Label: information for the user

Abraxane 5mg/ml powder for injection

paclitaxel

Read this label carefully before starting to use this medication,because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this label. See section 4.

6. Contents of the container and additional information

What is Abraxane

Abraxane contains, as the active ingredient, paclitaxel bound to human albumin protein, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medications called “taxanes” that are used in cancer treatment.

• Paclitaxel is the part of the medication that affects cancer; it acts by preventing cancer cells from dividing, which means they die.
• Albumin is the part of the medication that helps paclitaxel dissolve in the blood and cross blood vessel walls to reach the tumor. This means thatno other chemical agentsare needed that can produce life-threatening side effects. These side effects occur much less frequently with Abraxane.

How is Abraxane used

Abraxane is used to treat the following types of cancer:

Breast cancer

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

Pancreatic cancer

• Abraxane is used in combination with a medication called gemcitabine if you have metastatic pancreatic cancer (cancer that has spread to other parts of the body). People with metastatic pancreatic cancer (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 in combination with a medication 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 radiation therapy is not suitable for treating the disease.

Do not use Abraxane

• if you are allergic (hypersensitive) to paclitaxel or any of the other components of Abraxane (listed in section 6);;
• if you are breastfeeding;
• if you have a low white blood cell count (neutrophil count <1500 cells/mm3) before starting treatment. Your doctor will advise you about this).

Warnings and precautions

Consult your doctor or nurse before starting to use Abraxane

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

If you experience any of these conditions while receiving treatment with Abraxane, inform your doctor or nurse. Your doctor may decide to interrupt treatment or reduce the dose:

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

Children and adolescents

Abraxane is only indicated for adults and should not be administered to children or adolescents under 18 years.

Other medicines and Abraxane

Inform your doctor if you are using or have recently used any other medicine, including those purchased without a prescription, including herbal medicines. This is because Abraxane may affect the way some medicines work. Similarly, some medicines may affect the way Abraxane works.

Be careful and consult your doctor when using Abraxane with any of the following:

• medicines to treat infections (e.g. 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 seizures (epilepsy) (e.g. carbamazepine, phenytoin)
• medicines used to help reduce 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, breastfeeding, and fertility

Paclitaxel may cause severe congenital defects, so it should not be used if you are pregnant. Your doctor will request a pregnancy test before starting treatment with Abraxane.

Women of childbearing age should use effective contraceptive methods during and for one month after completing treatment with Abraxane.

Abraxane should not be used during breastfeeding as it is unknown whether the active ingredient paclitaxel passes into breast milk.

Men treated with Abraxane are advised to use effective contraceptive methods and avoid fathering children during treatment and for six months after completing treatment, as well as to inform themselves about the possibility of preserving sperm before starting treatment, given the possibility of irreversible infertility.

Consult your doctor before using this medicine.

Driving and operating machinery

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

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

Abraxane contains sodium

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

A healthcare professional will administer 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 typical dose for breast cancer is 260mg/m2of body surface area, administered over 30minutes. The typical dose for advanced pancreatic cancer is 125mg/m2of body surface area, administered over 30minutes. The typical dose for non-small cell lung cancer is 100mg/m2of body surface area, administered over 30minutes.

How often will Abraxane be administered?

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

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

For the treatment of non-small cell lung cancer, Abraxane is administeredonce a week (i.e., on days1, 8, and 15 of a 21day cycle), with carboplatin administered once every three weeks (i.e., only on day1 of each 21day cycle), immediately after administering the dose of Abraxane.

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

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

Side effectsvery commonmay affect more than 1 in 10people:

• Hair loss (most cases of hair loss occurred within less than a month after starting treatment with Abraxane. When it occurs, hair loss is pronounced (more than 50%) in most patients)
• Skin rash
• Abnormal decrease in the number of some types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• Decrease in red blood cells
• Decrease in platelets in the blood
• Effect on peripheral nerves (pain, numbness, tinglingor loss of sensation)
• Joint 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
• Difficulty breathing
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver values in liver function tests
• Pain in the extremities
• Coughing
• Abdominal pain
• Nosebleed

Side effectscommonmay affect up to 1 in 10people:

• Itching, dry skin, nail problems

• Infection, fever with a decrease in the number of a type of white blood cell (neutrophils) in the blood, redness, cold sores, severe blood infection that may be due to a decrease in white blood cells
• Decrease in all blood cell values
• Chest or throat pain
• Indigestion, abdominal discomfort
• Stuffy nose
• Back or bone pain
• Decreased muscle coordination or difficulty reading, increased or decreased tear production, eyelash loss
• Changes in heart rate or rhythm, heart failure
• Low or high blood pressure
• Redness or swelling at the injection site
• Anxiety
• Pulmonary 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
• Weakness of the muscles
• Blurred vision

Side effectsuncommonmay affect up to 1 in 100people:

• Weight gain, increased lactate dehydrogenase in the blood, renal function alteration, increased blood glucose, increased blood phosphorus
• Decreased or absent reflexes, involuntary movements, nerve pain, fainting, dizziness when standing, tremors, facial nerve paralysis
• Irritated eyes, eye pain, red eyes, itchy eyes, double vision, reduced vision, or flashing lights, blurred vision due to inflammation of the retina (macular cystoid edema)
• Ear pain, ringing in the ears
• Coughing up mucus, shortness of breath when walking or climbing stairs, nasal congestion, decreased respiratory sounds, fluid in the lung, loss of voice, blood clots in the lungs, dry throat
• Gas, stomach cramps, tooth pain, rectal bleeding
• Painful urination (dysuria), frequent urination, blood in the urine, involuntary loss of urine (urinary incontinence)
• Nail pain, nail problems, nail loss, hives, skin pain, photosensitivity reaction, skin pigmentation disorders, increased sweating, night sweats, white spots on the skin, sores, facial swelling
• Decreased phosphorus in the blood, fluid retention, low albumin in the blood, increased thirst, decreased calcium in the blood, decreased blood sugar, decreased sodium in the blood
• Nasal pain, skin infections, catheter-related infection
• Contusion
• Tumor pain, tumor necrosis
• Decreased blood pressure when standing, cold extremities
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Nervousness
• Small skin bleeding due to blood clots
• A condition that involves the destruction of red blood cells and acute kidney failure

Side effectsraremay affect up to 1 in 1,000people:

• Reaction to another agent or pulmonary inflammation after radiation
• Blood clots
• Slow pulse, heart attack
• Medication leakage outside the vein
• Conduction disorder of the heart's electrical system (atrioventricular block)

Side effectsvery raremay affect up to 1 in 10,000people:

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

Frequencyunknown(cannot be estimated from available data)

• Sclerosis/ thickening of the skin (scleroderma).

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the vial after CAD/EXP. The expiration date is the last day of the month indicated.

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

After the first reconstitution, the dispersion must be used immediately. If not used immediately, the vial with the dispersion must be placed inside its outer packaging to protect it from light and must 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 medication 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.

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

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).

Appearance of the product and contents of the package

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 package contains 1 vial.

Marketing Authorization Holder

Bristol Myers Squibb Pharma EEIG

254 Plaza

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Responsible for manufacturing

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

Netherlands

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

Last review date of this leaflet:

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu/.

-------------------------------------------------------------------------------------------------------------------------

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 anticancer drug, so Abraxane must be handled with caution, as with other potentially toxic substances. 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 washed thoroughly with plenty of water. Abraxane should only be prepared and administered by experienced personnel in the handling of cytotoxic agents. Pregnant women should not handle Abraxane.

Due to the possibility of extravasation, it is recommended to closely monitor the infusion site for any signs of extravasation during administration of the medication. Limiting the infusion time of Abraxane to 30 minutes, as instructed, reduces the likelihood of reactions associated with infusion.

Reconstitution and administration of the medication

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 lyophilized sterile powder for reconstitution before 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 device that includes a 15 µm filter.

Reconstitution of 100 mg:

Using a sterile syringe, slowly inject 20 ml of 0.9% sodium chloride solution for infusion into the 100 mg Abraxane vial over a minimum of 1 minute.

Reconstitution of 250 mg:

Using a sterile syringe, slowly inject 50 ml of 0.9% sodium chloride solution for infusion into the 250 mg Abraxane vial over a minimum of 1 minute.

The solution should be directed directly towards the inner wall of the vial. The solution should not be injected directly into the powder, as foam will form.

After adding the solution, the vial should be left to stand for a minimum of 5 minutes to ensure proper hydration of the solute. Then, the vial should be gently and carefully agitated or inverted slowly for at least 2 minutes until the powder is fully redispersed. Foam formation should be avoided. If foam or lumps form, the dispersion should be left to stand for at least 15 minutes until the foam disappears.

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

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

The use of medical devices containing silicone oil as a lubricant (e.g., syringes and IV administration bags) to reconstitute and administer Abraxane may lead to the formation of protein filaments. Abraxane should be administered using an infusion device that includes a 15 µm filter to prevent the administration of these filaments. The use of a 15 µm filter eliminates the filaments without altering the physical or chemical properties of the reconstituted medication.

The use of filters with a pore size less than 15 µm may result in filter blockage.

No special containers or equipment without DEHP are required to prepare or administer Abraxane infusions.

After administration, it is recommended to thoroughly flush the intravenous route with 0.9% sodium chloride solution to ensure complete administration of the dose.

The disposal of unused medication and all materials that have come into contact with it should be carried out in accordance with local regulations.

Stability

Unopened vials of Abraxane remain stable until the date indicated on the packaging, provided they are stored in the outer packaging to protect them from light. Freezing or refrigeration do not negatively affect the stability of the medication.This medication 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 2-8°C in the original packaging, protected from light.

Stability of the reconstituted dispersion in the infusion bag

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

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

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

The total storage time combining the reconstituted medication 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.