Zarzio

Package leaflet: Information for the user

Zarzio 30 MU/0.5 mL solution for injection or infusion in pre-filled syringe, 48 MU/0.5 mL solution for injection or infusion in pre-filled syringe

filgrastim
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Zarzio is and what it is used for

Zarzio is a white blood cell growth factor (granulocyte colony-stimulating factor) and belongs to a group of proteins called cytokines. Growth factors are proteins normally produced by the body, but they can also be manufactured using biotechnology and used as medicines. Zarzio stimulates the bone marrow to produce a greater number of white blood cells.
The number of white blood cells may decrease (neutropenia) for various reasons, reducing the body's effectiveness in defending against infections. Zarzio stimulates the bone marrow to rapidly produce new white blood cells.
Zarzio can be used:

• to increase the number of white blood cells after chemotherapy and thereby improve prevention of infections;
• to increase the number of white blood cells after a bone marrow transplant and thereby improve prevention of infections;
• prior to high-dose chemotherapy to stimulate the bone marrow to produce a greater number of stem cells, which can be collected and re-administered after treatment. These cells may be collected from you or from a donor. Re-infused stem cells travel to the bone marrow and produce blood cells;
• to increase the number of white blood cells in cases of severe chronic neutropenia and thereby improve prevention of infections;
• in patients with advanced HIV infection to reduce the risk of infections.

2. What you need to know before using Zarzio

Do not use Zarzio

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Zarzio.
Inform your doctor before starting treatment if you have:

• osteoporosis (a bone disease);
• sickle cell anemia, as Zarzio may trigger a sickle cell crisis.

Inform your doctor immediately during treatment with Zarzio if:

• you experience pain in the upper left part of the abdomen, pain on the left side under the ribs, or pain at the tip of the left shoulder [these may be symptoms of an enlarged spleen (splenomegaly) or possible spleen rupture].
• you notice unusual bleeding or bruising [these may be symptoms of a reduced number of platelets in the blood (thrombocytopenia), resulting in decreased blood clotting ability].
• you develop 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 difficulty breathing, as these may indicate a severe allergic reaction (hypersensitivity).
• your face or ankles become swollen, you notice blood in your urine, your urine is brown in color, or you observe that you are urinating less than usual (glomerulonephritis).
• you experience symptoms of inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body); this effect has been reported in rare cases in cancer patients and healthy donors. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Inform your doctor if you experience any of these symptoms.

Loss of response to filgrastim
If during treatment with filgrastim you notice a loss of response or inability to maintain a response, your doctor will investigate the reasons, including the possibility that you have developed antibodies that neutralize the activity of filgrastim.
Your doctor may wish to monitor you particularly closely; see section 4 of the package leaflet.
If you are a patient with severe chronic neutropenia, you may be at risk of developing a blood cancer (leukemia, myelodysplastic syndrome [MDS]). Discuss with your doctor the risk of developing blood cancers and the necessary tests. You must not use Zarzio if you have developed or are likely to develop blood cancers, unless otherwise directed by your doctor.
If you are a stem cell donor, you must be between 16 and 60 years of age.
Pay special attention to other products that stimulate white blood cells.
Zarzio belongs to a group of medicines that stimulate the production of white blood cells. Healthcare professionals must always record the exact name of the medicine you are using.
Other medicines and Zarzio
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Zarzio has not been studied in pregnant or breastfeeding women.
Zarzio is not recommended during pregnancy.
It is important that you inform your doctor if

• you are pregnant or breastfeeding;
• you suspect you may be pregnant; or
• you are planning a pregnancy.

If you become pregnant while being treated with Zarzio, inform your doctor.
Unless otherwise advised by your doctor, if you are using Zarzio, you must stop breastfeeding.
Driving and using machines
Zarzio may slightly affect the ability to drive or use machines. This medicine may cause dizziness. Before driving or operating machinery, it is advisable to wait and observe how you feel after receiving Zarzio.
Zarzio contains sorbitol and sodium
Zarzio contains sorbitol (E420).
Sorbitol is a source of fructose. If your doctor has diagnosed you (or your child) with hereditary fructose intolerance, a rare genetic disorder, you (or your child) must not take this medicine. Patients with hereditary fructose intolerance are unable to metabolize fructose, and its accumulation may cause serious side effects.
Before taking this medicine, inform your doctor if you (or your child) have hereditary fructose intolerance or if your child feels unwell, vomits, or experiences unpleasant reactions such as bloating, stomach cramps, or diarrhea after consuming sweetened foods or drinks.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially 'sodium-free'.

3. How to use Zarzio

Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor, nurse, or pharmacist.
How is Zarzio administered and how much should I use?
Zarzio is normally administered as a daily injection into the tissue just beneath the skin (subcutaneous injection). It may also be given as a daily slow injection into a vein (intravenous infusion). The usual dose depends on your condition and body weight. Your doctor will tell you the dose of Zarzio you should take.
Patients undergoing bone marrow transplantation after chemotherapy:
You will normally receive your first dose of Zarzio at least 24 hours after chemotherapy and at least 24 hours after bone marrow transplantation.
You or your caregivers may be taught how to perform subcutaneous injections so that treatment can continue at home. However, you must not attempt this without first receiving adequate training from a healthcare professional.
How long should I take Zarzio?
You should take Zarzio until your white blood cell count has returned to normal. Blood tests will be performed at regular intervals to monitor your white blood cell count. Your doctor will advise you on how long to continue treatment.
Use in children
Zarzio is used to treat children undergoing chemotherapy or suffering from severe reduction in white blood cell count (neutropenia). The dose used in children undergoing chemotherapy is the same as that used in adults.
Administration of small doses
Do not inject a volume less than 0.3 mL using the pre-filled syringe, as accurate measurement is not possible due to the unavailability of markings on the scale for 0.1 and 0.2 mL.
If necessary, the injectable solution may be diluted.
If you use more Zarzio than you should
Do not increase the dose beyond that prescribed by your doctor. If you think you have injected more Zarzio than you should, contact your doctor as soon as possible.
If you forget to use Zarzio
If you missed an injection or injected less than the prescribed amount, contact your doctor as soon as possible.
Do not take a double dose to make up for a missed dose.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor immediately during treatment

• if you experience an allergic reaction including weakness, low blood pressure, difficulty breathing, swelling of the face (anaphylaxis), rash, rash accompanied by itching (urticaria), swelling of the face, lips, mouth, tongue or throat (angioedema), and shortness of breath (dyspnoea).
• if you develop cough, fever and difficulty breathing (dyspnoea), as this may be a sign of acute respiratory distress syndrome (ARDS).
• if you experience pain in the upper left part of the abdomen (abdominal pain), pain under the left ribs or pain at the tip of the shoulder, as this may indicate 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 (haematuria). 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 puffiness, which may be associated with passing water less frequently, difficulty breathing, abdominal swelling and a feeling of fullness, and a general feeling of fatigue. These symptoms usually develop rapidly. These may be symptoms of a condition called "capillary leak syndrome", which causes blood to leak from small blood vessels into body tissues and requires urgent medical treatment.
• if you experience a combination of any of the following symptoms:
  • fever or chills, or intense feeling of cold, rapid heart rate, confusion or disorientation, shortness of breath, extreme pain or discomfort, and moist or sweaty skin. These may be symptoms of a condition called "sepsis" (also known as "septicaemia"), a serious infection with a systemic inflammatory response, which can be life-threatening and requires urgent medical treatment.
• if you experience kidney damage (glomerulonephritis). Kidney damage has been observed in patients receiving filgrastim. Seek immediate medical advice if you have a swollen face or ankles, blood in your urine or brown-coloured urine, or if you notice that you are urinating less than usual.

A common side effect of filgrastim is pain in the muscles or bones (musculoskeletal pain), which can be relieved by taking normal painkillers (analgesics).
In patients undergoing stem cell or bone marrow transplantation, graft-versus-host disease (GvHD) may occur, which is a reaction of donor cells against 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, intestine, liver, skin or eyes, in the lungs, vagina and joints. In healthy stem cell donors, a very common occurrence is an increase in white blood cells (leucocytosis) and a reduction in platelets, which reduces the blood's ability to clot (thrombocytopenia); your doctor will monitor these reactions.

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

• decrease in platelets, reducing the blood's ability to clot (thrombocytopenia)
• low red blood cell count (anaemia)
• headache
• diarrhoea
• vomiting
• nausea
• unusual hair loss or thinning (alopecia)
• tiredness (fatigue)
• sores and swelling of the lining of the digestive tract from mouth to anus (mucositis)
• fever (pyrexia)

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

• inflammation of the lungs (bronchitis)
• upper respiratory tract infection
• urinary tract infection
• reduced appetite
• difficulty sleeping (insomnia)
• dizziness
• reduced sensation, especially of the skin (hypoesthesia)
• tingling or numbness of the hands or feet (paraesthesia)
• low blood pressure (hypotension)
• high blood pressure (hypertension)
• cough
• coughing up blood (haemoptysis)
• pain in the mouth and throat (oropharyngeal pain)
• nosebleed (epistaxis)
• constipation
• mouth pain
• enlargement of the liver (hepatomegaly)
• rash
• redness of the skin (erythema)
• muscle spasm
• pain during urination (dysuria)
• chest pain
• pain
• generalised weakness (asthenia)
• general feeling of being unwell
• swelling of the hands and feet (peripheral oedema)
• increase in 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)

• increase in white blood cells (leucocytosis)
• allergic reaction (hypersensitivity)
• rejection of bone marrow transplant (graft-versus-host disease)
• high levels of uric acid in the blood, which may cause gout (hyperuricaemia) (increase in uric acid in the blood)
• liver damage caused by blockage of small veins in the liver (veno-occlusive disease)
• inadequate lung function causing breathlessness (respiratory failure)
• swelling and/or fluid accumulation in the lungs (pulmonary oedema)
• inflammation of the lungs (interstitial pneumonitis)
• abnormalities on lung X-ray (pulmonary infiltration)
• bleeding from the lung (pulmonary haemorrhage)
• impaired oxygen uptake in the lungs (hypoxia)
• skin rash with pustules (maculopapular exanthema)
• a disease that makes bones less dense and therefore weaker, more fragile and prone to fractures (osteoporosis)
• injection site reaction

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

• severe bone, chest, intestinal or joint pain (sickle cell anaemia with crisis)
• sudden potentially fatal allergic reaction (anaphylactic reaction)
• joint pain and swelling, similar to gout (pseudogout)
• a disturbance in the body's fluid regulation, which may cause swelling (fluid volume disorders)
• inflammation of blood vessels in the skin (cutaneous vasculitis)
• painful, purplish lesions on limbs and sometimes on the face and neck, with fever (Sweet's syndrome)
• worsening of rheumatoid arthritis
• unusual changes in urine
• reduced bone density
• inflammation of the aorta (the large blood vessel carrying blood from the heart to the rest of the body), see section 2
• formation of blood cells outside the bone marrow (extramedullary haematopoiesis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via 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 Zarzio

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 carton and on the label of the
syringe after Scad./EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C).
Keep the pre-filled syringe in the outer packaging to protect the medicine from light.
Accidental freezing will not damage Zarzio.
The syringe may be kept outside the refrigerator and allowed to remain at room temperature for one
single time only, for up to 8 days (however, not above 25 °C). After this period, the product must not
be returned to the refrigerator and must be discarded.
Do not use this medicine if you notice any change in colour, cloudiness or the presence of particles;
the medicine should be a clear, colourless to pale yellow liquid.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Zarzio contains

• The active substance is filgrastim. Zarzio 30 MU/0.5 mL solution for injection or infusion in a pre-filled syringe: each pre-filled syringe contains 30 MU of filgrastim in 0.5 mL, corresponding to 60 MU/mL. Zarzio 48 MU/0.5 mL solution for injection or infusion in a pre-filled syringe: each pre-filled syringe contains 48 MU of filgrastim in 0.5 mL, corresponding to 96 MU/mL.
• The other components are glutamic acid, sorbitol (E420), polysorbate 80, sodium hydroxide and water for injections. See section 2 “Zarzio contains sorbitol and sodium”.

Description of the appearance of Zarzio and contents of the pack
Zarzio is a solution for injection or infusion, clear, colourless to pale yellow, in a pre-filled syringe containing 0.5 mL of solution.
Zarzio is available in packs containing 1, 3, 5 or 10 pre-filled syringes made of glass (Type I glass) with a plunger stopper (bromobutyl rubber), a 29-gauge stainless steel needle with an automatic needle safety device, and a needle cap (thermoplastic elastomer).
The pre-filled syringe is marked with indicators from 0.1 mL to 1 mL; however, the syringe is not designed to measure volumes below 0.3 mL due to the spring mechanism.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestr. 10
6250 Kundl
Austria

Manufacturer
Sandoz GmbH
Biochemiestr. 10
6336 Langkampfen
Austria
Novartis Pharmaceutical Manufacturing GmbH
Biochemiestrasse 10
6336 Langkampfen
Austria

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

België/Belgique/Belgien Lietuva
Sandoz nv/sa Sandoz Pharmaceuticals d.d filialas
Tél/Tel: +32 2 722 97 97 Tel: +370 5 2636 037

България Luxembourg/Luxemburg
Сандоз България КЧТ Sandoz nv/sa (Belgique/Belgien)
Тел.: +359 2 970 47 47 Tél/Tel.: +32 2 722 97 97

Česká republika Magyarország
Sandoz s.r.o. Sandoz Hungária Kft.
Tel: +420 234 142 222 Tel.: +36 1 430 2890

Danmark/Norge/Ísland/Sverige Malta
Sandoz A/S Sandoz Pharmaceuticals d.d.
Tlf/Sími/Tel: +45 63 95 10 00 Tel: +35699644126

Deutschland Nederland
Hexal AG Sandoz B.V.
Tel: +49 8024 908 0 Tel: +31 36 52 41 600

Eesti Österreich
Sandoz d.d. Eesti filiaal Sandoz GmbH
Tel: +372 665 2400 Tel: +43 5338 2000

Ελλάδα Polska
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz Polska Sp. z o.o.
Τηλ: +30 216 600 5000 Tel.: +48 22 209 70 00

España Portugal
Sandoz Farmacéutica, S.A. Sandoz Farmacêutica Lda.
Tel: +34 900 456 856 Tel: +351 21 000 86 00

France România
Sandoz SAS Sandoz Pharmaceuticals SRL
Tél: +33 1 49 64 48 00 Tel: +40 264 50 15 00

Hrvatska Slovenija
Sandoz d.o.o. Sandoz farmacevtska družba d.d.
Tel: +385 1 23 53 111 Tel: +386 1 580 29 02

Ireland Slovenská republika
Rowex Ltd. Sandoz d.d. - organizačná zložka
Tel: +353 27 50077 Tel: +421 2 48 200 600

Italia Suomi/Finland
Sandoz S.p.A. Sandoz A/S
Tel: +39 02 96541 Puh/Tel: +358 10 6133 400

Κύπρος United Kingdom (Northern Ireland)
SANDOZ HELLAS ΜΟΝΟΠΡΟΣΩΠΗ Α.Ε. Sandoz GmbH (Austria)
Τηλ: +30 216 600 5000 Tel: +43 5338 2000

Latvija
Sandoz d.d. Latvia filiāle
Tel: +371 67 892 006

More detailed information on this medicinal product is available on the European Medicines Agency website, http://www.ema.europa.eu.

7. Instructions for Use

To avoid possible infections, follow these instructions carefully.
It is important not to attempt to self-inject the medicine or administer the injection to another person
before receiving instructions from a doctor, nurse, or pharmacist. Read these instructions carefully
before administering the injection. Each sealed blister contains a pre-filled syringe.
Each pre-filled syringe contains 30 MU/0.5 mL or 48 MU/0.5 mL of filgrastim.
Figure 7-1 Zarzio in pre-filled syringe with needle safety device

After injecting the medicine, the needle safety device will be activated to cover the needle. This
device is intended to protect healthcare professionals, caregivers, and patients from accidental needlesticks
after injection.
Other materials required for injection:

• 1 alcohol-impregnated swab Figure 7-2 Other required materials

• 1 cotton ball or gauze pad
• Sharps disposal container
• 1 adhesive plaster

Important Safety Information
Caution: Keep the pre-filled syringe out of the reach of children.

1. Do not open the outer packaging until the moment of using the pre-filled syringe.
2. Do not use the pre-filled syringe if the blister seal is broken, as it may not be safe for use.
3. Do not use the pre-filled syringe if there is liquid in the plastic tray. Do not use the pre-filled syringe if the needle cap is missing or not securely attached. In all these cases, return the entire product package to the pharmacy.
4. Do not attempt to inject a dose smaller than 0.3 mL with a pre-filled syringe. It is not possible to accurately measure a dose smaller than 0.3 mL using the Zarzio pre-filled syringe, as the 0.1 and 0.2 mL graduation marks on the syringe barrel are not visible.
5. Never leave the pre-filled syringe unattended where others could tamper with it.
6. Do not shake the pre-filled syringe.
7. Be careful not to touch the needle safety wings before use, as this may cause premature activation of the needle safety device.
8. Do not remove the needle cap before administering the injection.
9. The pre-filled syringe cannot be reused. Dispose of the used pre-filled syringe immediately after use in a sharps disposal container.
10. Do not use the syringe if it has fallen onto a hard surface or if it has been dropped after removing the needle cap.

Storage of Zarzio Pre-filled Syringe

1. Store the pre-filled syringe in its outer packaging to protect it from light. Store in a refrigerator at a temperature between 2 °C and 8 °C (36 °F and 46 °F). Do not freeze.
2. Before preparing the syringe for injection, remember to remove the blister from the refrigerator and allow it to reach room temperature for 15–30 minutes.
3. Do not use the pre-filled syringe after the expiry date stated on the outer packaging or syringe label. If the medicine has expired, return the entire package to the pharmacy.
4. The syringe may be kept outside the refrigerator and stored at room temperature for one single period of up to 8 days (but not above 25 °C). After this period, the product must not be returned to the refrigerator and must be discarded.

Injection Site
Figure 7-3 Injection Sites
The injection site is the part of the body where the

pre-filled syringe will be used.

• The recommended area is the front of the thigh. The lower abdomen may also be used, but avoiding the area within 5 cm (2 inches) of the navel.

• If the injection is administered by a caregiver, the outer upper arms and upper buttocks may also be used.

• Choose a different site for each self-injection.

• Do not administer the injection into areas where the skin is tender, bruised, red, flaky, or hard. Avoid areas with scars or stretch marks.

Preparing the Zarzio Pre-filled Syringe for Use

1. Remove the blister containing the pre-filled syringe from the refrigerator and leave it closed for approximately 15–30 minutes to allow it to reach room temperature.
2. At the time of using the pre-filled syringe, open the blister and wash hands thoroughly with water and soap.
3. Clean the selected injection site with an alcohol-impregnated swab.
4. Remove the pre-filled syringe from the blister by holding it in the center as shown in Figure 7-4. Do not grasp the plunger. Do not grasp the needle cap.

Figure 7-4 Removing the pre-filled syringe from the blister

5. Check that the transparent plastic needle safety device is positioned over the glass syringe barrel. If the transparent needle safety device covers the needle cap (as shown in Figure 7-5 below), the syringe has been activated. DO NOT USE this syringe and use a new one instead. Figure 7-6 shows a syringe ready for use.

Figure 7-5 DO NOT USE

In this configuration, the needle safety device is ACTIVATED: DO NOT USE the pre-filled syringe
Figure 7-6 Ready for use

In this configuration, the needle safety device is NOT ACTIVATED and the pre-filled syringe is ready for use

6. Inspect the pre-filled syringe. The liquid should be clear. It may be colourless or slightly yellowish. DO NOT USE if other particles or colour changes are observed, and return the pre-filled syringe and its packaging to the pharmacy.
7. DO NOT USE if the pre-filled syringe is damaged or if the needle safety device is activated. In all these cases, return the entire product package to the pharmacy.

How to Use the Zarzio Pre-filled Syringe
Figure 7-7 Remove the needle cap Carefully pull off the needle cap from the pre-filled syringe.
Discard the needle cap. A small drop of liquid may be observed at the tip of the needle. This is normal.
Holding the syringe as illustrated, slowly press the plunger to expel excess medicine until the edge of the conical base of the plunger stopper aligns with the graduation mark on the syringe corresponding to the prescribed dose. Below is an example for a 0.4 mL dose.
Be careful not to touch the needle safety wings before use, as this may cause premature activation of the needle safety device.
Double-check that the correct dose of Zarzio is present in the pre-filled syringe.
If you experience any difficulties in measuring or injecting the Zarzio dose, contact your doctor or nurse.
Figure 7-8 Example of partial dose for a 0.4 mL dose

Figure 7-9 Insert the needle Gently pinch the skin at the injection site and insert the needle as illustrated. To ensure complete delivery of the medicine, insert the needle fully.

Figure 7-10 Press the plunger Holding the pre-filled syringe as shown, press the plunger slowly and fully until the plunger head moves completely between the needle safety wings.
Keep the plunger fully depressed while holding the syringe steady for 5 seconds.

Figure 7-11 Remove the needle Keep the plunger fully depressed while carefully withdrawing the needle from the injection site.

Figure 7-12 Release the plunger Slowly release the plunger and allow the needle safety device to automatically cover the exposed needle.

A small amount of blood may appear at the injection site. You may press a cotton ball or gauze pad over the injection site and hold it for 10 seconds. Do not rub the injection site. If needed, the injection site may be covered with a small adhesive plaster.

Disposal Instructions
Figure 7-13 Disposal
Dispose of the used syringe in a dedicated sharps disposal container (a closable, puncture-resistant container). For your safety and health, and that of others, used needles and syringes must never be reused.

The following information is intended for healthcare professionals only:

The solution should be inspected visually before use. Only clear, particle-free solutions should be used.
Accidental exposure to freezing temperatures does not have negative effects on the stability of Zarzio.
Zarzio contains no preservatives: due to the risk of bacterial contamination, Zarzio syringes are for single use only.

Dilution prior to administration (optional)
If necessary, Zarzio may be diluted in glucose 50 mg/mL (5%) solution. Zarzio must not be diluted with sodium chloride solutions.
Dilution to final concentrations < 0.2 MU/mL (2 micrograms/mL) is not recommended.
In patients treated with filgrastim diluted to concentrations < 1.5 MU/mL (15 micrograms/mL), human serum albumin (HSA) should be added to a final concentration of 2 mg/mL.
Example: for a final volume of 20 mL, total filgrastim doses below 30 MU (300 micrograms) should be supplemented with 0.2 mL of human serum albumin solution Ph. Eur. 200 mg/mL (20%).

When diluted with glucose 50 mg/mL (5%) solution, filgrastim is compatible with glass and various plastic materials including polyvinyl chloride, polyolefin (a copolymer of polypropylene and polyethylene), and polypropylene.

After dilution: the chemical and physical in-use stability of the diluted infusion solution has been demonstrated for 24 hours at 2 °C – 8 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the user is responsible for ensuring the duration and conditions of storage prior to use; the product may be stored for up to 24 hours at 2 °C – 8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.

Use of the pre-filled syringe with needle safety device
The needle safety device covers the needle after injection, preventing needle-stick injuries to the operator.
The safety device does not interfere with the normal use of the syringe. Press slowly and evenly on the plunger until the full dose is delivered and the plunger can no longer be depressed. Remove the syringe from the patient while continuing to press on the plunger. The safety device will cover the needle as soon as the plunger is released.

Disposal
Any unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.