PACLITAXEL 6 mg /Ml Koncentrat Do Sporządzania Roztworu Infuzyjnego

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1. Paclitaxel Sandoz 6 mg/ml, concentrate for solution for infusion
   1. WHAT IS PACLITAXEL SANDOZ AND WHAT IS IT USED FOR
   2. WHAT YOU NEED TO KNOW BEFORE YOU USE PACLITAXEL SANDOZ
   3. HOW TO USE PACLITAXEL SANDOZ
   4. POSSIBLE SIDE EFFECTS
   5. HOW TO STORE PACLITAXEL SANDOZ
   6. PACKAGE CONTENTS AND OTHER INFORMATION
   7. Incompatibilities
   8. Instructions for Use and Handling
   9. Shelf Life
   10. Special precautions for storage

Paclitaxel Sandoz 6 mg/ml, concentrate for solution for infusion

Equivalent Medicinal Product

Read this leaflet carefully before you start to use the medicine as it contains
important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• If any side effects occur, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. WHAT IS PACLITAXEL SANDOZ AND WHAT IS IT USED FOR

PACLITAXEL SANDOZ is used to treat:

Ovarian Cancer:In first-line chemotherapy for Ovarian Cancer, paclitaxel is indicated for
the treatment of patients with advanced ovarian cancer or with residual disease (>1 cm) after initial laparotomy,
in combination with cisplatin.
In second-line chemotherapy for Ovarian Cancer, paclitaxel is indicated for the treatment of
metastatic ovarian cancer after failure of standard platinum-based therapy.

Breast Cancer:In the adjuvant setting, paclitaxel is indicated for the treatment of patients with
lymph node-positive breast cancer, after therapy with anthracyclines and cyclophosphamide (AC). The
adjuvant treatment with paclitaxel should be considered as an alternative to prolonged therapy with AC.
Paclitaxel is indicated for the initial treatment of locally advanced or
metastatic breast cancer, in combination with anthracyclines in patients in whom anthracycline therapy is appropriate, or in
combination with trastuzumab in those who overexpress HER-2 at level 3+, as determined by
immunohistochemical method, or in whom anthracyclines are not appropriate.
As monotherapy, paclitaxel is indicated in the treatment of metastatic breast cancer in
patients in whom standard anthracycline-based therapy has failed or who are not candidates for it.

Advanced Stage Non-Small Cell Lung Cancer:Paclitaxel, in combination with
cisplatin, is indicated in the treatment of non-small cell lung cancer (NSCLC) in patients who
are not candidates for potentially curative surgical and/or radiation therapies.

AIDS-Related Kaposi's Sarcoma:Paclitaxel is indicated for the treatment of patients with advanced
Kaposi's Sarcoma (KS) related to AIDS, in whom previous therapy with liposomal anthracyclines has not
been successful.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE PACLITAXEL SANDOZ

Do not use PACLITAXEL SANDOZ

• if you are allergic to paclitaxel or to any of the other ingredients of this medicine (listed in section 6), and in particular to polyoxyethylated castor oil (ricinoleate macrogolglycerol)
• if you are pregnant or breastfeeding
• if the number of your white blood cells, as measured by healthcare professionals, is too low (neutrophils)
• if you have Kaposi's sarcoma and severe, uncontrolled concomitant infections.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking PACLITAXEL SANDOZ

• if you have a liver disease
• if you have an uncontrolled infection
• if you are taking other medicines
• if hypersensitivity (allergic) reactions occur (e.g., hypotension, respiratory distress, skin rash)
• if you have had neurological problems in your hands or feet (peripheral neuropathy)
• when severe or persistent diarrhea occurs during or immediately after treatment with paclitaxel
• if you have a heart condition
• because this medicine contains alcohol and macrogol glycerol ricinoleate (see section “Important information about some of the ingredients of Paclitaxel Sandoz”)
• when you have changes in your blood cell counts
• when Paclitaxel Sandoz is administered in combination with radiation therapy to the lungs
• if you have Kaposi's sarcoma and if severe inflammation of the mucous membranes occurs.

Other medicines and PACLITAXEL SANDOZ
Tell your doctor or pharmacist if you are taking, have recently taken or might take any
other medicines, including those available without a prescription.
Paclitaxel Sandoz must be administered:

• before cisplatin, when used in combination
• 24 hours after doxorubicin. Talk to your doctor when taking paclitaxel at the same time as any of the following:
• medicines to treat 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 to treat fungal infections (e.g., ketoconazole)
• medicines used to help stabilize your mood, sometimes called antidepressants (e.g., fluoxetine)
• medicines used to treat seizures (epilepsy) (e.g., carbamazepine, phenytoin)
• medicines used to help lower your blood fat levels (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.

Use of PACLITAXEL SANDOZ with food and drinks
PACLITAXEL SANDOZ can be taken with food and drinks. However, you should check,
together with your doctor, whether it is advisable for you to drink alcohol during treatment with PACLITAXEL
SANDOZ.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy: Do not use PACLITAXEL SANDOZ during pregnancy.
Breastfeeding: Do not use PACLITAXEL SANDOZ while breastfeeding. Do not resume breastfeeding until
your doctor tells you that it is safe to do so.
Avoid becoming pregnant while taking Paclitaxel Sandoz. If pregnancy occurs, inform
your doctor immediately. While you are being treated with Paclitaxel Sandoz, you should stop breastfeeding.

Driving and using machines
There is no reason why you should not be able to continue driving between treatment cycles with PACLITAXEL
SANDOZ, but you should remember that this medicine contains a certain amount of alcohol, and that driving
immediately after a treatment cycle may be unwise. However, you should not drive if you feel dizzy or lightheaded.

PACLITAXEL SANDOZ contains alcohol
This medicine contains 50% (by volume) ethanol (alcohol), which is 20 g per dose, equivalent to
52 cl of beer or 21 cl of wine. This amount can be harmful to alcoholics.
This medicine also contains polyoxyethylated castor oil (ricinoleate macrogolglycerol), which can
cause severe hypersensitivity reactions.

3. HOW TO USE PACLITAXEL SANDOZ

The doctor has determined what dose you should take and how many doses.
PACLITAXEL SANDOZ is administered under the supervision of a doctor, who can provide you with more
information.
The dose depends on the type of cancer and its severity. PACLITAXEL SANDOZ is injected into a vein
by means of an intravenous infusion lasting approximately 3 hours. The treatment is generally repeated with a
treatment-free interval of 3 weeks (2 weeks in patients with Kaposi's sarcoma).

Before starting treatment with PACLITAXEL SANDOZ
Before starting treatment with PACLITAXEL SANDOZ you will receive premedication with numerous
other medicines. This premedication is necessary to prevent severe hypersensitivity reactions.

If you take more PACLITAXEL SANDOZ than you should
Not applicable, because PACLITAXEL SANDOZ is administered by a doctor or nurse.

If you forget to take PACLITAXEL SANDOZ
Not applicable, because PACLITAXEL SANDOZ is administered by a doctor or nurse.

If you stop taking PACLITAXEL SANDOZ
The doctor will decide when to stop treatment with PACLITAXEL SANDOZ.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

Use in children and adolescents
Paclitaxel is not recommended for use in children under 18 years of age.

4. POSSIBLE SIDE EFFECTS

Like all medicines, PACLITAXEL SANDOZ can cause side effects, although not everybody gets them.

Tell your doctor immediatelyif you notice any signs of allergic reactions. These can
include one or more of the following:

• flushing,
• skin reactions,
• itching,
• chest tightness,
• shortness of breath or difficulty breathing,
• swelling. These can all be signs of serious side effects.

Tell your doctor immediately if

• you have fever, severe chills, sore throat or mouth ulcers(signs of bone marrow suppression).
• you have numbness or weakness in your arms and legs(signs of peripheral neuropathy).
• you develop severe or persistent diarrhea, with fever and stomach pain

Very common (affects more than 1 in 10 people):
Hair loss (most cases of hair loss occurred less than a month
after starting treatment with paclitaxel. When this happens, hair loss is evident [over 50%] in most patients), nausea, vomiting and diarrhea, allergic reactions such as flushing, skin rashes, itching and general infections. Low blood pressure. Blood disorders (this is why
regular blood tests are performed) which can lead to mild anemia (feeling weak or tired) or
increase the risk of infections, or make you bruise more easily. Numbness and/or
tingling of the hands and/or feet, muscle and joint pain, pain in the mouth and tongue.

Common (affects 1 to 10 people in 100):
Changes in heart rate or rhythm, high blood pressure and bleeding. Patients with Kaposi's sarcoma may have serious liver problems. Temporary changes in nails and skin. Symptoms
due to extravasation: sometimes pain, redness of the skin, a feeling of warmth, swelling, and possible
skin breakdown at the injection/infusion site. Other skin disorders.
Inflammation of a vein occurs less frequently. Chest pain and/or shortness of breath may
occur if you are also being treated with other chemotherapy agents and/or with radiotherapy. In addition, bowel disorders, abdominal pain, increased sweating and limb pain have been reported.

Uncommon (affects 1 to 10 people in 1,000):
Low blood pressure and low blood flow due to a very severe infection, sometimes with
resulting severe organ dysfunction. Fainting, seizures, temporary loss of consciousness. Heart attack.

Rare (affects 1 to 10 people in 10,000):
Increased body temperature, dehydration and anaphylaxis – that is, an allergic reaction with swelling of the
face/throat, wheezing, feeling faint and shortness of breath. Chills and back pain associated with the allergic
reaction. Pneumonia and other lung disorders, scarring or thickening of deep lung tissue, with resulting shortness of breath and cough; blood clots in the lungs, with resulting shortness of breath, chest or shoulder pain, cough; critical lung and respiratory failure. Swelling and/or weakness in the hands and/or feet have also been reported. Peritonitis (severe abdominal pain); intestinal obstruction with partial or complete blockage of the intestine; full-thickness ulceration of the intestine, with leakage of the
intestinal contents into the abdominal cavity; areas of intestinal inflammation due to low blood
flow to the intestine; inflammation of the pancreas. Heart problems that can cause shortness of breath or
swelling of the ankles.
Other heart disorders have also been reported.

Very rare (affects less than 1 in 10,000):
Severe infections, vision and hearing disorders, dizziness, vertigo, cough, severe or life-threatening allergic reactions, hives; widespread skin redness (due to allergy), with destruction
of parts of the skin, large blisters, sometimes extending to large areas of the body surface and the mucous membrane of the
mouth (Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme), skin redness with
peeling, often with itching and hair loss. Detachment of nails from the nail bed. Sudden
lowering of blood pressure immediately after moving to the upright position, with resulting
dizziness. Seizure-like attacks (convulsions); these attacks affect the whole body; confusion and
other effects on the brain up to severe brain damage. Intestinal obstruction with
resulting partial or complete blockage of the intestine. Blood clots in the blood vessels of the abdomen and
intestine. Severe inflammation of the intestine with resulting bloody diarrhea, abdominal pain or
fever. Inflammation of the esophagus. Large amount of fluid in the abdominal cavity. Inflammation
of the colon, due to a low number of white blood cells in the blood. Liver disorders; death of part of the
liver tissue, with resulting severe liver disorders. Damage to the brain and nervous system as a complication of liver disorders. Loss of appetite, constipation, headache, difficulty coordinating movements, effects on hearing and/or balance, rapid heartbeat, weight loss (anorexia) have also been reported. Neoplasms of the hematopoietic (blood-forming) tissues of the bone marrow; a group of bone marrow diseases that cause ineffective production of blood cells (and which after many years can have as a consequence a confirmed tumor of the blood-forming tissues of the bone marrow).

Not known (frequency cannot be estimated from the available data):
Tumor lysis syndrome with consequent:

• high levels of potassium in the blood that can cause heart rhythm abnormalities (hyperkalemia),
• tetany, seizures, mental retardation, movement disorders, emotional instability/agitation/anxiety, muscle pain or weakness (hypocalcemia)
• fatigue, loss of appetite, headache, fluid accumulation in the limbs and lungs (renal failure) Macular edema with consequent distortion of central vision

Photopsia with consequent perception of flashes of light.
Vitreous floaters that appear as spots, threads, or cobweb-like fragments, slowly floating
in front of the observer's eyes.
Inflammation of a vein (phlebitis)
Symmetrical thickening of the skin (Scleroderma)
Systemic lupus erythematosus with consequent fever, malaise, joint pain, myalgia, asthenia and temporary loss of cognitive abilities.
Disseminated intravascular coagulation or “DIC” has been reported. This is a serious condition that
makes people easily susceptible to bleeding, blood clot formation, or both.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in this leaflet. You can also report side effects directly
through the national reporting system at www.aifa.gov.it/content/segnalazioni-
reazioni-avverse. By reporting side effects you can help provide more
information on the safety of this medicine.

5. HOW TO STORE PACLITAXEL SANDOZ

Do not use PACLITAXEL SANDOZ after the expiry date indicated on the packaging and the vial after EXP. The expiry date refers to the last day of the month.
Keep this medicine out of the sight and reach of children.
Vial before opening: keep the vial in the outer packaging to protect the medicine
from light. This medicine does not require any particular storage temperature.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. PACKAGE CONTENTS AND OTHER INFORMATION

What PACLITAXEL SANDOZ contains

• The active ingredient is paclitaxel. Each ml of solution contains 6 mg of paclitaxel. One 5 ml vial contains 30 mg of paclitaxel. One 16.7 ml vial contains 100 mg of paclitaxel. One 25 ml vial contains 150 mg of paclitaxel. One 50 ml vial contains 300 mg of paclitaxel. One 100 ml vial contains 600 mg of paclitaxel.
• The excipients are castor oil polyethoxylated (macrogol glycerol ricinoleate) and ethanol.

Description of the appearance of PACLITAXEL SANDOZ and contents of the pack
Paclitaxel Sandoz concentrate for solution for infusion is a clear, colorless or yellowish-
light viscous solution.
Pack sizes:
1, 5 or 10 vials of 5 ml,
1 vial of 16.7 ml,
1 vial of 25 ml,
1 vial of 50 ml,
1 vial of 100 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sandoz S.p.A. Largo U Boccioni 1 - 21040, Origgio (VA) Italy

Manufacturer responsible for batch release
EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestrasse 11
4866 Unterach
Austria

This medicinal product is authorised in the Member States of the European Economic Area under the following
names:

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The following information is intended for healthcare professionals only
CYTOTOXIC

1. Incompatibilities

Polyoxyethylated castor oil (macrogol ricinoleate glyceride) may cause leaching of DEHP [di(2-
ethylhexyl) phthalate] from polyvinyl chloride (PVC) plastic containers, in an amount proportional to the time and
concentration. Consequently, preparation, storage and administration of Paclitaxel Sandoz
diluted must be carried out using devices not containing PVC.

2. Instructions for Use and Handling

Handling:
As with all other antineoplastic agents, paclitaxel should be handled with care.
Pregnant women or those of childbearing potential should be warned to avoid handling cytotoxic agents.
Dilution must be carried out under aseptic conditions, by trained personnel, in a dedicated area.
Suitable protective gloves must be worn and contact with skin and mucous membranes must be avoided. In case
of contact with the skin, the skin should be washed with soap and water. Tingling, burning and redness have been observed
after topical exposure. In case of contact with mucous membranes, wash with plenty of water. Dyspnea, chest pain, burning in the throat and nausea have been reported after
inhalation.
If unopened vials are stored in the refrigerator, a precipitate may form that dissolves with
gentle shaking or without shaking when it reaches room temperature. The quality of the product
is not affected. If the solution remains cloudy or if an insoluble precipitate is noted, the vial
should be discarded.
After multiple needle insertions and product withdrawals, the vials remain microbiologically, chemically and physically stable for 28 days at 25°C. Other storage times and methods during product use
are the responsibility of the user.

Preparation for Intravenous Infusion: Before infusion, Paclitaxel Sandoz must
be diluted, under aseptic conditions, with 0.9% sodium chloride injection solutions, 5% dextrose for
injection, or 5% dextrose and 0.9% sodium chloride for injection, to a final concentration of 0.3-1.2
mg/ml.
The chemical and physical stability during use of the solution prepared for infusion has been demonstrated at 5°C and
at 25°C for 48 hours, when diluted in 5% dextrose solution, and for 48 hours when diluted in 0.9% sodium chloride
injection. From a microbiological point of view, the product should be used immediately. If not used
immediately, the in-use storage times and conditions before use are the responsibility of
the user, and should normally not exceed 24 hours at 2 – 8°C, unless the dilution has been carried out
under controlled and validated aseptic conditions.
After dilution, the solution should be used only once.
After preparation, solutions may show turbidity, attributable to the vehicle of the formulation and
which is not eliminated by filtration. Paclitaxel Sandoz should be administered through an in-line filter with
a microporous membrane diameter ≤0.22 µm. No significant loss of drug potency was observed after simulated administration of the solution through an
infusion set equipped with an in-line filter.
There have been rare reports of precipitation during paclitaxel infusions, usually at the end of a
24-hour infusion period. Although not clarified, the cause of this precipitation is likely
related to supersaturation of the diluted solution. To reduce the risk of precipitation, paclitaxel should be
used as soon as possible after dilution, and excessive shaking, vibration and
shaking should be avoided. Infusion sets should be flushed thoroughly before use. During infusion, the
appearance of the solution should be inspected regularly, and if precipitation is present, the infusion should
be stopped.
To minimize patient exposure to DEHP that may be released from PVC-plasticized infusion bags, infusion sets or other medical devices, diluted solutions of Paclitaxel Sandoz should be
stored in non-PVC containers (glass, polypropylene) or in plastic bags (polypropylene,
polyolefins) and administered through polyethylene sets. No significant leaching of DEHP was observed with the use of filters incorporating short
PVC-plasticized inlet and/or outlet devices.

Disposal: All equipment used for preparation and administration or that otherwise comes
into contact with paclitaxel must be disposed of in accordance with current local regulations relating to
the handling of cytotoxic compounds.

3. Shelf Life

Unopened vials: 3 years.
After opening, before dilution
Chemical and physical stability in use has been demonstrated for 28 days at 25°C, after needle insertions and
repeated withdrawals of the product.
From a microbiological point of view, after opening the product can be stored for a maximum of 28 days
at 25°C. Other storage times and conditions in use are the responsibility of the user.
After dilution
The chemical and physical stability after dilution is documented for 48 hours at 25°C and at 2-8°C. From a
microbiological point of view, the medicinal product must be used immediately .If not used immediately, the in-use
storage times and conditions before use are the responsibility of the user, and normally should not
exceed 24 hours at 2-8°C, unless the dilution has taken place under controlled and validated aseptic conditions.

4. Special precautions for storage

Vial before opening: keep the vial in the outer packaging to protect the medicine
from light.