ABRAXANE 5 mg/mL POWDER FOR DISPERSION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Abraxane 5mg/ml powder for dispersion for infusion

paclitaxel

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 further questions, ask your doctor or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Abraxane and what is it used for

What is Abraxane

Abraxane contains the active substance paclitaxel bound to human albumin in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines called taxanes, which are used in cancer.

• Paclitaxel is the part of the medicine that affects cancer. It works by preventing cancer cells from dividing, which means they die.
• Albumin is the part of the medicine that helps paclitaxel dissolve in the blood and pass through the walls of blood vessels to reach the tumor. This means that other chemical agents that can cause life-threatening side effects are not needed. Such side effects occur much less frequently with Abraxane.

What is Abraxane used for

Abraxane is used to treat the following types of cancer:

Breast cancer

• Breast cancer that has spread to other parts of the body (this is called metastatic breast cancer).
• Abraxane is used in metastatic breast cancer when at least one other therapy has been tried but has not worked and your case is not suitable for treatment with a group of medicines called anthracyclines.
• People with metastatic breast cancer who received Abraxane when another treatment had failed had a greater chance of experiencing a reduction in tumor size and lived longer than people who received an alternative treatment.

Pancreatic cancer

• Abraxane is used together with a medicine called gemcitabine if you have metastatic pancreatic cancer. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) who received Abraxane with gemcitabine in a clinical trial lived longer than people who only received gemcitabine.

Lung cancer

• Abraxane is also used together with a medicine called carboplatin if you have the most common type of lung cancer, called non-small cell lung cancer.
• Abraxane is used in non-small cell lung cancer when surgery or radiotherapy are not suitable to treat the disease.

2. What you need to know before you use Abraxane

Do not use Abraxane

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of Abraxane (listed in section 6);
• if you are breast-feeding;
• if you have a low white blood cell count (neutrophil count <1500 cells mm3 before starting treatment. your doctor will advise you about this).< li>

Warnings and precautions

Tell your doctor or nurse before you start using Abraxane

• if you have reduced kidney function;
• if you have severe liver disorders;
• if you have heart problems.

If you experience any of these disorders while being treated with Abraxane, tell your doctor or nurse. Your doctor may decide to stop treatment or reduce the dose:

• if you experience any unusual bruising, bleeding, or signs of infection such as sore throat or fever;
• if you experience numbness, tingling, pinching, sensitivity to touch, or muscle weakness;
• if you experience breathing problems, such as difficulty breathing or dry cough.

Children and adolescents

Abraxane is only intended for adults and should not be given to children or adolescents under 18 years of age.

Other medicines and Abraxane

Tell your doctor if you are using or have recently used any other medicines, including those obtained without a prescription, including herbal medicines. This is because Abraxane may affect how some medicines work. Similarly, some medicines may affect how Abraxane works.

Be careful and talk to your doctor when using Abraxane at the same time as any of the following:

• medicines to treat infections (i.e. antibiotics such as erythromycin, rifampicin, etc.; if in doubt about whether the medicine you are taking is an antibiotic, ask your doctor, nurse, or pharmacist), and medicines to treat fungal infections (e.g. ketoconazole)
• medicines used to help stabilize mood, also called antidepressants (e.g. fluoxetine)
• medicines used to treat seizure disorders (epilepsy) (e.g. carbamazepine, phenytoin)
• medicines used to help lower lipid levels in the blood (e.g. gemfibrozil)
• medicines used to treat stomach acid or stomach ulcers (e.g. cimetidine)
• medicines used to treat HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• the medicine called clopidogrel, which is used to prevent blood clots.

Pregnancy, breast-feeding, and fertility

Paclitaxel may cause serious birth defects, so it should not be used if you are pregnant. Your doctor will ask for a pregnancy test before starting treatment with Abraxane.

Women of childbearing age must use effective contraceptive methods during treatment and for at least six months after finishing treatment with Abraxane.

Abraxane should not be used during breast-feeding as it is not known whether the active substance paclitaxel passes into breast milk.

Men treated with Abraxane are advised to use effective contraceptive methods and avoid having children during treatment and for at least three months after finishing treatment, as well as to inform themselves about the possibility of preserving their sperm before starting treatment, given the possibility that treatment with Abraxane may cause irreversible infertility.

Talk to your doctor before using this medicine.

Driving and using machines

Some people may feel tired or dizzy after receiving Abraxane. If this happens to you, do not drive or use any tools or machines.

If you are taking other medicines as part of your treatment, talk to your doctor about your ability to drive and use machines.

Abraxane contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg; this is essentially "sodium-free".

3. How to use Abraxane

A doctor or nurse will give you Abraxane into a vein through an intravenous infusion system. The dose you receive will be calculated based on your body surface area and blood test results. The usual dose for breast cancer is 260 mg/m2 of body surface area, given over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m2 of body surface area, given over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m2 of body surface area, given over 30 minutes.

How often will you be given Abraxane?

For the treatment of metastatic breast cancer, Abraxane is usually given once every three weeks (on day 1 of a 21-day cycle).

For the treatment of metastatic pancreatic cancer, Abraxane is given on days 1, 8, and 15 of each 28-day cycle, with gemcitabine given immediately after Abraxane.

For the treatment of non-small cell lung cancer, Abraxane is given once a week (i.e. on days 1, 8, and 15 of a 21-day cycle), with carboplatin given once every three weeks (i.e. only on day 1 of each 21-day cycle), immediately after the Abraxane dose.

If you have any further questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

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

The very commonside effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within a month after starting treatment with Abraxane. When it occurs, hair loss is usually severe [more than 50%] in most patients)
• Rash
• Abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes, or leucocytes) in the blood
• Decrease in red blood cells
• Decrease in platelet count in the blood
• Effect on peripheral nerves (pain, numbness, tingling, or loss of sensitivity)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhea, constipation, mouth pain, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep problems
• Headache
• Chills
• Breathing difficulties
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver values in liver function tests
• Pain in the limbs
• Cough
• Abdominal pain
• Nosebleeds

The commonside effects may affect up to 1 in 10 people:

• Itching, dry skin, nail disorders
• Infection, fever with a decrease in the number of a type of white blood cell (neutrophils) in the blood, flushing, mouth sores, severe blood infection that can be due to a reduction in white blood cells
• Reduction in all blood cell values
• Chest pain or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Decrease in muscle coordination or difficulty reading, increased or decreased tearing, loss of eyelashes
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the injection site
• Anxiety
• Lung infection
• Urinary tract infection
• Intestinal obstruction, inflammation of the large intestine, inflammation of the bile duct
• Acute kidney failure
• Increased bilirubin in the blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurred vision

The uncommonside effects may affect up to 1 in 100 people:

• Weight gain, increased lactate dehydrogenase in the blood, altered kidney function, increased glucose in the blood, increased phosphorus in the blood
• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itching eyes, double vision, reduced vision, or flashing lights, blurred vision due to inflammation of the retina (cystoid macular edema)
• Ear pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, fluid in the lungs, loss of voice, blood clots in the lungs
• Gas, stomach cramps, gum pain, rectal bleeding
• Painful urination (dysuria), need to urinate more often than usual (urinary frequency), blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail disorders, nail loss, hives, skin pain, photosensitivity reaction, pigmentation disorders, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• Low phosphorus levels in the blood, fluid retention, low albumin levels in the blood, increased thirst, low calcium levels in the blood, low blood sugar levels, low sodium levels in the blood
• Nose and skin infections, catheter-related infections
• Bruising
• Pain and swelling at the tumor site, tumor necrosis
• Low blood pressure when standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, increased liver size
• Chest pain
• Nervousness
• Small bleeding spots on the skin due to blood clots
• A condition that involves the destruction of red blood cells and acute kidney failure

The rareside effects may affect up to 1 in 1,000 people:

• Skin reaction to another agent or radiation pneumonitis
• Blood clots
• Very slow heart rate, heart attack
• Medicine leakage outside the vein
• Disorder of the heart's electrical conduction system (atrioventricular block)

The very rareside effects may affect up to 1 in 10,000 people:

• Severe skin and mucous membrane inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis)

Frequency not known(cannot be estimated from the available data)

• Hardening/thickening of the skin (scleroderma).

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Abraxane

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 vial after EXP. The expiry date is the last day of the month stated.

Unopened vial: Store the vial in the outer packaging to protect it from light.

After the first reconstitution, use the dispersion immediately. If not used immediately, the vial with the dispersion should be placed in its outer packaging to protect it from light and should be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours.

The reconstituted dispersion in the infusion bag can be stored in the refrigerator (2°C-8°C) for a maximum of 24 hours, protected from light.

The total storage time combining the reconstituted medicinal product in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. After this, it can be stored in the infusion bag for 4 hours at a temperature below 25°C.

Your doctor or pharmacist is responsible for disposing of any unused Abraxane correctly.

6. Container contents and additional information

Composition of Abraxane

The active ingredient is paclitaxel.

Each vial contains 100 mg or 250 mg of paclitaxel bound to albumin in a nanoparticle formulation.

After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation.

The other component is human albumin solution (contains sodium caprylate and N-acetyl-L-tryptophan), see section 2 "Abraxane contains sodium".

Appearance and container contents of the product

Abraxane is a powder for dispersion for infusion, white to yellow in color. Abraxane is available in glass vials containing 100 mg or 250 mg of paclitaxel bound to albumin in a nanoparticle formulation.

Each container contains 1 vial.

Marketing authorization holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

You can request more information about this medicine by contacting the marketing authorization holder.

Date of last revision of this prospectus:

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

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Doctors or healthcare professionals

This information is intended only for doctors or healthcare professionals:

Instructions for use, preparation, and disposal

Precautions for preparation and administration

Paclitaxel is a cytotoxic antineoplastic medicinal product, so Abraxane should be handled with caution, as with other potentially toxic drugs. Gloves, safety glasses, and protective clothing should be used. In case of skin contact, the affected area should be washed immediately and thoroughly with water and soap. In case of contact with mucous membranes, they should be rinsed thoroughly with plenty of water. Abraxane should only be prepared and administered by personnel experienced in handling cytotoxic agents. Pregnant women should not handle Abraxane.

Due to the possibility of extravasation, it is advisable to closely monitor the infusion site in case it occurs during administration of the medicinal product. Limiting the infusion time of Abraxane to 30 minutes, as instructed, reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medicinal product

Abraxane should be administered under the supervision of a qualified oncologist in specialized units for the administration of cytotoxic agents.

Abraxane is supplied as a sterile lyophilized powder for reconstitution prior to use. After reconstitution, each ml of dispersion contains 5 mg of paclitaxel bound to albumin in a nanoparticle formulation. The reconstituted Abraxane dispersion is administered intravenously using an infusion set that incorporates a 15 µm filter.

Reconstitution of 100 mg:

Using a sterile syringe, slowly inject 20 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion into the 100 mg Abraxane vial over at least 1 minute.

Reconstitution of 250 mg:

Using a sterile syringe, slowly inject 50 ml of sodium chloride 9 mg/ml (0.9%) solution for infusion into the 250 mg Abraxane vial over at least 1 minute.

The solution should be directed towards the inner wall of the vial. The solution should not be injected directly into the powder as this will cause foaming.

After adding the solution, the vial should be allowed to stand for at least 5 minutes to ensure the powder is fully wetted. The vial should then be gently agitated and/or slowly inverted for at least 2 minutes until the powder is completely redispersed. Foaming should be avoided. If foaming or clumping occurs, the dispersion should be allowed to stand for at least 15 minutes until the foam has dissipated.

The reconstituted dispersion should have a milky and homogeneous appearance without visible precipitates. Some sedimentation of the reconstituted dispersion may occur. If there are signs of precipitation or sedimentation, the vial should be gently inverted again to achieve complete redispersion before use.

Inspect the dispersion in the vial for particles. Do not administer the reconstituted dispersion if particles are observed in the vial.

The exact total volume of 5 mg/ml dispersion required for the patient should be calculated and the appropriate amount of reconstituted Abraxane should be injected into an empty, sterile intravenous infusion bag made of PVC or non-PVC material.

The use of medical devices containing silicone oil as a lubricant (i.e., syringes and IV administration bags) to reconstitute and administer Abraxane may result in the formation of protein filaments. Abraxane should be administered through an infusion set that incorporates a 15 µm filter to prevent the administration of these filaments. The use of a 15 µm filter removes the filaments and does not alter the physical or chemical properties of the reconstituted medicinal product.

The use of filters with a pore size smaller than 15 µm may cause filter blockage.

There is no need to use DEHP-free infusion bags or administration sets to prepare or administer Abraxane infusions.

After administration, it is recommended to flush the intravenous line thoroughly with sodium chloride 9 mg/ml (0.9%) solution for injection to ensure complete administration of the dose.

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Stability

Unopened Abraxane vials remain stable until the expiry date stated on the label, provided they are stored in the outer packaging to protect them from light. Freezing or refrigeration does not adversely affect the stability of the medicinal product. This medicinal product does not require any special storage temperature.

Stability of the reconstituted dispersion in the vial

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C in the original container, protected from light.

Stability of the reconstituted dispersion in the infusion bag

Chemical and physical stability has been demonstrated for 24 hours at 2°C-8°C followed by 4 hours at 25°C, protected from light.

However, from a microbiological point of view, unless the method of reconstitution and filling of the infusion bags precludes the risk of microbial contamination, the product should be used immediately after reconstitution and filling of the infusion bags.

If not used immediately, the in-use storage times and conditions of the product are the responsibility of the user.

The total storage time for the reconstituted medicinal product in the vial and in the infusion bag when refrigerated and protected from light is 24 hours. It can then be stored in the infusion bag for 4 hours at a temperature below 25°C.