PATIENT INFORMATION LEAFLET

Accofil 30 MU/0.5 ml (0.6 mg/ml) injectable solution and for infusion in pre-filled syringe

filgrastim

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

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

What is Accofil

Accofil contains the active ingredient filgrastim. Filgrastim is a protein produced in the Escherichia coli bacteria using recombinant DNA technology. It belongs to a group of proteins called cytokines and is very similar to a natural protein (granulocytes and colony-stimulating factor [G-CSF]) produced by the body. Filgrastim stimulates the bone marrow (the tissue where new blood cells are produced) to produce more white blood cells that help fight infections.

What is Accofil used for

Your doctor has prescribed Accofil to help your body produce more white blood cells. Your doctor will tell you why you are being treated with Accofil. Accofil is useful in several different situations, including:

• chemotherapy
• bone marrow transplant
• severe chronic neutropenia (low number of a type of white blood cell)
• neutropenia (low number of a type of white blood cell) in patients with HIV infection
• mobilization of peripheral blood stem cells (to stimulate stem cells to enter the bloodstream to be collected and used in bone marrow transplant).

Do not use Accofil

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Accofil:

Tell your doctor if you have:

• sickle cell anemia, Accofil may cause sickle cell crises.
• osteoporosis (bone disease)

Inform your doctor immediately during treatment with Accofil if:

• You have upper left abdominal pain, left side pain under the ribs, or left shoulder tip pain (these may be symptoms of spleen enlargement (splenomegaly) or possibly spleen rupture).
• Unusual bleeding or bruises that may be symptoms of a reduced number of platelets in the blood (thrombocytopenia) with reduced blood clotting ability.
• You experience sudden signs of allergy such as skin rashes, itching, or urticaria on the skin, facial swelling, lip, tongue, or other body part swelling, shortness of breath, wheezing (a whistling sound when breathing) or breathing difficulties, as they may be symptoms of a severe allergic reaction.
• You experience swelling in the face or ankles, blood in the urine, or dark-colored urine, or note that you urinate less than usual (glomerulonephritis).

The needle cover of the pre-filled syringe contains natural rubber (a latex derivative) that may cause an allergic reaction.

In rare cases, aortic inflammation (the large blood vessel that carries blood from the heart to the rest of the body) has been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general discomfort, back pain, and increased inflammatory markers. Inform your doctor if you experience these symptoms.

Loss of response to filgrastim

If you experience a loss of response or failure to maintain response with filgrastim treatment, your doctor will investigate the reasons, including whether you have developed antibodies that neutralize filgrastim activity.

Your doctor may want to monitor you closely, see section 4 of the leaflet.

If you are a patient with chronic severe neutropenia, you may have a risk of developing blood cancer (leukemia, myelodysplastic syndrome (MDS)). You should discuss the risks of developing blood cancer with your doctor and what tests should be done. If you develop or are likely to develop blood cancer, do not use Accofil unless your doctor tells you to. If you are a stem cell donor, you must be between 16 and 60 years old.

Be especially careful with other leukocyte-stimulating products

Accofil is one of a group of products that stimulate white blood cell production. Your healthcare professional should always record the exact product you are using.

Other medicines and Accofil

You should not receive Accofil within 24 hours before and 24 hours after receiving chemotherapy.

Please inform your doctor or pharmacist if you are taking or have recently taken other medicines, including those purchased without a prescription.

Pregnancy and breastfeeding

Accofil has not been tested in pregnant women.

It is essential to tell your doctor if:

• You are pregnant or breastfeeding;
• You think you may be pregnant; or you intend to become pregnant.

It is unknown whether filgrastim passes into breast milk. Therefore, your doctor may decide that you should not use this medicine if you are breastfeeding.

Driving and operating machines

The influence of Accofil on driving or operating machines is small. This medicine may cause dizziness. It is recommended to wait and see how you feel after taking Accofil and before driving or operating machines.

Accofil contains sorbitol and sodium

This medicine contains sorbitol. If your doctor has told you that you have an intolerance to certain sugars (fructose), consult with them before taking this medicine.

This medicine also contains less than 1 mmol of sodium (0.035 mg) per dose, that is, it is essentially "sodium-free".

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

The amount of Accofil you need will depend on the disease for which you are taking Accofil and your body weight.

Dose

Accofil and neutropenia (low number of a type of white blood cells) associated with chemotherapy

The usual dose is 0.5 million units (5 micrograms) per kilogram of body weight per day. For example, if you weigh 60 kilograms, your daily dose will be 30 million units (300 micrograms). The treatment with Accofil usually lasts about 14 days. However, in some types of disease, a longer treatment may be necessary, lasting up to approximately one month.

Accofil and bone marrow transplant

The usual initial dose is 1 million units (10 micrograms) per kilogram of body weight per day administered by infusion. For example, if you weigh 60 kg, your daily dose will be 60 million units (600 micrograms). You will usually receive your first dose of Accofil at least 24 hours after chemotherapy and at least 24 hours after receiving your bone marrow transplant. Your doctor will then examine your blood to see how the treatment is working and how long it will last.

Accofil chronic and severe neutropenia (low number of a type of white blood cells)

The usual initial dose is 0.5 million units (5 micrograms) and 1.2 million units (12 micrograms) per kilogram of body weight per day in a single dose or divided dose. Your doctor will then examine your blood to see how well your Accofil treatment is working and to find the most suitable dose for you. Long-term treatment with Accofil is required for the reduction of neutropenia.

Accofil and neutropenia (low number of a type of white blood cells) in patients with HIV infection

The usual initial dose is 0.1 million units (1 microgram) and 0.4 million units (4 micrograms) per kilogram of body weight per day. Your doctor may examine your blood regularly to see if the Accofil treatment is working. Once your white blood cell count has returned to normal, it may be possible to reduce the frequency of the dose to less than once a day. Long-term treatment with Accofil may be necessary to maintain a normal number of white blood cells in the blood.

Accofil and peripheral blood stem cell transplant (stem cells collected from the blood to be used in bone marrow transplant)

If you are donating stem cells for yourself, the usual dose is 0.5 million units (5 micrograms) to 1 million units (10 micrograms) per kilogram of body weight per day. The Accofil treatment will last up to 2 weeks. Your doctor will monitor your blood to determine the best time to collect the stem cells.

If you are donating stem cells for another person, the usual dose is 1 million units (10 micrograms) per kilogram of body weight per day. The Accofil treatment will last 4 to 5 days. Your doctor will perform blood tests to determine the best time to collect the stem cells.

Administration form

This medication is administered by injection, either by intravenous infusion (IV) or by subcutaneous injection (SC) in the tissue under the skin.

If you are receiving this medication by subcutaneous injection, your doctor may suggest that you learn how to administer the injections. Your doctor or nurse will give you instructions on how to do this (see information below for instructions on injecting Accofil). Do not attempt to self-inject without these instructions. Part of the information you need is given at the end of this leaflet, but the proper treatment of your disease requires close and constant collaboration with your doctor.

Information for self-injection

This section contains information on how to administer Accofil to yourself. It is essential that you do not attempt to administer an injection without having received the necessary training from your doctor or nurse. If you are unsure of how to inject or have any doubts, consult your doctor or nurse.

How do I inject Accofil?

You should administer the injection in the tissue just under the skin. This is known as subcutaneous injection. The injection should be administered approximately at the same time every day.

Equipment needed

To administer a subcutaneous injection, you will need:

What should I do before administering a subcutaneous injection of Accofil?

Ensure that the needle cover remains on the syringe until just before you are ready to inject.

1. Take the preloaded Accofil syringe out of the refrigerator.
2. Check the expiration date indicated on the syringe (CAD). Do not use it if the date is beyond the last day of the month shown or if it has been kept out of the refrigerator for more than 15 days or has otherwise expired.
3. Check the appearance of Accofil. It should be a clear and colorless liquid. If there are particles inside, do not use it.
4. To make the injection more comfortable, let the preloaded syringe stand at room temperature for 30 minutes or hold the preloaded syringe gently in your hands for a few minutes. Do not heat Accofil in any other way (for example, do not heat it in a microwave or in hot water)

1. Wash your hands carefully.
2. Find a comfortable and well-lit place and place everything you need within reach (the preloaded Accofil syringe, and the alcohol-impregnated gauze).

How should I prepare the Accofil injection?

Before injecting Accofil, you should:

1. Take the syringe and remove the needle cover gently without tilting it. Separate it as indicated in figures 1 and 2. Do not touch the needle or push the plunger.

1. You may notice a small air bubble in the preloaded syringe. It is not necessary to remove the air bubble before the injection. The injection of the solution with the air bubble is harmless.
2. The syringe may contain more liquid than you need. Use the syringe scale as indicated below to adjust the correct dose of Accofil prescribed by your doctor. Expel the unnecessary liquid by pushing the plunger until the number (ml) on the syringe corresponds to the prescribed dose.
3. Check again that the Accofil dose is correct.
4. You can now use the preloaded syringe.

Where should I put the injection?

The most suitable places for the injection are:

If someone else is administering the injection, you can also use the back of your arms (see image 4).

To avoid the risk of pain at a specific point, it is best to change the injection site every day.

How do I inject?

1. Disinfect the injection site using alcohol-impregnated gauze and pinch the skin between your thumb and index finger, without squeezing (see image 5).

Preloaded syringe without safety needle cover

1. Insert the needle completely into the skin as indicated by your nurse or doctor (see image 6).
2. Draw back on the plunger to check that you have not hit a blood vessel. If you see blood in the syringe, remove the needle and reinsert it in another place.
3. Keeping the skin pinched, slowly push the plunger until you have administered the entire dose, until the plunger cannot move any further. Do not stop pressing the plunger!
4. Only administer the prescribed dose by your doctor.
5. After injecting the liquid, remove the needle while maintaining the pressure on the plunger, and then release the skin.
6. Place the syringe in the special container for disposal. Each syringe is for a single injection.

Preloaded syringe with safety needle cover

h. Insert the needle completely into the skin as indicated by your nurse or doctor (see image 7).

i. Draw back on the plunger to check that you have not hit a blood vessel. If you see blood in the syringe, remove the needle and reinsert it in another place.

j. Administer only the dose prescribed by your doctor following the instructions below.

k. Keeping the skin pinched, slowly push the plunger and hold the syringe at the same angle while maintaining the pressure on the plunger, and then release the skin. The safety needle cover will automatically activate, and you will hear an audible "click" to confirm that it has been activated (see image 8). The needle cover will not activate unless the entire dose has been administered.

Remember

If you have any doubts, ask for help and advice from your doctor or nurse.

How to dispose of used syringes

If you use more Accofil than you should

If you use more Accofil than you should, consult your doctor or pharmacist as soon as possible.

If you forget to use Accofil

Do not administer a double dose to compensate for the missed doses. Contact your doctor to discuss when you should inject the next dose.

If you interrupt Accofil treatment

Your doctor will indicate when you should stop Accofil treatment. It is very common to have multiple cycles of Accofil treatment.

If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

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

Inform your doctor immediately during treatment:

A very common side effect of Accofil use is muscle or bone pain (musculoskeletal pain), which can be relieved by taking conventional analgesics. In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease (GVHD) may occur: this is a reaction of the donor cells against the recipient; among the signs and symptoms are skin rash on the palms of the hands and soles of the feet and ulcers and sores in the mouth, intestine, liver, skin, or eyes, lungs, vagina, and joints. In healthy stem cell donors, a frequent observation is an increase in white blood cells (leukocytosis) and a decrease in platelets that reduces the blood's ability to clot (thrombocytopenia); your doctor will monitor these reactions.

Very common side effects (may affect more than 1 in 10 people using Accofil):

Common side effects(may affect up to 1 in 10 people using Accofil):

Rare side effects(may affect up to 1 in 10,000 patients using Accofil):

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a side effect that does not appear in this leaflet.

Reporting side effects

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

Keep out of sight and reach of children.

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

Store in refrigerator (between 2 °C-8 °C). Do not freeze.

The syringe can be removed from the refrigerator and left at room temperature (but not above 25ºC) for a single period of up to a maximum of 15 days and never beyond the expiration date on the label. After this period, the medication should not be refrigerated again and should be discarded.

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

Do not use Accofil if you observe turbidity or discoloration or if there are particles in it.

Do not place the cap on used needles, as you may accidentally prick yourself. Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of medications you no longer need. This will help protect the environment.

Composition of Accofil

Aspect of the product and content of the packaging

Accofil is a transparent and colourless solution for injection or infusion in a pre-filled syringe marked with 1/40 printed marks of 0.1 ml to 1 ml on the syringe barrel with a needle for injection. Each pre-filled syringe contains 0.5 ml of solution.

Accofil is available in packaging of 1, 3, 5, 7 and 10 pre-filled syringes, with or without a safety guard for the prefixed needle and alcohol-impregnated gauzes.

Only some sizes of packaging may be commercially marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6th floor,

08039 Barcelona,

Spain

Responsible for manufacturing

Accord Healthcare Limited

Sage House, 319 Pinner Road,

North Harrow,

Middlesex HA1 4HF,

United Kingdom

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

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

---------------------------------------------------------------------------------------------------------------

The following information is intended only for healthcare professionals:

Accofil does not contain preservatives. Due to a possible risk of microbial contamination, the pre-filled syringes of Accofil are for single use.

Accidental exposure to freezing temperatures up to a maximum of 24 hours does not affect the stability of Accofil. If exposure exceeds 24 hours or if it is frozen more than once, DO NOT use Accofil.

To improve the traceability of granulocyte colony-stimulating factors, the product name (Accofil) and the batch number of the product administered must be clearly recorded in the patient's medical history.

Accofil should not be diluted with sodium chloride. This medicine should not be mixed with other medicines except for those mentioned below. The dilution of filgrastim may be adsorbed by glass and plastic materials except if it is diluted as mentioned below.

If necessary, Accofil may be diluted in 5% glucose. Dilution to a final concentration of less than 0.2 MU (2 g) per ml is not recommended at any time.

The solution must be visually inspected before use. Only transparent solutions without particles should be used.

For patients treated with filgrastim diluted to concentrations below 1.5 MU (15 g) per ml, human serum albumin (HSA) should be added to a final concentration of 2 mg/ml. Example: in a final injection volume of 20 ml, total doses of filgrastim below 30 MU (300 μg) should be administered with the addition of 0.2 ml of human serum albumin 200 mg/ml (20%).

When diluted in 5% glucose, Accofil is compatible with glass and a variety of plastics such as PVC, polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.

After dilution

The chemical and physical stability of the diluted solution for infusion has been demonstrated for 24 hours stored between 2 and 8 °C. From a microbiological point of view, the medicine should be used immediately. If not used immediately, the time and storage conditions of the diluted solution are the responsibility of the user and should normally not exceed 24 hours between 2 and 8 °C, unless the dilution was made in validated and controlled aseptic conditions.

Use of the syringe with a safety guard for the needle

The safety guard covers the needle after injection to prevent needlestick injuries. This does not affect the normal functioning of the syringe. Press the plunger of the syringe slowly and uniformly until the entire dose has been administered, until the plunger can no longer move. Holding the pressure on the plunger, remove the syringe from the patient. The safety guard will cover the needle when the plunger is released.

Use of the pre-filled syringe without a safety guard for the needle

Administer the dose following the standard protocol.

Disposal

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.