Accofil 48 MU/0.5 ml solution for injection and for infusion in pre-filled syringe

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Accofil 48 MU/0.5 ml (0.96 mg/ml) solution for injection and infusion in a pre-filled syringe

filgrastim

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

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

Contents of the leaflet

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

1. What Accofil is and what it is used for

What Accofil is

Accofil is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins that occur naturally in the body, but can also be produced by biotechnology for use as medicines. Accofil works by stimulating the bone marrow to produce more white blood cells. A reduction in the number of white blood cells (neutropenia) can occur for various reasons and makes your body less able to fight infections. Accofil stimulates the bone marrow to rapidly produce new white blood cells.

Accofil can be used:

• to increase the number of white blood cells after chemotherapy treatment to help prevent infections;
• to increase the number of white blood cells after a bone marrow transplant to help prevent infections;
• prior to high-dose chemotherapy, to stimulate the bone marrow to produce more stem cells which can be collected and later returned to you after treatment. These stem cells may be collected from yourself or from a donor. The stem cells will then return to the bone marrow and produce blood cells;
• to increase the number of white blood cells if you have severe chronic neutropenia, to help prevent infections;
• in patients with advanced HIV infection to help reduce the risk of infections.

2. What you need to know before using Accofil

Do not use Accofil

• If you are allergic to filgrastim or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

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

Before starting treatment, tell your doctor if you have:

• sickle cell anaemia; Accofil may trigger a sickle cell crisis.
• osteoporosis (a bone disease).

Tell your doctor immediately during treatment with Accofil if:

• you have pain in the upper left part of your abdomen, pain under the left ribs, or pain in the tip of your left shoulder (these may be symptoms of an enlarged spleen (splenomegaly) or possibly a ruptured spleen).
• you notice unusual bleeding or bruising (these may be symptoms of a lower number of platelets in the blood (thrombocytopenia), resulting in reduced blood clotting ability).
• you experience sudden signs of allergy such as skin rash, itching, hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing (a whistling sound when breathing), or difficulty breathing, as these could be signs of a serious allergic reaction (hypersensitivity).
• you develop swelling of the face or ankles, blood in your urine, brown-coloured urine, or notice that you are urinating less than usual (glomerulonephritis).
• you have symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body). This has rarely been reported in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, general malaise, 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 during treatment with filgrastim, your doctor will investigate possible causes, including whether you have developed antibodies that neutralize the activity of filgrastim.

Your doctor may wish to monitor you closely; see section 4 of the package leaflet.

If you are a patient with severe chronic neutropenia, you may be at risk of developing blood cancer (leukaemia, myelodysplastic syndrome (MDS)). You should discuss with your doctor the risks of developing blood cancer and which tests should be performed. If you have developed or are likely to develop blood cancer, you should not use Accofil unless instructed by your doctor. If you are a stem cell donor, you must be between 16 and 60 years of age.

Take special care with other products that stimulate white blood cells

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

Other medicines and Accofil

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

Pregnancy and breastfeeding

Accofil has not been studied in pregnant or breastfeeding women.

Accofil is not recommended during pregnancy.

It is important that you tell your doctor if:

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

If you become pregnant while being treated with Accofil, inform your doctor.

Unless your doctor tells you otherwise, you should stop breastfeeding if you are using Accofil.

Driving and using machines

Accofil may have a slight influence on your ability to drive or operate machinery. This medicine may cause dizziness. It is advisable to wait and see how you feel after taking Accofil before driving or operating machinery.

Accofil contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free".

Accofil contains sorbitol

This medicine contains 50 mg of sorbitol per ml. Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, this medicine must not be administered. Patients with HFI cannot metabolize fructose, which may lead to serious adverse effects.

Consult your doctor before receiving this medicine if you (or your child) have HFI, or if your child cannot consume sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhoea.

Allergy to natural rubber (latex): The needle cap of the pre-filled syringe contains dry natural rubber (a derivative of latex), which may cause a severe allergic reaction.

3. How to use Accofil

Follow exactly the instructions given by your doctor for administering this medicine. If in doubt, please consult your doctor, nurse, or pharmacist again.

How is Accofil administered and what amount should I use?

Accofil is usually administered as a daily injection into the tissue just beneath the skin (this is called a subcutaneous injection). It may also be given as a daily slow injection into a vein (known as intravenous infusion). The usual dose varies depending on your condition and body weight. Your doctor will tell you how much Accofil you should use.

Patients undergoing bone marrow transplantation following chemotherapy:

You will usually receive your first dose of Accofil at least 24 hours after chemotherapy and at least 24 hours after the bone marrow transplant.

You or your caregivers may learn how to administer subcutaneous injections so that you can continue treatment at home. However, you must not attempt this unless your doctor or nurse has previously trained you.

How long will I need to take Accofil?

You should continue taking Accofil until your white blood cell count returns to normal. Your blood will be tested periodically to monitor your white blood cell count. Your doctor will advise you how long to continue treatment with Accofil.

Use in children and adolescents

Accofil is used to treat children and adolescents who are receiving chemotherapy or who have severe reduction in white blood cells (neutropenia). The dosage for children and adolescents receiving chemotherapy is the same as that for adults.

Information for self-injection

This section contains information on how to self-administer an Accofil injection. It is important that you do not attempt to inject yourself unless you have received proper training from your doctor or nurse. If you are unsure whether you can self-inject or have any questions, consult your doctor or nurse.

How should I inject Accofil?

You should administer the injection into the tissue just under the skin. This is known as a subcutaneous injection. The injection should be given daily at approximately the same time.

Equipment needed

To give a subcutaneous injection, you will need:

• a pre-filled syringe of Accofil, and
• an alcohol-impregnated gauze pad or similar.

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

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

1. Remove the pre-filled syringe of Accofil from the refrigerator.
2. Check the expiry date on the pre-filled syringe (EXP). Do not use if the date is later than the last day of the month shown, if it has been kept outside the refrigerator for more than 15 days, or if it has otherwise expired.
3. Check the appearance of Accofil. It should be a clear, colourless liquid. Do not use if you see particles in the solution.
4. For a more comfortable injection, allow the pre-filled syringe to sit at room temperature for 30 minutes or gently hold it in your hands for a few minutes. Do not heat Accofil in any other way (for example, do not use a microwave or warm water).
5. Wash your hands thoroughly.
6. Find a comfortable, well-lit place and arrange all necessary items within reach (the pre-filled syringe of Accofil and the alcohol-impregnated gauze).

How should I prepare the Accofil injection?

Before injecting Accofil:

Never use a pre-filled syringe that has been dropped on a hard surface.

Step 1: Check the integrity of the system

Ensure that the system is intact and undamaged. Do not use the product if it appears damaged (if the syringe or needle cap is broken), if any components are loose, or if the needle cap is in the open position as shown in Figure 9, as this indicates that the system has already been activated. In general, do not use the product if it does not match Figure 1. If so, the product should be discarded in a container for the disposal of hazardous biological waste.

Figure 1

Step 2: Remove the needle cap

1. Remove the needle cap as shown in Figure 2. Hold the needle cap with one hand, with the needle pointing away from you, without touching the syringe plunger. Remove the needle cap with the other hand. After removal, discard the cap in a container for the disposal of hazardous biological waste.
2. You may notice a small air bubble in the pre-filled syringe. It is not necessary to remove the air bubble before injection. Injecting the solution with the air bubble is harmless.
3. The syringe may contain more liquid than needed. Use the syringe scale as described below to adjust to the correct dose of Accofil prescribed by your doctor. Expel excess liquid by pushing the plunger to the number (ml) on the syringe corresponding to the prescribed dose.
4. Double-check that the Accofil dose is correct.
5. The pre-filled syringe is now ready for use.

Figure 2

Where should I give the injection?

The most suitable injection sites are:

• the upper thighs, and
• the abdomen, except the area around the navel (see Figure 3).

Figure 3

If someone else is administering the injection, the back of the upper arms may also be used (see Figure 4).

Figure 4

To avoid the risk of localised discomfort, it is best to change the injection site each day.

Step 3: Insert the needle

• With one hand, gently pinch the skin at the injection site;
• With the other hand, insert the needle at the injection site without touching the syringe plunger (at an angle of 45 to 90°). (See Figures 6 and 7)

How should I inject myself?

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

Figure 5

Pre-filled syringe without needle safety guard

1. Insert the needle fully into the skin as instructed by your nurse or doctor (see Figure 6).
2. Gently pull back on the plunger to check that you have not punctured a blood vessel. If you see blood in the syringe, remove the needle and reinsert it at another site.
3. While keeping the skin pinched, slowly push the plunger until the full dose has been administered and the plunger can no longer move forward. Do not stop pushing the plunger!
4. Inject only the dose prescribed by your doctor.
5. After injecting the liquid, withdraw the needle while maintaining pressure on the plunger, then release the skin.
6. Place the syringe in the special container for disposal. Each syringe is for single use only.

Figure 6

Pre-filled syringe with needle safety guard

1. Insert the needle completely into the skin as instructed by your nurse or doctor.
2. Gently pull back on the plunger to check that you have not punctured a blood vessel. If blood appears in the syringe, remove the needle and reinsert it at another site. Inject only the dose prescribed by your doctor, following the instructions below.

Figure 7

Step 4: Injection

Place your thumb on the end of the plunger. Press the plunger rod and push firmly to ensure the syringe is completely emptied (see Figure 8). Hold the skin firmly until administration is complete.

Figure 8

Step 5: Protection against accidental needlestick injuries

The safety mechanism activates when the plunger is fully depressed:

• Without moving the syringe, slowly lift your thumb from the end of the plunger;
• The plunger will rise with your thumb and the spring will retract the needle from the injection site into the safety guard (see Figure 9).

Figure 9

Remember

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

How to dispose of used syringes

The needle safety guard prevents accidental needlestick injuries after use, so no special precautions are needed for disposal. Dispose of the syringe as instructed by your doctor, nurse, or pharmacist.

If you use more Accofil than you should

Do not increase the dose prescribed by your doctor. If you use more Accofil than recommended, contact your doctor or pharmacist as soon as possible.

If you forget to use Accofil

If you miss an injection or inject less than the prescribed amount, contact your doctor to discuss when to administer the next dose as soon as possible. Do not take a double dose to make up for a missed injection.

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

4. Possible adverse effects

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

Please inform your doctor immediately during treatment:

• If you experience an allergic reaction with weakness, drop in blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnea).

• If you experience kidney injury (glomerulonephritis). Kidney injuries have been observed in patients receiving Accofil. Call your doctor immediately if you experience swelling of the face or ankles, blood in the urine, or brown-colored urine, or if you notice that you are urinating less than usual.

• If you experience cough, fever, and difficulty breathing (dyspnea), as this may be a sign of acute respiratory distress syndrome (ARDS).

• If you notice pain in the upper left part of the abdomen, pain under the left side of the ribcage, or pain at the tip of the shoulder, as you may have a problem with your spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).

• If you are being treated for chronic severe neutropenia and have blood in your urine (hematuria). Your doctor may periodically test your urine if you experience this adverse effect or if proteins are found in your urine (proteinuria).

• If you experience any of the following adverse effects or a combination of them: swelling or fluid retention, which may be associated with reduced frequency of urination, difficulty breathing, abdominal swelling and feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly.

These could be symptoms of a condition called "capillary leak syndrome," which causes fluid to leak from the small blood vessels of the body and requires urgent medical attention.

• If you experience a combination of any of the following symptoms:

• fever or chills, or feeling very cold, high heart rate, confusion or disorientation, shortness of breath, severe pain or discomfort, and sweaty, sticky skin.

These could be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a serious infection with a systemic inflammatory response that can be life-threatening and requires urgent medical attention.

A very common adverse effect with the use of Accofil is pain in the muscles or bones (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 donor cells against the transplant recipient; signs and symptoms include skin rash on the palms of the hands and soles of the feet, and ulcers or sores in the mouth, intestines, liver, skin, eyes, lungs, vagina, and joints.

In healthy stem cell donors, an increase in white blood cells (leukocytosis) and a decrease in platelets, reducing the blood's ability to clot (thrombocytopenia), may be observed; your doctor will monitor these reactions.

Very common adverse effects (may affect more than 1 in 10 people):

• vomiting
• nausea
• hair loss or thinning (alopecia)
• tiredness (fatigue)
• inflammation of the lining of the digestive tract from mouth to anus (mucosal inflammation)
• decrease in platelets, reducing the blood's ability to clot (thrombocytopenia)
• low red blood cell count (anemia)
• fever (pyrexia)
• headache
• diarrhea

Common adverse effects (may affect up to 1 in 10 people):

• lung inflammation (bronchitis)

• upper respiratory tract infection

• urinary tract infection

• decreased appetite

• difficulty sleeping (insomnia)

• dizziness

• reduced sensation, especially in the skin (hypoesthesia)

• tingling or numbness in hands or feet (paresthesia)

• low blood pressure (hypotension)

• high blood pressure (hypertension)

• cough

• coughing up blood (hemoptysis)

• pain in mouth and throat (oropharyngeal pain)

• nosebleeds (epistaxis)

• constipation

• oral pain

• enlargement of the liver (hepatomegaly)

• rash

• redness of the skin (erythema)

• muscle spasms

• pain when urinating (dysuria)

• chest pain

• pain

• general weakness (asthenia)

• general feeling of being unwell (malaise)

• swelling of hands and feet (peripheral edema)

• increase in certain blood enzymes

• changes in blood chemistry

• transfusion reaction

Uncommon adverse effects (may affect up to 1 in 100 people):

• increase in white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• rejection of transplanted bone marrow (graft-versus-host disease)
• high levels of uric acid in the blood which may cause gout (hyperuricemia) (increased uric acid in blood)
• liver damage caused by blockage of capillaries within the liver (veno-occlusive disease)
• lungs not functioning properly, causing shortness of breath (respiratory failure)
• swelling or fluid in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial lung disease)
• abnormal X-ray findings in the lungs (pulmonary infiltration)
• bleeding from the lungs (pulmonary hemorrhage)
• poor oxygen absorption in the lungs (hypoxia)
• scaly skin rash (maculopapular rash)
• disease causing bones to become less dense, making them weaker, more fragile and more likely to break (osteoporosis)
• reaction at injection site

Rare adverse effects (may affect up to 1 in 1,000 people):

• inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2.

• severe pain in bones, chest, intestines or joints (sickle cell crisis)

• sudden, life-threatening allergic reaction (anaphylactic reaction)

• joint pain and swelling, similar to gout (pseudogout)

• change in how the body regulates body fluids, which may cause swelling (volume regulation disorders)

• inflammation of blood vessels in the skin (cutaneous vasculitis)

• painful plum-colored raised lesions on limbs, and sometimes on face and neck, along with fever (Sweet's syndrome)

• worsening of rheumatoid arthritis

• rare change in urine

• decrease in bone density

• formation of blood cells outside the bone marrow (extramedullary hematopoiesis)

Reporting of adverse effects

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

5. Storage of Accofil

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

Do not use this medicine after the expiry date stated on the carton and on the pre-filled syringe after EXP. The expiry date refers to the last day of the month.

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

The syringe may be removed from the refrigerator and kept at room temperature (but not above 25°C) for a single period of up to a maximum of 15 days, and never beyond the expiry date indicated on the label. After this period, the medicine must not be returned to the refrigerator and should be discarded.

Keep the pre-filled syringe in its original packaging to protect it from light.

Do not use Accofil if it appears cloudy or discoloured, or if particles are present.

Do not recap used needles, as accidental needle-stick injuries may occur. Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer need. This will help protect the environment.

6. Package contents and other information

Composition of Accofil

• The active substance is filgrastim. Each pre-filled syringe contains 48 MU (480 micrograms) of filgrastim in 0.5 ml, corresponding to 0.96 mg/ml.
• The other components are acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80, and water for injections.

Appearance of the product and contents of the container

Accofil is a clear, colourless solution for injection or infusion in a pre-filled syringe marked with printed 1/40 graduations from 0.1 ml to 1 ml on the syringe barrel, with an attached injection needle. Each pre-filled syringe contains 0.5 ml of solution.

Accofil is available in pack sizes of 1, 3, 5, 7 and 10 pre-filled syringes, with or without a fixed needle safety guard and alcohol-impregnated swabs.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare S.L.U.

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

Edifici Est, 6th floor,

08039 Barcelona,

Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

AT / BE / BG / CY / CZ / DE / DK / EE / FI / FR / HR / HU / IE / IS / IT / LT / LV / LU / MT / NL / NO / PT / PL / RO / SE / SI / SK / ES

Accord Healthcare S.L.U.

Tel: +34 93 301 00 64

EL

Win Medica A.E.

Tel: +30 210 7488 821

Date of the most recent revision of this leaflet: May 2025

Detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu

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The following information is intended for healthcare professionals only:

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

Accidental exposure to freezing temperatures for up to a maximum of 48 hours does not affect the stability of Accofil. If exposure exceeds 48 hours or if freezing occurs more than once, Accofil must not be used.

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

Accofil must not be diluted with sodium chloride. This medicinal product must not be mixed with other medicinal products except as mentioned below. Filgrastim may be adsorbed onto glass and plastic materials unless diluted as described below.

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

The solution should be inspected visually before use. Only clear, particle-free solutions should be used.

For patients receiving filgrastim diluted to concentrations below 1.5 MU (15 µg) 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 filgrastim doses below 30 MU (300 µg) should be administered with the addition of 0.2 ml of 200 mg/ml (20%) human albumin solution.

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

After dilution

Chemical and physical stability of the diluted infusion solution has been demonstrated for up to 30 hours at 25 °C ± 2 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage conditions prior to use are the responsibility of the user and, in general, should not exceed 30 hours at 25 °C ± 2 °C, unless dilution has taken place under controlled and validated aseptic conditions.

Use of the pre-filled syringe with needle safety guard

The safety guard covers the needle after injection to prevent needlestick injuries. This does not affect the normal operation of the syringe. Press the plunger rod and push firmly at the end of the injection to ensure complete emptying of the syringe. Hold the skin firmly until the injection is complete. Keep the syringe steady and slowly lift your thumb from the plunger rod head. The plunger rod will move upward with your thumb, and the spring will retract the needle into the needle safety guard.

Use of the pre-filled syringe without needle safety guard

Administer the dose according to standard protocol.

Never use a pre-filled syringe that has been dropped onto a hard surface.

Disposal

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