ABRAXANE 5 мг/мл Порошок для инъекционного раствора

Содержание инструкции

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

Abraxane 5 mg/mL powder for dispersion for infusion

paclitaxel

Read this leaflet carefully before you start to use 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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

• 1. What Abraxane is and what it is used for
• 2. What you need to know before you use Abraxane
• 3. How to use Abraxane
• 4. Possible side effects
• 5. How to store Abraxane
• 6. 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 ingredient, paclitaxel bound to albumin, a human protein, 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 part of the medicine that has an effect on the tumor, it works by stopping the division of tumor cells, which therefore die.
• Albumin is the part of the medicine that helps paclitaxel dissolve in the blood and cross the walls of blood vessels to reach the tumor. This means that no other chemical substances are needed that can cause undesirable effects, which can be life-threatening. Some undesirable effects are much less frequent with Abraxane.

What is Abraxane used for
Abraxane is used for the treatment of 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 attempted, but has not been effective and if the patient is not eligible for treatments containing a group of medicines called “anthracyclines”.
• People with metastatic breast cancer who have received Abraxane, in cases where another therapy had not been successful, have been more likely to observe a reduction in tumor size and have lived longer compared to people who have taken an alternative therapy.

Pancreatic cancer

• Abraxane is used together with a medicine called gemcitabine in case of metastatic pancreatic cancer. People with metastatic pancreatic cancer (pancreatic cancer that has spread to other parts of the body) treated with Abraxane and gemcitabine in a clinical study have lived longer compared to people who received only gemcitabine.

Lung cancer

• Abraxane is used together with a medicine called carboplatin in the treatment of the most common type of lung cancer, called “non-small cell lung cancer”.
• Abraxane is used in non-small cell lung cancer in cases where surgery or radiotherapy are not suitable for the treatment of the disease.

2. What you need to know before using Abraxane

Do not use Abraxane

• if you are allergic (hypersensitive) to paclitaxel or any of the other ingredients of this medicine (listed in section 6);
• if you are breastfeeding;
• if you have a low number of white blood cells (initial neutrophil count <1,500 cells/mm - your doctor will provide information on this).

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

• if your kidney function is reduced;
• if you have serious liver problems;
• if you have heart disorders.

Consult your doctor or nurse if you experience any of these conditions during treatment with
Abraxane; your doctor may decide to stop treatment or reduce the dose:

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

Children and adolescents
Abraxane is only for adults and should not be used in children and 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
available without a prescription and herbal medicines. This is because Abraxane can affect
the action of other medicines and other medicines can affect the action of Abraxane.
Be careful and consult your doctor when taking Abraxane together with any of the following:

• medicines for the treatment of infections (i.e. antibiotics, such as erythromycin, rifampicin, etc.; ask your doctor, nurse or pharmacist if you are not sure whether the medicine you are taking is an antibiotic), including medicines for the treatment of fungal infections (e.g. ketoconazole)
• medicines used to stabilize mood, sometimes also called antidepressants (e.g. fluoxetine)
• medicines used for the treatment of 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 for the treatment of HIV and AIDS (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine)
• a medicine called clopidogrel used for the prevention of blood clots.

Pregnancy, breastfeeding and fertility
Paclitaxel can cause serious birth defects (at birth) 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 contraceptive methods during therapy with Abraxane and for 1
month after stopping therapy.
Do not breastfeed during treatment with Abraxane, because it is not known whether the active ingredient paclitaxel passes into
breast milk.
For male patients, it is recommended to use effective contraceptive measures and to avoid
conceiving children during therapy and for six months after stopping it, and to inquire about
semen preservation before treatment, due to the possibility that therapy with Abraxane may produce
permanent infertility.
Ask your doctor for advice before taking this medicine.

Driving and using machines
Some people may feel tired or dizzy after receiving Abraxane. If this
happens, do not drive vehicles and do not use tools or machinery.
If other medicines are prescribed as part of the therapy, consult your doctor about the possibility of driving
and using machinery.

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 via intravenous infusion by a doctor or nurse. The
amount administered depends on the body surface area and the results of blood tests. The usual dose
for breast cancer is 260 mg/m of body surface area, administered over 30
minutes. The usual dose for advanced pancreatic cancer is 125 mg/m of body surface area,
administered over 30 minutes. The usual dose for non-small cell lung cancer is of
100 mg/m of body surface area, administered over 30 minutes.

How often is Abraxane administered?
For the treatment of metastatic breast cancer, Abraxane is usually administered once
every three weeks (day 1 of a 21-day cycle).
For the treatment of advanced pancreatic cancer, Abraxane is administered 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 administered once a
week (i.e. days 1, 8 and 15 of a 21-day cycle) with carboplatin administered once every three
weeks (i.e. only day 1 of each 21-day cycle), immediately after the administration of the
Abraxane dose.
If you have any doubts about the use of this medicine, please ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Very common side effects may affect more than 1 in 10 people:

• Hair loss (most cases of hair loss occurred within one month of starting treatment with Abraxane. When it occurs, hair loss is pronounced (over 50%) in most patients)
• Skin rash
• Abnormally low number of certain types of white blood cells (neutrophils, lymphocytes, or leukocytes) in the blood
• Red blood cell (erythrocyte) deficiency
• Reduced number of platelets in the blood
• Effects on peripheral nerves (pain, numbness, tingling, or loss of sensation)
• Pain in one or more joints
• Muscle pain
• Nausea, diarrhea, constipation, mouth irritation, loss of appetite
• Vomiting
• Weakness and fatigue, fever
• Dehydration, altered taste, weight loss
• Low potassium levels in the blood
• Depression, sleep disorders
• Headache
• Chills
• Difficulty breathing
• Dizziness
• Swelling of the mucous membranes and soft tissues
• Increased liver function values
• Pain in the extremities
• Cough
• Abdominal pain
• Nosebleeds

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

• Itching, dry skin, changes in nails
• Infection, fever with a reduction in the number of a type of white blood cells (neutrophils) in the blood, hot flashes, oral candidiasis, serious blood infection that may be caused by a reduction in white blood cells
• Reduced number of all types of blood cells
• Chest pain or sore throat
• Indigestion, abdominal problems
• Stuffy nose
• Back pain, bone pain
• Reduced muscle coordination or difficulty reading, increased or decreased tearing, 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
• Blockage in the intestine, inflammation of the colon, 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 lactate dehydrogenase (an enzyme) in the blood, decreased kidney function, increased blood sugar, increased phosphorus in the blood
• 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 edema)
• Ear pain, ringing in the ears
• Cough with mucus, shortness of breath when walking or climbing stairs, runny or dry nose, decreased breath sounds, water in the lungs, hoarseness, blood clot in the lung, dry throat
• Flatulence (intestinal gas), stomach cramps, gum pain, blood in the stool
• Painful urination, frequent urination, blood in the urine, urinary incontinence
• Nail pain, painful nail sensitivity, nail loss, hives, skin pain, photosensitivity reaction, changes in pigmentation, increased sweating, night sweats, white spots on the skin, skin lesions, facial swelling
• Decreased phosphorus in the blood, fluid retention, low albumin levels in the blood, increased thirst, decreased calcium in the blood, decreased blood sugar, decreased sodium in the blood
• Nasal congestion and pain, skin infections, catheter infection
• Bruising
• Pain at the site of the tumor, tumor necrosis
• Decreased blood pressure in the upright position, cold extremities (hands and feet)
• Difficulty walking, swelling
• Allergic reaction
• Decreased liver function, enlarged liver
• Chest pain
• Restlessness
• Small blood leaks in the skin due to blood clots
• A condition involving the 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 pulmonary inflammation following radiation
• Blood clot formation
• Very slow pulse, heart attack
• Leakage of the 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/mucous membrane inflammation/rash (Stevens-Johnson syndrome, toxic epidermal necrolysis)

Side effects with unknown frequency (frequency cannot be estimated based on available data):

• Hardening/thickening of the skin (scleroderma)

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you 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 which is stated on the package and vial after
Expiry/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 the first reconstitution, the dispersion must be used immediately. If not used
immediately, the dispersion can be stored in a refrigerator (2 °C - 8 °C) for up to 24 hours in the vial
kept in the outer packaging that protects the medicine from light.
The dispersion reconstituted for intravenous infusion can be stored in a refrigerator (2 °C - 8 °C) for up to
24 hours protected from light.
The total storage time of the medicine reconstituted in the vial and in the infusion bag, if
refrigerated and protected from light, is 24 hours. This can be followed by storage for 4 hours in the
infusion bag at temperatures below 25 °C.
The doctor or pharmacist is responsible for the correct disposal of unused Abraxane.

6. Contents of the pack and other information

What Abraxane contains
The active ingredient 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 powder from white to yellow for dispersion for infusion. Abraxane is available in vials
of glass 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
Netherlands
For further information on this medicinal product, contact the marketing authorisation holder.
More detailed information on this medicine is available on the European Medicines Agency’s website,
http://www.ema.europa.eu.
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Physicians or 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, goggles and protective clothing.
If the dispersion comes into contact with the skin, wash the skin immediately and thoroughly with water and
soap. If contact occurs with mucous membranes, they should be rinsed well with plenty of water. Abraxane
must be prepared and administered exclusively by personnel adequately trained in the handling of cytotoxic
agents. Abraxane should not be handled by pregnant women.
Given the possibility of extravasation, it is recommended to carefully monitor the infusion site for any
infiltration during administration of the medicinal product. Limiting the infusion of Abraxane to 30 minutes,
as indicated, reduces the probability of infusion-related reactions.

Reconstitution and administration of the medicinal product
Abraxane must be administered under the supervision of a qualified oncologist in departments specialising
in the administration of cytotoxic agents.
Abraxane is supplied as a sterile lyophilised 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 towards the inner wall of the vial. The solution should not be
injected directly onto the powder as this will create foam.
Once the addition of solution is complete, allow to stand for at least 5 minutes to allow the powder to be
completely permeated. Then, rotate and/or invert the vial gently and slowly for at least 2 minutes, until all
the powder is completely redispersed. Avoid foam formation. If foam or clumps form, allow the dispersion
to stand for at least 15 minutes until the foam disappears.
The reconstituted dispersion should have a milky and homogeneous appearance without visible precipitate.
Deposits may occur in the reconstituted dispersion. If precipitates or deposits are visible, gently invert the
vial again to ensure complete redispersal before use.
Examine the dispersion in the vial to check for 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 must be injected into an empty, sterile PVC or other material
intravenous infusion bag.
The use of medical devices containing silicone oil lubricant (syringes and IV bags) to reconstitute and
administer Abraxane may cause the formation of protein filaments. Administer Abraxane using an infusion
set equipped with a 15 micron filter to prevent the administration of these filaments. The use of a 15 micron
filter removes the filaments and does not alter the physical or chemical properties of the reconstituted product.
The use of filters with a pore diameter less than 15 microns may cause the filter to become blocked.
The use of special containers or administration sets not containing DEHP is not necessary 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%)
injectable solution to ensure the complete dose is administered.
Unused medicinal product and waste materials derived from such medicinal product should be disposed of in
accordance with local regulations.

Stability
Closed vials of Abraxane are stable until the date indicated on the packaging, provided the vial is
stored in the outer packaging to protect the medicinal product from light. Freezing and refrigeration do not
have any adverse effects on the stability of the medicinal product. This medicinal product does not require
any particular storage temperature.

Stability of the reconstituted dispersion in the vial
The medicinal product has been shown to be chemically and physically stable in use 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 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 excludes the risk of microbial contamination, the product should be used immediately after
reconstitution and filling of the infusion bags.
If the product is not used immediately, the times and conditions of storage during use are the responsibility
of the user.
The total storage time of the medicinal product reconstituted in the vial and in the infusion bag, if
refrigerated and protected from light, is 24 hours. This may be followed by storage for 4 hours in the
infusion bag at temperatures below 25 °C.