Active ingredients: Darbepoetin alfa
Aranesp 10 micrograms solution for injection in pre-filled syringe
Aranesp 15 micrograms solution for injection in pre-filled syringe
Aranesp 20 micrograms solution for injection in pre-filled syringe
Aranesp 30 micrograms solution for injection in pre-filled syringe
Aranesp 40 micrograms solution for injection in pre-filled syringe
Aranesp 50 micrograms solution for injection in pre-filled syringe
Aranesp 60 micrograms solution for injection in pre-filled syringe
Aranesp 80 micrograms solution for injection in pre-filled syringe
Aranesp 100 micrograms solution for injection in pre-filled syringe
Aranesp 130 micrograms solution for injection in pre-filled syringe
Aranesp 150 micrograms solution for injection in pre-filled syringe
Aranesp 300 micrograms solution for injection in pre-filled syringe
Aranesp 500 micrograms solution for injection in pre-filled syringe
Aranesp package inserts are available for pack sizes: - Aranesp 10 micrograms solution for injection in pre-filled syringe, Aranesp 15 micrograms solution for injection in pre-filled syringe, Aranesp 20 micrograms solution for injection in pre-filled syringe, Aranesp 30 micrograms solution for injection in pre-filled syringe, Aranesp 40 micrograms solution for injection in 50 micrograms solution for injection, Aranesp 40 micrograms solution for injection in 50 micrograms solution for injection in pre-filled syringe, Aranesp 60 micrograms solution for injection in pre-filled syringe, Aranesp 80 micrograms solution for injection in pre-filled syringe, Aranesp 100 micrograms solution for injection in pre-filled syringe, Aranesp 130 micrograms solution for injection in pre-filled syringe, Aranesp 150 micrograms solution for injection in pre-filled syringe, Aranesp 150 micrograms solution for injection in pre-filled syringe, Aranesp 150 micrograms solution for injection in pre-filled syringe 300 micrograms solution for injection in pre-filled syringe, Aranesp 500 micrograms solution for injection in pre-filled syringe
- Aranesp 10 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 15 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 20 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 30 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 40 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 50 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 60 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 80 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 100 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 130 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 150 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 300 micrograms solution for injection in pre-filled pen (SureClick), Aranesp 500 micrograms solution for injection in pre-filled pen (SureClick
- Aranesp 25 micrograms solution for injection in vial, Aranesp 40 micrograms solution for injection in vial, Aranesp 60 micrograms solution for injection in vial, Aranesp 100 micrograms solution for injection in vial, Aranesp 200 micrograms solution for injection in vial, Aranesp 300 micrograms solution for injection in vial
Why is Aranesp used? What is it for?
The doctor prescribed Aranesp (an anti-anemic) to treat her anemia. You suffer from anemia when there is not a sufficient number of red blood cells in the blood and the symptoms of anemia can be exhaustion, weakness and shortness of breath.
Aranesp works in exactly the same way as the natural hormone erythropoietin. Erythropoietin is produced by the kidneys and stimulates the bone marrow to produce more red blood cells. The active substance in Aranesp is darbepoetin alfa, which is produced by genetic engineering in Chinese hamster ovary cells (CHO-K1).
If you suffer from chronic kidney failure
Aranesp is used to treat symptomatic anemia associated with chronic renal failure in adults and children. In renal failure, the kidneys do not produce enough of the natural hormone erythropoietin which can often cause anemia.
It will take your body some time to make more red blood cells, and then it will take you about four weeks before you notice any effects.Aranesp's ability to treat anemia will not be affected by the normal practice of dialysis.
If you are receiving chemotherapy
Aranesp is used in the treatment of symptomatic anemia in adult patients with non-bone marrow tumors (non-myeloid malignancies) receiving chemotherapy.
One of the main side effects of chemotherapy is that it prevents the bone marrow from producing enough blood cells. Towards the end of your chemotherapy treatment, particularly if you have received a lot of chemotherapy, your red blood cell count may decrease, making you anemic.
Contraindications When Aranesp should not be used
Do not use Aranesp
- if you are allergic to darbepoetin alfa or any of the other ingredients of this medicine (listed in section 6).
- if you have been diagnosed with high blood pressure which is not currently controlled with other medicines prescribed by your doctor
Precautions for use What you need to know before you take Aranesp
Talk to your doctor or pharmacist or nurse before using Aranesp.
Tell your doctor if you have or have suffered from:
- high blood pressure which is currently controlled with medically prescribed medicines;
- sickle cell anemia;
- seizures (convulsions);
- convulsions (fits or fits);
- liver disease;
- significant lack of response to medicines used to treat anemia;
- allergy to latex (the needle cap of the pre-filled syringe contains a derivative of latex); or
- hepatitis C.
Special warnings:
- If you experience symptoms including unusual tiredness and loss of strength, you may have pure red cell aplasia (PRCA) which has been reported in patients. PRCA means that the body stops producing or reduces the production of red blood cells, which causes severe anemia. If you experience these symptoms you should inform your doctor who will decide on the best anemia treatment strategy.
- Take special care when taking other medicines that stimulate the production of red blood cells: Aranesp belongs to a group of products that stimulate the production of red blood cells as well as human erythropoietin. Your healthcare professional should always record the correct name of the medicine you are taking.
- Your doctor should try to keep your hemoglobin between 10 and 12 g / dl. Your doctor will check that your hemoglobin level does not exceed a specific level as high hemoglobin levels could put you at risk of having heart or blood vessel problems and could increase the risks of myocardial infarction, stroke and death.
- If you have chronic kidney failure there is an increased risk of serious heart or blood vessel problems (cardiovascular events) if hemoglobin is kept too high.
- If you have symptoms that include severe headache, sleepiness, confusion, vision problems, nausea, vomiting or seizures it could mean that you have very high blood pressure. If you experience these symptoms you should contact your doctor.
- If you have cancer, you should be aware that Aranesp can act as a growth factor for blood cells and that, in some circumstances, it can have negative effects on the cancer. Depending on the specific situation, a blood transfusion may be preferable. Discuss this with your doctor.
- Improper use by healthy subjects can cause heart and vascular problems that place the subject in immediate danger of life.
Interactions Which drugs or foods may change the effect of Aranesp
Other medicines and Aranesp
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.
The medicines ciclosporin and tacrolimus (medicines that suppress the immune system) can be affected by the number of red blood cells. It is important that you tell your doctor if you are taking any of these medicines.
Aranesp with food and drink
Food and drink do not affect Aranesp.
Warnings It is important to know that:
Pregnancy and breastfeeding
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.
Aranesp has not been tested in pregnant women. It is important to tell your doctor if:
- are pregnant;
- you think you may be pregnant; or
- is planning a pregnancy.
It is not known whether darbepoetin alfa is secreted in human milk. If you use Aranesp you must stop breastfeeding.
Driving and using machines
Aranesp is not expected to limit the ability to drive or use machines.
Aranesp contains sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodium-free.
Dose, Method and Time of Administration How to use Aranesp: Posology
Always use this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Based on some blood tests, your doctor has determined that you need Aranesp since your hemoglobin level is 10 g / dl or less. Your doctor will tell you how much and how often Aranesp is given in order to maintain a hemoglobin level between 10 and 12 g / dl. This can vary depending on whether it is an adult or a child.
How to inject yourself with Aranesp
Your doctor may decide that it is best for you or your caregiver to inject Aranesp. Your doctor, nurse or pharmacist will show you how to inject yourself with the pre-filled syringe. Do not try to inject yourself if you have not been told how to do it. Never inject Aranesp into a vein yourself.
If you suffer from chronic kidney failure
For all adult and pediatric patients ≥ 11 years of age with chronic renal failure, Aranesp is administered as a single injection under the skin (subcutaneous) or into a vein (intravenous).
The starting dose of Aranesp per kilogram of body weight to correct the anemia will be:
- 0.75 micrograms once every two weeks, or
- 0.45 micrograms once a week.
For adult patients not on dialysis, 1.5 micrograms / kg once a month may also be used as the starting dose.
All adult and pediatric patients aged ≥ 11 years with chronic renal failure, once their anemia has been corrected, will continue to receive Aranesp as a single injection, either once a week or once every two weeks. If you are not on dialysis, Aranesp could also be given as an injection once a month.
Your doctor will have regular blood tests to check how your anemia is responding and may adjust your dose once every four weeks as needed.
Once your anemia is corrected, your doctor will continue to have regular blood tests and the dose can still be adjusted to maintain long-term control of the anemia. Your doctor will inform you if the dosage will change.
Your blood pressure will also be checked regularly, particularly at the start of treatment.
In some cases, your doctor may suggest that you take iron supplements.
Your doctor may decide to change the way the injection is given (either under the skin or into a vein). If you change the method of administration, you will start with the same dose you received before and your doctor will do some tests. blood tests to ensure that anemia is always treated correctly.
If your doctor has decided to change your treatment from r-HuEPO (erythropoietin produced by genetic technology) to Aranesp, he will also decide how often Aranesp should be given once a week or once every two weeks. administration of the injection is the same as for r-HuEPO, but your doctor will tell you how much to take and when and may adjust the dose if necessary.
If you are receiving chemotherapy
Aranesp is given once a week or once every three weeks as a single injection under the skin.
The starting dose to correct the anemia will be:
- 500 micrograms once every three weeks (6.75 micrograms of Aranesp per kilogram of body weight), or
- 2.25 micrograms (once weekly) of Aranesp per kilogram of body weight.
Your doctor will have regular blood tests to check how your anemia is responding and may adjust the dose as needed. Treatment will continue for approximately four weeks after the course of chemotherapy is finished. Your doctor will tell you exactly when to stop taking it. by Aranesp.
In some cases, your doctor may suggest that you take iron supplements.
Instructions for injecting yourself with the Aranesp pre-filled syringe
This section contains information on how to inject Aranesp yourself. It is important that you do not try to inject yourself if you have not been told how to inject by your doctor, nurse or pharmacist. If you have any questions about how to inject, ask your doctor, nurse or pharmacist for help.
How to use Aranesp in a pre-filled syringe by you or the person giving you the injection
Your doctor has prescribed Aranesp in a pre-filled syringe for injection into the tissue immediately under the skin. Your doctor, nurse or pharmacist will tell you how much Aranesp you need and how often to inject.
What is needed:
To give yourself an injection you will need:
- a new pre-filled syringe of Aranesp; And
- alcohol wipes or similar disinfectants.
What should I do before giving myself a "subcutaneous injection of Aranesp?"
- Take the pre-filled syringe out of the refrigerator. Leave the pre-filled syringe at room temperature for about 30 minutes. This will make the injection more comfortable. Do not heat Aranesp in any other way (for example, in a microwave oven or in hot water). Also, do not leave the syringe in direct sunlight.
- Do not shake the pre-filled syringe.
- Do not remove the needle cap from the syringe until you are ready to inject.
- Check that the dosage is the exact one prescribed by your doctor.
- Check the expiry date on the pre-filled syringe label (EXP). Do not use it if this is after the last day of the month shown.
- Check the appearance of Aranesp. It must be a clear, colorless or slightly opalescent liquid. If it is cloudy or you see particles, you should not use it.
- Wash your hands thoroughly.
- Find a comfortable, well-lit, clean surface and keep everything you need close at hand.
How do I prepare the Aranesp injection?
Before injecting Aranesp you must do the following: 1. To avoid bending the needle, gently remove the cap from the needle without twisting it as shown in figures 1 and 2. 2. Do not touch the needle and do not push the plunger. 3. You may notice a small air bubble in the pre-filled syringe. You must not remove the air bubble before injecting. Injecting the solution with the air bubble is harmless. 4. You can now use the syringe pre-filled.
Where should I get the injection?
The best places to inject yourself are the upper thighs and abdomen. If someone else gives you the injection, you can also use the back of your arms.
Change the injection site if you notice that the area is red or sore.
How do I give myself the injection?
- Disinfect the skin using the alcohol wipe and lift the skin between your thumb and forefinger (without squeezing it).
- Push the needle completely into your skin as shown by your doctor, nurse or pharmacist.
- Inject the prescribed dose subcutaneously as directed by your doctor, nurse or pharmacist.
- Push the plunger with slow, steady pressure, always keeping the skin pinched, until the syringe is empty.
- Pull out the needle and let go of the skin.
- If you notice a blood spot, you can gently press a cotton ball or gauze onto the injection site. Do not rub the injection site. If necessary, you can cover the injection site with an adhesive plaster.
- Only use each syringe for one injection. Do not reuse the leftover Aranesp in the syringe.
Remember: If you have any problems, don't hesitate to consult your doctor or nurse for help or advice.
Disposal of used syringes
- Do not put the cap back on used needles as you may accidentally prick yourself.
- Keep used syringes out of the sight and reach of children.
- Used pre-filled syringes should be disposed of in accordance with local requirements. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Overdose What to do if you have taken too much Aranesp
If you use more Aranesp than you should
You may have serious problems if you take more Aranesp than you need, such as very high blood pressure. If this happens, you should contact your doctor, nurse or pharmacist. If you feel unwell, contact your doctor, nurse or pharmacist immediately.
If you forget to use Aranesp
Do not take a double dose to make up for a forgotten dose.
If you have forgotten a dose of Aranesp, you should contact your doctor to find out when you should have your next injection.
If you stop taking Aranesp
If you want to stop using Aranesp, you should discuss this with your doctor first.
Side Effects What are the side effects of Aranesp
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Following administration of Aranesp, some patients experienced the following side effects:
Patients with chronic renal insufficiency
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 at the injection site
- Skin rashes and / or redness of the skin
Uncommon: may affect up to 1 in 100 people
- Blood clots (thrombosis)
- Convulsions (seizures)
Not known: frequency cannot be estimated from the available data
- Pure red cell aplasia (PRCA) - (anemia, unusual tiredness, loss of strength)
Cancer patients
Very common: may affect more than 1 in 10 people
- Allergic reactions
- Fluid retention (edema)
Common: may affect up to 1 in 10 people
- High blood pressure (hypertension)
- Blood clots (thrombosis)
- Pain at the injection site
- Skin rashes and / or redness of the skin
Uncommon: may affect up to 1 in 100 people
- Convulsions (seizures)
All patients
Not known: frequency cannot be estimated from the available data
Serious allergic reactions which can include:
- Sudden allergic reactions that can be fatal (anaphylaxis)
- Swelling of the face, lips, mouth, tongue or throat which may make it difficult to swallow or breathe (angioedema)
- Shortness of breath (allergic bronchospasm)
- Skin rashes
- Hives (hives)
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
Expiry and Retention
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 carton and pre-filled syringe label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 ° C - 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 to protect the medicine from light.
Once the 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 discarded.
Do not use this medicine if you notice that the contents of the pre-filled syringe are cloudy or there are visible particles in it.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Aranesp contains
- The active substance is darbepoetin alfa, r-HuEPO (erythropoietin produced by genetic engineering). The pre-filled syringe contains 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300 or 500 micrograms of darbepoetin alfa.
- The other ingredients are monobasic sodium phosphate, dibasic sodium phosphate, sodium chloride, polysorbate 80 and water for injections.
What Aranesp looks like and contents of the pack
Aranesp is a clear, colorless or slightly opalescent solution for injection in a pre-filled syringe.
Aranesp is available in packs of 1 or 4 pre-filled syringes. The syringes are packaged with blisters (packs of 1 or 4 syringes) or without blisters (packs of 1 syringe). Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ARANESP
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Aranesp 10 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 10 micrograms of darbepoetin alfa in 0.4 mL (25 micrograms / mL).
Aranesp 15 micrograms solution for injection in pre-filled syringeEach pre-filled syringe contains 15 mcg of darbepoetin alfa in 0.375 mL (40 mcg / mL).
Aranesp 20 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 20 micrograms of darbepoetin alfa in 0.5 mL (40 micrograms / mL).
Aranesp 30 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 30 micrograms of darbepoetin alfa in 0.3 mL (100 micrograms / mL).
Aranesp 40 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 40 mcg of darbepoetin alfa in 0.4 mL (100 mcg / mL).
Aranesp 50 micrograms solution for injection in pre-filled syringeEach pre-filled syringe contains 50 mcg of darbepoetin alfa in 0.5 mL (100 mcg / mL).
Aranesp 60 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 60 mcg of darbepoetin alfa in 0.3 mL (200 mcg / mL).
Aranesp 80 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 80 micrograms of darbepoetin alfa in 0.4 mL (200 mcg / mL).
Aranesp 100 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 100 mcg of darbepoetin alfa in 0.5 mL (200 mcg / mL).
Aranesp 130 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 130 mcg of darbepoetin alfa in 0.65 mL (200 mcg / mL).
Aranesp 150 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 150 mcg of darbepoetin alfa in 0.3 mL (500 mcg / mL).
Aranesp 300 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 300 mcg of darbepoetin alfa in 0.6 mL (500 mcg / mL).
Aranesp 500 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 500 mcg of darbepoetin alfa in 1 mL (500 mcg / mL).
Aranesp 10 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 10 micrograms of darbepoetin alfa in 0.4 mL (25 micrograms / mL).
Aranesp 15 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 15 micrograms of darbepoetin alfa in 0.375 mL (40 mcg / mL).
Aranesp 20 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 20 micrograms of darbepoetin alfa in 0.5 mL (40 micrograms / mL).
Aranesp 30 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 30 micrograms of darbepoetin alfa in 0.3 mL (100 micrograms / mL).
Aranesp 40 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 40 micrograms of darbepoetin alfa in 0.4 mL (100 micrograms / mL).
Aranesp 50 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 50 micrograms of darbepoetin alfa in 0.5 mL (100 micrograms / mL).
Aranesp 60 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 60 micrograms of darbepoetin alfa in 0.3 mL (200 micrograms / mL).
Aranesp 80 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 80 micrograms of darbepoetin alfa in 0.4 mL (200 mcg / mL).
Aranesp 100 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 100 mcg of darbepoetin alfa in 0.5 mL (200 mcg / mL).
Aranesp 130 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 130 mcg of darbepoetin alfa in 0.65 mL (200 mcg / mL).
Aranesp 150 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 150 mcg of darbepoetin alfa in 0.3ml (500mcg / ml).
Aranesp 300 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 300 mcg of darbepoetin alfa in 0.6 mL (500 mcg / mL).
Aranesp 500 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 500 mcg of darbepoetin alfa in 1 mL (500 mcg / mL).
Aranesp 25 mcg solution for injection in vial
Each vial contains 25 micrograms of darbepoetin alfa in 1 mL (25 micrograms / mL).
Aranesp 40 mcg solution for injection in vial
Each vial contains 40 mcg of darbepoetin alfa in 1 mL (40 mcg / mL).
Aranesp 60 mcg solution for injection in vial
Each vial contains 60 mcg of darbepoetin alfa in 1 mL (60 mcg / mL).
Aranesp 100 mcg solution for injection in vial
Each vial contains 100 mcg of darbepoetin alfa in 1 mL (100 mcg / mL).
Aranesp 200 mcg solution for injection in vial
Each vial contains 200 mcg of darbepoetin alfa in 1 mL (200 mcg / mL).
Aranesp 300 mcg solution for injection in vial
Each vial contains 300 mcg of darbepoetin alfa in 1 mL (300 mcg / mL).
Darbepoetin alfa is produced by genetic engineering in Chinese Hamster Ovary (CHO-K1) cells.
Excipient (s) with known effect:
Aranesp 10 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.52 mg of sodium in 0.4 ml.
Aranesp 15 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.42 mg of sodium in 0.375 mL.
Aranesp 20 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.90 mg of sodium in 0.5 ml.
Aranesp 30 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.14 mg of sodium in 0.3 ml.
Aranesp 40 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.52 mg of sodium in 0.4 ml.
Aranesp 50 mcg solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.90 mg of sodium in 0.5 ml.
Aranesp 60 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.14 mg of sodium in 0.3 ml.
Aranesp 80 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.52 mg of sodium in 0.4 ml.
Aranesp 100 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.90 mg of sodium in 0.5 ml.
Aranesp 130 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 2.46 mg of sodium in 0.65 mL.
Aranesp 150 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 1.14 mg of sodium in 0.3 ml.
Aranesp 300 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 2.27 mg of sodium in 0.6 ml.
Aranesp 500 micrograms solution for injection in pre-filled syringe
Each pre-filled syringe contains 3.79 mg of sodium in 1 ml.
Aranesp 10 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.
Aranesp 15 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.42 mg of sodium in 0.375 mL.
Aranesp 20 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.
Aranesp 30 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.
Aranesp 40 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.
Aranesp 50 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.
Aranesp 60 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.
Aranesp 80 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.52 mg of sodium in 0.4 ml.
Aranesp 100 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 1.90 mg of sodium in 0.5 ml.
Aranesp 130 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 2.46 mg of sodium in 0.65 mL.
Aranesp 150 micrograms solution for injection in pre-filled pen
Each pre-filled pen contains 1.14 mg of sodium in 0.3 ml.
Aranesp 300 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 2.27 mg of sodium in 0.6 ml.
Aranesp 500 mcg solution for injection in pre-filled pen
Each pre-filled pen contains 3.79 mg of sodium in 1 ml.
Aranesp 25 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
Aranesp 40 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
Aranesp 60 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
Aranesp 100 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
Aranesp 200 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
Aranesp 300 mcg solution for injection in vial
Each vial contains 3.79 mg of sodium.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Solution for injection (injection) in pre-filled syringe.
Solution for injection (injection) in pre-filled pen (SureClick).
Solution for injection (injection) in vial.
Clear, colorless solution.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of symptomatic anemia associated with chronic renal failure (CRI) in adults and pediatric patients (see section 4.2).
Treatment of symptomatic anemia in adult patients with non-myeloid malignancies receiving chemotherapy.
04.2 Posology and method of administration
Aranesp treatment should be initiated by a physician experienced in the above indications.
Dosage
Treatment of symptomatic anemia in adult and pediatric patients with chronic renal failure
The symptoms and sequelae of anemia may vary according to age, sex and the general severity of the disease; it is therefore necessary that the clinical course and conditions of each individual patient be evaluated by the physician. Aranesp should be administered subcutaneously or intravenously in order to increase the hemoglobin concentration to no more than 12 g / dl (7.5 mmol / l). Subcutaneous use is preferable in patients who are not undergoing hemodialysis, to avoid puncture of peripheral veins.
Patients should be closely monitored to achieve adequate control of anemia symptoms using the lowest approved dose of Aranesp while maintaining hemoglobin concentrations below or equal to 12 g / dl (7 , 5 mmol / l). Caution should be exercised in increasing doses of Aranesp in patients with chronic renal failure.
In the case of patients with poor hemoglobin response to Aranesp, alternative causes of the poor response should be considered (see sections 4.4 and 5.1).
Due to intra-patient variability, single hemoglobin values above and below the desired hemoglobin level may occasionally be observed in the same subject. Variability of hemoglobin should be controlled by dose management, taking into account the target hemoglobin range, which is 10 g / dl (6.2 mmol / l) to 12 g / dl (7.5 mmol / l) . Continuation of hemoglobin values above 12 g / dl (7.5 mmol / l) should be avoided; guidelines for appropriate dose adjustment are provided below for hemoglobin values above 12 g / dl ( 7.5 mmol / l) An increase in hemoglobin of greater than 2 g / dl (1.25 mmol / l) over a period of 4 weeks should also be avoided. Should this occur, the dose will need to be adjusted.
Treatment with Aranesp is divided into two phases, a correction phase and a maintenance phase. Instructions are provided separately for adult and pediatric patients.
Adult patients with chronic renal failure
Correction phase:
The starting dose for subcutaneous or intravenous administration is 0.45 mcg / kg body weight, as a single injection once a week. Alternatively, the following starting doses may also be administered subcutaneously as a single injection to patients not on dialysis: 0.75 mcg / kg once every two weeks or 1.5 mcg / kg once monthly. If the rise in hemoglobin is inadequate (less than 1 g / dl (0.6 mmol / l) in four weeks), the dose should be increased by approximately 25%. Dose increases should not be made more than once every 4 weeks.
If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) in four weeks, the dose should be reduced by approximately 25%. If the hemoglobin value is greater than 12 g / dl (7.5 mmol / l) a dose reduction should be considered. If the hemoglobin continues to increase, the dose should be reduced by approximately 25%. If the hemoglobin value continues to increase after a dose reduction, the administration should be temporarily suspended until a decrease in the dose is observed. "hemoglobin, then restarting therapy at a dose approximately 25% lower than the previous dose.
Hemoglobin should be measured every one to two weeks until it has stabilized. Thereafter, hemoglobin can be measured at longer intervals.
Maintenance phase:
In patients on dialysis, Aranesp can be continued as a single injection once a week or once every two weeks. Dialysis patients switching from once weekly Aranesp to once every two weeks should initially receive a dose equivalent to twice the previous weekly dose.
In patients not on dialysis, Aranesp can continue to be given as a single injection once a week or once every two weeks or once a month. For patients treated with Aranesp once every two weeks, after reaching the goal of hemoglobin concentration, Aranesp can be administered by subcutaneous injection once a month starting with a dose equal to twice that previously given once every two weeks.
Dosage should be titrated as needed to maintain the target hemoglobin concentration.
If a dose adjustment is necessary to maintain hemoglobin at the desired level, it is recommended that the dose be adjusted by approximately 25%.
If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) in four weeks, the dose should be reduced by approximately 25%, depending on the rate of the increase. is greater than 12 g / dL (7.5 mmol / L), a dose reduction should be considered. If the hemoglobin continues to rise, the dose should be reduced by approximately 25%. In the event that, after a dose reduction, the hemoglobin value continues to increase, the administration must be temporarily suspended until a decrease in hemoglobin is observed, thus restarting therapy at a dose approximately 25% lower than the dose. previous.
After any adjustment of the dose or dosage regimen, hemoglobin should be checked every one to two weeks. Dose changes in the maintenance phase should not be made more frequently than once every two weeks.
When the route of administration is changed, the same dose should be used and the hemoglobin should be checked every one to two weeks to adjust the dose to maintain hemoglobin at the desired level.
Clinical studies have shown that adult patients receiving r-HuEPO once, twice or three times per week can be switched to once per week or every two weeks of Aranesp. The starting weekly dose of Aranesp (mcg / week) can be calculated by dividing the total weekly dose of r-HuEPO (IU / week) by 200. The starting dose of Aranesp to be administered every two weeks (mcg for two weeks) can be calculated by dividing the total dose of r-HuEPO administered over a two-week period by 200. Given the individual variability, it is expected that the dose will have to be modulated to define the optimal therapeutic dose for the individual patient. When replacing r-HuEPO with Aranesp, hemoglobin should be checked every one to two weeks and the same route of administration should be used.
Pediatric population with chronic renal insufficiency
There are no data regarding the treatment of pediatric patients less than 1 year of age in randomized clinical trials (see section 5.1).
Correction phase:
For patients ≥ 1 year of age, the starting dose for subcutaneous or intravenous administration is 0.45 mcg / kg body weight, as a single injection once weekly. Alternatively, patients not on dialysis may be given an initial dose of 0.75 mcg / kg as a single subcutaneous injection once every two weeks. If the rise in hemoglobin is inadequate (less than 1 g / dl (0.6 mmol / l) in four weeks), the dose should be increased by approximately 25%. Dose increases should not be made more than once every four weeks.
If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) in four weeks, the dose should be reduced by approximately 25%, depending on the rate of the increase. is greater than 12 g / dL (7.5 mmol / L), a dose reduction should be considered. If the hemoglobin continues to rise, the dose should be reduced by approximately 25%. In the event that, after a dose reduction, the hemoglobin value continues to increase, the administration must be temporarily suspended until a decrease in hemoglobin is observed, thus restarting therapy at a dose approximately 25% lower than the dose. previous.
Hemoglobin should be measured every one to two weeks until it has stabilized. Thereafter, hemoglobin can be measured at longer intervals.
Correction of anemia using Aranesp at a frequency of once monthly has not been studied in pediatric patients.
Maintenance phase:
For pediatric patients ≥ 1 year of age, during the maintenance phase, Aranesp can be continued as a single injection once a week or once every two weeks. Patients aged hemoglobin levels compared to older patients. Dialysis patients switching from once weekly Aranesp to once every two weeks should initially receive a dose equivalent to twice the previous weekly dose.
In non-dialysis patients aged 3 to 11 years, once the target hemoglobin concentration is achieved with once every two weeks, Aranesp can be administered by subcutaneous injection once a month starting with twice the previously administered dose. once every two weeks.
Clinical data in pediatric patients have shown that patients receiving r-HuEPO, two or three times per week can be switched to once weekly Aranesp, and patients receiving r-HuEPO once per week can switch to once weekly administration of r-HuEPO. Aranesp every two weeks. The initial weekly pediatric dose of Aranesp (mcg / week) can be calculated by dividing the total weekly dose of r-HuEPO (IU / week) by 240. The starting every two week dose of Aranesp (mcg / every two weeks) can be calculated by dividing the total cumulative dose of r-HuEPO administered over two weeks by 240. Given individual variability, it is expected that each individual dose will need to be titrated. patient the optimal therapeutic dose. When replacing r-HuEPO with Aranesp, hemoglobin should be checked every one to two weeks, and the same route of administration should be used.
Dosage should be titrated as needed to maintain the target hemoglobin concentration.
If a dose adjustment is necessary to maintain hemoglobin at the desired level, it is recommended that the dose be adjusted by approximately 25%.
If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) in four weeks, the dose should be reduced by approximately 25%, depending on the rate of the increase. is greater than 12 g / dl (7.5 mmol / l), a dose reduction should be considered. If the hemoglobin value continues to increase, the dose should be reduced by approximately 25%. a reduction in the dose, the hemoglobin value continues to increase, the administration will have to be temporarily suspended until a decrease in hemoglobin is observed, thus restarting therapy at a dose approximately 25% lower than the previous dose.
Patients starting dialysis during treatment with Aranesp should be closely monitored for adequate control of their hemoglobin levels.
After any adjustment of the dose or dosage regimen, hemoglobin should be checked every one to two weeks. Dose changes in the maintenance phase should not be made more frequently than once every two weeks.
When the route of administration is changed, the same dose should be used and the hemoglobin should be checked every one to two weeks to adjust the dose to maintain hemoglobin at the desired level.
Treatment of symptomatic anemia induced by chemotherapy in cancer patients
Aranesp should be administered subcutaneously to anemic patients (e.g. hemoglobin concentration ≤ 10 g / dl (6.2 mmol / l) in order to increase the hemoglobin value to no more than 12 g / dl (7.5 mmol / l). Symptoms and sequelae of anemia may vary according to age, sex and general severity of the disease, therefore it is necessary that the clinical course and condition of each individual patient be evaluated by the physician.
Due to intra-patient variability, single hemoglobin values above and below the desired hemoglobin level may occasionally be observed in the same subject. Variability of hemoglobin should be controlled by dose management, taking into account the target hemoglobin range, which is 10 g / dl (6.2 mmol / l) to 12 g / dl (7.5 mmol / l) . It is necessary to avoid persisting hemoglobin values above 12 g / dl (7.5 mmol / l); below are the indications for an appropriate dose adjustment in case of hemoglobin values above 12 g / dl (7 , 5 mmol / l).
The recommended starting dose is 500 micrograms (6.75 micrograms / kg) given once every three weeks or 2.25 micrograms / kg of body weight once weekly. If the patient's clinical response (fatigue, hemoglobin response) is inadequate after nine weeks, continued therapy may not be effective.
Aranesp therapy should be discontinued approximately 4 weeks after the end of the chemotherapy course.
Once the treatment goal for the individual patient is achieved, the dose should be reduced by 25-50% to ensure that the lowest approved dose of Aranesp is used to keep hemoglobin at a level that controls the symptoms of anemia. Appropriate dose titration between 500 mcg, 300 mcg and 150 mcg should be considered.
Patients should be monitored closely, reducing the dose by approximately 25-50% if hemoglobin exceeds 12 g / dl (7.5 mmol / l). If hemoglobin levels exceed 13 g / dl (8 , 1 mmol / l), treatment with Aranesp should be temporarily interrupted. Therapy should be restarted at a dose approximately 25% lower than the previous dose, after the hemoglobin level has dropped to 12 or below g / dl (7.5 mmol / l).
If the increase in hemoglobin is greater than 2 g / dl (1.25 mmol / l) over a 4-week period, the dosage should be reduced by 25-50%.
Method of administration
Aranesp 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300, 500 mcg solution for injection in pre-filled syringe
Aranesp is administered subcutaneously or intravenously as described in the posology.
Alternate injection sites and inject slowly to minimize discomfort at the injection site. Aranesp is supplied ready to use in pre-filled syringes.
Aranesp 10, 15, 20, 30, 40, 50, 60, 80, 100, 130, 150, 300, 500 mcg solution for injection in pre-filled pen
Aranesp in a pre-filled pen is for subcutaneous administration only.
Alternate injection sites to minimize discomfort at the injection site.
Aranesp is supplied ready to use in a pre-filled pen.
Aranesp 25, 40, 60, 100, 200, 300 mcg solution for injection in vial
Aranesp is administered subcutaneously or intravenously as described in the posology.
Alternate injection sites and inject slowly to minimize discomfort at the injection site.
Aranesp is supplied ready to use in a vial.
Instructions for use, handling and disposal are given in section 6.6.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Uncontrolled hypertension.
04.4 Special warnings and appropriate precautions for use
General
In order to improve the traceability of erythropoiesis stimulating agents (ESA), the trade name of the administered ESA must be clearly recorded (or reported) in the patient record.
Blood pressure should be monitored in all patients, particularly during initiation of Aranesp therapy. If blood pressure is difficult to control by taking appropriate measures, hemoglobin can be reduced by decreasing or stopping the administration of Aranesp (see paragraph 4.2). Cases of severe hypertension, including hypertensive crisis, hypertensive encephalopathy, and seizure, have been observed in CRF patients treated with Aranesp.
To ensure effective erythropoiesis, iron stores must be checked in all patients before and during therapy and supplemental iron therapy may be required.
The lack of response to therapy with Aranesp should lead to investigating the causative factors. Deficiencies in iron, folic acid or vitamin B12 reduce the effectiveness of ESAs and must therefore be corrected. Intercurrent infections, inflammatory or traumatic episodes, occult blood loss, haemolysis, severe aluminum poisoning, underlying haematological diseases or bone marrow fibrosis can compromise the erythropoietic response. A reticulocyte count should be considered as part of the assessment. If typical causes of non-response have been excluded and the patient presents with reticulocytopenia, a bone marrow examination should be considered. If the bone marrow is compatible with a diagnosis of PRCA, antibody testing should be performed -erythropoietin.
Pure red cell aplasia caused by neutralizing antibodies to erythropoietin has been reported in association with ESA therapy, including Aranesp. This finding has predominantly been reported in patients with chronic renal failure (CRI) treated by the subcutaneous route. These antibodies have been shown to cross-react with all erythropoietic proteins, and patients with suspected or confirmed presence of neutralizing antibodies to erythropoietin should not be initiated for treatment with Aranesp (see section 4.8).
A paradoxical decrease in hemoglobin and the onset of severe anemia associated with low reticulocyte counts should lead to an immediate interruption of treatment with epoetin and to the execution of the anti-erythropoietin antibody test. Cases have been reported in patients with hepatitis C treated with interferon and ribavirin when epoetins were used concomitantly. Epoetins are not approved for the management of anemia associated with hepatitis C.
Active liver disease was an exclusion criterion in all studies with Aranesp, therefore no data is available in patients with impaired liver function. As the liver is thought to be the major route of elimination for darbepoetin alfa and r-HuEPO, Aranesp should be used with caution in patients with liver disease.
Aranesp should be used with caution in patients with sickle cell anemia.
Misuse of Aranesp by healthy individuals can cause an excessive increase in hematocrit. This can be associated with cardiovascular complications that place the subject in immediate danger of life.
The needle cap of the pre-filled syringe or pre-filled pen contains dry natural rubber (a derivative of latex) which may cause allergic reactions.
Aranesp should be used with caution in patients with epilepsy. Seizures have been reported in patients receiving Aranesp.
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially sodium-free.
Patients with chronic renal insufficiency
In chronic renal failure patients, hemoglobin should be maintained at a level that does not exceed the upper limit of the target hemoglobin concentration recommended in section 4.2. An increased risk of death, serious cardiovascular or cardiovascular events has been observed in clinical trials. cerebrovascular including stroke and thrombosis of the vascular accesses in case of administration of ESA aimed at reaching a hemoglobin value greater than 12 g / dl (7.5 mmol / l).
Caution should be exercised in increasing doses of Aranesp in patients with chronic renal failure as cumulative high doses of epoetin may be associated with an increased risk of mortality, serious cardiovascular and cerebrovascular events. In the case of patients with poor hemoglobin response to epoetins. , alternative causes for the poor response should be considered (see sections 4.2 and 5.1).
Controlled clinical trials have shown no significant benefit attributable to the administration of epoetins when the hemoglobin concentration has been increased beyond the level necessary to control symptoms of anemia and avoid blood transfusions.
Supplemental iron therapy is recommended in all patients with serum ferritin values below 100 mcg / L or transferrin saturation below 20%.
Serum potassium levels should be monitored regularly during Aranesp therapy. Elevations in potassium have been reported in some patients receiving Aranesp, although correlation to treatment has not been established. If elevated or increasing potassium levels are observed, consideration should be given to discontinuing Aranesp administration until this level is corrected.
Cancer patients
Effect on tumor progression
Epoetins are growth factors that primarily stimulate the production of red blood cells. Erythropoietin receptors can be expressed on the surface of various cancer cells. As with all growth factors, there is concern that epoetins may stimulate the growth of tumors. In several controlled clinical trials, epoetins have not been shown to improve overall survival or reduce the risk of tumor progression in patients with anemia associated with malignant neoplasms.
In controlled clinical trials with administration of Aranesp and other ESAs, the following has been shown:
• Reduction of time to tumor progression in patients with advanced head and neck cancer treated with radiotherapy, when ESAs have been administered to achieve a target hemoglobin value greater than 14 g / dl (8 , 7 mmol / l); the use of ESA is not indicated in this patient population.
• Reduction in overall survival and increase in deaths attributed to disease progression at 4 months in patients with metastatic breast cancer treated with chemotherapy, when administered to achieve a target hemoglobin value of 12-14 g / dl (7.5-8.7 mmol / l).
• Increased risk of death in case of posology aimed at achieving a hemoglobin value of 12 g / dl (7.5 mmol / l) in patients with active malignant neoplasms not treated with chemotherapy or radiotherapy. The use of ESA is not indicated in this patient population.
Based on the above, in some clinical conditions blood transfusion should be the preferred treatment for the management of anemia in cancer patients. The decision to administer recombinant erythropoietins should be based on an assessment of the benefit-risk ratio with the involvement of the individual patient and must take into account the specific clinical context. Factors that must be considered in this evaluation must include the type of cancer and its stage, the degree of anemia, the life expectancy, the environment in which the patient is treated and the patient's preferences (see section 5.1).
In patients with solid tumors or lymphoproliferative neoplasms, if the hemoglobin value exceeds 12 g / dl (7.5 mmol / l), the dose adjustment described in section 4.2 must be strictly observed in order to minimize the risk of thromboembolic events. Platelet count and hemoglobin level should be checked at regular intervals.
04.5 Interactions with other medicinal products and other forms of interaction
Clinical results obtained to date do not indicate any interaction of darbepoetin alfa with other substances. However, there is the possibility of an "interaction with substances that bind significantly to red blood cells, such as cyclosporine and tacrolimus. If Aranesp is administered concomitantly with one of these treatments, the blood levels of the latter must be monitored and their dose adjusted according to the increase in hemoglobin.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate and well-controlled studies on the use of Aranesp in pregnant women.
Animal studies did not indicate direct harmful effects on pregnancy, embryonal / fetal development, parturition or postnatal development. No impairment of fertility was observed.
Caution should be used when prescribing Aranesp to pregnant women.
Women who become pregnant while being treated with Aranesp are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Contact details are given in section 6 of the Package Leaflet.
Feeding time
It is not known whether Aranesp is excreted in human milk. A risk to infants cannot be excluded.A decision must be made whether to discontinue breast-feeding or to discontinue / abstain from Aranesp therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
04.7 Effects on ability to drive and use machines
Aranesp has no or negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Summary of the safety profile
The identified adverse reactions associated with the use of Aranesp are hypertension, stroke, thromboembolic events, convulsions, allergic reactions, rash / erythema and pure red cell aplasia (PRCA); see section 4.4.
Injection site pain was considered attributable to treatment in studies where Aranesp was given as a subcutaneous injection. Injection site discomfort was generally mild and transient and predominantly occurred after the first injection.
Table of adverse reactions
The incidence of adverse reactions is presented below by system organ class and by frequency class. Frequencies are defined as: Very common (≥ 1/10); common (≥ 1/100,
Data are presented separately for chronic renal failure patients and cancer patients to reflect the different adverse reaction profiles in these populations.
Patients with chronic renal insufficiency
Data presented from controlled clinical trials included 1,357 patients, 766 treated with Aranesp and 591 patients treated with r-HuEPO. In the Aranesp group, 83% of patients received dialysis therapy and 17% were not on dialysis. Stroke was identified as an adverse reaction in an additional clinical study (TREAT, see section 5.1).
The incidence of adverse reactions in controlled clinical trials and post-marketing use is as follows:
* see section "Description of selected adverse reactions"
Cancer patients
Adverse reactions were determined based on data collected from seven randomized, double-blind, placebo-controlled studies involving a total of 2,112 patients (1,200 Aranesp, 912 placebo). Clinical trials enrolled patients with solid tumors (eg lung, breast, colon and ovarian cancers) and lymphoid malignancies (eg lymphoma, multiple myeloma).
The incidence of adverse reactions in controlled clinical trials and post-marketing use is as follows:
* see section "Description of selected adverse reactions"
Description of selected adverse reactions
Patients with chronic renal insufficiency
In TREAT, stroke was reported as common in CRF patients (see section 5.1).
In isolated cases, pure red cell aplasia (PRCA) with neutralizing antibodies to erythropoietin associated with Aranesp therapy, predominantly in CRF patients treated subcutaneously. If PRCA is diagnosed, Aranesp therapy should be discontinued and patients should not be treated with another recombinant erythropoietic protein (see section 4.4).
Based on clinical trial data, the frequency of all hypersensitivity reactions was defined as very common in CRF patients. There have been reports of serious hypersensitivity reactions associated with the use of darbepoetin alfa including anaphylactic reaction, angioedema, allergic bronchospasm, skin rash and urticaria.
Seizures have been reported in patients receiving darbepoetin alfa (see section 4.4).
Based on clinical trial data, frequency is defined as uncommon in CRF patients.
Cancer patients
During post-marketing use, hypertension has been observed in cancer patients (see section 4.4). Based on clinical trial data, the frequency is defined as common in cancer patients and also common in the groups treated with placebo.
During post-marketing use, hypersensitivity reactions have been observed in cancer patients. Based on clinical trial data, the frequency is defined as very common in cancer patients. Hypersensitivity reactions were very common. also in the placebo groups. There have been reports of severe hypersensitivity reactions associated with the use of darbepoetin alfa including anaphylactic reaction, angioedema, allergic bronchospasm, skin rash and urticaria.
During post-marketing use, seizures have been reported in patients receiving darbepoetin alfa (see section 4.4). Based on clinical trial data, frequency is defined as uncommon in cancer patients. Seizures are were common in the placebo groups.
Pediatric population with chronic renal insufficiency
In all pediatric clinical trials in the IRC, no additional adverse reactions were identified in pediatric patients than previously reported in adult patients (see section 5.1).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicine is important, as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to the national reporting system. Italiana del Farmaco - Website: http // www.agenziafarmaco.gov.it / it / managers).
04.9 Overdose
The maximum amount of Aranesp that can be safely administered in single or multiple doses has not been determined. Aranesp therapy may result in polycythemia if hemoglobin is not carefully monitored and the dose is not adjusted appropriately. Cases of severe hypertension have been observed following overdose with Aranesp (see section 4.4).
In the event of polycythemia, Aranesp should be temporarily suspended (see section 4.2). If clinically indicated, phlebotomy can be performed.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-anemic preparations, other anti-anemic preparations. ATC code: B03XA02.
Mechanism of action
Human erythropoietin, an endogenous glycoprotein hormone, is the main regulator of erythropoiesis through specific interaction with the erythropoietin receptor on erythroid progenitor cells in the bone marrow. Erythropoietin production occurs primarily and is regulated in the kidney in response to changes in tissue oxygenation. Endogenous erythropoietin production is reduced in patients with chronic renal failure and erythropoietin deficiency is the primary cause of anemia in these patients. In cancer patients receiving chemotherapy, the etiology of anemia is multifactorial. In these patients, erythropoietin deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin are both contributing factors significantly to anemia.
Pharmacodynamic effects
Darbepoetin alfa stimulates erythropoiesis with the same mechanism as the endogenous hormone. Darbepoetin alfa has five carbohydrate chains linked to the N-terminus, while the endogenous hormone and recombinant human erythropoietins (r-HuEPO) have three. The additional carbohydrate residues are not distinguishable at the molecular level from those present on the endogenous hormone. Due to the higher carbohydrate content, darbepoetin alfa has a longer terminal half-life than r-HuEPO and therefore greater activity. in vivo. Despite these molecular modifications, darbepoetin alfa maintains a very high specificity for the erythropoietin receptor.
Clinical efficacy and safety
Patients with chronic renal insufficiency
In two clinical studies, CRF patients had a greater risk of death and serious cardiovascular events when ESAs were administered to achieve higher hemoglobin levels than lower hemoglobin levels (13.5 g / dl (8 , 4 mmol / l) versus 11.3 g / dl (7.1 mmol / l); 14 g / dl (8.7 mmol / l) versus 10 g / dl (6.2 mmol / l)).
In a randomized, double-blind, correction study (n = 358) comparing once-every-two-week and once-monthly dosing schedules in CRF patients not on dialysis, darbepoetin alfa dosing once daily month resulted in the correction of anemia not less than once every two weeks. The median time (quartile 1, quartile 3) to achieve hemoglobin correction (≥ 10.0 g / dL and increase of ≥ 1.0 g / dL from baseline) was 5 weeks for both once-every-two-week (3.7-weeks) and once-monthly (3.9-weeks) dosing. During the evaluation period (weeks 29 - 33), the mean weekly equivalent dose (95% CI) was 0.20 (0.17 - 0.24) mcg / kg in the once every two week arm and 0.27 (0.23 - 0.32) mcg / kg in the arm once a month.
In a randomized, double-blind, placebo-controlled study (TREAT) of 4,038 CRF patients not on dialysis with type 2 diabetes and with hemoglobin levels ≤ 11 g / dL, patients received either darbepoetin alfa treatment to achieve target hemoglobin levels of 13 g / dl or placebo (with recovery treatment with darbepoetin alfa at hemoglobin levels below 9 g / dl). The study did not meet the primary objective of demonstrating a reduction in the risk of all cause mortality or cardiovascular morbidity (darbepoetin alfa versus placebo; HR 1.05, 95% CI (0.94-1.17)), o All-cause mortality o End-stage renal disease (ESRD) (darbepoetin alfa versus placebo; HR 1.06, 95% CI (0.95-1.19)). An "individual component analysis of the composite end point shown the following HR (95% CI): death 1.05 (0.92-1.21), congestive heart failure (CHF) 0.89 (0.74-1.08), myocardial infarction (MI) 0.96 (0.75-1.23), stroke 1.92 (1.38-2.68), hospitalization for myocardial ischaemia 0.84 (0.55-1.27), ESRD 1.02 ( 0.87-1.18).
Pooled post-hoc analyzes of clinical trials with ESA were performed in patients with chronic renal failure (on dialysis, not on dialysis, diabetic, non-diabetic). There was a trend towards increased estimated risk of all cause mortality, cardiovascular and cerebrovascular events associated with higher cumulative doses of ESA, regardless of diabetes or dialysis status (see sections 4.2 and 4.4).
Pediatric population
In a randomized clinical trial, 114 pediatric patients aged 2 to 18 years with chronic kidney disease, on or off dialysis, who were anemic (hemoglobin
In a clinical study of 124 pediatric chronic kidney disease patients on dialysis or nondialysis aged 1 to 18 years, patients who were stable on epoetin alfa were randomized to receive darbepoetin alfa administered once weekly (subcutaneously). or intravenous) using a dose conversion rate of 238: 1, or continue with epoetin alfa therapy at the same dose, schedule and route of administration. The primary efficacy endpoint [change in hemoglobin levels between baseline and the assessment period (week 21-28)] was similar between the two groups. The mean hemoglobin levels for rHuEPO and darbepoetin alfa at baseline were 11, 1 (SD 0.7) g / dL and 11.3 (SD 0.6) g / dL, respectively. The mean hemoglobin levels at week 28 for rHuEPO and darbepoetin alfa were 11.1 (SD 1.4) g / dl and 11.1 (SD 1.1) g / dl, respectively.
In a European observational registry study enrolling 319 pediatric patients with chronic kidney disease (13 (4.1%) patients aged
In these studies, no significant differences were identified between the safety profile for pediatric patients and that reported previously for adult patients (see section 4.8).
Patients with cancer and undergoing chemotherapy
In a prospective, randomized, double-blind, placebo-controlled study of 314 lung cancer patients receiving platinum-based chemotherapy, there was a significant reduction in the need for transfusions (p
Clinical studies have shown that darbepoetin alfa has similar efficacy when given as a single injection once every 3 weeks, once every two weeks or weekly without the need to increase the total dose.
The tolerability and efficacy of administering Aranesp therapy once every 3 weeks in reducing the need for transfusions in patients undergoing chemotherapy was evaluated in a randomized, double-blind, international study. This study was conducted in 705 patients. Anemic with non-myeloid malignancies and undergoing several courses of chemotherapy. Patients were randomized to receive Aranesp at doses of 500 mcg once every 3 weeks or at doses of 2.25 mcg / kg once weekly. In both groups, the dose was reduced by 40% from the previous dose (e.g. for the first dose reduction, this was reduced to 300 mcg in the once every 3 week group, and to 1.35 mcg / kg in the once weekly group ), in the case of an increase in hemoglobin of more than 1 g / dl in 14 days. In the once every 3 week group, 72% of patients required a dose reduction. In the once weekly group, 75% of patients required a dose reduction. This study demonstrates that dosing of 500 micrograms every 3 weeks is comparable to dosing once a week in terms of the incidence of patients requiring at least one transfusion between week 5 and the end of treatment.
In a prospective, randomized, double-blind, placebo-controlled study of 344 anemic patients with lymphoproliferative neoplasms and undergoing chemotherapy, a significant reduction in the need for transfusions and an improvement in hemoglobin response was found (p
Erythropoietin is a growth factor that primarily stimulates the production of red blood cells. Erythropoietin receptors can be expressed on the surface of various cancer cells.
Survival and tumor progression were assessed in five large controlled clinical trials which included a total of 2,833 patients; four of which were placebo-controlled and double-blind studies and one was open-label. Two of these studies enrolled patients who were being treated with chemotherapy. The target hemoglobin concentration was greater than 13 g / dL in two studies; in the remaining three studies it was 12-14 g / dL. In the open-label study, no differences in overall survival were observed between patients treated with recombinant human erythropoietins and control patients. In the four placebo-controlled studies, the hazard ratios for overall survival ranged from 1.25 to 2.47 in favor of the control group. These studies showed, compared to controls, a constant and unexplained statistically significant increase in mortality in patients with anemia associated with various types of common tumors and receiving recombinant human erythropoietin. The overall survival outcome in these studies could not be satisfactorily explained based on the difference in the incidence of thrombosis and associated complications between patients treated with recombinant human erythropoietin and those in the control group.
A systematic analysis of 57 clinical studies including more than 9,000 cancer patients was also conducted. The meta-analysis of the overall survival data showed a point estimate of the Hazard Ratio of 1.08 in favor of controls (95% CI : 0.99-1.18; 42 studies and 8,167 patients).
An increased relative risk of thromboembolic events (RR 1.67, 95% CI: 1.35-2.06, 35 studies and 6,769 patients) was observed in patients treated with recombinant human erythropoietin. There is therefore consistent evidence suggesting that there may be significant harm in cancer patients treated with recombinant human erythropoietin. It is unclear to what extent these outcomes are applicable to recombinant human erythropoietin administration to cancer patients undergoing chemotherapy to achieve hemoglobin concentrations below 13 g / dl as few patients with these characteristics were included in the data analyzed. .
An analysis of individual patient data was also performed on over 13,900 cancer patients (chemo, radio, chemoradio or no therapy) who participated in 53 controlled clinical trials using different epoetins. Meta-analysis of the overall survival data generated a punctual Hazard Ratio estimate of 1.06 in favor of controls (95% CI: 1.00-1.12; 53 studies and 13,933 patients) and a Hazard Ratio of 1.04 for cancer patients receiving chemotherapy (95% CI: 0.97-1.11; 38 studies and 10,441 patients). The meta-analysis also consistently indicates a significantly increased relative risk of thromboembolic events in cancer patients receiving recombinant human erythropoietin (see section 4.4).
05.2 Pharmacokinetic properties
Given the higher carbohydrate content, the circulating level of darbepoetin alfa remains above the minimum erythropoiesis stimulating concentration for longer than the molar equivalent dose of r-HuEPO, allowing less frequent administration of darbepoetin alfa to achieve the same biological response.
Patients with chronic renal insufficiency
The pharmacokinetics of darbepoetin alfa have been studied clinically in chronic renal failure patients following intravenous and subcutaneous administration. The terminal half-life of darbepoetin alfa is 21 hours (SD 7.5) when administered intravenously. The clearance of darbepoetin alfa is 1.9 ml / hour / kg (SD 0.56) and the volume of distribution at steady state (Vss) is approximately equal to the plasma volume (50 ml / kg). Bioavailability is 37% for subcutaneous administration. After monthly subcutaneous administration of darbepoetin alfa, at doses of 0.6 to 2.1 μg / kg, l "terminal half-life was 73 hours (SD 24). The subcutaneous absorption kinetics result in a longer terminal half-life of darbepoetin alfa when administered subcutaneously than when administered intravenously. In clinical studies, minimal accumulation was observed with both routes of administration. Preclinical studies have shown that renal clearance is minimal (maximum 2% of total clearance), and does not affect the serum half-life.
Data from 809 patients treated with Aranesp in European clinical trials were analyzed to define the dose required to maintain hemoglobin; no difference was observed between the mean weekly dose administered intravenously or subcutaneously.
The pharmacokinetics of darbepoetin alfa in pediatric (2-16 years) patients with CRF on both dialysis and non-dialysis were evaluated for sampling periods up to 2 weeks (336 hours) after one or two subcutaneous or intravenous doses. Using the same sampling duration, the observed pharmacokinetic data and the population pharmacokinetic model demonstrated that the pharmacokinetic profile of darbepoetin alfa was similar in pediatric and adult CRF patients.
In a phase I pharmacokinetic study, after intravenous administration, a difference of approximately 25% was observed between pediatric and adult patients for the area under the curve from 0 to infinity (AUC [0-∞]); however this difference was less than twice the AUC [0-∞] range observed in pediatric patients. The AUC [0-∞] after subcutaneous administration was similar in adult and pediatric patients with CRF. The half-life was also similar in adult patients. and pediatric with CRF after both intravenous and subcutaneous administration.
Patients with cancer and undergoing chemotherapy
After subcutaneous administration of 2.25 μg / kg to adult cancer patients, a mean peak concentration of 10.6 ng / ml (SD 5.9) of darbepoetin alfa was achieved after a mean time of 91 hours (SD 19.7). These parameters were consistent with linear dose-related pharmacokinetics over a wide dose range (0.5 to 8 mcg / kg weekly and 3 to 9 mcg / kg every two weeks). Pharmacokinetic parameters did not change after multiple dosing for 12 weeks (weekly or every 2 weeks). There was an expected moderate increase (
05.3 Preclinical safety data
In all studies in rats and dogs darbepoetin alfa resulted in an increase in hemoglobin, hematocrit, red blood cell count and reticulocyte, which corresponded to the expected pharmacological effects. Adverse events occurring at very high doses were all considered attributable to an exaggerated pharmacological effect (decreased tissue perfusion due to "increased blood viscosity). These events include myelofibrosis, splenic hypertrophy and also an elongation of the ECG-QRS complex at" electrocardiogram in dogs, but no arrhythmia or effect on QT interval was observed.
Darbepoetin alfa did not show any genotoxic potential nor did it have any effect on proliferation in vitro or in vivo of non-haematological cells. In chronic toxicity studies no unexpected oncogenic or mitogenic responses were observed in any type of tissue. The carcinogenic potential of darbepoetin alfa has not been evaluated in long-term animal studies.
In studies in rats and rabbits, no clinically relevant evidence of adverse effects on pregnancy, embryonal / fetal development, parturition or postnatal development was observed. Transplacental passage was minimal. No impairment of fertility was observed.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Monobasic sodium phosphate
Dibasic sodium phosphate
Sodium chloride
Polysorbate 80
Water for injections
06.2 Incompatibility
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products or administered by infusion with other medicinal products.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store in a refrigerator (2 ° C - 8 ° C).
Do not freeze.
Keep the container in the outer carton to protect the medicine from light.
For outpatient use, Aranesp can be kept at room temperature (up to 25 ° C) for one time only and for up to seven days. Once it has been removed from the refrigerator and has reached room temperature (up to 25 ° C) it must be used within 7 days or disposed of.
06.5 Nature of the immediate packaging and contents of the package
Aranesp 10 micrograms solution for injection in pre-filled syringe
0.4 ml solution for injection (25 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 15 micrograms solution for injection in pre-filled syringe
0.375 ml solution for injection (40 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 20 micrograms solution for injection in pre-filled syringe
0.5 ml solution for injection (40 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 30 micrograms solution for injection in pre-filled syringe
0.3 ml solution for injection (100 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 40 micrograms solution for injection in pre-filled syringe
0.4 ml solution for injection (100 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 50 mcg solution for injection in pre-filled syringe
0.5 ml solution for injection (100 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 60 micrograms solution for injection in pre-filled syringe
0.3 ml solution for injection (200 μg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 80 micrograms solution for injection in pre-filled syringe
0.4 ml solution for injection (200 μg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 100 micrograms solution for injection in pre-filled syringe
0.5 ml solution for injection (200 μg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 130 micrograms solution for injection in pre-filled syringe
0.65 ml solution for injection (200 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 150 micrograms solution for injection in pre-filled syringe
0.3 ml solution for injection (500 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 300 micrograms solution for injection in pre-filled syringe
0.6 ml solution for injection (500 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
Aranesp 500 micrograms solution for injection in pre-filled syringe
1 ml solution for injection (500 mcg / ml darbepoetin alfa) in a type 1 glass pre-filled syringe with stainless steel 27 gauge needle. Pack size of 1 or 4 pre-filled syringes.
The syringes can be packaged in blister packs (packs of 1 and 4 syringes), with or without an automatic needle guard, or without blisters (packs of 1 syringe only).
The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex). See section 4.4.
Aranesp 10 micrograms solution for injection in pre-filled pen
0.4 ml solution for injection (25 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 15 micrograms solution for injection in pre-filled pen
0.375 ml solution for injection (40 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 20 micrograms solution for injection in pre-filled pen
0.5 ml solution for injection (40 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 30 micrograms solution for injection in pre-filled pen
0.3 ml solution for injection (100 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 40 micrograms solution for injection in pre-filled pen
0.4 ml solution for injection (100 μg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 50 mcg solution for injection in pre-filled pen
0.5 ml solution for injection (100 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 60 micrograms solution for injection in pre-filled pen
0.3 ml solution for injection (200 μg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 80 micrograms solution for injection in pre-filled pen
0.4 ml solution for injection (200 μg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 100 mcg solution for injection in pre-filled pen
0.5 ml solution for injection (200 μg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 130 mcg solution for injection in pre-filled pen
0.65 mL solution for injection (200 mcg / mL darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 150 micrograms solution for injection in pre-filled pen
0.3 ml solution for injection (500 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 300 mcg solution for injection in pre-filled pen
0.6 ml solution for injection (500 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack of 1 or 4 pre-filled pens.
Aranesp 500 mcg solution for injection in pre-filled pen
1 ml solution for injection (500 mcg / ml darbepoetin alfa) in a pre-filled pen with type 1 glass syringe and stainless steel 27 gauge needle. Pack size of 1 or 4 Aranesp pre-filled pens.
The needle cap of the pre-filled pen contains dry natural rubber (a derivative of latex). See section 4.4.
Aranesp 25 mcg solution for injection in vial
1 ml solution for injection (25 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Aranesp 40 mcg solution for injection in vial
1 ml solution for injection (40 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Aranesp 60 mcg solution for injection in vial
1 ml solution for injection (60 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Aranesp 100 mcg solution for injection in vial
1 ml solution for injection (100 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Aranesp 200 mcg solution for injection in vial
1 ml solution for injection (200 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Aranesp 300 mcg solution for injection in vial
1 ml solution for injection (300 mcg / ml darbepoetin alfa) in a type I glass vial with fluoropolymer coated rubber stoppers and an aluminum seal with dust flip-off. Pack size of 1 or 4 vials.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
The box contains a package insert with complete instructions for use and handling.
The Aranesp pre-filled pen (SureClick) delivers the full dose for each presentation.
Aranesp is a sterile product but does not contain preservatives. Do not administer more than one dose. Any amount of drug remaining should be discarded.
Before administering the Aranesp solution the absence of visible particles should be checked. Only colorless, clear or slightly opalescent solutions should be injected. Do not shake. Allow the container to reach room temperature before injecting the solution.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Amgen Europe B.V.
Minervum 7061
NL-4817 ZK Breda
Netherlands
08.0 MARKETING AUTHORIZATION NUMBER
Aranesp 10 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/001 1 piece with blister
EU / 1/01/185/002 4 pieces with blister
EU / 1/01/185/033 1 piece without blister
EU / 1/01/185/074 1 piece with blister with needle protection
EU / 1/01/185/075 4 pieces with blister with needle protection
Aranesp 15 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/003 1 piece with blister
EU / 1/01/185/004 4 pieces with blister
EU / 1/01/185/034 1 piece without blister
EU / 1/01/185/076 1 piece with blister with needle protection
EU / 1/01/185/077 4 pieces with blister with needle protection
Aranesp 20 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/005 1 piece with blister
EU / 1/01/185/006 4 pieces with blister
EU / 1/01/185/035 1 piece without blister
EU / 1/01/185/078 1 piece with blister with needle protection
EU / 1/01/185/079 4 pieces with blister with needle protection
Aranesp 30 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/007 1 piece with blister
EU / 1/01/185/008 4 pieces with blister
EU / 1/01/185/036 1 piece without blister
EU / 1/01/185/080 1 piece with blister with needle protection
EU / 1/01/185/081 4 pieces with blister with needle protection
Aranesp 40 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/009 1 piece with blister
EU / 1/01/185/010 4 pieces with blister
EU / 1/01/185/037 1 piece without blister
EU / 1/01/185/082 1 piece with blister with needle protection
EU / 1/01/185/083 4 pieces with blister with needle protection
Aranesp 50 mcg solution for injection in pre-filled syringe
EU / 1/01/185/011 1 piece with blister
EU / 1/01/185/012 4 pieces with blister
EU / 1/01/185/038 1 piece without blister
EU / 1/01/185/084 1 piece with blister with needle protection
EU / 1/01/185/085 4 pieces with blister with needle protection
Aranesp 60 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/013 1 piece with blister
EU / 1/01/185/014 4 pieces with blister
EU / 1/01/185/039 1 piece without blister
EU / 1/01/185/086 1 piece with blister with needle protection
EU / 1/01/185/087 4 pieces with blister with needle protection
Aranesp 80 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/015 1 piece with blister
EU / 1/01/185/016 4 pieces with blister
EU / 1/01/185/040 1 piece without blister
EU / 1/01/185/088 1 piece with blister with needle protection
EU / 1/01/185/089 4 pieces with blister with needle protection
Aranesp 100 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/017 1 piece with blister
EU / 1/01/185/018 4 pieces with blister
EU / 1/01/185/041 1 piece without blister
EU / 1/01/185/090 1 piece with blister with needle protection
EU / 1/01/185/091 4 pieces with blister with needle protection
Aranesp 130 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/069 1 piece with blister
EU / 1/01/185/070 4 pieces with blister
EU / 1/01/185/071 1 piece without blister
EU / 1/01/185/092 1 piece with blister with needle protection
EU / 1/01/185/093 4 pieces with blister with needle protection
Aranesp 150 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/019 1 piece with blister
EU / 1/01/185/020 4 pieces with blister
EU / 1/01/185/042 1 piece without blister
EU / 1/01/185/094 1 piece with blister with needle protection
EU / 1/01/185/095 4 pieces with blister with needle protection
Aranesp 300 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/021 1 piece with blister
EU / 1/01/185/022 4 pieces with blister
EU / 1/01/185/043 1 piece without blister
EU / 1/01/185/096 1 piece with blister with needle protection
EU / 1/01/185/097 4 pieces with blister with needle protection
Aranesp 500 micrograms solution for injection in pre-filled syringe
EU / 1/01/185/031 1 piece with blister
EU / 1/01/185/032 4 pieces with blister
EU / 1/01/185/044 1 piece without blister
EU / 1/01/185/098 1 piece with blister with needle protection
EU / 1/01/185/099 4 pieces with blister with needle protection
Aranesp 10 micrograms solution for injection in pre-filled pen
EU / 1/01/185/045 1 piece
EU / 1/01/185/057 4 pieces
Aranesp 15 micrograms solution for injection in pre-filled pen
EU / 1/01/185/046 1 piece
EU / 1/01/185/058 4 pieces
Aranesp 20 micrograms solution for injection in pre-filled pen
EU / 1/01/185/047 1 piece
EU / 1/01/185/059 4 pieces
Aranesp 30 micrograms solution for injection in pre-filled pen
EU / 1/01/185/048 1 piece
EU / 1/01/185/060 4 pieces
Aranesp 40 micrograms solution for injection in pre-filled pen
EU / 1/01/185/049 1 piece
EU / 1/01/185/061 4 pieces
Aranesp 50 mcg solution for injection in pre-filled pen
EU / 1/01/185/050 1 piece
EU / 1/01/185/062 4 pieces
Aranesp 60 micrograms solution for injection in pre-filled pen
EU / 1/01/185/051 1 piece
EU / 1/01/185/063 4 pieces
Aranesp 80 micrograms solution for injection in pre-filled pen
EU / 1/01/185/052 1 piece
EU / 1/01/185/064 4 pieces
Aranesp 100 mcg solution for injection in pre-filled pen
EU / 1/01/185/053 1 piece
EU / 1/01/185/065 4 pieces
Aranesp 130 mcg solution for injection in pre-filled pen
EU / 1/01/185/072 1 piece
EU / 1/01/185/073 4 pieces
Aranesp 150 micrograms solution for injection in pre-filled pen
EU / 1/01/185/054 1 piece
EU / 1/01/185/066 4 pieces
Aranesp 300 mcg solution for injection in pre-filled pen
EU / 1/01/185/055 1 piece
EU / 1/01/185/067 4 pieces
Aranesp 500 mcg solution for injection in pre-filled pen
EU / 1/01/185/056 1 piece
EU / 1/01/185/068 4 pieces
Aranesp 25 mcg solution for injection in vial
EU / 1/01/185/100 1 piece
EU / 1/01/185/101 4 pieces
Aranesp 40 mcg solution for injection in vial
EU / 1/01/185/102 1 piece
EU / 1/01/185/103 4 pieces
Aranesp 60 mcg solution for injection in vial
EU / 1/01/185/104 1 piece
EU / 1/01/185/105 4 pieces
Aranesp 100 mcg solution for injection in vial
EU / 1/01/185/106 1 piece
EU / 1/01/185/107 4 pieces
Aranesp 200 mcg solution for injection in vial
EU / 1/01/185/108 1 piece
EU / 1/01/185/109 4 pieces
Aranesp 300 mcg solution for injection in vial
EU / 1/01/185/110 1 piece
EU / 1/01/185/111 4 pieces
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09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 8 June 2001
Date of most recent renewal: 19 May 2006
10.0 DATE OF REVISION OF THE TEXT
September 2015
