Consumer medicine information

Pelgraz

Pegfilgrastim

BRAND INFORMATION

Brand name

Pelgraz

Active ingredient

Pegfilgrastim

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Pelgraz.

What is in this leaflet

This leaflet answers some common questions about this medicine. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may want to read it again.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available

What this medicine is used for

The name of your medicine is Pelgraz. It contains the active ingredient, pegfilgrastim.

Pelgraz is used to help fight infection, following chemotherapy. It belongs to a group of medicines called immunostimulants.

Some chemotherapy will reduce the number of neutrophils in your body. Although Pelgraz is not a treatment for cancer, it does help the body to make new neutrophils. This will reduce your chance of developing infections that might require antibiotics and/or hospital stays. It may even increase your chance of receiving your chemotherapy on time and at the right dose.

How it works

Pelgraz is a long acting form of Recombinant Human Granulocyte Colony Stimulating Factor or G-CSF.

G-CSF is produced in the bone marrow and assists in the production of neutrophils, which are a type of white blood cell. Neutrophils help the body fight infections by surrounding and destroying the bacteria that cause the infections. G-CSF also helps neutrophils to do this work better.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is available only with a doctor's prescription.

Before you use or are given this medicine

When you must not use it

You must not use or be given this medicine if you have an allergy to:

  • any medicine containing pegfilgrastim or filgrastim
  • any medicines or products that are produced using the bacteria, E.coli
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin.

Do not use Pelgraz at the same time as your chemotherapy or radiotherapy.

Do not use Pelgraz within 24 hours after you receive chemotherapy. This is because the chemotherapy medicine may stop Pelgraz from increasing the number of infection-fighting neutrophils.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should use or be given this medicine, talk to your doctor.

Before you use or are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • a medical condition affecting the bone marrow or blood
  • a family history of a genetic disorder
  • sickle cell disease
  • problems with your kidneys, liver, heart or other organs
  • previous treatment for cancer
  • any infections, cancers or tumours.

Tell your doctor if you are pregnant or plan to become pregnant, or are breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor any of the above, tell him/her before you use or are given this medicine.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

These medicines may be affected by this medicine or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How this medicine is used or given

This medicine is given by injection, into the tissues, just below the skin. This is called a subcutaneous injection.

Your doctor, nurse or pharmacist may suggest that you or your carer be taught how to give a subcutaneous injection. This will allow you to give yourself the injection at home.

It is important that you get special training from your doctor or nurse before you give yourself the injection.

If you are not sure about giving yourself the injection or you have any questions, ask your doctor, nurse or pharmacist for help.

Carefully follow all directions given to you by your doctor, nurse or pharmacist. They may differ from the information in this leaflet.

If you do not understand the instructions in this leaflet, ask your doctor, pharmacist or nurse for help.

How much to inject

The usual dose is one subcutaneous injection (6 mg/0.6 mL), 24 hours after the end of each chemotherapy cycle.

How to give yourself the injection

This section contains information on how to give yourself an injection of Pelgraz (pre-filled syringe with passive needle guard).

Before you give yourself the injection, read this important information:

  • Tell your doctor if you have an allergy to latex. The needle cover on the pre-filled syringe contains a derivative of latex and may cause severe allergic reactions.
  • DO NOT remove the needle cover from the pre-filled syringe until you are ready to inject.
  • DO NOT use the pre-filled syringe if it has been dropped on a hard surface. Use a new pre-filled syringe and call your doctor or healthcare provider.
  • DO NOT attempt to remove the clear pre-filled syringe needle guard from the pre-filled syringe.

Things to do before you inject

Remove the pre-filled syringe tray from the package and gather the supplies needed for your injection: alcohol wipes, a cotton ball or gauze pad, an adhesive bandage and a sharps disposal container (may be provided).

For a more comfortable injection, leave the pre-filled syringe at room temperature for about 30 minutes before injecting.

On a clean, well-lit work surface, place the new pre-filled syringe and the other supplies.

  • DO NOT try to warm the syringe by using a heat source, such as hot water or microwave.
  • DO NOT leave the pre-filled syringe exposed to direct sunlight.
  • DO NOT shake the pre-filled syringe.
  • Keep pre-filled syringes out of the sight and reach of children.

Follow these below instructions for correct handling technique when removing the pre-filled syringe with the passive needle guard from the packaging; otherwise, the needle’s safety mechanism may be triggered, making the syringe unusable.

1. Open the tray, peeling away the cover.

To remove the individual syringe from the blister packaging, start with the corner (as shown by the arrow and “Peel here”) and open the blister pack by completely peeling back the top layer

2. Hold onto the pre-filled syringe safety guard to remove the prefilled syringe from the tray.

Remove the syringe from the blister pack by the body as shown below:

For safety reasons:

  • DO NOT lift the product by the plunger or needle cover.
  • DO NOT touch the needle guard activation clips at any time during use. This may trigger the needle's safety mechanism causing the needle to retract (pull back) before your injection is given. This will make the syringe unusable.

3. Inspect the medicine and prefilled syringe. DO NOT use the pre-filled syringe if:

  • the medicine is cloudy or there are particles in it. It must be a clear and colourless liquid
  • any part appears cracked or broken
  • the needle cover is missing or not securely attached
  • the expiry date printed on the label has passed the last day of the month shown
  • in all cases, call your doctor or healthcare provider.

Selecting and preparing the injection site

You will need to give yourself an injection into the tissue under the skin, known as a subcutaneous injection:

  • Wash hands thoroughly with soap and water.
  • Before you inject this medicine, you must always disinfect the skin on the selected injection site by using an alcohol swab. Let the skin dry.
  • Choose an injection site from the most suitable place on your body (listed and shown here):
    - outer area of your upper arms
    - front of your middle thighs
    - abdomen, except for the 5 centimetre area around the navel
    - upper outer area of your buttocks

  • DO NOT touch the selected injection area before injecting.
  • DO NOT inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
  • From the above options, change the injection site each time you take an injection so that you do not develop soreness in one area.

Injecting the prescribed dose of medicine

  1. Before you inject this medicine, you must always clean the skin on the selected injection site by using an alcohol wipe.
  2. Hold the pre-filled syringe by the body (needle guard) with the needle pointing up and away from your body, as this helps to prevent the medicine from accidentally expelling from the syringe.
  • DO NOT remove the needle cover from the pre-filled syringe until you are ready to inject.
  1. Carefully remove the needle cover straight off, without twisting it.

  • DO NOT touch the needle or the plunger.
  • DO NOT use if the syringe is damaged or the needle is bent.
  • DO NOT use the pre-filled syringe if it has been dropped on a hard surface. The prefilled syringe may be broken even if you cannot see the break. Use a new pre-filled syringe.
  • DO NOT push the plunger on the syringe before injection. This may release the needle guard by springing and completely covering the needle.
  • DO NOT use the pre-filled syringe if any liquid is accidentally expelled from the syringe. Dispose of that syringe in a puncture-proof disposal container. Use a new pre-filled syringe.
  • DO NOT push the plunger on the syringe before injection. This may release the needle guard by springing and completely covering the needle.
  1. Hold the pre-filled syringe between the thumb and the forefinger of the hand that you will use to inject the medicine.
  2. Use the other hand to pinch a fold of the skin at the cleaned injection site between your thumb and forefinger without squeezing it, as shown below:

  1. Insert the needle into the skin at an angle greater than or equal to 45° (45 degrees), as shown by your nurse, doctor or pharmacist, and as shown below:

  1. After the needle is inserted, let go pinching on the fold of skin.
Inject the prescribed dose subcutaneously by pushing the plunger with your thumb while grasping the finger grips, as directed by your doctor, nurse, or pharmacist, and as shown below:

  1. Press the plunger slowly and completely, until all of the medicine has been injected, as shown below:

The needle guard will not be activated unless the entire dose has been administered and you remove downward pressure on the plunger.
  1. When the syringe is emptied of all the medicine, slowly lift your thumb from the plunger, which will release the needle guard. The needle will then withdraw from the skin and be covered and locked in place by the needle guard.

  1. After the injection, immediately place cotton or gauze on the injected site and apply pressure for several seconds.

Disposal

Place the pre-filled syringe with the needle guard-covered needle into a puncture-proof container for proper disposal.

Medicines should be disposed of in accordance with local requirements. These measures will help protect the environment.

Follow the instructions given by your doctor, nurse, or pharmacist on how to properly dispose of containers with used syringes and needle guards.

Always keep the disposal container out of the reach and sight of children.

  • DO NOT re-use the pre-filled syringes.
  • DO NOT recycle pre-filled syringes.
  • DO NOT throw the pre-filled syringes into household bins.

Examining the injection site

If there is blood, press a cotton ball or gauze pad on your injection site. DO NOT rub the injection site.

Apply an adhesive bandage if needed.

If you have any problems, please ask your doctor, nurse or pharmacist for help and advice.

When to inject

Use this medicine 24 hours after the end of each chemotherapy cycle.

Your doctor will tell you when to begin your treatment and when to stop.

If you forget your injection

If you miss your scheduled dose, talk to your doctor, nurse or pharmacist as soon as possible.

If you receive too much (overdose)

If you inject more of this medicine than you need, talk to your doctor, nurse or pharmacist. If you feel unwell in any way you talk to your doctor, nurse or pharmacist immediately.

While you are using this medicine

Things you must do

Watch for any signs or symptoms of infection.

There are many ways an infection may show itself.

Symptoms of an infection include:

  • fever (a temperature of 38.2°C or greater, or as your doctor suggests)
  • chills
  • rash
  • sore throat
  • diarrhoea
  • earache
  • difficult or painful breathing, coughing or wheezing.

Go straight to your hospital if you develop any of these symptoms.

If you are about to be started on any new medicine, remind your doctor, nurse and pharmacist that you are using this medicine.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your health can be monitored. Your doctor may order blood tests to check the levels of infection-fighting neutrophils and other blood cells, as well as to investigate unwanted side effects.

Things you must not do

Do not use this medicine to treat any other complaints unless your doctor tells you to.

Do not give this medicine to anyone else, even if they have the same condition as you.

Side effects

Tell your doctor as soon as possible if you do not feel well after using this medicine or if you have any questions or concerns.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

If you are over 65 years of age, you may have an increased chance of getting side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • temporary bone pain, such as in the lower back or in the long bones of the arms or legs.
    This pain is usually relieved with non-prescription painkillers, such as paracetamol. If you continue to have bone pain even after having taken this form of pain relief, you should speak to your doctor, as you may need a prescription medicine.
  • headache
  • general aches and pains in joints and muscles
  • reddish or purplish blotches under the skin
  • injection site pain and redness of the skin at the injection site.

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • pain in the upper left side of the stomach (abdomen)
  • left shoulder pain
  • dizziness
  • fever and painful skin lesions most commonly on your arms, legs and sometimes on your face and neck
  • blood in the urine.

The above list includes serious side effects that may require medical attention.

If any of the following happen, tell your doctor or nurse immediately, or go to the Emergency department at your nearest hospital:

  • swelling or puffiness
  • less frequent urination
  • swelling of your stomach-area (abdomen) and feeling of fullness
  • general feeling of tiredness.

These may be serious side effects. You may need urgent medical attention.

If any of the following happen, stop taking this medicine and go to the Emergency department at your nearest hospital, as you may need urgent medical attention:

  • rash over a large area of the body, itching or hives
  • shortness of breath, wheezing or difficulty breathing
  • coughing up blood, bleeding from the lung
  • swelling of the face, lips, tongue or other parts of the body
  • faintness
  • rapid pulse or sweating.

The above list includes very serious side effects. If you have them you may have had a serious allergic reaction to this medicine. You may need urgent medical attention or hospitalisation.

Tell your doctor, nurse or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may occur in some people.

Storage and presentation

Storage

Keep this medicine in a refrigerator at a temperature of 2°C to 8°C.

This medicine can be removed from the refrigerator and left at room temperature (not above 25°C) for a single period of up to 15 days that ends within the labelled expiry date. Once it has been out at room temperature, it should not be put back into the refrigerator.

You should avoid freezing this medicine; however, if it has been accidentally frozen, allow the medicine to thaw in the refrigerator before use.

Do not use this medicine if it has been frozen a second time.

Keep your medicine in the carton. Protect it from light.

Keep it where children cannot reach it.

Disposal

Once you have finished the injection, do not put the needle cover back on the used syringe.

Discard the used syringe into an approved, puncture-resistant sharps container, as instructed by your doctor, nurse or pharmacist. Keep it out of the reach of children.

Never put the used syringes into your normal household rubbish bin.

Use each pre-filled syringe only for one injection.

DO NOT recycle.

DO NOT try to put the needle cover back on the needle.

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Pelgraz is a clear, colourless solution. It is supplied in a carton as a pre-filled syringe with a passive needle guard.

Ingredients

Each syringe contains 6 mg of pegfilgrastim, as the active ingredient.

This medicine also contains the following:

  • 0.35 mg glacial acetic acid
  • 30 mg sorbitol
  • 0.024 mg polysorbate 20
  • 0.034 mg sodium hydroxide
  • water for injection (to 0.6 mL).

This medicine does not contain gluten, lactose, sucrose, tartrazine or other azo dyes.

Australian Registration Number

Pelgraz 6 mg/0.6 mL solution for injection, pre-filled syringe: AUST R 308177.

Supplier

Accord Healthcare Pty Ltd
Level 24, 570 Bourke Street
Melbourne, VIC, 3000
Australia

This leaflet was prepared in November 2019.

Published by MIMS September 2020

BRAND INFORMATION

Brand name

Pelgraz

Active ingredient

Pegfilgrastim

Schedule

S4

 

1 Name of Medicine

Pelgraz contains pegfilgrastim (rbe), a long-acting form of recombinant human granulocyte colony stimulating factor (G-CSF).
Pelgraz is a biosimilar medicinal product (i.e. a medicine that has been demonstrated to be similar in quality, safety and efficacy to the reference medicinal product, Neulasta). The evidence for comparability supports the use of Pelgraz for the listed indication.

2 Qualitative and Quantitative Composition

Pelgraz is composed of filgrastim (recombinant methionyl human G-CSF) with a 20,000 dalton polyethylene glycol (PEG) molecule covalently bound to the N-terminal methionine residue.
Filgrastim is a 175 amino acid protein manufactured by recombinant DNA technology. Filgrastim is produced by Escherichia coli (E.coli) bacteria into which has been inserted the human G-CSF gene. Filgrastim is unglycosylated and contains an N-terminal methionine necessary for expression in E. coli. Pegfilgrastim has a total molecular weight of 39,000 daltons.
Each single-use pre-filled syringe with needle guard of Pelgraz contains 6 mg of pegfilgrastim (based on protein mass only).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Pelgraz is a sterile, clear, colourless, preservative-free liquid for subcutaneous (SC) administration.

4 Clinical Particulars

4.1 Therapeutic Indications

Pegfilgrastim is indicated for the treatment of cancer patients following chemotherapy, to decrease the duration of severe neutropenia and so reduce the incidence of infection, as manifested by febrile neutropenia.

4.2 Dose and Method of Administration

Dosage (dose and interval).

The recommended dosage of Pelgraz is a single SC injection of 6 mg administered once per chemotherapy cycle. Pelgraz should be administered approximately 24 hours after the administration of cytotoxic chemotherapy. In clinical studies, pegfilgrastim has been safely administered 14 days before chemotherapy (see Section 4.4 Special Warnings and Precautions for Use).

Method of administration.

Pelgraz contains no antimicrobial agent. Pelgraz is for single-use in one patient only.
Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration. Do not use any products exhibiting particulate matter or discolouration.
Avoid shaking. Allow the ready-to-use pre-filled syringe with needle guard to reach room temperature before injecting.
Pelgraz is supplied in single-use, pre-filled syringes with a needle guard to prevent accidental needle stick injury. When the pre-filled syringe is emptied of all the medication, the needle-guard mechanism pushes over the needle, withdrawing it from the skin and covering it completely. The pre-filled syringe should be disposed of by placing it into an approved puncture-proof container.
The needle cover on the single-use pre-filled syringe contains dry natural rubber (a derivative of latex), which may cause allergic reactions and should not be handled by individuals who are sensitive to latex.

4.3 Contraindications

Pegfilgrastim is contraindicated in patients with known hypersensitivity to E. coli-derived proteins, pegfilgrastim, filgrastim, or any other component of the product.

4.4 Special Warnings and Precautions for Use

Splenomegaly and splenic rupture.

Cases of splenic rupture, including some fatal cases, have been reported following administration of pegfilgrastim. Patients who report left upper abdominal pain and/or shoulder tip pain should be evaluated for an enlarged spleen or splenic rupture.

Sickle cell crisis.

Sickle cell crises have been associated with the use of pegfilgrastim in patients with sickle cell disease. Clinicians should exercise caution, monitor patients accordingly when administering pegfilgrastim to patients with sickle cell trait or sickle cell disease and only consider use after careful evaluation of the potential benefits and risks.

Pulmonary haemorrhage and haemoptysis.

Pulmonary haemorrhage and haemoptysis requiring hospitalisation have been reported in G-CSF-treated healthy donors undergoing peripheral blood progenitor cell (PBPC) collection mobilisation. Haemoptysis resolved with discontinuation of G-CSF.

Acute respiratory distress syndrome.

In patients with sepsis receiving pegfilgrastim, the physician should be alert to the possibility of acute respiratory distress syndrome, due to the possible influx of neutrophils at the site of inflammation.

Glomerulonephritis.

Glomerulonephritis has been reported in patients receiving pegfilgrastim. Generally, after withdrawal of pegfilgrastim, events of glomerulonephritis resolved. Monitoring of urinalysis is recommended.

Myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in patients with breast and lung cancer.

In the post-marketing observational study setting, myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) have been associated with the use of pegfilgrastim in conjunction with chemotherapy and/or radiotherapy in breast and lung cancer patients. Monitor patients for signs and symptoms of MDS/AML in these settings.

Concurrent use with chemotherapy and radiotherapy.

The safety and efficacy of pegfilgrastim given concurrently with cytotoxic chemotherapy have not been established. Because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, the use of pegfilgrastim is not recommended in the period 24 hours after the administration of chemotherapy (see Section 4.2 Dose and Method of Administration). In clinical studies, pegfilgrastim has been safely administered 14 days before chemotherapy. Clinical trials with pegfilgrastim have not involved patients treated with fluorouracil or other anti-metabolites. In studies in mice, administration of pegfilgrastim at 0, 1 and 3 days before fluorouracil resulted in increased mortality; administration of pegfilgrastim 24 hours after fluorouracil did not adversely affect survival.
The safety and efficacy of pegfilgrastim have not been evaluated in patients receiving chemotherapy associated with delayed myelosuppression (e.g. nitrosoureas).
The safety and efficacy of pegfilgrastim have not been evaluated in patients receiving radiotherapy.

Use in myelodysplasia and leukaemia.

The safety and efficacy of pegfilgrastim administration in patients with myelodysplasia or chronic myeloid leukaemia have not been established.
Randomised studies of filgrastim in patients undergoing chemotherapy for acute myeloid leukaemia demonstrate no stimulation of disease as measured by remission rate, relapse and survival.

Leukocytosis.

In pegfilgrastim clinical studies, self-limiting leukocytosis (WBC counts > 100 x 109/L) have been reported in < 0.5% of 930 subjects with non-myeloid malignancies receiving pegfilgrastim.
Leukocytosis was not associated with any reported adverse clinical effects.

Immunogenicity.

As with all therapeutic proteins, there is potential for immunogenicity. Rates of antibody generation against pegfilgrastim are generally low. Binding antibodies do develop but have not been associated with neutralising activity or adverse clinical consequences.
The detection of antibody formation is dependent on the sensitivity and specificity of the assay. The observed incidence of antibody positivity (including neutralising antibody) in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease, therefore comparison of the incidence of antibodies to other products may be misleading.

Thrombocytopenia and anaemia.

Thrombocytopenia has been reported in patients receiving pegfilgrastim. Platelet counts should be monitored closely.
In studies of pegfilgrastim administration following chemotherapy, most reported side effects were consistent with those usually seen as a result of cytotoxic chemotherapy (see Section 4.8 Adverse Effects (Undesirable Effects)). Because of the potential for patients to receive higher doses of chemotherapy (i.e. full doses on the prescribed schedule for a longer period), patients may be at greater risk of thrombocytopenia which should be monitored carefully. Anaemia and non-haematologic consequences of increased chemotherapy doses (please refer to the prescribing information for specific chemotherapy agents used) may also occur. If there is a risk of these conditions, regular monitoring of the complete blood count is recommended. Furthermore, care should be exercised in the administration of pegfilgrastim in conjunction with drugs known to lower the platelet count and in the presence of moderate or severe organ impairment.

Aortitis.

Aortitis has been reported in patients receiving pegfilgrastim and may present with generalised signs and symptoms such as fever and increased inflammatory markers. Consider aortitis in patients who develop these signs and symptoms without known aetiology.

Laboratory monitoring.

To assess a patient's haematologic status and ability to tolerate myelosuppressive chemotherapy, a complete blood count and platelet count should be obtained before chemotherapy is administered. Pegfilgrastim produced ANC profiles similar to daily filgrastim, including earlier ANC nadir, shorter duration of severe neutropenia and accelerated ANC recovery, compared with ANC profiles observed without growth factor support. Due to neutrophil mediated clearance, pegfilgrastim is likely to produce post-recovery ANC levels in the normal range, and the above-normal peak ANC levels commonly seen with daily filgrastim do not occur.

Use in hepatic impairment.

See Section 5.2 Pharmacokinetic Properties.

Use in renal impairment.

See Section 5.2 Pharmacokinetic Properties.

Use in elderly patients.

See Section 5.2 Pharmacokinetic Properties.

Paediatric use.

See Section 5.2 Pharmacokinetic Properties.

Effects on laboratory tests.

None known.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Drug interactions between pegfilgrastim and other drugs have not been fully evaluated.

Bone imaging.

Increased haemopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.

Lithium.

The potential for pharmacodynamic interaction with lithium, which also promotes the release of neutrophils, has not been specifically investigated. There is no evidence that such an interaction would be harmful.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Pegfilgrastim did not affect the fertility of male or female rats when administered once weekly at SC doses of up to 1 mg/kg (about 2 to 13 x the recommended human dose of 6 mg based on plasma AUC data for a single dose).
(Category B3)
Pegfilgrastim crosses the placenta in pregnant rats. Administration of pegfilgrastim every second day over the period of organogenesis to rats and rabbits at SC doses up to 1 mg/kg and 200 microgram/kg, respectively, produced no evidence of teratogenicity. The rat dose was 2-fold of the anticipated exposure at the maximal recommended human dose (based on AUC), while the rabbit dose was 0.6 fold the human dose (based on body surface area). An increased incidence of wavy ribs, considered a reversible change, was observed in rats at doses greater than 100 microgram/kg.
Decreased maternal body weight gain, accompanied by decreased maternal food consumption and decreased fetal body weights were observed in rabbits at doses of 50 microgram/kg SC and above. Increased post-implantation loss due to early resorptions and an increased incidence of abortions were observed at pegfilgrastim doses above 50 microgram/kg SC. Once weekly SC injections of pegfilgrastim to female rats from day 6 of gestation through day 18 of lactation at doses up to 1000 microgram/kg/dose did not result in any adverse maternal effects. There were no deleterious effects on the growth and development of the offspring and no adverse effects were found upon fertility indices.
There are no adequate and well-controlled studies in pregnant women. Pegfilgrastim should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
 Whether pegfilgrastim is excreted in human milk is not known. Because many drugs are excreted in human milk, caution should be exercised if pegfilgrastim is administered to breastfeeding women.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines have not been assessed.

4.8 Adverse Effects (Undesirable Effects)

Safety data for pegfilgrastim are based on seven randomised clinical trials involving over 930 patients with lymphoma and solid tumours (breast, lung and thoracic tumours) receiving pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most adverse experiences were the sequelae of the underlying malignancy or cytotoxic chemotherapy. They occurred at similar rates in subjects who received pegfilgrastim (n = 930), filgrastim (n = 331) or placebo (n = 463). These adverse experiences occurred at rates between 15% and 72%. They included: nausea, fatigue, alopecia, diarrhoea, vomiting, constipation, fever, anorexia, skeletal pain, headache, taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalised weakness, peripheral oedema, dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever. The most common observed adverse reaction related to pegfilgrastim therapy was medullary bone pain, which was reported in 26% of patients. This was comparable to the incidence of medullary bone pain related to filgrastim therapy. This bone pain was generally reported to be of mild-to-moderate severity, could be controlled in most patients with non-narcotic analgesics, and had a comparable duration for both pegfilgrastim and filgrastim-treated patients. Infrequently, bone pain was severe enough to require narcotic analgesics. No patient withdrew from study due to bone pain. In these randomised clinical trials, the following adverse events related to pegfilgrastim were reported. See Tables 1 and 2.
Across all studies, no life-threatening or fatal adverse events were attributed to pegfilgrastim. In these studies, there was only 1 serious adverse event (dyspnoea) reported in a single patient as possibly related to pegfilgrastim.
Spontaneously reversible elevations in lactate dehydrogenase (LDH), alkaline phosphatase and uric acid of mild-to-moderate severity were observed. Most changes have been attributed to post-cytokine bone marrow expansion as well as to chemotherapy and metastatic disease. The incidences of these changes, presented for pegfilgrastim relative to filgrastim and placebo, were: LDH (18% versus 29% and 18%), alkaline phosphatase (11% versus 16% and 12%) and uric acid (11% versus 9% and 13% [1% of reported cases for pegfilgrastim and filgrastim groups were classified as severe]).

Comparability of Pelgraz with Neulasta.

Adverse effects.

In both clinical studies conducted, Pelgraz was well tolerated, and the safety profile of Pelgraz was similar to that of Neulasta.
In the PK/PD study (APO-Peg-02) with 66 healthy subjects, both Pelgraz and Neulasta were well tolerated. The overall safety profile of Pelgraz was consistent with Neulasta in terms of adverse events.
During the Phase III clinical study (APO-Peg-03), 589 subjects with breast cancer were exposed to pegfilgrastim. The safety profile of pegfilgrastim observed in this clinical study was consistent with that reported for the reference products used in this study. The pattern of treatment-emergent adverse events and serious adverse events was comparable between treatment groups and consistent with the safety profile of Neulasta.
Results from the Phase III efficacy and safety clinical study (APO-Peg-03) demonstrated similar safety profile between treatment arms. This is shown in Table 3.

Immunogenicity.

Samples from the clinical studies were tested in an assay using a multi-tiered approach to first screen, then confirm and provide a relative anti-pegfilgrastim Anti-drug Antibody (ADA) concentration (titre). Any confirmed positive samples were then further characterized to determine if the anti-pegfilgrastim antibodies present in a sample were specific for the protein moiety (G-CSF) or PEG moiety by competition with Pelgraz (G-CSF) and PEG, respectively. Lastly, the assay was also used to determine whether the confirmed anti-pegfilgrastim antibodies bind to the endogenous counterpart of the drug. The confirmed positive samples were also tested in a neutralizing antibody assay.
In the PK/PD study (APO-Peg-02), of the samples tested for Anti-Drug Antibody (ADA), 10 samples (6 subjects) out of 190 samples (66 subjects) were confirmed ADA positive and as having treatment-emergent ADAs. Within these 6 subjects, 3 were from Pelgraz and the other 3 from Neulasta treated groups. Two subjects were confirmed ADA negative following Period 2 of the study. All confirmed ADA positive samples tested negative for neutralizing antibodies. There is no evidence to support a significant impact of ADA development on the PK or PD of Pelgraz or Neulasta.
In the Phase III efficacy and safety study (APO-Peg-03), 3.1% of subjects (18 out of 589) assessed for immunogenicity were confirmed to be positive for ADAs at one or more time points. Incidence of treatment-emergent induced ADAs was low and similar between the three treatment groups: 1.0% in Pelgraz, 0.7% in US-Neulasta and 0.7% in EU-Neulasta treatment arms. The samples from the 18 patients with confirmed ADA positive results were tested in the cell based assay to evaluate the presence of antibodies with neutralizing activity.
Neutralizing activity could have been specific to pegfilgrastim or endogenous rhuG-CSF. Neither Pelgraz nor Neulasta exposure resulted in the induction of neutralizing antibodies to pegfilgrastim. Neutralizing antibodies to endogenous rhuG-CSF were detected in 3 subjects (0.5%). Two of these subjects were positive at the screening visit, of which one was negative at all post-dosing time points and one was positive for rhuG-CSF neutralizing antibodies at one other time point (Week 20). The third subject was positive for rhuG-CSF neutralizing antibodies at two post-treatment time points. The rhuG-CSF neutralizing antibodies were transient, and all 3 subjects were negative for neutralizing antibodies at their last time points tested. The presence of neutralising antibodies did not have any impact on PD activity and was unrelated to any adverse events. There were no instances of anaphylaxis or other immunologically-related adverse events.
Collectively, these findings confirmed the low immunogenic potential of Pelgraz.

Post-marketing experience.

Extremely rare cases of capillary leak syndrome have been reported in subjects receiving filgrastim, the parent compound of pegfilgrastim.
Allergic reactions: allergic-type reactions, including anaphylactic reactions, skin rash, urticaria and erythema/flushing occurring on initial or subsequent treatment have been reported in patients receiving pegfilgrastim. In some cases, symptoms have recurred with rechallenge, suggesting a causal relationship. Allergic-type reactions to pegfilgrastim have rarely been reported in post-marketing experience.
If a serious reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Pegfilgrastim should be permanently discontinued in patients who experience a serious allergic reaction.
Injection site pain and erythema have been reported in patients receiving pegfilgrastim.
Cases of glomerulonephritis have been reported uncommonly (≥ 1/1,000 and < 1/100) in patients receiving pegfilgrastim.
Cases of pulmonary haemorrhage and haemoptysis have been reported in patients receiving pegfilgrastim.
Cases of aortitis have been reported in patients receiving pegfilgrastim.
Rare cases (≥ 1/10,000 and < 1/1,000) of Sweet's syndrome (acute febrile dermatosis), splenomegaly, splenic rupture and sickle cell crisis have been reported in patients receiving pegfilgrastim.
Cases of thrombocytopenia have been reported commonly (≥ 1/100 and < 1/10) in patients receiving pegfilgrastim.
Cases of myelodysplastic syndrome and acute myeloid leukaemia have been reported in breast and lung cancer patients receiving chemotherapy and/or radiotherapy.
Very rare (< 1/10,000) reactions of cutaneous vasculitis have been reported in patients receiving pegfilgrastim.
There has been no evidence for the development of neutralising antibodies, or of a blunted or diminished response to pegfilgrastim in treated patients, including those receiving up to 6-cycles of pegfilgrastim.

Reporting of suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no experience with overdose of pegfilgrastim in humans. In subjects administered doses of up to 5-times the recommended dose, adverse events were similar to those observed in subjects administered lower doses of pegfilgrastim.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Human G-CSF is a glycoprotein which regulates the production and release of neutrophils from the bone marrow. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo compared to filgrastim. Pegfilgrastim and filgrastim have been shown to have identical modes of action. They cause a marked increase in peripheral blood neutrophil counts within 24 hours in subjects with healthy bone marrow, with minor increases in monocytes and/or lymphocytes. Similarly to filgrastim, neutrophils produced in response to pegfilgrastim show normal or enhanced function as demonstrated by tests of chemotactic and phagocytic function.

Comparability of Pelgraz with Neulasta.

Comparability assessments, between Pelgraz and Neulasta, of primary pharmacodynamics (PD) have been conducted in vitro in M-NFS-60 cells (a murine myeloblastic cell line) and in vivo in neutropaenic mice on receptor binding and biological activity, respectively. In addition, pharmacokinetics (PK) and PD from a Phase 1 clinical study in healthy subjects support similar/equivalent pharmacological activity of Pelgraz and Neulasta.
In the Phase 1 clinical study (APO-Peg-02) in healthy subjects, the 95% CI of the relative mean of each of the primary PD endpoint parameters for Absolute Neutrophil Count (ANC), AUECt, and Emax were contained within the pre-defined acceptance margins of 80-125%. While not defined as a primary PD endpoint parameter, the 95% CI for the relative mean of the Tmax parameter was also contained within these acceptance limits, demonstrating the biosimilarity of Pelgraz to the reference product, Neulasta.
The results from APO-Peg-02, following SC administration of a single 6 mg dose of Pelgraz or Neulasta, are summarised in Table 4.

Clinical trials.

Clinical trials with the reference biological product.

Three pivotal, randomised, double-blind clinical studies have been conducted using Neulasta in patients with solid tumours receiving a variety of chemotherapy regimens. Pegfilgrastim administered 24 hours after chemotherapy in the first cycle and all subsequent cycles of chemotherapy has been shown to be safe and effective in reducing neutropenia and associated clinical sequelae.
Studies 1 and 2 met the primary objective of demonstrating that the mean days of severe neutropenia of pegfilgrastim-treated patients (ANC < 0.5 x 109/L) did not exceed that of filgrastim-treated patients by more than one day in cycle 1 of chemotherapy.
Results from Study 1, a randomised, double-blind study conducted in patients with breast cancer (n = 155) undergoing 4 cycles of the highly myelosuppressive chemotherapy regimen doxorubicin and docetaxel (AT), demonstrated a clinically and statistically similar reduction in the duration of severe neutropenia (ANC < 0.5 x 109/L) in cycle 1 in patients who received pegfilgrastim as a fixed dose of 6 mg compared with patients who received a mean of 11 daily injections of filgrastim 5 microgram/kg/day (see Table 5). Durations of severe neutropenia were also comparable between treatment groups in all subsequent cycles. There was no significant difference in the incidence of febrile neutropenia between the groups in Study 1.
In study 2, patients with breast cancer (n = 301) were randomised to receive a single injection of pegfilgrastim 100 microgram/kg or daily injections of filgrastim 5 microgram/kg/day after each of 4 cycles of the highly myelosuppressive chemotherapy regimen doxorubicin and docetaxel (AT). In cycle 1, a single SC injection of pegfilgrastim resulted in a duration of severe neutropenia that was clinically and statistically similar to that observed after a mean of 11 daily injections of filgrastim (see Table 5). Durations of severe neutropenia were also comparable between treatment groups in all subsequent cycles. There is a significant difference in the incidence of febrile neutropenia between the groups in Study 2.
Study 3 was a placebo-controlled study evaluating the effect of pegfilgrastim on the incidence of febrile neutropenia following administration of a moderately myelosuppressive chemotherapy regimen (docetaxel 100 mg/m2 every 3 weeks for 4 cycles). This regimen is associated with a febrile neutropenia rate of up to 20%. In this study, 928 patients were randomised to receive either pegfilgrastim or placebo on Day 2 of each cycle. The incidence of patients with febrile neutropenia, was significantly lower in the patients randomised to receive pegfilgrastim versus placebo (1% versus 17%, p < 0.001, respectively). The incidence of hospitalisation and IV anti-infective use associated with a clinical diagnosis of febrile neutropenia was significantly lower in patients randomised to pegfilgrastim compared to placebo (1% versus 14%, p < 0.001; and 2% versus 10%, p < 0.001, respectively).
Data from phase 2 studies in patients with various malignancies undergoing a variety of chemotherapy regimens further support the safety and efficacy of pegfilgrastim. Dose-finding studies in patients with breast cancer (n = 152), thoracic tumours (n = 92) and Non-Hodgkin's Lymphoma (NHL) (n = 50) demonstrated that the efficacy of a single injection of pegfilgrastim 100 microgram/kg was similar to daily injections of filgrastim 5 microgram/kg/day and was superior to the lower dose of 30 microgram/kg. A randomised phase 2 study of patients with NHL or Hodgkin's lymphoma (n = 60) further supports the safety and efficacy of pegfilgrastim.
A phase 2, randomised, double-blind study (n = 83) in patients receiving chemotherapy for de novo acute myeloid leukaemia compared pegfilgrastim (single dose of 6 mg) with filgrastim, administered during induction chemotherapy. Median time to recovery from severe neutropenia was estimated as 22 days in both treatment groups. Long term outcome was not studied.

Comparability of Pelgraz with Neulasta.

Therapeutic equivalence of Pelgraz and Neulasta was demonstrated in a comparative phase III efficacy and safety study (APO-Peg-03). A single, fixed SC dose of 6 mg/0.6 mL was administered on Day 2 of each chemotherapy cycle. There were 589 subjects (all female of median age 52 years, range 22-80 years) dosed in the following treatment arms: Pelgraz (n = 294), EU-approved Neulasta (n = 147) and US licensed Neulasta (n = 148). The dose was administered to early-stage breast cancer patients undergoing 6 cycles of (each cycle 21 days apart) of TAC chemotherapy (docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) in an adjuvant setting.
The primary efficacy endpoint was Duration of Severe Neutropenia (DSN) in cycle 1. Equivalence of Pelgraz and Neulasta was considered to be demonstrated if the two-sided 95% CI for the difference in mean DSN in Cycle 1 was within the equivalence range [-0.5 day, +0.5 day].
The results of DSN in Cycle 1 are described in Table 6 and the results of the treatment comparisons are described in Table 7:
The results of DSN data in Cycle 1 show the similarity in efficacy of Pelgraz and US-Neulasta (-0.04 to 0.50) as well as of Pelgraz and EU-Neulasta (-0.29 to 0.26) since the 95% CI are within the equivalence range of -0.5 to 0.5 days for both comparisons.
The results for secondary efficacy endpoints are presented below:
In Cycle 1, blood samples were collected for complete blood counts with differentials on Day 0, 1, 3, 5, 6, 7, and every day until post-nadir ANC recovery to ≥ 2 x 109/L or up to Day 15, if recovery did not occur earlier. The mean day to reach the peak ANC was Day 3.4, 3.1 and 3.1 in the Pelgraz, US-Neulasta and EU-Neulasta arms, and the mean peak values were similar across the treatment arms: 28.4, 29.9 and 28.7 x 109/L, respectively. Mean day to reach the ANC nadir was Day 7.1, 7.1 and 7.3 in the Pelgraz, US-Neulasta and EU-Neulasta arms and mean recovery of ANC (≥ 2.0 x 109/L) was reached on Day 9.4, 9.5 and 9.2, respectively. The mean depth of the nadir was comparable across the treatment arms: 0.6, 0.4 and 0.4 x 109/L in the Pelgraz, US-Neulasta and EU-Neulasta arms, respectively.
The frequency of Grade 3 neutropenia (ANC below 1.0 x 109/L) across all cycles was reported in 24 subjects (8.2%) for Pelgraz, 18 subjects (12.2%) for US-Neulasta and 14 subjects (9.5%) for EU-Neulasta arms. The frequency of Grade 4 neutropenia (ANC below 0.5 x 109/L) across all cycles was reported as 233 subjects (79.3%) for Pelgraz, 116 subjects (78.4%) for US-Neulasta and 117 subjects (79.6%) for EU-Neulasta arms, respectively.
The rates of Febrile Neutropenia (FN) by cycle and across the cycles (defined as: single temperature: ≥ 38.3°C measured orally or ≥ 38.0°C for over 1 hour; neutropenia: ANC < 0.5 x 109/L or < 1 x 109/L and a predicted decline to ≤ 0.5 x 109/L over the next 48 hours) was assessed. Overall during the treatment phase, FN occurred in 5.8%, 4.7% and 3.4% of subjects in the Pelgraz, US-Neulasta and EU-Neulasta treatment arms, respectively. For the majority of subjects, FN occurred in Cycle 1: 5.1% in the Pelgraz arm, 4.1% in the US-Neulasta arm and 3.4% in the EU-Neulasta arm.

5.2 Pharmacokinetic Properties

Absorption.

After a single SC dose of pegfilgrastim in man, the time to peak serum concentration of pegfilgrastim was variable, ranging from 8 to 120 hours. After a 6 mg SC dose, the range was from 15.9 to 120.5 hours with a median value of 39.9 hours. Serum concentrations of pegfilgrastim were maintained during the period of neutropenia after myelosuppressive chemotherapy.

Distribution.

The distribution of pegfilgrastim was limited to the plasma compartment.

Metabolism.

The metabolic pathway of pegfilgrastim has not been characterised.

Excretion.

The elimination of pegfilgrastim was non-linear with respect to dose; serum clearance of pegfilgrastim decreased with increasing dose. The saturable clearance pathway was attributed to neutrophils and neutrophil precursors (neutrophil-mediated, self-regulating clearance). Results from pharmacokinetic/pharmacodynamic modelling support neutrophil-mediated clearance as the main route of elimination (> 99%). Consistent with a self-regulating clearance mechanism, the serum concentration of pegfilgrastim declined rapidly at the onset of neutrophil recovery following myelosuppressive chemotherapy (see Figure 1).

Special populations.

Hepatic impairment.

No studies have been conducted in patients with hepatic failure; however, the pharmacokinetics of pegfilgrastim are not expected to be affected by impaired hepatic function.

Renal impairment.

Renal impairment, including end-stage renal disease, appears to have no effects on the pharmacokinetics of pegfilgrastim.

Elderly patients.

The pharmacokinetics of pegfilgrastim in elderly cancer patients (≥ 65 years of age) were similar to those in younger subjects.

Paediatric patients.

The safety and pharmacokinetics of pegfilgrastim were studied in 37 paediatric patients with sarcoma. The mean (± Standard Deviation) systemic exposure (AUC0-inf) of pegfilgrastim after subcutaneous administration at 100 microgram/kg was 22.0 (± 13.1) microgram.hr/mL in the 6-11 years age group (n = 10), 29.3 (± 23.2) microgram.hr/mL in the 12-21 years age group (n = 13) and 47.9 (± 22.5) microgram.hr/mL in the youngest age group (0-5 years, n = 11). The terminal elimination half-lives of the corresponding age groups were 20.2 (± 11.3) hours, 21.2 (± 16.0) hours and 30.1 (± 38.2) hours, respectively. The most common adverse reaction was bone pain.

Comparability of Pelgraz with Neulasta.

Pharmacokinetic (PK) profiles of Pelgraz and Neulasta were compared in a single-dose, randomized, two-way crossover, assessor-blinded, active controlled, phase 1 PK/PD study in 66 healthy male and female volunteers (APO-Peg-02). A single, fixed SC dose of 6 mg was administered over two 28-day periods with an 8 week washout. The 90% CI of the primary PK endpoint parameters (AUCt and Cmax for pegfilgrastim) were contained within the pre-defined acceptance range of 80-125%, demonstrating the biosimilarity of Pelgraz to the reference product, Neulasta.
Table 8 shows the PK results following the administration of Pelgraz and US-Neulasta. The ratios of the geometric means for the test/reference (Pelgraz/Neulasta) were within the pre-defined acceptance range of 80 - 125% for AUCt, AUCinf and Cmax. In addition, the 90% confidence interval of the geometric mean ratio for AUCinf was also contained within this acceptance range whereas the upper bound of the AUCt ratio was 125.5%. The marginally high upper bound is a consequence of a smaller drug content in the US-Neulasta dose (less than 95% of the label claim) administered during the study, as supported by the results from the potency corrected data in Table 9.
Table 9 shows results from the potency corrected pegfilgrastim concentration data for both Pelgraz and US-Neulasta. For the primary pharmacokinetic endpoint of AUCt, the 90% confidence interval of the Pelgraz/Neulasta ratio of geometric means was contained within the acceptance range of 80 - 125%.

5.3 Preclinical Safety Data

As with other haematopoietic growth factors, G-CSF has shown in vitro stimulating properties on human endothelial cells. G-CSF can promote growth of myeloid cells, including malignant cells, in vitro and similar effects may be seen on some non-myeloid cells in vitro.

Carcinogenicity.

No carcinogenicity testing has been conducted for pegfilgrastim.

Genotoxicity.

No mutagenicity studies have been conducted with pegfilgrastim, although the parent protein (filgrastim) was negative in bacterial mutagenicity assays, a test for chromosome aberrations in Chinese hamster lung cells in vitro and in an in vivo mouse micronucleus test.

6 Pharmaceutical Particulars

6.1 List of Excipients

The product is formulated at pH 4.0 with 0.35 mg glacial acetic acid, 30.0 mg sorbitol, 0.02 mg polysorbate-20, 0.034 mg sodium hydroxide in water for injections to 0.6 mL.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C (Refrigerate. Do not freeze). Avoid shaking. Protect from light.
Pelgraz may be exposed to room temperature (up to 25°C) for a maximum single period of up to 15 days that ends within the labelled expiry date. Once Pelgraz has been out at room temperature, it should not be put back into the refrigerator. Pelgraz left at room temperature for more than 15 days should be discarded.
Freezing should be avoided; however, if accidentally frozen, Pelgraz should be allowed to thaw in the refrigerator before administration and administered within the labelled expiry date. If frozen a second time, Pelgraz should be discarded.

6.5 Nature and Contents of Container

Each carton contains 1 blister-packaged, ready-to-use, pre-filled syringe with needle guard, containing 6 mg of pegfilgrastim in 0.6 mL (10 mg/mL) solution for SC injection.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

C849H1347N223O244S9,(C2H4O)n.

CAS number.

208265-92-3.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes