Zefylti 48 MU/0.5 mL solution for injection/infusion in – patient leaflet, side effects, dosage

1. What Zefylti is and what it is used for

Zefylti is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of medicines called cytokines. Growth factors are proteins that are produced naturally in the body, but they can also be made using biotechnology for use as a medicine. Zefylti works by encouraging the bone marrow to produce more white blood cells.

A reduction in the number of white blood cells (neutropenia) can occur for several reasons and makes your body less able to fight infection. Zefylti stimulates the bone marrow to produce new white cells quickly.

Zefylti can be used:

• to increase the number of white blood cells after treatment with

  chemotherapy to help prevent infections;

• to increase the number of white blood cells after a bone marrow

  transplant to help prevent infections;

• before high-dose chemotherapy to make the bone marrow

  produce more stem cells which can be collected and given back to you after your treatment. These can be taken from you or from a donor. The stem cells will then go back into the bone marrow and produce blood cells;

• to increase the number of white blood cells if you suffer from

  severe chronic neutropenia to help prevent infections;

• in patients with advanced HIV infection which will help reduce

  the risk of infections.

2. What you need to know before you use Zefylti

Do not use Zefylti

• 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 Zefylti.

Please tell your doctor before starting treatment if you have:

• sickle cell anaemia, as Zefylti may cause sickle cell crisis.
• osteoporosis (bone disease).

Please tell your doctor immediately during treatment with Zefylti, if you:

• have sudden signs of allergy such as rash, itching or hives on

  the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing as these could be signs of a severe allergic reaction (hypersensitivity).

• experience puffiness in your face or ankles, blood in your urine

  or brown-coloured urine or you notice you urinate less than usual (glomerulonephritis).

• get left upper belly (abdominal) pain, pain below the left rib

  cage or at the tip of your left shoulder (these may be symptoms of an enlarged spleen (splenomegaly), or possibly rupture of the spleen).

  • notice unusual bleeding or bruising (these may be symptoms of

    a decrease in blood platelets (thrombocytopenia), with a reduced ability of your blood to clot).

Inflammation of the aorta (the large blood vessel which transports blood from the heart to the body) has been reported rarely in cancer patients and healthy donors. The symptoms can include fever, abdominal pain, malaise, back pain and increased inflammatory markers. Tell your doctor if you experience these symptoms.

Loss of response to filgrastim

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

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

If you are a patient with severe chronic neutropenia, you may be at risk of developing cancer of the blood (leukaemia, myelodysplastic syndrome (MDS)). You should talk to your doctor about your risks of developing cancers of the blood and what testing should be done. If you develop or are likely to develop cancers of the blood, you should not use Zefylti, unless instructed by your doctor.

If you are a stem cell donor, you must be aged between 16 and 60 years.

Take special care with other products that stimulate white blood cells

Zefylti is one of a group of products that stimulate the production of white blood cells. Your healthcare professional should always record the exact medicine you are using.

Other medicines and Zefylti

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

Pregnancy and breast-feeding

Zefylti has not been tested in pregnant or breast-feeding women.

Zefylti is not recommended during pregnancy.

It is important to tell your doctor if you:

• are pregnant or breast-feeding;
• think you may be pregnant; or
• are planning to have a baby.

If you become pregnant during Zefylti treatment, please inform your doctor. Unless your doctor directs you otherwise, you must stop breast-feeding if you use Zefylti.

Driving and using machines

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

Zefylti contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per pre-filled syringe, that is to say essentially ‘sodium-free’.

Zefylti contains polysorbate 80 (E433)

This medicine contains 0.02 mg of polysorbate 80 in each pre-filled syringe. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergies.

Zefylti contains sorbitol (E420)

This medicine contains 50 mg sorbitol(E420) in each mL.

Sorbitol (E420) is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you (or your child) must not receive this medicine. Patients with HFI cannot break down fructose, which may cause serious side effects.

You must tell your doctor before receiving this medicine if you (or your child) have HFI or if your child can no longer take sweet foods or drinks because they feel sick, vomit or get unpleasant effects such as bloating, stomach cramps or diarrhoea.

3. How to use Zefylti

Always use this medicine exactly as your doctor has told you. Check with your doctor, nurse or pharmacist if you are not sure.

How is Zefylti given and how much should I take?

Zefylti is usually given as a daily injection into the tissue just under the skin (known as a subcutaneous injection). It can also be given as a daily slow injection into the vein (known as an intravenous infusion). The usual dose varies depending on your illness and weight. Your doctor will tell you how much Zefylti you should take.

Patients having a bone marrow transplant after chemotherapy:

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

You, or people caring for you, can be taught how to give subcutaneous injections so that you can continue your treatment at home. However, you should not attempt this unless you have been properly trained first by your healthcare provider.

How long will I have to take Zefylti?

You will need to take Zefylti until your white blood cell count is normal. Regular blood tests will be taken to monitor the number of white blood cells in your body. Your doctor will tell you how long you will need to take Zefylti.

Use in children

Zefylti is used to treat children who are receiving chemotherapy or who suffer from severe low white blood cell count (neutropenia). The dosing in children receiving chemotherapy is the same as for adults.

If you use more Zefylti than you should

Do not increase the dose your doctor has given you. If you think you have injected more than you should, contact your doctor as soon as possible.

If you forget to use Zefylti

If you have missed an injection, or injected too little, contact your doctor as soon as possible. Do not take a double dose to make up for any missed doses. If you have any further questions on the use of this product, ask your doctor, nurse or pharmacist.

4. Possible side effects

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

Please tell your doctor immediately during treatment:

• if you experience an allergic reaction including weakness, drop

  in 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 (dyspnoea).

• if you experience a cough, fever and difficulty breathing

  (dyspnoea) as this can be a sign of Acute Respiratory Distress Syndrome (ARDS).

• if you experience kidney injury (glomerulonephritis). Kidney

  injury has been seen in patients who received filgrastim. Call your doctor right away if you experience puffiness in your face or ankles, blood in your urine or brown-coloured urine or you notice you urinate less than usual.

• if you have any of the following or combination of the

  following side effects:

  • swelling or puffiness, which may be associated with

    passing water less frequently, difficulty breathing, abdominal swelling and feeling of fullness, and a general feeling of tiredness. These symptoms generally develop in a rapid fashion.

These could be symptoms of a condition called “Capillary Leak Syndrome” which causes blood to leak from the small blood vessels into your body and needs urgent medical attention.

• if you have a combination of any of the following symptoms:

  • fever, or shivering, or feeling very cold, high heart rate,

    confusion or disorientation, shortness of breath, extreme pain or discomfort and clammy or sweaty skin.

These could be symptoms of a condition called “sepsis” (also

called “blood poisoning”), a severe infection with whole-body inflammatory response which can be life threatening and needs urgent medical attention.

• if you get left upper belly (abdominal) pain, pain below the left

  rib cage or pain at the tip of your shoulder, as there may be a problem with your spleen (enlargement of the spleen (splenomegaly) or rupture of the spleen).

• if you are being treated for severe chronic neutropenia and you

  have blood in your urine (haematuria). Your doctor may regularly test your urine if you experience this side effect or if protein is found in your urine (proteinuria).

  A common side effect of filgrastim use is pain in your muscles or bones (musculoskeletal pain), which can be helped by taking standard pain relief medicines (analgesics). In patients undergoing a stem cell or bone marrow transplant, Graft versus host disease (GvHD) may occur - this is a reaction of the donor cells against the patient receiving the transplant; signs and symptoms include rash on the palms of your hands or soles of your feet and ulcer and sores in your mouth, gut, liver, skin, or your eyes, lungs, vagina and joints.

  In normal stem cell donors, an increase in white blood cells (leucocytosis) and a decrease of platelets may be seen. This reduces the ability of your blood to clot (thrombocytopenia). These will be monitored by your doctor.

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

  • decrease of platelets which reduces the ability of blood to clot

    (thrombocytopenia)

  • low red blood cell count (anaemia)
  • headache
  • diarrhoea
  • vomiting
  • nausea
  • unusual hair loss or thinning (alopecia)
  • tiredness (fatigue)

  • soreness and swelling of the digestive tract lining which runs

    from the mouth to the anus (mucosal inflammation)

  • fever (pyrexia)

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

• inflammation of the lung (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• decreased appetite
• trouble sleeping (insomnia)
• dizziness

• decreased feeling of sensitivity, especially in the skin

  (hypoaesthesia)

• tingling or numbness of the hands or feet (paraesthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough, coughing up blood (haemoptysis)
• pain in your mouth and throat (oropharyngeal pain)
• nose bleeds (epistaxis)
• constipation
• oral pain
• enlargement of the liver (hepatomegaly)
• rash
• redness of the skin (erythema)
• muscle spasm
• pain when passing urine (dysuria)
• chest pain
• pain
• generalised weakness (asthenia)
• generally feeling unwell (malaise)
• swelling in the hands and feet (oedema peripheral)
• increase of certain enzymes in the blood
• changes in blood chemistry
• transfusion reaction

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

• increase in white blood cells (leucocytosis)
• allergic reaction (hypersensitivity)

• rejection of transplanted bone marrow (graft versus host

  disease)

• high uric acid levels in the blood, which may cause gout

  (hyperuricaemia) (Blood uric acid increased)

• liver damage caused by blocking of the small veins within the

  liver (veno-occlusive disease)

• lungs do not function as they should, causing breathlessness

  (respiratory failure)

• swelling and/or fluid in the lungs (pulmonary oedema)
• inflammation of the lungs (interstitial lung disease)
• abnormal x-rays of the lungs (lung infiltration)
• bleeding from the lung (pulmonary haemorrhage)
• lack of absorption of oxygen in the lung (hypoxia)
• bumpy skin rash (rash maculo-papular)

• disease which causes bones to become less dense, making them

  weaker, more brittle and likely to break (osteoporosis)

• injection site reaction

Rare side effects (may affect up to 1 in 1000 people):

• severe pain in the bones, chest, gut or joints (sickle cell

  anaemia with crisis)

• sudden life-threatening allergic reaction (anaphylactic

  reaction)

• pain and swelling of the joints, similar to gout (pseudogout)

• a change in how your body regulates fluids within your body

  and may result in puffiness (fluid volume disturbances)

• inflammation of the blood vessels in the skin (cutaneous

  vasculitis)

• plum-coloured, raised, painful sores on the limbs and

  sometimes the face and neck with a fever (Sweets syndrome)

• worsening of rheumatoid arthritis

  • unusual change in the urine
  • bone density decreased

  • inflammation of the aorta (the large blood vessel which

    transports blood from the heart to the body), see section 2

  • formation of blood cells outside of the bone marrow

    (extramedullary haematopoiesis).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. Healthcare professionals are asked to report any suspected adverse reactions (see details below).By reporting side effects you can help provide more information on the safety of this medicine. United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

5. How to store Zefylti

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 carton and on the pre-filled syringe after EXP. The expiry date refers to the last day of that month.

Store and transport refrigerated (2 °C – 8 °C). Do not freeze. Keep the pre-filled syringe in the outer carton in order to protect from light.

Within its shelf -life and for the purpose of ambulatory use, the patient may remove the product from the refrigerator and store it at room temperature (not above 25 °C) for one single period of up to 72 hours. At the end of this period, the product should not be put back in the refrigerator and should be disposed of.

Do not use this medicine if you notice it is cloudy or there are particles in it.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Zefylti contains

• Zefylti 30 MU/0.5 mL solution for injection/infusion: each

  pre-filled syringe contains

• 30 million units (MU), 300 mcg of filgrastim in 0.5 mL

  (corresponding to 0.6 mg/mL).

• Zefylti 48 MU/0.5 mL solution for injection/infusion: each

  pre-filled syringe contains

• 48 million units (MU), 480 mcg of filgrastim in 0.5 mL

  (corresponding to 0.96 mg/mL).

• The other ingredients are sodium acetate, sorbitol (E420),

  polysorbate 80 (E433), nitrogen gas and water for injections. See section 2 “Zefylti contains sorbitol(E420), polysorbate 80 (E433) and sodium”

What Zefylti looks like and contents of the pack

Zefylti is a clear colourless or slightly yellowish solution for injection/infusion in a glass pre-filled syringe with an injection needle (stainless steel) with a needle guard and without needle safety guard.

Zefylti is available in packs containing 1 and 5 pre-filled syringes (with needle safety guard and without needle safety guard. Not all pack sizes may be marketed.

Marketing Authorisation Holder

CuraTeQ Biologics (Malta) Limited

Vault 14 Level 2,

Valletta Waterfront,

Floriana, FRN 1914, Malta

Manufacturer

APL Swift Services Malta Ltd.

HF26, Hal Far Industrial Estate,

Qasam Industrijali Hal Far,

Birzebbugia, BBG 3000

Malta

Distributed By:

Milpharm Limited

Ares,Odyssey Business Park,

West End Road,Ruislip,Middlesex,

HA4 6QD,United Kingdom.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

This leaflet was last revised in 08/2026

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu.

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Instructions on how to inject yourself.

This section contains information on how to give yourself an injection of Zefylti. It is important that you do not try to give yourself the injection unless you have received special training from your doctor or nurse. Zefylti is provided with a needle safety guard, and you will be shown how to use this by your doctor or nurse. If you are not sure about giving the injection or you have any questions, please ask your doctor or nurse for help.

1. 1. Wash your hands.
2. 2. Remove the syringe from the pack and remove the protective cap from the injection needle. Syringes are embossed with graduation rings in order to enable partial use if required. Each graduation ring corresponds to a volume of 0.025 mL. If partial use of a syringe is required, remove unwanted solution before injection.
3. 3. Check the expiry date on the pre-filled syringe label (EXP). Do not use it if the date has passed the last day of the month shown.
4. 4. Check the appearance of Zefylti. It must be a clear and colourless liquid. If there is discolouration, cloudiness or particles in it, you must not use it.
5. 5. Clean the skin at the injection site using an alcohol wipe.
6. 6. Form a skin fold by pinching the skin between thumb and forefinger.
7. 7. Insert the needle into the skin fold with a quick, firm action.
8. 8. Keeping your skin pinched, depress the plunger slowly and evenly until the entire dose has been given and the plunger cannot be depressed any further. Do not release the pressure on the plunger.
9. 9. After injecting the liquid, remove the syringe from your skin while maintaining pressure on the plunger and then let go of your skin.
10. 10. Let go of the plunger. The needle safety guard will rapidly move to cover the needle.
11. 11. Discard any unused product or waste material. Only use each syringe for one injection.

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The following information is intended for healthcare professionals only

The solution should be visually inspected prior to use. Only clear solutions without particles should be used. Before use, inspect the syringe and use only if it is integral and there are no cracks, or any sign of breakage, needle shield is intact and properly fixed, and needle is not exposed/bent.

Accidental exposure to freezing temperatures does not adversely affect the stability of Zefylti.

Zefylti syringes are for single use only.

Dilution prior to administration (optional)

If required, Zefylti may be diluted in glucose 50 mg/mL (5%) solution. Zefylti must not be diluted with sodium chloride solutions.

Dilution to a final concentration < 0.2 MU/mL (2 mcg/mL) is not recommended at any time.

For patients treated with filgrastim diluted to concentrations < 1.5 MU/mL (15 mcg/mL), human serum albumin (HSA) should be added to a final concentration of 2 mg/mL.

Example: In a final volume of 20 mL, total doses of filgrastim less than 30 MU (300 mcg) should be given with 0.2 mL of human serum albumin 200 mg/mL (20%) solution Ph. Eur. added.

When diluted in glucose 50 mg/mL (5%) solution, filgrastim is compatible with glass and polypropylene.

After dilution: Chemical and physical in-use stability of the diluted solution for infusion has been demonstrated for 24 hours at 2 °C to 8 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.

Use of Pre-filled syringe with UltraSafe Passive Needle Guard

The pre-filled syringe has an UltraSafe Needle Guard attached in order to protect from needle stick injury. When handling the pre-filled syringe, keep hands behind the needle.

1. 1. Perform the injection using the technique described above.
2. 2. Depress the plunger while grasping the finger flange until the entire dose has been given. The passive needle guard will NOT activate unless the ENTIRE dose has been given.
3. 3. Remove the syringe from your skin, then let go of the plunger and allow the needle to move up until the entire needle is guarded and locks into place.

Disposal

Any unused product or waste material should be disposed of in accordance with local requirements.

Leaflet Dimensions: 720 mm (L) x 470 mm (W)

45° ZEFYLTI