Abraxane: detailed information

Package leaflet: Information for the user

Abraxane 5 mg/mL powder for dispersion for infusion

paclitaxel
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet

What Abraxane is and what it is used for
What you need to know before using Abraxane
How to use Abraxane
Possible side effects
How to store Abraxane
Contents of the pack and other information

1. What is Abraxane and what is it used for

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

Paclitaxel is the component of the medicine that acts on the tumour by stopping tumour cells from dividing, thereby causing them to die.
Albumin is the component of the medicine that helps paclitaxel dissolve in the blood and cross blood vessel walls to reach the tumour. This means that additional chemical substances, which may cause potentially life-threatening side effects, are not required. Such side effects are much less common 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 (known as "metastatic" breast cancer).
Abraxane is used in metastatic breast cancer when at least one other therapy has been tried but was ineffective, and when the patient is not suitable for treatments containing a group of medicines called "anthracyclines".
Patients with metastatic breast cancer who received Abraxane after prior unsuccessful therapy were more likely to experience tumour shrinkage and lived longer compared to those who received alternative therapy.

Pancreatic cancer

Abraxane is used in combination with a medicine called gemcitabine for metastatic pancreatic cancer. In a clinical study, patients with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) treated with Abraxane and gemcitabine lived longer than those who received gemcitabine alone.

Lung cancer

Abraxane is also used in combination with a medicine called carboplatin for the treatment of 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 treatment options.

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 components of Abraxane (listed in section 6);
if you are breastfeeding;
if you have a low white blood cell count (baseline neutrophil count < 1,500 cells/mm³ – your doctor will provide information on this).

Warnings and precautions
Talk to your doctor or nurse before using Abraxane

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

Contact your doctor or nurse if you develop any of the following conditions during treatment with Abraxane; your doctor may decide to stop treatment or reduce the dose:

unusual bruising, bleeding, or signs of infection such as sore throat or fever;
numbness, tingling, burning sensations, sensitivity to touch, or muscle weakness;
breathing problems, such as shortness of breath or dry cough.

Children and adolescents
Abraxane is intended for adults only and must not be used in children and adolescents under 18 years of age.
Other medicines and Abraxane
Inform your doctor if you are taking or have recently taken any other medicines, including those obtained without a prescription and herbal medicines. This is because Abraxane may affect the action of other medicines, and other medicines may affect the action of Abraxane.
Be cautious and consult your doctor when taking Abraxane together with any of the following:

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

Pregnancy, breastfeeding and fertility
Paclitaxel can cause severe congenital abnormalities (birth defects) and therefore must not be used during pregnancy. Your doctor will perform a pregnancy test before starting treatment with Abraxane.
Women of childbearing potential must use effective contraception during treatment with Abraxane and for at least 6 months after stopping treatment.
Do not breastfeed during treatment with Abraxane, as it is not known whether the active substance paclitaxel passes into breast milk.
Male patients are advised to use effective contraception and to avoid fathering a child during treatment and for at least 3 months after stopping treatment. You should also discuss sperm preservation before starting treatment, due to the possibility that treatment with Abraxane may cause permanent infertility.
Ask your doctor for advice before taking this medicine.
Driving and using machines
Some people may experience fatigue or dizziness after receiving Abraxane. If this occurs, do not drive or operate machinery.
If other medicines are prescribed as part of your treatment, consult your doctor about whether it is safe to drive and use machines.
Abraxane contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 100 mg, i.e. essentially 'sodium-free'.

3. How to use Abraxane

Abraxane will be administered intravenously by infusion under the supervision of a doctor or nurse. The amount administered depends on body surface area and blood test results. The usual dose for breast cancer is 260 mg/m² of body surface area, administered over 30 minutes. The usual dose for advanced pancreatic cancer is 125 mg/m² of body surface area, administered over 30 minutes. The usual dose for non-small cell lung cancer is 100 mg/m² of body surface area, administered over 30 minutes.

How often is Abraxane 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 advanced pancreatic cancer, Abraxane is given on days 1, 8, and 15 of each 28-day treatment 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 administration of Abraxane.

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

4. Possible side effects

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

Very common side 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 leucocytes) in the blood
Anaemia (low red blood cell count)
Low platelet count in the blood
Peripheral nerve effects (pain, numbness, tingling or loss of sensation)
Pain in one or more joints
Muscle pain
Nausea, diarrhoea, constipation, mouth irritation, loss of appetite
Vomiting
Weakness and fatigue, fever
Dehydration, altered taste, weight loss
Low blood potassium levels
Depression, sleep disorders
Headache
Chills
Difficulty breathing
Dizziness
Swelling of mucous membranes and soft tissues
Increased liver function test values
Pain in extremities
Cough
Abdominal pain
Nosebleed

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

Itching, dry skin, nail changes
Infection, fever with low levels of a type of white blood cells (neutrophils) in the blood, hot flushes, candidiasis, severe blood infection that may be caused by low white blood cell count
Reduced number of all types of blood cells
Chest pain or sore throat
Indigestion, abdominal discomfort
Stuffy nose
Back pain, bone pain
Reduced muscle coordination or difficulty reading, increased or decreased tear production, loss of eyelashes
Changes in heart rate or rhythm, heart failure
Decreased or increased blood pressure
Redness or swelling at the injection site
Anxiety
Lung infection
Urinary tract infection
Bowel 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

Uncommon side effects (may affect up to 1 in 100 people):

Weight gain, increased blood lactate dehydrogenase, reduced kidney function, increased blood sugar, increased blood phosphorus
Decreased or absent reflexes, involuntary movements, neuralgia, fainting, dizziness upon standing, tremor, facial nerve paralysis
Eye irritation, eye pain, eye redness, eye itching, double vision, reduced visual acuity or seeing flashing lights, blurred vision due to swelling of the retina (cystoid macular oedema)
Ear pain, ringing in the ears
Cough with mucus, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, fluid in the lungs, hoarseness, blood clot in the lung, dry throat
Flatulence (intestinal gas), stomach cramps, gum pain, rectal bleeding
Painful urination, frequent urination, blood in the urine, urinary incontinence
Hand nail pain, hand nail discomfort, hand nail loss, hives, skin pain, photosensitivity reaction, pigmentation disorders, increased sweating, night sweats, white spots on the skin, skin lesions, facial swelling
Low blood phosphorus, fluid retention, low blood albumin, increased thirst, low blood calcium, low blood sugar, low blood sodium
Nasal pain and swelling, skin infections, catheter-related infection
Bruising
Pain at the tumour site, tumour necrosis
Drop in blood pressure when standing up, feeling cold in hands and feet
Difficulty walking, swelling
Allergic reaction
Reduced liver function, enlarged liver
Breast pain
Restlessness
Small areas of bleeding under the skin due to blood clots
A condition involving destruction of red blood cells and acute kidney failure

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

Skin reaction to another agent or radiation-induced lung inflammation
Blood clot formation
Very slow heart rate, heart attack
Leakage of medicine from the vein
A disorder of the heart's electrical conduction system (atrioventricular block)

Very rare side effects (may affect up to 1 in 10,000 people):

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

Side effects with unknown frequency (frequency cannot be estimated from the available data):

Hardening/thickening of the skin (scleroderma)

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

5. How to store 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 Exp./EXP. The expiry date refers to the last day of that month.
Closed vials: keep the vial in the outer packaging to protect the medicine from light.
After initial reconstitution, the dispersion must be used immediately. If not used immediately, the dispersion may be stored in the refrigerator (2 °C - 8 °C) for up to 24 hours in the vial kept in the outer packaging which protects the medicine from light.
The reconstituted dispersion for intravenous infusion may be stored in the refrigerator (2 °C - 8 °C) for up to 24 hours, protected from light.
The total combined storage time of the reconstituted medicine in the vial and in the infusion bag, when refrigerated and protected from light, is 24 hours. This may be followed by storage in the infusion bag for up to 4 hours at temperatures below 25 °C.
The doctor or pharmacist is responsible for the proper disposal of unused Abraxane.

6. Package contents and other information

What Abraxane contains
The active substance is paclitaxel.
Each vial contains 100 mg or 250 mg of paclitaxel bound to albumin formulated in
nanoparticles.
After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin formulated in nanoparticles.
The other component is human albumin solution (containing sodium caprylate and
N-acetyl-L-tryptophan), see section 2 “Abraxane contains sodium”.

Description of the appearance of Abraxane and contents of the pack
Abraxane is a white to yellow powder for dispersion for infusion. Abraxane is available in
glass vials containing 100 mg or 250 mg of paclitaxel bound to albumin formulated in
nanoparticles.
Each pack contains 1 vial.

Marketing Authorisation 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
The Netherlands

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

Belgique/België/Belgien Lietuva
N.V. Bristol-Myers Squibb Belgium S.A. Swixx Biopharma UAB
Tél/Tel: +32 2 352 76 11 Tel: +370 52 369140
[email protected] [email protected]

България Luxembourg/Luxemburg
Swixx Biopharma EOOD N.V. Bristol-Myers Squibb Belgium S.A.
Tel: +359 2 4942 480 Tél/Tel: +32 2 352 76 11
[email protected] [email protected]

Česká republika Magyarország
Bristol-Myers Squibb spol. s r.o. Bristol-Myers Squibb Kft.
Tel: +420 221 016 111 Tel.: +36 1 301 9797
[email protected] [email protected]

Danmark Malta
Bristol-Myers Squibb Denmark A.M. Mangion Ltd
Tlf: +45 45 93 05 06 Tel: +356 23976333
[email protected] [email protected]

Deutschland Nederland
Bristol-Myers Squibb GmbH & Co. KGaA Bristol-Myers Squibb B.V.
Tel: 0800 0752002 (+49 89 121 42 350) Tel: +31 (0)30 300 2222
[email protected] [email protected]

Eesti Norge
Swixx Biopharma OÜ Bristol-Myers Squibb Norway AS
Tel: +372 640 1030 Tlf: +47 67 55 53 50
[email protected] [email protected]

Ελλάδα Österreich
Bristol-Myers Squibb A.E. Bristol-Myers Squibb GesmbH
Τηλ: +30 210 6074300 Tel: +43 1 60 14 30
[email protected] [email protected]

España Polska
Bristol-Myers Squibb, S.A. Bristol-Myers Squibb Polska Sp. z o.o.
Tel: +34 91 456 53 00 Tel.: +48 22 2606400
[email protected] [email protected]

France Portugal
Bristol-Myers Squibb SAS Bristol-Myers Squibb Farmacêutica Portuguesa, S.A.
Tél: +33 (0)1 58 83 84 96 Tel: +351 21 440 70 00
[email protected] [email protected]

Hrvatska România
Swixx Biopharma d.o.o. Bristol-Myers Squibb Marketing Services S.R.L.
Tel: +385 1 2078 500 Tel: +40 (0)21 272 16 19
[email protected] [email protected]

Ireland Slovenija
Bristol-Myers Squibb Pharmaceuticals Ltd Swixx Biopharma d.o.o.
Tel: 1 800 749 749 (+353 (0)1 483 3625) Tel: +386 1 2355 100
[email protected] [email protected]

Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 20833 600
[email protected] [email protected]
[email protected]

Italia Suomi/Finland
Bristol-Myers Squibb S.r.l. Oy Bristol-Myers Squibb (Finland) Ab
Tel: +39 06 50 39 61 Puh/Tel: +358 9 251 21 230
[email protected] [email protected]

Κύπρος Sverige
Bristol-Myers Squibb A.E. Bristol-Myers Squibb Aktiebolag
Τηλ: 800 92666 (+30 210 6074300) Tel: +46 8 704 71 00
[email protected] [email protected]

Latvija
Swixx Biopharma SIA
Tel: +371 66164750
[email protected]

For further information about this medicinal product, contact the Marketing Authorisation Holder.
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu.

Healthcare professionals
The following information is intended exclusively for physicians or healthcare professionals:

Instructions for use, handling and disposal
Precautions for preparation and administration
Paclitaxel is a cytotoxic antineoplastic medicinal product; as with other potentially toxic compounds, certain precautions should be taken when handling Abraxane. Wear gloves, eye protection and protective clothing. If the dispersion comes into contact with the skin, wash the skin immediately and thoroughly with soap and water. If contact occurs with mucous membranes, rinse thoroughly with copious amounts of water. Abraxane must be prepared and administered only by personnel adequately trained in handling cytotoxic agents.
Abraxane must not be handled by pregnant women.

Due to the risk of extravasation, the infusion site should be closely monitored for signs of infiltration during administration. Limiting the infusion of Abraxane to 30 minutes, as indicated, reduces the likelihood of infusion-related reactions.

Reconstitution and administration of the medicinal product
Abraxane must be administered under the supervision of a qualified oncologist in specialized units experienced in the administration of cytotoxic agents.
Abraxane is supplied as a sterile lyophilized powder and must be reconstituted before use.
After reconstitution, each mL of dispersion contains 5 mg of paclitaxel bound to albumin formulated in nanoparticles. The reconstituted dispersion of Abraxane is administered intravenously using an infusion set equipped with a 15-micron 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.

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 vial of Abraxane over at least 1 minute.

The solution should be directed toward the inner wall of the vial. The solution must not be injected directly onto the powder, as this may cause foaming.
After completing the addition of solution, allow the vial to stand undisturbed for at least 5 minutes to allow complete wetting of the powder. Then, gently and slowly rotate and/or invert the vial for at least 2 minutes until the powder is completely redispersed. Avoid foaming. 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 precipitate. Sediment may occur in the reconstituted dispersion. If precipitates or sediment are visible, gently invert the vial again to ensure complete redispersion before use.

Inspect the dispersion in the vial for the presence of precipitate. Do not administer the reconstituted dispersion if precipitates are observed in the vial.

The exact total volume of the 5 mg/mL dispersion required for the patient must be calculated, and the appropriate amount of reconstituted Abraxane should be transferred into an empty, sterile intravenous infusion bag made of PVC or another suitable material.

The use of medical devices containing silicone lubricant (e.g., syringes and infusion bags) for reconstitution and administration of Abraxane may lead to the formation of proteinaceous filaments.
Administer Abraxane using an infusion set equipped with a 15-micron filter to prevent administration of these filaments. The use of a 15-micron filter removes filaments without altering the physical or chemical properties of the reconstituted product.
The use of filters with pore sizes smaller than 15 microns may cause filter clogging.

Special containers or administration sets free of DEHP are not required for the preparation and administration of Abraxane infusions.

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

Unused medicinal product and waste materials derived from its use must be disposed of in accordance with local regulations.

Stability
Unopened vials of Abraxane are stable until the expiry date indicated on the packaging, provided the vial is stored in the original outer packaging to protect from light. Freezing and refrigeration do not adversely affect the stability of the medicinal product. This medicinal product does not require specific storage temperature conditions.

Stability of the reconstituted dispersion in the vial
The medicinal product has been shown to be chemically and physically stable for 24 hours at 2 °C – 8 °C in the original packaging, protected from light.

Stability of the reconstituted dispersion in the infusion bag
The medicinal product has been shown to be chemically and physically stable for 24 hours at 2 °C – 8 °C, followed by up to 4 hours at 25 °C, protected from light.

However, from a microbiological standpoint, unless the reconstitution and filling of infusion bags are performed under conditions that exclude the risk of microbial contamination, the product should be used immediately after reconstitution and filling.
If the product is not used immediately, the user is responsible for ensuring appropriate storage conditions and duration of use.
The total combined storage time of the reconstituted medicinal product in the vial and in the infusion bag, when refrigerated and protected from light, is 24 hours. This may be followed by up to 4 hours of storage in the infusion bag at temperatures below 25 °C.