Accofil 30 MU/0.5 ml solution for injection and for infusion in pre-filled syringe

Patient Information Leaflet

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

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

filgrastim

Read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse, or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, as 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 naturally produced in the body, but they can also be manufactured using 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, helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, helping to prevent infections;
• prior to undergoing 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 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 in patients with severe chronic neutropenia, helping to 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, as Accofil may cause sickle cell crisis.
• osteoporosis (a bone disease)

Tell your doctor immediately during treatment with Accofil if:

• You have pain in the upper left abdomen, pain under the left ribs or at the tip of the 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) with reduced ability to clot blood).
• You have sudden signs of allergy such as rash, itching or hives on the skin, 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 experience swelling of the face or ankles, blood in the urine or 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 that carries 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 with filgrastim treatment, your doctor will investigate possible causes, including whether you have developed neutralizing antibodies against 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. You should not use Accofil if you have or are likely to develop blood cancer, unless otherwise directed 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 belongs to a group of products that stimulate the production of white blood cells. Your healthcare professional 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 to tell your doctor if:

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

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

Unless otherwise instructed by your doctor, you should stop breastfeeding while using Accofil.

Driving and using machines

Accofil may have a minor 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; 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 cover 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 administration instructions for this medicine as given by your doctor. If in doubt, 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 the 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 after chemotherapy:

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

You, or the people caring for you, 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. You will have periodic blood tests to monitor your white blood cell count. Your doctor will tell you how long you should continue taking Accofil.

Use in children and adolescents

Accofil is used to treat children and adolescents who are receiving chemotherapy or who have severe low white blood cell count (neutropenia). The dosage for children and adolescents receiving chemotherapy is the same as 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 give yourself an injection unless you have received proper training from your doctor or nurse. If you are unsure whether you can inject yourself or if you have any doubts, consult your doctor or nurse.

How should I inject Accofil?

You should inject Accofil 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 injecting Accofil subcutaneously?

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 beyond the last day of the month shown, or 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 it.
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 heat it in a microwave or in hot water).
5. Wash your hands thoroughly.
6. Find a comfortable, well-lit area and place 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, you must:

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

Step 1: Check the system's integrity

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

Figure 1

Step 2: Remove the needle shield

1. Remove the needle shield as shown in Figure 2. Hold the needle shield with one hand, pointing the needle away from you, without touching the syringe plunger. Remove the needle shield with the other hand. After removal, discard the protective cap into a container for 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 you need. 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 until the syringe scale shows the prescribed dose (in ml).
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 forearms may also be used (see Figure 4).

Figure 4

To reduce the risk of local 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 into 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 shield

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

Figure 6

Pre-filled syringe with needle safety shield

1. Insert the needle completely into the skin as instructed by your nurse or doctor.
2. Gently pull back on the plunger to check whether you have entered a blood vessel. If blood appears in the syringe, remove the needle and reinsert it at another site.
3. 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 throughout the administration.

Figure 8

Step 5: Protection against accidental needlestick injuries

The safety system 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 needle shield (see Figure 9).

Figure 9

Remember

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

How to dispose of used syringes

The needle safety shield prevents accidental needlesticks 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 think you have injected more than you should, contact your doctor as soon as possible.

If you forget to use Accofil

If you missed an injection or injected too little, contact your doctor as soon as possible to discuss when to administer the next dose. Do not take a double dose to make up for a missed injection.

If you have any other 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 tell 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).
• 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, brown-colored urine, or notice that you are urinating less than usual.
• You experience cough, fever, and difficulty breathing (dyspnea), as this may be a sign of acute respiratory distress syndrome (ARDS).
• You notice pain in the upper left part of the abdomen, pain under the left rib cage, or shoulder tip pain, as there may be a problem with your spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).
• You are being treated for severe chronic neutropenia and have blood in your urine (hematuria). Your doctor may periodically analyze your urine if you experience this adverse effect or if proteins are found in your urine (proteinuria).
• 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, 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 blood to leak from small blood vessels in 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, clammy skin.

These could be symptoms of a condition called "sepsis" (also known as "blood poisoning"), a serious infection with a body-wide 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 patient receiving the transplant; 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)
• pain and swelling 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 of the 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 the 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 small veins 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 pneumonitis)
• abnormal X-ray finding in the lungs (pulmonary infiltration)
• bleeding in the lungs (pulmonary hemorrhage)
• poor oxygen absorption in the lungs (hypoxia)
• scaly skin rash (maculopapular rash)
• condition causing bones to become less dense, making them weaker, more fragile, and more likely to break (osteoporosis)
• reaction at the 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)
• pain and swelling of the joints, similar to gout (pseudogout)
• rare change in how the body regulates body fluids, which may cause swelling (volume alterations)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• painful, plum-colored, raised lesions on the limbs, and sometimes on the 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 type of 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 listed 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 prefilled syringe after EXP. The expiry date refers to the last day of the stated 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 stated on the label. After this period, the medicine must not be refrigerated again and should be discarded.

Keep the prefilled syringe in its outer packaging to protect it from light.

Do not use Accofil if you notice cloudiness, discoloration, or particles in the solution.

Do not replace the cap onto used needles, as you may accidentally prick yourself. Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer need. Doing so helps protect the environment.

6. Contents of the pack and other information

Composition of Accofil

• The active substance is filgrastim. Each pre-filled syringe contains 30 MIU (300 micrograms) of filgrastim in 0.5 ml, corresponding to 0.6 mg/ml.
• The other ingredients are acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80, water for injections.

Appearance of the product and contents of the pack

Accofil is a clear, colourless solution for injection or infusion in a pre-filled syringe marked with 1/40 printed marks 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 packs of 1, 3, 5, 7 and 10 pre-filled syringes, with or without a safety needle shield 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 medicine, 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:

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

In order to improve the traceability of granulocyte colony-stimulating factors, the product name (Accofil) and the batch number of the administered product should be clearly recorded 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 those mentioned below. Diluted 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 MIU (2 µg) per ml is not recommended at any time.

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

For patients receiving filgrastim diluted to concentrations below 1.5 MIU (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 MIU (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 use within a maximum of 30 hours at 25 °C ± 2 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, storage conditions and duration 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 occurred under controlled and validated aseptic conditions.

Use of the pre-filled syringe with needle safety shield

The safety shield covers the needle after injection to prevent needlestick injuries. This does not affect the normal operation of the syringe. Push 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 upwards with your thumb and the spring will retract the needle into the needle safety shield.

Use of the pre-filled syringe without needle safety shield

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