ACCOFIL 30 MU/0.5 ML Инъекционный раствор

Содержание инструкции

1. Accofil 30 MU/0,5 mL (0,6 mg/mL) solution for injection/infusion in pre-filled syringe
   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. Package contents and other information
2. Accofil 48 MU/0,5 mL (0,96 mg/mL) solution for injection/infusion in pre-filled syringe
   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. Package contents and other information
3. Accofil 12 MU/0,2 mL (0,6 mg/mL) solution for injection/infusion in pre-filled syringe
   1. What is Accofil and what is it used for
   2. What you need to know before you use Accofil
   3. How to use Accofil
   4. Possible side effects
   5. How to store Accofil
   6. Package contents and other information
4. Accofil 70 MU/0,73 mL (0,96 mg/mL) solution for injection/infusion in pre-filled syringe
   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. Package contents and other information

Accofil 30 MU/0,5 mL (0,6 mg/mL) solution for injection/infusion in pre-filled syringe

filgrastim

Read 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

• 1. What Accofil is and what it is used for
• 2. What you need to know before you use 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 produced naturally in the body, but they can be produced with the aid of biotechnology, to be used as medicines. Accofil stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against infections. Accofil stimulates the bone marrow to produce new white blood cells quickly.
Accofil can be used:

• to increase the number of white blood cells after chemotherapy treatment, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections;
• before high-dose chemotherapy to induce the bone marrow to produce more stem cells that can be collected and re-infused after treatment. These cells can be taken from you 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, thus helping to prevent infections;
• in patients with advanced stage 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 any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Accofil:
Before starting treatment, tell your doctor if you have:

• Sickle cell anemia, as Accofil may cause a sickle cell crisis.
• Osteoporosis (bone disease).

Tell your doctor immediately if, during treatment with Accofil:

• you experience pain in the upper left side of your abdomen or at the tip of your left shoulder (these may be symptoms of enlargement [splenomegaly] or possibly rupture of the spleen).
• you notice unusual bleeding or bruising (these may be symptoms of a decrease in the number of platelets in the blood [thrombocytopenia], with a reduced ability of the blood to clot).
• you experience sudden symptoms of an allergy, such as skin rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing, or difficulty breathing, as these symptoms may indicate a severe allergic reaction (hypersensitivity).
• you have swelling of the face or ankles, blood in your urine or brown-colored urine, or notice that you urinate 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), which has been rarely reported in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain, and increased markers of inflammation. Tell your doctor if you experience such symptoms.

Loss of response to filgrastim
If you notice a loss of effectiveness or an inability to maintain effectiveness with filgrastim treatment,
your doctor will investigate the reasons, including the possibility that you have developed antibodies that
neutralize the activity of filgrastim.
Your doctor may want to monitor you more closely (see section 4).
If you are a patient with severe chronic neutropenia, you may be at risk of developing a
blood cancer (leukemia, myelodysplastic syndrome). Talk to your doctor about the risk of
developing blood cancers and the necessary tests. If you develop or are likely to develop blood cancers, do not use Accofil unless directed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.

Pay particular attention to other products that stimulate white blood cells.
Accofil belongs to a group of medicines that stimulate the production of white blood cells.
The healthcare professional should always record the exact name of the medicine you are using.

Other medicines and Accofil
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Pregnancy and breastfeeding
Accofil has not been studied in pregnant women or breastfeeding women.
Accofil is not recommended during pregnancy.
It is important to tell your doctor if:

• you are pregnant or breastfeeding;
• you suspect you may be pregnant, or
• you are planning to become pregnant.

If you become pregnant during treatment with Accofil, tell your doctor.
Unless otherwise indicated by your doctor, you should stop breastfeeding if you use Accofil.

Driving and using machines
Accofil has modest effects on the ability to drive and operate machines. This medicine
may cause dizziness, so it is advisable to wait and see
how you feel after administering Accofil before driving or using machines.

Accofil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, which is
essentially “sodium-free”

Accofil contains sorbitol
This medicine contains 50 mg of sorbitol per ml. Sorbitol is a source of fructose. If your
doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic
disease, you (or your child) should not take this medicine. Patients with hereditary fructose intolerance are unable to break down fructose, the accumulation of which can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary
fructose intolerance or if the child is feeling unwell, vomiting or has unpleasant reactions such as bloating and
stomach cramps or diarrhea when consuming sweet foods or drinks.
An allergy to natural rubber latex. The needle cap of the pre-filled syringe contains
dry natural rubber (a derivative of latex) which may cause serious allergic reactions.

3. How to use Accofil

Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor, pharmacist, or nurse.

How is Accofil administered and how much should I take?
Accofil is generally administered by daily injection into the tissue just
below the skin (known as a subcutaneous injection). It can also be administered as a slow-release daily injection
into a vein (known as an intravenous infusion). The usual dose varies depending
on your condition and your weight. Your doctor will tell you how much Accofil you should take.
Patients receiving bone marrow transplant after chemotherapy:
You will normally receive the first dose of Accofil at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people who care for you may be taught how to administer subcutaneous injections
so that you can continue treatment at home. However, do not attempt to give yourself an injection
unless you have first received appropriate instructions from your doctor.

For how long will I need to take Accofil?
You will need to take Accofil until the number of white blood cells has returned to normal. Blood tests will be
performed to monitor the number of white blood cells in your blood. Your doctor
will tell you how long you will need to take Accofil.

Use in children
Accofil is used for the treatment of children undergoing chemotherapy or who suffer from a severe
reduction in the number of white blood cells (neutropenia). The dosage in children treated with
chemotherapy is the same as used in adults.

Information for performing self-injection
This paragraph contains the information needed to perform a self-injection of Accofil. It is
important that you do not attempt to perform the injection yourself without first receiving appropriate
instructions from your doctor or
nurse. If you have any doubts about how to perform the injection or
would like more information, ask your doctor or nurse for advice.

How to perform a self-injection of Accofil?
The injection must be administered into the tissue under the skin: this method is known as
subcutaneous injection. You must administer the injection at the same time each day.

Equipment required
To perform a subcutaneous injection, you must use:

• a pre-filled syringe of Accofil;
• a swab soaked in alcohol or an equivalent disinfectant.

What to do before performing a subcutaneous injection of Accofil
Make sure that the needle safety device remains on the syringe until you are ready to
administer the injection.

• a. Remove the pre-filled syringe of Accofil from the refrigerator.
• b. Check the expiration date (Exp.) on the label of the pre-filled syringe. Do not use the syringe if the date exceeds the last day of the indicated month or if it has been kept out of the refrigerator for more than 15 days or if it is otherwise expired.
• c. Check the appearance of Accofil. It should appear as a clear and colorless liquid. If you notice particles inside, do not use it.
• d. To make the injection easier, remove the pre-filled syringe from the refrigerator and let it stand at room temperature for 30 minutes, or hold it gently in your hand for a few minutes. Do not heat Accofil in any other way (e.g. do notheat Accofil in a microwave oven or in hot water).
• e. Wash your hands thoroughly.
• f. Find a comfortable and well-lit place and have everything you need at hand (the pre-filled syringe of Accofil and the alcohol-soaked swab).

How to prepare the Accofil injection?
Before administering the Accofil injection, you must proceed as follows:

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Step 1: System integrity check
Verify that the system is intact/not damaged. Do not use the product if you find
damage (syringe or needle safety device broken) or detached components and if the needle safety device is in the safety position before use, as
shown in Figure 9, as this indicates that the system has already been activated. In general, the
product should not be used if it does not conform to Figure 1. In this case, dispose of the
product in a container for biological risk materials (sharps).

Figure 1

Step 2: Removing the needle cap

• a. Remove the protective cap as shown in Figure 2. Hold the device protection body in one hand, pointing the needle end away from you and without touching the plunger rod. Remove the needle cap with the other hand. After removing the needle cap, dispose of it in a container for biological risk materials (sharps).
• b. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before the injection. Injecting the solution containing the air bubble is harmless.
• c. The syringe may contain more liquid than necessary. Use the scale on the syringe as indicated below to measure the correct dose of Accofil prescribed by your doctor. Expel the excess liquid by pushing the plunger to the number (mL) on the syringe that corresponds to the prescribed dose of Accofil.
• d. Check again to make sure the syringe contains the correct dose of Accofil.
• e. The pre-filled syringe is now ready for use.

Figure 2

Where to administer the injection?
The most suitable areas for administering the injection are:

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

Figure 3

If the injection is performed by another person, the medicine can also be injected into the back of the arm (see Figure 4).

Figure 4

It is preferable to change the injection site every day to avoid the risk of hardening at the administration site.

Step 3: Inserting the needle

• Pinch the skin at the injection site lightly with one hand;
• With the other hand, insert the needle into the injection site without touching the end of the plunger rod (at an angle of 45-90 degrees) (see Figures 6 and 7).

How to administer the injection?
Disinfect the injection site using the alcohol-soaked swab and take the skin between your
thumb and index finger, without compressing (see Figure 5).

Figure 5

Prefilled syringe
without needle safety
device
or Insert the needle
fully into the skin,
as shown to you
by the nurse or
doctor (see
Figure 6).
or Gently pull the
plunger to
check that a
blood vessel has not been punctured. If
you see blood in the
syringe, withdraw the needle and insert it into another site.
or Keeping the skin fold in place, slowly and evenly press the plunger to
administer the entire dose and until you can no longer push the
plunger. Do not release pressure on the plunger!
or Inject only the dose that your doctor has told you to inject.
or After injecting the liquid, withdraw the needle while maintaining pressure on the plunger and release
the skin.
or Place the used syringe in the disposal container. Use each syringe only for
one injection.

Figure 6

Prefilled syringe with needle safety device

• 1. Insert the needle fully into the skin, as shown to you by the nurse or doctor.
• 2. Gently pull the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, withdraw the needle and insert it into another site.
• 3. Inject only the dose indicated by your doctor following the instructions below.

Figure 7

Step 4: Injection
Place your thumb on the end of the plunger rod. Press the plunger and push firmly
at the end of the injection to make sure the syringe is completely emptied (see Figure 8).
Keep the skin firm in place until the injection is complete.

Figure 8

Step 5: Needle protection
The safety system will be activated once the plunger rod is fully pressed:

• Hold the syringe firmly and slowly lift your thumb from the end of the plunger rod;
• The plunger rod will rise together with your thumb and the spring will retract the needle from the site, inside the needle protection device (see Figure 9),

Figure 9

Remember
If you have any doubts or problems, contact your doctor or nurse for help or advice.

Disposal of used syringes
The needle safety device prevents accidental punctures after use, and for this reason
no special precautions are required. To dispose of the used syringe, follow the instructions provided 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 given yourself more than
you should, contact your doctor as soon as possible.

If you forget to use Accofil
If you have forgotten an injection, or the amount injected is too little, contact your doctor as soon as possible.
Do not take a double dose to make up for the missed dose.
If you have any doubts about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

It is important to inform your doctor immediatelyduring treatment

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing (dyspnea), facial swelling (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as it may be a sign of acute respiratory distress syndrome (ARDS).
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving filgrastim. Seek immediate medical attention if you have swelling of the face or ankles, blood in your urine, or brown-colored urine, or if you notice that you urinate less than usual.
• if you experience pain in the upper left side of the abdomen, pain under the left side of the ribs, or pain at the tip of the shoulder, as this could indicate a problem with the spleen (splenomegaly or splenic rupture);
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). If you experience this side effect or if you have protein in your urine (proteinuria), your doctor may perform urine tests at regular intervals;
• if you experience one or a combination of the following side effects: swelling or bloating, which may be associated with fluid retention, difficulty breathing, abdominal swelling and a feeling of fullness, general feeling of fatigue. These symptoms usually develop rapidly.

This may be a condition called “Capillary Leak Syndrome” which
causes blood to leak from small blood vessels in your body and requires urgent medical care.

• If you experience a combination of any of the following symptoms:
• fever, chills, feeling cold, rapid heartbeat, confusion, disorientation, shortness of breath, severe pain or discomfort, and moist or sweaty skin.

These may be symptoms of a condition called “sepsis” (also called
“blood poisoning”), a serious infection that triggers the inflammatory response of the entire
body which can be life-threatening and requires urgent medical attention.
A common side effect of Accofil is muscle or bone pain (musculoskeletal pain), which can be relieved by taking normal pain relievers (analgesics). In
patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease may occur, i.e. rejection of donor cells by the patient receiving the
transplant; signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and lesions in the mouth, intestines, liver, skin or eyes, lungs,
vagina and joints.
In healthy stem cell donors, an increase in white blood cells (leukocytosis) and
a decrease in the number of platelets with a consequent reduced ability of the blood to coagulate
(thrombocytopenia) may be observed; the doctor will monitor this reaction.

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

• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue (tiredness)
• injury and inflammation of the lining of the digestive tract between the mouth and the anus (mucosal inflammation)
• decreased number of platelets with a consequent reduced ability of the blood to coagulate (thrombocytopenia)
• low number of red blood cells (anemia)
• fever (pyrexia)
• headache
• diarrhea

Common side 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
• loss of sensation, especially of the skin (hypoesthesia)
• tingling or numbness of hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleed (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• skin rash
• skin redness (erythema)
• muscle spasm
• pain during urination (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• general feeling of discomfort (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in the chemical composition of the blood
• transfusion reaction

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

• increased white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• bone marrow transplant rejection (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of the small veins of the liver (veno-occlusive disease)
• insufficient lung function, causing shortness of breath (respiratory failure)
• swelling and/or fluid accumulation in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial pneumopathy)
• abnormal chest X-ray (pulmonary infiltration)
• bleeding from the lung (pulmonary hemorrhage)
• defect in oxygen absorption in the lung (hypoxia)
• skin rash with lesions (maculopapular rash)
• condition that causes loss of bone density, making them weaker, more fragile and easily fractured (osteoporosis)
• reaction at the injection site

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

• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see section 2.
• severe bone, chest, bowel or joint pain (sickle cell crisis)
• sudden, potentially life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling of the joints, similar to gout (pseudogout)
• alteration of fluid regulation in the body, which can cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• painful and raised purple lesions on the limbs and sometimes on the face and neck, with fever (Sweet's syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• decreased bone density
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell
your doctor or nurse. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects you can help
to provide more information on the safety of this medicine.

5. How to store Accofil

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 outer packaging and on the pre-filled syringe
after the abbreviation “Exp.”. The expiry date refers to the last day of that
month.
Store in a refrigerator (2°C - 8°C). Do not freeze.
The syringe can be kept outside the refrigerator and left at room temperature (not exceeding
25°C) for a single period, which ends within the expiry date stated on the label, for a
maximum of 15 days. At the end of this period, the product must not be returned to the refrigerator
and must be discarded.
Keep the syringe in the outer packaging to protect the medicine from light.
Do not use Accofil if you notice that the solution is cloudy, has changed colour or if it contains particles.
Do not put the cap on used needles, as you could accidentally prick yourself. Medicines should not
be disposed of via drains or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Accofil contains

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

Description of the appearance of Accofil and contents of the pack
Accofil is a clear and colourless solution for injection or infusion in a pre-filled syringe
marked with a graduated scale with 40 graduations from 0.1 mL to 1 mL, with an 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
device for the pre-attached needle and alcohol-soaked pads.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50,95-200 Pabianice, Poland
Accord Healthcare Single Member S.A.,
64th Km National Road Athens Lamia, Schimatari,
32009, Greece
For further information on this medicinal product, 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
More detailed information on this medicinal product is available on the following website: European
Medicines Agency https://www.ema.europa.eu
---------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Accofil does not contain preservatives. To avoid potential risks of microbial contamination, Accofil
syringes are for single use only.
Accidental exposure to freezing temperatures for up to 48 hours does not affect the stability of
Accofil. If exposure has been longer than 48 hours or it has been frozen more than once, Accofil
should 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 must be clearly recorded in the
patient’s medical record.
Accofil must not be diluted with sodium chloride solution. This medicinal product must not be
mixed with other medicinal products, except those indicated below. Diluted filgrastim may be adsorbed
by glass and plastic materials, unless diluted as specified below.
If necessary, 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 must be visually inspected before use. Only clear and particle-free solutions must be used.
For patients treated with filgrastim diluted to concentrations less than 1.5 MU (15 µg) per mL, human
serum albumin must be added to a final concentration of 2 mg/mL.
Example: in a final injection volume of 20 mL, total doses of filgrastim less than 30 MU (300
µg) must be administered with 0.2 mL of 200 mg/mL (20%) human albumin solution.
When diluted in 5% glucose, Accofil is compatible with glass and plastic materials including PVC,
polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.
After dilution
The chemical and physical in-use stability of the diluted solution for infusion has been demonstrated for 30 hours
at a temperature of 25 °C ± 2 °C. From a microbiological point of view, the medicinal product must be
used immediately. If not, the storage times and conditions are the responsibility of the user and must not exceed 30 hours at a temperature of 25 °C ± 2 °C, unless the
solution has been prepared in controlled and validated aseptic conditions.
Using the pre-filled syringe with needle safety device
The needle safety device covers the needle after injection and prevents the operator from injury.
The device does not interfere with the normal use of the syringe. Press the plunger rod and push
firmlyat the end of the injection to ensure complete emptying of the syringe. Hold
the skin firmly until the injection is complete. Hold the syringe firmly and slowly lift your thumb from the plunger head. The plunger rod will move upwards with the
thumb and the spring will retract the needle from the site, into the needle protection.
Using the pre-filled syringe without a needle safety device
Administer the dose according to standard procedure.

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Disposal
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in accordance
with local regulations.

Accofil 48 MU/0,5 mL (0,96 mg/mL) solution for injection/infusion in pre-filled syringe

filgrastim

Read 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

• 1. What Accofil is and what it is used for
• 2. What you need to know before you use 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 produced naturally in the body, but they can be produced with the aid of biotechnology, to be used as medicines. Accofil stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons and makes the body less able to fight infections. Accofil stimulates the bone marrow to produce a greater number of white blood cells, which help to fight infections.
Accofil can be used:

• to increase the number of white blood cells after chemotherapy treatment, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections; before high-dose chemotherapy to induce the bone marrow to produce more stem cells that can be collected and re-infused after treatment. These cells can be taken from you or from a donor. The stem cells will then return to the bone marrow and produce blood cells;- in patients with advanced stage 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 any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Accofil:
Before treatment, tell your doctor if you have:

• Sickle cell anemia, as Accofil may cause a sickle cell crisis.
• Osteoporosis (bone disease).

Tell your doctor immediately if during treatment with Accofil:

• you experience pain in the upper left side of your abdomen or at the tip of your left shoulder (these may be symptoms of enlargement (splenomegaly) or possibly rupture of the spleen).
• you notice unusual bleeding or bruising (these may be symptoms of a reduced number of platelets in the blood (thrombocytopenia), with a reduced ability of the blood to clot).
• you experience sudden symptoms of an allergy, such as skin rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing, or difficulty breathing, as these symptoms may indicate a severe allergic reaction (hypersensitivity).
• you have swelling of the face or ankles, blood in your urine or brown-colored 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 been rarely reported in cancer patients and healthy people. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Tell your doctor if you experience such symptoms.

Loss of response to filgrastim
If you notice a loss of effectiveness or an inability to maintain effectiveness with filgrastim treatment,
your doctor will investigate the reasons, including the possibility that you have developed antibodies that
neutralize the activity of filgrastim.
Your doctor may want to monitor you more closely, see section 4.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a
blood cancer (leukemia, myelodysplastic syndrome). Talk to your doctor about the risk of
developing blood cancers and the necessary tests. If you develop or are likely to develop blood cancers, do not use Accofil unless directed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.

Pay particular attention to other products that stimulate white blood cells.
Accofil belongs to the group of medicines that stimulate the production of white blood cells.
The healthcare professional must always record the exact name of the medicine being used.

Other medicines and Accofil
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Pregnancy and breastfeeding
Accofil has not been studied in pregnant women or breastfeeding women.
Accofil is not recommended during pregnancy.
It is important to tell your doctor if:

• you are pregnant or breastfeeding;
• you suspect you may be pregnant, or
• you are planning to become pregnant.

If you become pregnant during treatment with Accofil, tell your doctor.
Unless otherwise indicated by your doctor, you should stop breastfeeding if you use Accofil.

Driving and using machines
Accofil has modest effects on the ability to drive vehicles or operate machinery. This medicine
may cause dizziness, so it is advisable to wait and see
how you feel after administering Accofil before driving or using machinery.

Accofil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e. it is
essentially “sodium-free”

Accofil contains sorbitol
This medicine contains 50 mg of sorbitol per ml. Sorbitol is a source of fructose. If your
doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic
disease, you (or your child) should not take this medicine. Patients with hereditary fructose
intolerance are unable to metabolize fructose, the accumulation of which can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary
fructose intolerance or if the child feels unwell, vomits or has unpleasant reactions such as bloating and
stomach cramps or diarrhea when consuming sugary foods or drinks.
An allergy to natural rubber latex. The needle cap of the pre-filled syringe contains
dry natural rubber (a latex derivative) which may cause severe allergic reactions.

3. How to use Accofil

Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.

How is Accofil administered and how much should I take?
Accofil is generally administered by daily injection into the tissue just
below the skin (known as a subcutaneous injection). It can also be administered as a slow-release daily injection into the vein (known as an intravenous infusion). The usual dose varies
depending on your condition and your weight. Your doctor will tell you how much Accofil you should take.
Patients receiving bone marrow transplant after chemotherapy:
You will normally receive the first dose of Accofil at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people who care for you may be taught how to administer subcutaneous injections so that you can continue treatment at home. However, do not attempt to give yourself an
injection unless you have first received appropriate instructions from your doctor.

For how long will I need to take Accofil?
You will need to take Accofil until the number of white blood cells has returned to normal. Blood tests will
be performed to monitor the number of white blood cells in your blood. Your doctor
will tell you how long you will need to take Accofil.

Use in children
Accofil is used for the treatment of children undergoing chemotherapy or who suffer from a severe
reduction in the number of white blood cells (neutropenia). The dosage in children treated with
chemotherapy is the same as used in adults.

Information for performing self-injection
This paragraph contains the information needed to perform a self-injection of Accofil. It is
important that you do not attempt to perform the injection yourself without first receiving appropriate instructions from your doctor or
nurse. If you have any doubts about how to perform the injection or
would like more information, ask your doctor or nurse for advice.

How to perform a self-injection of Accofil?
The injection must be administered into the tissue under the skin: this method is known as
subcutaneous injection. You must administer the injection at the same time each day.

Equipment required
To perform a subcutaneous injection, you must use:

• a pre-filled syringe of Accofil;
• a swab soaked in alcohol or an equivalent disinfectant.

What to do before performing a subcutaneous injection of Accofil?
Make sure that the needle safety device remains on the syringe until you are ready to
administer the injection.

• a. Remove the pre-filled syringe of Accofil from the refrigerator.
• b. Check the expiry date (Exp.) printed on the label of the pre-filled syringe. Do not use the syringe if the date exceeds the last day of the month indicated or if it has been kept out of the refrigerator for more than 15 days or if the medicine has otherwise expired.
• c. Check the appearance of Accofil. It should appear as a clear and transparent liquid. If you notice any particles inside, do not use it.
• d. To make the injection easier, remove the pre-filled syringe from the refrigerator and leave it at room temperature for 30 minutes, or hold it gently in your hand for a few minutes. Do not heat Accofil in any other way (e.g. do notheat Accofil in the microwave or in hot water).
• e. Wash your hands thoroughly.
• f. Find a comfortable and well-lit place and have everything you need at hand (the pre-filled syringe of Accofil and the alcohol-soaked swab).

How to prepare the Accofil injection?
Before administering the Accofil injection, you must proceed as follows:

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Step 1: Integrity check of the system
Verify that the system is intact/not damaged. Do not use the product if you find any damage (breakage of the syringe or the needle safety device) or detached components and if the
needle safety device is in the safety position before use, as shown in Figure
9, as this indicates that the system has already been activated. In general, the product should not be
used if it does not conform to Figure 1. In this case, dispose of the product in a container
for biohazardous materials (sharps).

Figure 1

Step 2: Removing the needle cap

• 1. Remove the protective cap as shown in Figure 2. Hold the device protection body in one hand, pointing the needle end away from you and without touching the plunger rod. Remove the needle cap with the other hand. After removing the needle cap, dispose of it in a container for biohazardous materials (sharps).
• 2. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before the injection. Injecting the solution containing the air bubble is harmless.
• 3. The syringe may contain more liquid than necessary. Use the scale on the syringe as indicated below to measure the correct dose of Accofil prescribed by your doctor. Expel the excess liquid by pushing the plunger to the number (mL) on the syringe that corresponds to the prescribed dose of Accofil.
• 4. Double-check to make sure the syringe contains the correct dose of Accofil.
• 5. The pre-filled syringe is now ready for use.

Figure 2

Where to administer the injection?
The most suitable areas for administering the injection are:

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

Figure 3

If the injection is performed by another person, the medicine can also be injected into the
back of the arm (see Figure 4).

Figure 4

It is preferable to change the injection site every day to avoid the risk of hardening at the
injection site.

Step 3: Inserting the needle

• Pinch the skin at the injection site lightly with one hand;
• With the other hand, insert the needle into the injection site without touching the end of the plunger rod (at an angle of 45-90 degrees) (see Figures 6 and 7).

How to administer the injection?
Disinfect the injection site using an alcohol-soaked swab and hold the skin between your thumb and
index finger, without compressing (see Figure 5).

Figure 5

Prefilled syringe without needle safety device

• a. Insert the needle fully into the skin, as shown to you by the nurse or doctor (see Figure 6).
• b. Gently pull back on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, withdraw the needle and insert it into another site.
• c. Keeping the skin fold, slowly and evenly press the plunger until the entire dose is administered and until you can no longer push the plunger. Do not release pressure on the plunger!
• d. Inject only the dose that your doctor has told you to inject.
• e. After injecting the liquid, withdraw the needle while maintaining pressure on the plunger and release the skin.
• f. Place the used syringe in the disposal container. Use each syringe only for one injection.

Figure 6

Prefilled syringe with needle safety device

• 1. Insert the needle fully into the skin, as shown to you by the nurse or doctor.
• 2. Gently pull back on the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, withdraw the needle and insert it into another site. Inject only the dose indicated by your doctor following the instructions below.

Figure 7

Step 4: Injection
Place your thumb on the end of the plunger rod. Press the plunger and push firmlyat the
end of the injection to make sure the syringe is completely emptied (see Figure 8).
Keep the skin firm in position until the injection is complete.

Figure 8

Step 5: Needle protection
The safety system will be activated once the plunger rod is fully pressed:

• Hold the syringe firmly and slowly lift your thumb from the end of the plunger rod;
• The plunger rod will rise together with your thumb and the spring will retract the needle into the needle protection device (see Figure 9),

Figure 9

Reminders
If you have any doubts or problems, contact your doctor or nurse for help or advice.

Disposal of used syringes

• The needle safety device prevents accidental punctures after use, and for this reason no special precautions are required. To dispose of the used syringe, follow the instructions provided 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 given yourself more than
you should, contact your doctor as soon as possible.

If you forget to use Accofil
If you have forgotten an injection, or the amount injected is too small, contact your doctor as soon as possible. Do not take a double dose to make up for the missed dose.
If you have any questions about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

It is important to inform your doctor immediatelyduring treatment

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing, facial swelling (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as it may be a sign of acute respiratory distress syndrome (ARDS).
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving filgrastim. Seek immediate medical attention if you have swelling in your face or ankles, blood in your urine, or dark-colored urine, or if you notice that you urinate less than usual.
• if you experience pain in the upper left side of the abdomen, pain under the left side of the ribs, or pain at the tip of the shoulder, as there may be a problem with the spleen (spleen enlargement (splenomegaly) or spleen rupture).
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). If you experience this side effect or have protein in your urine (proteinuria), your doctor may perform urine tests at regular intervals.
• if you experience one or a combination of the following side effects: swelling or bloating, which may be associated with fluid retention, difficulty breathing, abdominal bloating and a feeling of fullness, general feeling of fatigue. These symptoms usually develop rapidly.

This may be a condition called “Capillary Leak Syndrome” which
causes blood to leak from small blood vessels in your body and requires urgent medical attention.

• If you experience a combination of any of the following symptoms:
• fever, chills, widespread feeling of coldness, rapid heartbeat, confusion, disorientation, shortness of breath, severe pain or discomfort, and moist or sweaty skin.

These may be symptoms of a condition called “sepsis” (also called
“blood poisoning”), a serious infection that triggers the inflammatory response of the entire
body, which can be life-threatening and requires urgent medical attention.
A common side effect of Accofil is muscle or bone pain (musculoskeletal pain), which can be relieved by taking normal pain relievers (analgesics).
In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease may occur, i.e. rejection of donor cells by the patient receiving the
transplant; signs and symptoms include rash on the palms of the hands or soles of the feet, and ulcers and lesions in the mouth, intestines, liver, skin or eyes, lungs,
vagina, and joints.
In healthy stem cell donors, an increase in white blood cells (leukocytosis) and
a decrease in the number of platelets, resulting in reduced blood clotting ability
(thrombocytopenia) may be observed; the doctor will monitor this reaction.

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

• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue (asthenia)
• lesions and inflammation of the lining of the digestive tract between the mouth and the anus (mucosal inflammation)
• decreased number of platelets, which reduces the blood's ability to clot (thrombocytopenia)
• low number of red blood cells (anemia)
• fever (pyrexia)
• headache
• diarrhea

Common side 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
• loss of sensation, especially of the skin (hypoesthesia)
• tingling or numbness of hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• mouth and throat pain (oropharyngeal pain)
• nosebleed (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• skin rash
• skin redness (erythema)
• muscle spasm
• pain during urination (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• general feeling of discomfort (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in blood chemistry
• transfusion reaction

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

• increased white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• bone marrow transplant rejection (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of the small veins of the liver (veno-occlusive disease)
• insufficient lung function, causing shortness of breath (respiratory failure)
• swelling and/or fluid accumulation in the lungs (pulmonary edema)
• lung inflammation (interstitial pneumopathy)
• abnormal chest X-ray (pulmonary infiltration)
• bleeding from the lung (pulmonary hemorrhage)
• defect in oxygen absorption in the lung (hypoxia)
• skin rash with lesions (maculopapular rash)
• condition that causes loss of bone density, making them weaker, more fragile and easily fractured (osteoporosis)
• reaction at the injection site

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

• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see section 2.
• severe bone, chest, intestinal or joint pain (sickle cell crisis)
• sudden, potentially life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling of the joints, similar to gout (pseudogout)
• alteration of fluid regulation in the body, which can cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• painful, violet and raised lesions on the limbs and sometimes on the face and neck, with fever (Sweet's syndrome)
• worsening of rheumatoid arthritis
• unusual urine changes
• decreased bone density
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your
doctor or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Accofil

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 outer packaging and on the pre-filled syringe
after the abbreviation “Exp.”. The expiry date refers to the last day of that
month.
Store in a refrigerator (2°C- 8°C). Do not freeze.
The syringe can be kept out of the refrigerator and left at room temperature (not exceeding
25°C) for a single period, which ends within the expiry date stated on the label, for a maximum of 15 days. At the end of this period, the product must not be returned to the refrigerator
and must be discarded.
Keep the syringe in the outer packaging to protect the medicine from light.
Do not use Accofil if you notice that the solution is cloudy, has changed colour or if it contains particles.
Do not put the cap on used needles, as you could accidentally prick yourself. Medicines should not
be disposed of via drains or household waste. Ask your pharmacist how to dispose of
medicines that you no longer use. This will help protect the environment.

6. Package contents and other information

What Accofil contains

• The active ingredient 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 ingredients are acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80 and water for injections.

Description of Accofil and package contents
Accofil is a clear and colorless solution for injection or infusion in a pre-filled syringe
marked with a graduated scale with 40 graduations from 0.1 mL to 1 mL, with an 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 device for the
pre-attached needle and alcohol-soaked swabs.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50,95-200 Pabianice, Poland
Accord Healthcare Single Member S.A.,
64th Km National Road Athens Lamia, Schimatari,
32009, Greece
For further information on this medicinal product, contact the local representative of the marketing
authorization 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
More detailed information on this medicinal product is available on the following website: European
Medicines Agency https://www.ema.europa.eu
---------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Accofil does not contain preservatives. To avoid potential risks of microbial contamination, Accofil
syringes are for single use only.
Accidental exposure to freezing temperatures for up to 48 hours does not affect the stability of
Accofil. If exposure has been longer than 48 hours or it has been frozen more than once, Accofil
should NOT be used.
In order to improve traceability of granulocyte colony-stimulating factors, the product name
(Accofil) and the batch number of the administered product must be clearly recorded in the
patient's medical record
Accofil should not be diluted with sodium chloride solution. This medicinal product should not be
mixed with other medicinal products, except for those indicated below. Diluted filgrastim may be adsorbed
by glass and plastic materials, unless diluted as specified below.
If necessary, Accofil can be diluted in 5% glucose. Dilution to a final concentration lower than 0.2 MU (2 µg)
per mL is not recommended at any time.
The solution must be visually inspected before use. Only clear and particle-free solutions should be used.
For patients treated with filgrastim diluted to concentrations less than 1.5 MU (15 µg) per mL, human
serum albumin must be added to a final concentration of 2 mg/mL.
Example: in a final injection volume of 20 mL, total doses of filgrastim less than 30 MU (300
µg) must be administered with 0.2 mL of 200 mg/mL (20%) human albumin solution.
When diluted in 5% glucose, Accofil is compatible with glass and plastic materials including PVC,
polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.
After dilution:
The chemical and physical stability “in-use” of the diluted solution for infusion has been demonstrated for 30 hours
at a temperature of 25 °C ± 2 °C. From a microbiological point of view, the medicinal product must be
used immediately. If not, the storage times and conditions are the responsibility of the user and must not exceed 30 hours at a temperature of 25 °C ± 2 °C, unless the
solution has been prepared in controlled and validated aseptic conditions.
Use of the pre-filled syringe with needle safety device
The needle safety device covers the needle after injection and prevents the operator from injury.
The device does not interfere with the normal use of the syringe. Press the plunger rod and

push firmlyat 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 head. The plunger rod will move upwards with the
thumb and the spring will retract the needle from the site, into the needle protection
Use of the pre-filled syringe without a needle safety device
Administer the dose according to standard procedure.

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Disposal
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in
accordance with local regulations.

Accofil 12 MU/0,2 mL (0,6 mg/mL) solution for injection/infusion in pre-filled syringe

filgrastim

Read 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

• 1. What Accofil is and what it is used for
• 2. What you need to know before you use 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 is Accofil and what is it used for

What is Accofil
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 produced naturally in the body, but can be produced with the aid of biotechnology, for use as medicines. Accofil stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against 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, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections;
• before high-dose chemotherapy to induce the bone marrow to produce more stem cells that can be collected and re-infused after treatment. These cells can be taken from you 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, thus helping to prevent infections;
• in patients with advanced stage HIV infection, to help reduce the risk of infections.

2. What you need to know before you use Accofil

Do not use Accofil

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

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Accofil:
Before starting treatment, tell your doctor if you have:

• Sickle cell anemia, as Accofil may cause a sickle cell crisis.
• Osteoporosis (bone disease).

Tell your doctor immediately if during treatment with Accofil:

• you experience pain in the upper left side of your abdomen or at the tip of your left shoulder (these may be symptoms of enlargement (splenomegaly) or possibly rupture of the spleen).
• you notice unusual bleeding or bruising (these may be symptoms of a decrease in the number of platelets in the blood (thrombocytopenia), with a reduced ability of the blood to clot).
• you experience sudden symptoms of an allergy, such as skin rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing, or difficulty breathing, as these symptoms may indicate a severe allergic reaction (hypersensitivity).
• you have swelling of the face or ankles, blood in your urine or brown-colored 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 been rarely reported in cancer patients and healthy people. Symptoms may include fever, abdominal pain, malaise, back pain, and increased markers of inflammation. Tell your doctor if you experience such symptoms.

Loss of response to filgrastim
If you notice a loss of effectiveness or an inability to maintain effectiveness with filgrastim treatment,
your doctor will investigate the reasons, including the possibility that you have developed antibodies that
neutralize the activity of filgrastim.
Your doctor may want to monitor you more closely (see section 4).
If you are a patient with severe chronic neutropenia, you may be at risk of developing a
blood cancer (leukemia, myelodysplastic syndrome). Talk to your doctor about the risk of
developing blood cancers and the necessary tests. If you develop or are likely to develop blood cancers, do not use Accofil unless directed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.

Pay particular attention to other products that stimulate white blood cells.
Accofil belongs to the group of medicines that stimulate the production of white blood cells.
The healthcare professional must always record the exact name of the medicine you are using.

Other medicines and Accofil
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Pregnancy and breastfeeding
Accofil has not been studied in pregnant women or breastfeeding women.
Accofil is not recommended during pregnancy.
It is important to tell your doctor if:

• you are pregnant or breastfeeding;
• you suspect you are pregnant, or
• you are planning to become pregnant.

If you become pregnant during treatment with Accofil, tell your doctor.
Unless otherwise indicated by your doctor, you should stop breastfeeding if you use Accofil.

Driving and using machines
Accofil has modest effects on the ability to drive vehicles or use machines. This medicine
may cause dizziness, so wait and see how you feel after administering Accofil before driving or using machines.

Accofil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, i.e.
it is essentially “sodium-free”.

Accofil contains sorbitol
This medicine contains 50 mg of sorbitol per ml. Sorbitol is a source of fructose. If
your doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic
disease, you (or your child) should not take this medicine. Patients with hereditary fructose
intolerance cannot convert fructose, the accumulation of which can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary
fructose intolerance or if the child feels unwell, vomits or has unpleasant reactions such as bloating and
stomach cramps or diarrhea when consuming sweet foods or beverages.
An allergy to natural rubber latex. The needle cap of the pre-filled syringe contains
dry natural rubber (a latex derivative) which may cause severe allergic reactions.

3. How to use Accofil

Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor, pharmacist or nurse.

How is Accofil administered and how much should I take?
Accofil is generally administered by daily injection into the tissue just
below the skin (known as a subcutaneous injection). It can also be administered as a slow-release daily injection
into the vein (known as intravenous infusion). The usual dose varies depending
on your condition and your weight. Your doctor will tell you how much Accofil you should take.
Patients receiving bone marrow transplantation after chemotherapy:
You will normally receive the first dose of Accofil at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people who care for you may be taught how to administer subcutaneous injections
so that you can continue treatment at home. However, do not attempt to give yourself an injection
unless you have first received appropriate instructions from your doctor.

For how long will I need to take Accofil?
You will need to take Accofil until the number of white blood cells has returned to normal. Blood tests will be
performed to monitor the number of white blood cells in your blood. Your doctor
will tell you how long you will need to take Accofil.

Use in children
Accofil is used for the treatment of children undergoing chemotherapy or who suffer from a severe
reduction in the number of white blood cells (neutropenia). The dosage in children treated with
chemotherapy is the same as used in adults.

Information for performing self-injection
This paragraph contains the information needed to perform a self-injection of Accofil. It is
important that you do not attempt to perform the injection yourself without first receiving adequate
instructions from your doctor or
nurse. If you have any doubts about how to perform the injection or
would like more information, ask your doctor or nurse for advice.

How to perform a self-injection of Accofil?
The injection must be administered into the tissue under the skin: this method is known as
subcutaneous injection. You must administer the injection at the same time each day.

Equipment required
To perform a subcutaneous injection, you must use:

• a pre-filled syringe of Accofil;
• a swab soaked in alcohol or an equivalent disinfectant.

What to do before performing a subcutaneous injection of Accofil?
Make sure that the needle safety device remains on the syringe until you are ready to
administer the injection.

• a. Remove the pre-filled syringe of Accofil from the refrigerator.
• b. Check the expiry date (Exp.) on the label of the pre-filled syringe. Do not use the syringe if the date exceeds the last day of the month indicated or if it has been kept out of the refrigerator for more than 15 days or if it is otherwise expired.
• c. Check the appearance of Accofil. It should appear as a clear and colorless liquid. If you notice particles inside, do not use it.
• d. To make the injection easier, remove the pre-filled syringe from the refrigerator and leave it at room temperature for 30 minutes, or hold it gently in your hand for a few minutes. Do not heat Accofil in any other way (e.g. do notheat Accofil in the microwave or in hot water).
• e. Wash your hands thoroughly.
• f. Find a comfortable and well-lit place and have everything you need close at hand (the pre-filled syringe of Accofil and the alcohol-soaked swab).

How to prepare the Accofil injection?
Before administering the Accofil injection, you must proceed as follows:

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Step 1: Integrity check of the system
Verify that the system is intact/not damaged. Do not use the product if you find any damage (breakage of the syringe or the needle safety device) or detached components and if the
needle safety device is in the safety position before use, as shown in figure
9, as this indicates that the system has already been activated. In general, the product should not be
used if it does not conform to figure 1. In this case, dispose of the product in a container
for biological risk materials (sharps).

Figure 1

Step 2: Removing the needle cap

• 1. Remove the protective cap as shown in figure 2. Hold the device protection body in one hand, directing the needle end away from you and without touching the plunger rod. Remove the needle cap with the other hand. After removing the needle cap, dispose of it in a container for biological risk materials (sharps).
• 2. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before the injection. Injecting the solution containing the air bubble is harmless.
• 3. The syringe may contain more liquid than necessary. Use the scale on the syringe as indicated below to measure the correct dose of Accofil prescribed by your doctor. Expel the excess liquid by pushing the plunger to the number (mL) on the syringe that corresponds to the prescribed dose of Accofil.
• 4. Check again to make sure the syringe contains the correct dose of Accofil.
• 5. The pre-filled syringe is now ready for use.

Figure 2

Where to administer the injection?
The most suitable areas for administering the injection are:

• the upper thigh; and
• the abdomen, except for the area around the navel (see figure 3).

Figure 3

If the injection is performed by another person, the medicine can also be injected into the back of the arm (see figure 4).

Figure 4

It is preferable to change the injection site every day to avoid the risk of hardening at the injection site.

Step 3: Inserting the needle

• Pinch the skin at the injection site lightly with one hand;
• With the other hand, insert the needle into the injection site without touching the end of the plunger rod (at an angle of 45-90 degrees) (see figure 6 and 7).

How to administer the injection?
Disinfect the injection site using the alcohol-soaked swab and take the skin between your thumb and
index finger, without compressing (see figure 5).

Figure 5

Prefilled syringe without needle safety device

• a. Insert the needle fully into the skin, as shown to you by the nurse or doctor (see figure 6).
• b. Gently pull the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, withdraw the needle and insert it into another site.
• c. Keeping the skin pinched, slowly and evenly press the plunger until the entire dose is administered and until you can no longer push the plunger. Do not release pressure on the plunger!
• d. Inject only the dose that your doctor has told you to inject.
• e. After injecting the liquid, withdraw the needle while maintaining pressure on the plunger and release the skin.
• f. Place the used syringe in the disposal container. Use each syringe only for one injection.

Figure 6

Prefilled syringe with needle safety device

• 1. Insert the needle fully into the skin, as shown to you by the nurse or doctor.
• 2. Gently pull the plunger to check that a blood vessel has not been punctured. If you see blood in the syringe, withdraw the needle and insert it into another site.
• 3. Inject only the dose indicated by your doctor following the instructions below.

Figure 7

Step 4: Injection
Place your thumb on the end of the plunger rod. Press the plunger and push firmlyat the
end of the injection to make sure the syringe is completely emptied (see figure 8).
Keep the skin firm in position until the injection is complete.

Figure 8

Step 5: Needle protection
The safety system will be activated once the plunger rod has been fully pressed:

• Hold the syringe firmly and slowly lift your thumb from the end of the plunger rod;
• The plunger rod will rise together with your thumb and the spring will retract the needle into the protection device (see figure 9),

Figure 9

Remember
If you have any doubts or problems, contact your doctor or nurse for help or advice.

Disposal of used syringes
The needle safety device prevents accidental punctures after use, and for this reason
no special precautions are required. To dispose of the used syringe, follow the instructions provided
by your doctor, pharmacist or nurse.

If you use more Accofil than you should
Do not increase the dose prescribed by your doctor. If you think you have given yourself more than
you should, contact your doctor as soon as possible.

If you forget to use Accofil
If you have forgotten an injection, or the amount injected is too small, contact your doctor as soon as possible. Do not take a double dose to make up for the missed dose.
If you have any doubts about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

It is important to inform your doctor immediatelyduring treatment

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing (dyspnea), swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as it may be a sign of acute respiratory distress syndrome (ARDS).
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving filgrastim. Seek immediate medical attention if you have swelling in your face or ankles, blood in your urine, or dark-colored urine, or if you notice that you are urinating less than usual.
• if you experience pain in the upper left side of the abdomen, pain under the left side of the ribs, or pain at the tip of the shoulder, as this could indicate a problem with the spleen (splenomegaly or splenic rupture);
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). If you experience this side effect or have protein in your urine (proteinuria), your doctor may perform urine tests at regular intervals;
• if you experience one or a combination of the following side effects: swelling or bloating, which may be associated with fluid retention, difficulty breathing, abdominal bloating and a feeling of fullness, general feeling of fatigue. These symptoms usually develop rapidly.

This may be a condition called “Capillary Leak Syndrome” which causes blood to leak from small blood vessels in your body and requires urgent medical attention.

• If you experience a combination of any of the following symptoms:
• fever, chills, feeling of widespread coldness, rapid heartbeat, confusion, disorientation, shortness of breath, severe pain or discomfort, and moist or sweaty skin.

These may be symptoms of a condition called “sepsis” (also called “blood poisoning”), a severe infection that triggers the inflammatory response of the entire body which can be life-threatening and requires urgent medical attention. A common side effect of Accofil is muscle or bone pain (musculoskeletal pain), which can be relieved by taking normal pain relievers (analgesics). In patients undergoing hematopoietic stem cell or bone marrow transplantation, graft-versus-host disease may occur, i.e. rejection of the donor cells by the recipient patient; signs and symptoms include rash on the palms of the hands or soles of the feet and ulcers and lesions 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 the number of platelets with a consequent reduced ability of the blood to clot (thrombocytopenia) may be observed; the doctor will monitor this reaction.

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

• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• fatigue
• sores and inflammation of the lining of the digestive tract between the mouth and the anus (mucosal inflammation)
• decreased number of platelets with a consequent reduced ability of the blood to clot (thrombocytopenia)
• low number of red blood cells (anemia)
• fever (pyrexia)
• headache
• diarrhea

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• loss of appetite
• difficulty sleeping (insomnia)
• dizziness
• loss of sensation, especially of the skin (hypoesthesia)
• tingling or numbness of hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• sore throat and mouth (oropharyngeal pain)
• nosebleed (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• skin rash
• skin redness (erythema)
• muscle spasm
• pain during urination (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• general feeling of being unwell (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in blood chemistry
• transfusion reaction

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

• increased white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• bone marrow transplant rejection (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of the small veins of the liver (veno-occlusive disease)
• insufficient lung function, causing shortness of breath (respiratory failure)
• swelling and/or fluid accumulation in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial pneumopathy)
• abnormal chest X-ray (pulmonary infiltration)
• bleeding from the lung (pulmonary hemorrhage)
• defect in oxygen absorption in the lung (hypoxia)
• skin rash with lesions (maculopapular rash)
• condition that causes loss of bone density, making them weaker, more fragile and easily fractured (osteoporosis)
• reaction at the injection site

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

• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see section 2.
• severe bone, chest, bowel or joint pain (sickle cell crisis)
• sudden, potentially life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling of the joints, similar to gout (pseudogout)
• alteration of fluid regulation in the body, which can cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• painful and raised purple lesions on the limbs and sometimes on the face and neck, with fever (Sweet syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• decreased bone density
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please tell your doctor or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Accofil

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 outer packaging and on the pre-filled syringe after the abbreviation “Exp.”. The expiry date refers to the last day of that
month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
The syringe may be kept outside the refrigerator and left at room temperature (not exceeding
25°C) for a single period, which ends within the expiry date stated on the label, for a maximum of 15 days. At the end of this period, the product must not be returned to the refrigerator
and must be discarded.
Keep the syringe in the outer packaging to protect the medicine from light.
Do not use Accofil if you notice that the solution is cloudy, has changed colour or if it contains particles.
Do not put the cap back on used needles, as you could accidentally prick yourself. Medicines should not
be disposed of via drains or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Accofil contains

• The active substance is filgrastim. Each pre-filled syringe contains 12 MU (120 micrograms) of filgrastim in 0.2 mL, corresponding to 0.6 mg/mL.
• The other ingredients are acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80 and water for injections.

Description of the appearance of Accofil and contents of the pack
Accofil is a clear and colourless solution for injection or infusion in a pre-filled syringe
marked with a scale graduated with 40 divisions from 0.1 mL to 1 mL, with an injection needle. Each
pre-filled syringe contains 0.2 mL of solution.
Accofil is available in packs of 1, 3, 5, 7 and 10 pre-filled syringes, with or without a safety
device for the pre-attached needle and alcohol swabs.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50,95-200 Pabianice, Poland
Accord Healthcare Single Member S.A.,
64th Km National Road Athens Lamia, Schimatari,
32009, Greece
For further information on this medicinal product, 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
More detailed information on this medicinal product is available on the following website: European
Medicines Agency https://www.ema.europa.eu
---------------------------------------------------------------------------------------------------------------

The following information is intended exclusively for physicians or healthcare professionals:
Accofil does not contain preservatives. To avoid potential microbial contamination risks, Accofil
syringes are for single use only.
Accidental exposure to freezing temperatures for up to 48 hours does not affect the stability of
Accofil. If exposure has been longer than 48 hours or it has been frozen more than once, Accofil
should 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 must be clearly recorded in the
patient’s medical record.
Accofil must not be diluted with sodium chloride solution. This medicinal product must not be
mixed with other medicinal products, except those indicated below. Diluted filgrastim may be adsorbed
by glass and plastic materials, unless diluted as specified below.
If necessary, Accofil can 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 must be inspected visually before use. Only clear and particle-free solutions should be used.
For patients treated with filgrastim diluted to concentrations less than 1.5 MU (15 µg) per mL, human
serum albumin must be added to a final concentration of 2 mg/mL.
Example: in a final injection volume of 20 mL, total doses of filgrastim less than 30 MU (300
µg) must be administered with 0.2 mL of 200 mg/mL (20%) human albumin solution.
When diluted in 5% glucose, Accofil is compatible with glass and plastic materials including PVC,
polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.
After dilution
The chemical and physical stability “in-use” of the diluted solution for infusion has been demonstrated for 30 hours
at a temperature of 25 °C ± 2 °C. From a microbiological point of view, the medicinal product must be
used immediately. If not, the storage times and conditions are the responsibility of the user and must not exceed 30 hours at a temperature of 25 °C ± 2 °C, unless the
solution has been prepared in controlled and validated aseptic conditions.
Use of the pre-filled syringe with safety device for the needle
The needle safety device covers the needle after the injection and prevents the operator from injuring themselves.
The device does not interfere with the normal use of the syringe. Press the plunger rod and push
firmlyat the end of the injection to ensure complete emptying of the syringe. Hold
the skin firmly until the injection is complete. Hold the syringe firmly and slowly lift
the thumb from the plunger head. The plunger rod will move upwards with the
thumb and the spring will retract the needle into the needle protection
Use of the pre-filled syringe without a safety device for the needle
Administer the dose according to standard procedure.

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Disposal
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in accordance
with local regulations.

Accofil 70 MU/0,73 mL (0,96 mg/mL) solution for injection/infusion in pre-filled syringe

filgrastim

Read 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet:

• 1. What Accofil is and what it is used for
• 2. What you need to know before you use 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 produced naturally in the body, but they can be produced with the aid of biotechnology, for use as medicines. Accofil stimulates the bone marrow to produce a greater number of white blood cells.
A reduction in the number of white blood cells (neutropenia) can occur for various reasons, reducing the body's ability to defend itself against infections. Accofil stimulates the bone marrow to produce new white blood cells quickly.
Accofil can be used:

• to increase the number of white blood cells after chemotherapy treatment, thus helping to prevent infections;
• to increase the number of white blood cells after a bone marrow transplant, thus helping to prevent infections;
• before high-dose chemotherapy to induce the bone marrow to produce more stem cells that can be collected and re-infused after treatment. These cells can be taken from you 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, thus helping to prevent infections;
• in patients with advanced stage 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 excipients of this medicine (listed

in section 6).

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Accofil:
Before treatment, tell your doctor if you suffer from:

• Sickle cell anemia, because Accofil may cause a sickle cell crisis.
• Osteoporosis (bone disease)

Tell your doctor immediately if during treatment with Accofil:

• You experience pain in the upper left side of your abdomen or at the tip of your left shoulder (these may be symptoms of enlargement (splenomegaly) or possibly rupture of the spleen.)
• You notice unusual bleeding or bruising (these may be symptoms of a decreased number of platelets in the blood (thrombocytopenia), with a reduced ability of the blood to clot).
• You notice sudden symptoms of an allergy, such as skin rash, itching or hives, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing, or difficulty breathing, as these symptoms may indicate a severe allergic reaction (hypersensitivity).
• You have a swollen face or ankles, blood in your urine or brown-colored urine, or notice that you urinate 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 been rarely reported in cancer patients and healthy individuals. Symptoms may include fever, abdominal pain, malaise, back pain, and increased markers of inflammation. Tell your doctor if you experience such symptoms.

Loss of response to filgrastim
If you notice a loss of effectiveness or the inability to maintain effectiveness with filgrastim treatment,
your doctor will investigate the reasons, including the possibility that you have developed antibodies that
neutralize the activity of filgrastim.
Your doctor may want to monitor you more closely, see section 4.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a
blood cancer (leukemia, myelodysplastic syndrome). Talk to your doctor about the risk of
developing blood cancers and the necessary tests. If you develop or are likely to develop blood cancers, you should not use Accofil unless directed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.

Pay particular attention to other products that stimulate white blood cells.
Accofil belongs to the group of medicines that stimulate the production of white blood cells.
The healthcare professional must always record the exact name of the medicine being used.

Other medicines and Accofil
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.

Pregnancy and breastfeeding
Accofil has not been studied in pregnant women or breastfeeding women.
Accofil is not recommended during pregnancy.
It is important to tell your doctor if:

• you are pregnant or breastfeeding;
• you suspect you are pregnant, or
• you are planning to become pregnant. If you become pregnant during treatment with Accofil, tell your doctor.

Unless otherwise indicated by your doctor, you should stop breastfeeding if you use Accofil.

Driving and using machines
Accofil has modest effects on the ability to drive vehicles or use machines. This medicine
may cause dizziness, so wait and see
how you feel after administering Accofil before driving or using machines.

Accofil contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per pre-filled syringe, which is
essentially “sodium-free”.

Accofil contains sorbitol
This medicine contains 50 mg of sorbitol per ml. Sorbitol is a source of fructose. If
your doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic
disease, you (or your child) should not take this medicine. Patients with hereditary fructose
intolerance are unable to metabolize fructose, the accumulation of which can cause serious side effects.
Before taking this medicine, tell your doctor if you (or your child) suffer from hereditary
fructose intolerance or if the child feels unwell, vomits, or has unpleasant reactions such as bloating and
stomach cramps or diarrhea when consuming sweet foods or drinks.
An allergy to natural rubber latex. The needle cap of the pre-filled syringe contains
dry natural rubber (a latex derivative) which may cause serious allergic reactions.

3. How to use Accofil

Always use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor or pharmacist.

How is Accofil administered and how much should I take?
Accofil is generally administered by daily injection into the tissue just
below the skin (known as a subcutaneous injection). It can also be administered as a daily slow-release injection
into the vein (known as an intravenous infusion). The usual dose varies depending
on your condition and your weight. Your doctor will tell you how much Accofil you should take.
Patients receiving bone marrow transplant after chemotherapy:
You will normally receive the first dose of Accofil at least 24 hours after chemotherapy and at least
24 hours after receiving the bone marrow transplant.
You or the people who care for you may be taught how to administer subcutaneous injections
so that you can continue treatment at home. However, do not attempt to give yourself an
injection unless you have first received appropriate instructions from your doctor.

How long will I need to take Accofil?
You will need to take Accofil until the number of white blood cells has returned to normal. Blood tests will be
performed to monitor the number of white blood cells in your blood. Your doctor
will tell you how long you will need to take Accofil.

Use in children
Accofil is used for the treatment of children undergoing chemotherapy or who suffer from a severe
reduction in the number of white blood cells in the blood (neutropenia). The dosage in children treated with
chemotherapy is the same as used in adults.

Information for performing self-injection
This paragraph contains the information needed to perform a self-injection of Accofil. It is
important that you do not attempt to perform the injection yourself without first receiving appropriate
instructions from your doctor or
nurse. If you have any doubts about how to perform the injection or
would like more information, ask your doctor or nurse for advice.

How to perform a self-injection of Accofil?
The injection must be administered into the tissue under the skin: this method is known as
subcutaneous injection. It is necessary that you perform the injection at the same time each day.

Equipment required
To perform a subcutaneous injection, you must use:

• a pre-filled syringe of Accofil;
• an alcohol swab or equivalent disinfectant.

What to do before performing a subcutaneous injection of Accofil?
Make sure that the needle safety device remains on the syringe until you are ready to
perform the injection.

• a. Remove the pre-filled syringe of Accofil from the refrigerator.
• b. Check the expiration date (Exp.) on the label of the pre-filled syringe. Do not use the syringe if the date exceeds the last day of the month indicated or if it has been kept out of the refrigerator for more than 15 days or if the medicine has otherwise expired.
• c. Check the appearance of Accofil. It should appear as a clear and transparent liquid. If you notice particles inside, do not use it.
• d. To make the injection easier, remove the pre-filled syringe from the refrigerator and leave it at room temperature for 30 minutes, or hold it gently in your hand for a few minutes. Do not heat Accofil in any other way (e.g. do notheat Accofil in the microwave or in hot water).
• e. Wash your hands thoroughly.
• f. Find a comfortable and well-lit place and have everything you need close at hand (the pre-filled syringe of Accofil and the alcohol swab).

How to prepare the Accofil injection?
Before performing the Accofil injection, you must proceed as follows:

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Step 1: Integrity check of the system
Verify that the system is intact/not damaged. Do not use the product if you find any
damage (breakage of the syringe or needle safety device) or detached components and if the
needle safety device is in the safety position before use, as shown in figure
9, as this indicates that the system has already been activated. In general, the product should not be
used if it does not conform to figure 1. In this case, dispose of the product in a container
for biological risk materials (sharps).

Figure 1

Step 2: Removing the needle cap

• 1. Remove the protective cap as shown in figure 2. Hold the device protection body in one hand, pointing the needle end away from you and without touching the plunger rod. Remove the needle cap with your other hand. After removing the needle cap, dispose of it in a container for biological risk materials (sharps).
• 2. You may notice a small air bubble in the pre-filled syringe. You do not need to remove the air bubble before the injection. Injecting the solution containing the air bubble is harmless.
• 3. The syringe may contain more liquid than necessary. Use the scale on the syringe as indicated below to measure the correct dose of Accofil that your doctor has prescribed. Expel the excess liquid by pushing the plunger to the number (mL) on the syringe that corresponds to the prescribed dose of Accofil.
• 4. Check again to make sure the syringe contains the correct dose of Accofil.
• 5. The pre-filled syringe is now ready for use.

Figure 2

Where to perform the injection?
The most suitable areas for performing the injection are:

• the upper thigh; and
• the abdomen, except for the area around the navel (see figure 3).

Figure 3

If the injection is performed by another person, the medicine can also be injected into the back of the
arm (see figure 4).

Figure 4

It is preferable to change the injection site every day to avoid the risk of hardening at the
administration site.

Step 3: Needle insertion

• Pinch the skin at the injection site lightly with one hand;
• With the other hand, insert the needle into the injection site without touching the end of the plunger rod (at an angle of 45-90 degrees) (see figure 6 and 7).

How to perform the injection?
Disinfect the injection site using an alcohol swab and take the skin between your thumb and
index finger, without compressing (see figure 5).

Figure 5

Prefilled syringe without needle safety device

• a. Insert the needle fully into the skin, as shown to you by the nurse or doctor (see figure 6).
• b. Gently pull the plunger back to check that you have not punctured a blood vessel. If you see blood in the syringe, remove the needle and insert it into another site.
• c. Keeping the skin fold, slowly and evenly press the plunger until the entire dose is administered and until you can no longer push the plunger. Do not release pressure on the plunger!
• d. Inject only the dose that your doctor has told you to inject.
• e. After injecting the liquid, remove the needle while maintaining pressure on the plunger and release the skin.
• f. Place the used syringe in the disposal container. Use each syringe only for one injection.

Figure 6

Prefilled syringe with needle safety device

• Insert the needle fully into the skin, as shown to you by the nurse or doctor.
• Gently pull the plunger back to check that you have not punctured a blood vessel. If you see blood in the syringe, remove the needle and insert it into another site.
• Inject only the dose indicated by your doctor following the instructions below.

Figure 7

Step 4: Injection
Position your thumb on the end of the plunger rod. Press the plunger and push firmly
at the end of the injection to make sure the syringe is completely emptied (see figure 8).
Keep the skin firm in position until the injection is complete.

Figure 8

Step 5: Needle protection
The safety system will be activated once the plunger rod is fully pressed:

• Hold the syringe firmly and slowly lift your thumb from the end of the plunger rod;
• The plunger rod will rise together with your thumb and the spring will retract the needle into the needle protection device (see figure 9),

Figure 9

Remember
If you have any doubts or problems, contact your doctor or nurse for help or advice.

Disposal of used syringes
The needle safety device prevents accidental punctures after use, and for this reason
no special precautions are required. To dispose of the used syringe, follow the instructions provided by
your doctor, pharmacist or nurse.

If you use more Accofil than you should
Do not increase the dose prescribed by your doctor. If you think you have given yourself more than
you should, contact your doctor or pharmacist as soon as possible.

If you forget to use Accofil
If you have forgotten an injection, or the amount injected is too small, contact your
doctor as soon as possible. Do not take a double dose to make up for the missed dose.
If you have any doubts about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

It is important to inform your doctor immediatelyduring treatment

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), skin rash, itchy rash (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema) and shortness of breath (dyspnea).
• if you experience cough, fever and difficulty breathing (dyspnea), as this may be a sign of acute respiratory distress syndrome (ARDS).
• if you develop kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving filgrastim. See your doctor immediately if you have swelling of your face or ankles, blood in your urine, or dark brown urine, or if you notice that you are urinating less than usual.
• if you experience pain in the upper left side of the abdomen, pain under the left side of the ribs, or pain at the tip of the shoulder, as this could be a problem with the spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen);
• if you are being treated for severe chronic neutropenia and have blood in your urine (hematuria). If you experience this side effect or have protein in your urine (proteinuria), your doctor may perform urine tests at regular intervals;
• if you experience one or a combination of the following side effects: swelling or puffiness, which may be associated with fluid retention, difficulty breathing, abdominal swelling and a feeling of fullness, general feeling of tiredness. These symptoms usually develop rapidly.

This may be a condition called “Capillary Leak Syndrome” which
causes blood to leak from small blood vessels in your body and requires urgent medical attention.

• If you experience a combination of any of the following symptoms:
• fever, chills, feeling cold, rapid heartbeat, confusion, disorientation, shortness of breath, severe pain or discomfort, and moist or sweaty skin.

These may be symptoms of a condition called “sepsis” (also called
“blood poisoning”), a serious infection that triggers the inflammatory response of the whole
body which can be life-threatening and requires urgent medical attention.
A common side effect of Accofil is muscle or bone pain (musculoskeletal pain), which can be relieved by taking normal painkillers (analgesics).
In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease may occur, i.e. rejection of donor cells by the patient receiving the
transplant; signs and symptoms include rash on the palms of the hands or soles of the feet, and ulcers and lesions in the mouth, intestines, liver, skin or eyes, lungs,
vagina and joints.
In healthy stem cell donors, an increase in white blood cells (leukocytosis) and
a decrease in the number of platelets may be observed, resulting in reduced blood clotting ability
(thrombocytopenia); the doctor will monitor this reaction.

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

• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• tiredness (fatigue)
• sores and inflammation of the lining of the digestive tract between the mouth and the anus (mucosal inflammation)
• decreased number of platelets which reduces the blood’s ability to clot (thrombocytopenia)
• low number of red blood cells (anemia)
• fever (pyrexia)
• headache
• diarrhea

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

• lung inflammation (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• loss of appetite
• difficulty sleeping (insomnia)
• dizziness
• loss of sensation, especially of the skin (hypoesthesia)
• tingling or numbness of hands or feet (paresthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (hemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleed (epistaxis)
• constipation
• oral pain
• enlarged liver (hepatomegaly)
• skin rash
• skin redness (erythema)
• muscle spasm
• pain during urination (dysuria)
• chest pain
• pain
• general weakness (asthenia)
• general feeling of being unwell (malaise)
• swelling of hands and feet (peripheral edema)
• increased levels of certain enzymes in the blood
• changes in the chemical composition of the blood
• transfusion reaction

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

• increased white blood cells (leukocytosis)
• allergic reaction (hypersensitivity)
• rejection of bone marrow transplant (graft-versus-host disease)
• high levels of uric acid in the blood, which can cause gout (hyperuricemia) (increased uric acid in the blood)
• liver damage caused by blockage of the small veins of the liver (veno-occlusive disease)
• insufficient lung function, causing shortness of breath (respiratory failure)
• swelling and/or fluid accumulation in the lungs (pulmonary edema)
• inflammation of the lungs (interstitial pneumopathy)
• abnormal chest X-ray (pulmonary infiltration)
• bleeding from the lung (pulmonary hemorrhage)
• defect in oxygen absorption in the lung (hypoxia)
• skin rash with lesions (maculopapular rash)
• condition that causes loss of bone density, making them weaker, more fragile and easily broken (osteoporosis)
• reaction at the injection site

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

• inflammation of the aorta (the large blood vessel that carries blood from the heart to the rest of the body), see section 2.
• severe bone, chest, intestinal or joint pain (sickle cell crisis)
• sudden, potentially life-threatening allergic reaction (anaphylactic reaction)
• pain and swelling of the joints, similar to gout (pseudogout)
• alteration of fluid regulation in the body, which can cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• lesions detected violet and painful on the limbs and sometimes on the face and neck, with fever (Sweet's syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• decreased bone density
• formation of blood cells outside the bone marrow (extramedullary hematopoiesis).

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or nurse. You can also report side effects directly through the national reporting system listed in Annex V . By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Accofil

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 outer packaging and on the pre-filled syringe
after the abbreviation “Exp.”. The expiry date refers to the last day of that
month.
Store in a refrigerator (2°C- 8°C). Do not freeze.
The syringe may be kept outside the refrigerator and left at room temperature (not exceeding
25°C) for a single period, which ends within the expiry date stated on the label, for a
maximum of 15 days. At the end of this period, the product must not be returned to the refrigerator
and must be discarded.
Keep the syringe in the outer packaging to protect the medicine from light.
Do not use Accofil if you notice that the solution is cloudy, has changed colour or if it contains particles.
Do not put the cap on used needles, as you could accidentally prick yourself. Medicines should not
be disposed of via drains and household waste. Ask your pharmacist how to dispose of
medicines that you no longer use. This will help protect the environment.

6. Package contents and other information

What Accofil contains

• The active substance is filgrastim. Each pre-filled syringe contains 70 MU (700 micrograms) of filgrastim in 0.73 mL, corresponding to 0.96 mg/mL.
• The other ingredients are acetic acid, sodium hydroxide, sorbitol (E420), polysorbate 80 and water for injections.

Description of Accofil’s appearance and package contents
Accofil is a clear and colourless solution for injection or infusion in a pre-filled syringe
marked with a graduated scale with 40 notches from 0.1 mL to 1 mL, with an injection needle. Each
pre-filled syringe contains 0.73 mL of solution.
Accofil is available in packs of 1, 3, 5, 7 and 10 pre-filled syringes, with or without a safety
device for the pre-attached needle and alcohol-soaked swabs.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona,
Spain

Manufacturer
Accord Healthcare Polska Sp.z o.o.,
ul. Lutomierska 50,95-200 Pabianice, Poland
Accord Healthcare Single Member S.A.,
64th Km National Road Athens Lamia, Schimatari,
32009, Greece
For further information on this medicinal product, 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
More detailed information on this medicinal product is available on the following website: European
Medicines Agency https://www.ema.europa.eu
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The following information is intended exclusively for physicians or healthcare professionals:
Accofil does not contain preservatives. To avoid potential risks of microbial contamination, Accofil
syringes are for single use only.
Accidental exposure to freezing temperatures for up to 48 hours does not affect the stability of
Accofil. If exposure has been longer than 48 hours or it has been frozen more than once, Accofil
should 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 must be clearly recorded in the
patient’s medical record.
Accofil must not be diluted with sodium chloride solution. This medicinal product must not be
mixed with other medicinal products, except those indicated below. Diluted filgrastim may be adsorbed
by glass and plastic materials, unless diluted as specified below.
If necessary, Accofil can 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 must be visually inspected before use. Only clear and particle-free solutions must be used.
For patients treated with filgrastim diluted to concentrations less than 1.5 MU (15 µg) per mL, human
serum albumin must be added to a final concentration of 2 mg/mL.
Example: in a final injection volume of 20 mL, total doses of filgrastim less than 30 MU (300
µg) must be administered with 0.2 mL of 200 mg/mL (20%) human albumin solution.
When diluted in 5% glucose, Accofil is compatible with glass and plastic materials including PVC,
polyolefin (a copolymer of polypropylene and polyethylene) and polypropylene.
After dilution
The chemical and physical stability “in-use” of the diluted solution for infusion has been demonstrated for 30 hours
at a temperature of 25 °C ± 2 °C. From a microbiological point of view, the medicinal product must be
used immediately. If not, the storage times and conditions are the responsibility of the user and must not exceed 30 hours at a temperature of 25 °C ± 2 °C, unless the
solution has been prepared in controlled and validated aseptic conditions.
Use of the pre-filled syringe with needle safety device
The needle safety device covers the needle after injection and prevents the operator from injury.
The device does not interfere with the normal use of the syringe. Press the plunger rod and push
firmlyat 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 head. The plunger rod will move upwards with the
thumb and the spring will retract the needle from the site, into the needle protection.
Use of the pre-filled syringe without a needle safety device
Administer the dose according to standard procedure.

Do not use the pre-filled syringe if it has been dropped onto a hard surface.
Disposal
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in
accordance with local regulations.