudden life-threatening allergic reactions (anaphylaxis)
• Swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioedema)
• Shortness of breath (allergic bronchospasm)
• Skin rash
• Hives (urticaria)

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 ARANESP® if you develop these symptoms and contact your doctor or seek medical attention immediately. See also section 2.

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 to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of ARANESP® Alternatively, suspected adverse events can be reported to: Amgen South Africa (Pty) Ltd. Tel: +27 (0)11 100 5300, Email: [email protected]

Store all medicines out of reach and sight of children. Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Do not use ARANESP® if you think it has been frozen. Keep the pre-filled syringe in the outer carton in order to protect from light. When your syringe has been removed from the refrigerator and left at room temperature for approximately 30 minutes before injection it must either be used within 7 days or disposed of. Do not use this medicine if you notice the pre-filled syringe contents are cloudy or there are particles in it.

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. Return all unused medicine to your pharmacist. Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).