Abraxane 5 mg/ml powder for dispersion for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Abraxane 5mg/ml powder for dispersion for perfusion

paclitaxel

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Abraxane is and what it is used for

What Abraxane is

Abraxane contains, as its active substance, paclitaxel bound to the human protein albumin, in the form of tiny particles called nanoparticles. Paclitaxel belongs to a group of medicines known as “taxanes” used in cancer treatment.

• Paclitaxel is the part of the medicine that acts against cancer; it works by preventing cancer cells from dividing, which causes them to 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 it is not necessary to use additional chemical agents that may cause serious, potentially life-threatening side effects. Such side effects occur much less frequently with Abraxane.

What Abraxane is 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 was not effective, and your condition is not suitable for treatment with a group of medicines called “anthracyclines.”
• Patients with metastatic breast cancer who received Abraxane after another treatment had failed had a greater chance of tumor shrinkage and lived longer than patients who received an alternative treatment.

Pancreatic cancer

• Abraxane is used in combination with a medicine called gemcitabine if you have metastatic pancreatic cancer. Patients 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 those who received gemcitabine alone.

Lung cancer

• Abraxane is also used in combination with a medicine called carboplatin if you have the most common type of lung cancer, known as “non-small cell lung cancer.”
• Abraxane is used in non-small cell lung cancer when surgery or radiotherapy are not suitable for treating the disease.

2. What you need to know before using Abraxane

Do not use Abraxane

• if you are allergic (hypersensitive) to paclitaxel or to any of the other ingredients 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 on this.

Warnings and precautions

Talk to your doctor or nurse before starting Abraxane

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

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

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

Children and adolescents

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

Other medicines and Abraxane

Tell your doctor if you are taking or have recently taken any other medicines, including those obtained without a prescription, as well as herbal medicines. This is because Abraxane may affect how some medicines work. Likewise, some medicines may affect how Abraxane works.

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

• medicines used to treat infections (i.e., antibiotics such as erythromycin, rifampicin, etc.; if you are unsure whether your medicine is an antibiotic, ask your doctor, nurse, or pharmacist), and medicines used to treat fungal infections (e.g., ketoconazole);
• medicines used to help stabilize mood, also known as antidepressants (e.g., fluoxetine);
• medicines used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin);
• medicines used to help lower lipid levels in the blood (e.g., gemfibrozil);
• medicines used for stomach acidity 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 birth defects and therefore must not be used if you are pregnant. Your doctor will request 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 completion of treatment with Abraxane.

Abraxane must not be used during breastfeeding, as it is unknown whether the active substance paclitaxel passes into breast milk.

Men treated with Abraxane are advised to use effective contraception and to avoid fathering a child during treatment and for at least three months after treatment ends. They should also seek information about the possibility of sperm preservation before starting treatment, due to the risk that Abraxane treatment may cause irreversible infertility.

Consult your doctor before using this medicine.

Driving and use of machines

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

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

Abraxane contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg; hence, it is essentially “sodium-free”.

3. How to use Abraxane

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

How often will Abraxane be administered?

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 administered 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 administered 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 adverse effects

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

Very common adverse effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within less than one month after starting treatment with Abraxane. When it occurs, hair loss is severe [more than 50%] in most patients)
• Skin rash
• Abnormally low levels of certain types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• Reduction in red blood cells
• Decreased number of platelets in blood
• Effects on peripheral nerves (pain, numbness, tingling, or loss of sensation)
• 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 blood potassium levels
• Depression, sleep problems
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of mucous membranes and soft tissues
• Increased liver enzyme values in liver function tests
• Pain in the limbs
• Cough
• Abdominal pain
• Nosebleed

Common adverse effects may affect up to 1 in 10 people:

• Itching, dry skin, nail disorders
• Infection, fever with low levels of a type of white blood cell (neutrophils) in blood, flushing, mouth ulcers, severe blood infection possibly due to reduced white blood cells
• Reduction in all blood cell counts
• Chest or throat pain
• Indigestion, abdominal discomfort
• Nasal congestion
• Back pain, bone pain
• Decreased muscle coordination or difficulty reading, increased or decreased tear production, 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 blood
• Coughing up blood
• Dry mouth, difficulty swallowing
• Muscle weakness
• Blurred vision

Uncommon adverse effects may affect up to 1 in 100 people:

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

Rare adverse effects may affect up to 1 in 1,000 people:

• Skin reaction to another agent or lung inflammation following radiation
• Blood clots
• Very slow pulse, heart attack
• Leakage of medicine from the vein (extravasation)
• Disorder of the heart's electrical conduction system (atrioventricular block)

Very rare adverse effects may affect up to 1 in 10,000 people:

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

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

• Hardening/thickening of the skin (scleroderma)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse 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 stated on the carton and vial after CAD/EXP. The expiry date refers to 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 should be used immediately. If not used immediately, the vial containing the dispersion must be placed inside its outer packaging to protect it from light and stored in the refrigerator (2°C–8°C) for a maximum of 24 hours.

The reconstituted dispersion in the infusion bag may be stored in the refrigerator (2°C–8°C) for up to 24 hours, protected from light.

The total storage time combining the reconstituted medicine in the vial and in the infusion bag, when refrigerated and protected from light, is 24 hours. After this, it may be kept in the infusion bag for up to 4 hours at a temperature below 25°C.

Your doctor or pharmacist is responsible for the proper disposal of any unused Abraxane.

6. Contents of the container and other information

Composition of Abraxane

The active substance is paclitaxel.

Each vial contains 100 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 (containing sodium caprylate and N-acetyl-L-tryptophan), see section 2 “Abraxane contains sodium”.

Nature of the product and contents of the container

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

Each pack contains 1 vial.

Marketing Authorization Holder

Bristol‑Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer responsible for batch release

Celgene Distribution B.V.

Orteliuslaan 1000

3528 BD Utrecht

The Netherlands

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder:

You can request further information about this medicine by contacting the marketing authorisation holder.

Date of the most recent review of this leaflet:

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

For doctors or healthcare professionals

This information is intended for doctors or healthcare professionals only:

Instructions for use, preparation and disposal

Precautions for preparation and administration

Paclitaxel is a cytotoxic antineoplastic agent; therefore, Abraxane must be handled with care, as with other potentially toxic drugs. Gloves, safety goggles, and protective clothing should be worn. In case of skin contact, wash the affected area immediately and thoroughly with soap and water. In case of contact with mucous membranes, rinse thoroughly with copious amounts 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, the infusion site should be closely monitored for signs of extravasation during administration. Limiting the infusion time of Abraxane to 30 minutes, as per instructions, reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medicine

Abraxane must be administered under the supervision of a qualified oncologist in specialized units for 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 incorporating 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 vial of Abraxane over at least 1 minute.

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

After adding the solution, allow the vial to stand for at least 5 minutes to ensure proper wetting of the powder. Then gently and carefully shake and/or slowly invert the vial for at least 2 minutes until the powder is completely redispersed. Foaming should be avoided. If foam or clumps form, allow the dispersion to stand for at least 15 minutes until the foam disappears.

The reconstituted dispersion should appear milky and homogeneous without visible precipitates. Some sedimentation of the reconstituted dispersion may occur. If precipitate or sedimentation is observed, 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 either PVC or non-PVC material.

The use of medical devices containing silicone oil as a lubricant (e.g., syringes and IV administration bags) for reconstituting and administering Abraxane may lead to the formation of protein filaments. Abraxane should be administered using an infusion set incorporating a 15 µm filter to prevent 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 medicine.

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

There is no need for DEHP-free containers or administration sets specifically for the preparation or administration of Abraxane infusions.

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

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.

Stability

Unopened vials of Abraxane remain stable until the date indicated on the container when stored in the outer packaging to protect from light. Freezing or refrigeration does not adversely affect the stability of the medicine. This medicine does not require special storage temperature conditions.

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 standpoint, unless the reconstitution and filling process of the infusion bags excludes the risk of microbial contamination, the product should be used immediately after reconstitution and filling of the infusion bags.

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

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