RMS approved version DK/07.11.2005

Package leaflet: Information for the patient

Paclitaxel-Ebewe, 6 mg/ml, concentrate for solution for infusion
Paclitaxelum
Read the entire leaflet carefully before using this medicine, as it contains important information
for the patient.

Keep this leaflet for future reference.
If you have any further questions, consult your doctor, pharmacist, or nurse.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist immediately. See section 4.

Table of contents:

What Paclitaxel-Ebewe is and what it is used for
Important information before using Paclitaxel-Ebewe
How to use Paclitaxel-Ebewe
Possible side effects
How to store Paclitaxel-Ebewe
Contents of the pack and other information

1. What Paclitaxel-Ebewe is and what it is used for

Paclitaxel-Ebewe is indicated for the treatment of:
Ovarian cancer
In first-line chemotherapy of ovarian cancer, paclitaxel is indicated in combination with cisplatin for the treatment of patients with advanced ovarian cancer or residual tumour (>1 cm) following prior laparotomy.
In second-line chemotherapy of ovarian cancer, paclitaxel is indicated for the treatment of patients with metastatic ovarian cancer who have failed standard platinum-containing regimens.

Breast cancer
In adjuvant therapy, paclitaxel is indicated for patients with node-positive disease following anthracycline and cyclophosphamide (AC) therapy. Adjuvant treatment with paclitaxel should be considered an alternative to prolonged AC therapy.
Paclitaxel is indicated for first-line treatment of locally advanced or metastatic breast cancer, either in combination with an anthracycline in patients for whom anthracycline therapy is appropriate, or in combination with trastuzumab in patients with HER-2 overexpression (3+ by immunohistochemical assay) for whom anthracycline therapy is not appropriate.
Monotherapy with paclitaxel is indicated for the treatment of metastatic breast cancer in patients in whom standard anthracycline-containing therapy has failed or is inappropriate.

Advanced non-small cell lung cancer
Paclitaxel in combination with cisplatin is indicated for the treatment of non-small cell lung cancer in patients who are not candidates for potentially curative surgery and/or radiotherapy.

AIDS-related Kaposi's sarcoma
Paclitaxel is indicated for the treatment of advanced AIDS-related Kaposi's sarcoma in patients who have failed prior therapy with liposomal anthracyclines.
RMS approved version DK/07.11.2005

2. Important information before using Paclitaxel-Ebewe

When not to use Paclitaxel-Ebewe

if the patient is allergic to paclitaxel or to any of the other ingredients of this medicine (listed in section 6), especially polyoxyethylated castor oil (glycerol polyethylene glycol ricinoleate).
if the patient is pregnant or breastfeeding.
if the patient has a low number of white blood cells (neutrophils). The number of white blood cells is measured by medical personnel.
if the patient with Kaposi's sarcoma has severe, uncontrolled infections.

Warnings and precautions
Before starting or during treatment with Paclitaxel-Ebewe, discuss the following with the doctor,
pharmacist, or nurse:

if the patient has liver disease;
if the patient has any infection not controlled by medication;
if the patient is taking other medicines;
if the patient experiences hypersensitivity reactions (allergic reactions), e.g. hypotension, respiratory failure, rash;
if the patient has previously experienced neurological symptoms in hands or feet (peripheral neuropathy);
if severe or persistent diarrhoea occurs during or immediately after paclitaxel treatment;
if the patient has heart disease;
because the medicine contains alcohol and polyoxyethylated castor oil (see section "Paclitaxel-Ebewe contains alcohol and polyoxyethylated castor oil");
if blood count abnormalities have been observed in the patient;
if Paclitaxel-Ebewe is administered concurrently with lung irradiation (radiotherapy);
if the patient with Kaposi's sarcoma develops severe mucosal inflammation.

Paclitaxel-Ebewe and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken,
as well as any medicines the patient plans to take.
Paclitaxel-Ebewe should be administered:

before cisplatin, if both medicines are used in combination;
24 hours after administration of doxorubicin.

If the patient is receiving paclitaxel simultaneously with any of the following medicines, this should be
discussed with the doctor:

anti-infective medicines (e.g. antibiotics such as erythromycin, rifampicin; if the patient is unsure whether a medicine is an antibiotic, they should ask the doctor, nurse, or pharmacist), including antifungal medicines (e.g. ketoconazole);
medicines used to stabilise mood, sometimes called antidepressants (e.g. fluoxetine);
medicines used to treat seizures (epileptic fits) (e.g. carbamazepine, phenytoin);
medicines used to lower blood lipid levels (e.g. gemfibrozil);
medicines used to treat heartburn or stomach ulcers (e.g. cimetidine);
medicines used to treat HIV and AIDS infection (e.g. ritonavir, saquinavir, indinavir, nelfinavir, efavirenz, nevirapine);
the medicine clopidogrel, used to prevent blood clots.

Paclitaxel-Ebewe with food and drink
Paclitaxel-Ebewe may be used with food and drink. However, the patient should ask the
doctor whether alcohol consumption is permitted during treatment.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult her doctor or pharmacist before using this medicine.
Pregnancy
Paclitaxel-Ebewe must not be used during pregnancy.
Breastfeeding
Paclitaxel-Ebewe must not be used during breastfeeding. Breastfeeding must not be resumed
until the doctor considers it safe.
Pregnancy must be avoided during treatment with Paclitaxel-Ebewe. If the patient becomes
pregnant, she must inform the doctor immediately. Breastfeeding must be discontinued during
treatment with Paclitaxel-Ebewe.
Driving and operating machinery
There is no reason why the patient cannot drive between treatment cycles. However, it should be
remembered that Paclitaxel-Ebewe contains a certain amount of alcohol, and driving immediately
after administration of the medicine is not recommended. As in all cases, the patient should not drive
if experiencing dizziness or drowsiness.
Paclitaxel-Ebewe contains alcohol
Paclitaxel-Ebewe contains ethanol (alcohol) and polyoxyethylated castor oil
(glycerol polyethylene glycol ricinoleate).
Each 1 ml of Paclitaxel-Ebewe contains 401.7 mg of ethyl alcohol (40.2% m/V), equivalent to
10 ml of beer or 4 ml of wine.
The alcohol contained in this preparation may have harmful effects on children. Effects may include
drowsiness and changes in behaviour. It may also affect their ability to concentrate and participate
in physical activities.
The amount of alcohol in Paclitaxel-Ebewe may affect the ability to drive or operate machinery. This
is due to the possible effect of the medicine on the patient's assessment of situations and reaction
speed.
Patients with epilepsy or liver problems should inform their doctor or pharmacist before using this
medicine. The amount of alcohol in the medicine may alter the effects of other medicines.
If the patient is taking other medicines, they should inform the pharmacist.
If the patient is alcohol-dependent, they should inform their doctor or pharmacist before using this
medicine.
The medicine also contains polyoxyethylated castor oil (glycerol polyethylene glycol ricinoleate),
which may cause severe allergic reactions.

3. How to use Paclitaxel-Ebewe

The physician determines the dose and number of doses the patient should receive.
Paclitaxel-Ebewe is administered under the supervision of a physician who can provide more detailed information.
The dose of Paclitaxel-Ebewe depends on the type and stage of cancer. Paclitaxel-Ebewe is given as an intravenous infusion over approximately 3 hours. Treatment is usually repeated every 3 weeks (every 2 weeks in patients with Kaposi's sarcoma).
RMS approved version DK/07.11.2005

Before starting treatment with Paclitaxel-Ebewe
Before starting treatment with Paclitaxel-Ebewe, the patient receives premedication consisting of several other medicines. Premedication is necessary to prevent severe hypersensitivity reactions.

If more Paclitaxel-Ebewe is used than prescribed
This does not apply to the patient, as Paclitaxel-Ebewe is administered by a physician or nurse.

If a dose of Paclitaxel-Ebewe is missed
This does not apply to the patient, as Paclitaxel-Ebewe is administered by a physician or nurse.

Stopping treatment with Paclitaxel-Ebewe
The decision to discontinue treatment with Paclitaxel-Ebewe is made by the physician.

If you have any further questions about the use of this medicine, please consult your physician or pharmacist.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms of an allergic reaction occur, seek medical advice immediately:
skin redness
skin reactions
itching
feeling of tightness in the chest
shortness of breath or difficulty breathing
swelling

All of these reactions may be signs of serious adverse reactions.
Seek immediate medical attention if:
the patient has fever, severe chills, sore throat or mouth ulcers (symptoms of bone marrow suppression)
the patient experiences numbness or weakness in hands and feet (symptoms of peripheral neuropathy)*
the patient develops severe or persistent diarrhoea accompanied by fever and abdominal pain.
*These symptoms may persist for more than 6 months after completion of paclitaxel treatment.

Very common adverse reactions (may affect more than 1 in 10 people)
Hair loss (in most cases, hair loss began within one month of starting paclitaxel treatment; in the majority of these patients [over 50%], hair loss was extensive), nausea, vomiting and diarrhoea, allergic reactions such as skin redness (mainly face), skin rash, itching and general infections. Low blood pressure. Blood disorders (hence the need for regular blood tests), which may lead to mild anaemia (with feelings of weakness or fatigue), increased risk of infection, or easy bruising. Numbness and (or) tingling in hands and (or) feet*, muscle and joint pain, ulceration of the mucous membranes of the mouth and tongue.
*These symptoms may persist for more than 6 months after completion of paclitaxel treatment.

Common adverse reactions (may affect fewer than 1 in 10 people)
Changes in heart rate or rhythm, high blood pressure and bleeding. In patients with Kaposi's sarcoma, severe liver function disorders may occur. Transient changes affecting nails and skin. Infusion site reactions: sometimes pain, redness, warmth, swelling, peeling of the skin at the injection/infusion site. Other skin reactions. Phlebitis occurs less frequently. In patients also receiving other chemotherapeutic agents and (or) radiation therapy, chest pain and (or) shortness of breath may occur. Gastrointestinal disturbances, abdominal pain, excessive sweating and limb pain have also been reported.

Uncommon adverse reactions (may affect fewer than 1 in 100 people)
Low blood pressure and slow blood flow due to severe infection, sometimes leading to serious internal organ dysfunction. Fainting, temporary loss of consciousness. Myocardial infarction.

Rare adverse reactions (may affect fewer than 1 in 1000 people)
Fever, dehydration and anaphylaxis, i.e. hypersensitivity reaction with facial and (or) throat swelling, wheezing, feeling of faintness and shortness of breath. Chills and back pain associated with allergic reaction. Pneumonitis and other lung disorders, lung tissue scarring or thickening causing shortness of breath and cough; pulmonary embolism causing shortness of breath, chest or shoulder pain, cough; significant lung and breathing disorders. Swelling and (or) weakness in hands and (or) feet have also been reported. Peritonitis (severe abdominal pain); intestinal obstruction with partial or complete blockage of the intestine; intestinal perforation with leakage of intestinal contents into the abdominal cavity; partial intestinal inflammation due to poor blood supply to the intestine; pancreatitis; heart disorders which may cause shortness of breath or ankle swelling. Other heart disorders have also been reported.

Very rare adverse reactions (may affect fewer than 1 in 10,000 people)
Severe infections, vision and hearing disturbances, dizziness (including vestibular origin), cough, severe allergic reactions, life-threatening allergic reaction, urticaria; severe skin redness (due to allergy) with skin damage, formation of large blisters, sometimes spreading over large areas of the body and oral mucosa (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), skin redness with peeling, often accompanied by itching and hair loss. Nail detachment from the nail bed. Sudden drop in blood pressure immediately upon changing position from lying to standing, leading to dizziness. Seizures (fits); generalized convulsions; confusion and other effects on the brain, up to severe brain dysfunction. Thrombosis in blood vessels supplying the abdominal cavity and intestines. Severe colitis causing bloody diarrhoea, abdominal pain or fever. Oesophagitis. Fluid accumulation in the abdominal cavity. Colitis due to low white blood cell count. Liver disorders; partial necrosis of liver tissue causing severe liver dysfunction. Brain and nervous system damage as a complication of liver dysfunction. Loss of appetite, constipation, headache, difficulty with coordination, hearing disturbances and (or) balance disturbances, increased heart rate, weight loss (anorexia) have also been reported. Cancer of blood-forming tissues in the bone marrow; various bone marrow disorders leading to ineffective blood cell production (which may, after many years, result in advanced bone marrow cancer).

Adverse reactions with unknown frequency (frequency cannot be estimated from available data)
Tumour lysis syndrome, which causes:

high levels of potassium in the blood, which may lead to abnormal heart rhythm (hyperkalaemia),
tetany, seizures, mental retardation, movement disorders, emotional lability, agitation, anxiety, muscle pain or weakness (hypocalcaemia)
feeling of fatigue, loss of appetite, headache, fluid accumulation in limbs and lungs

(renal failure).
Macular oedema distorting central vision.
Photopsia causing the sensation of flashing lights in the eyes.
Vitreous opacities appearing as spots, threads or fragments of spider web, slowly drifting in front of the eyes.
Phlebitis.
Symmetrical skin thickening (scleroderma).
Systemic lupus erythematosus, causing fever, malaise, joint pain, muscle pain, feeling of fatigue and temporary loss of cognitive function.
Cases of disseminated intravascular coagulation (DIC) have been reported; this is a serious condition causing excessive bleeding, excessive thrombosis, or both simultaneously.
Redness and swelling of the palms and soles, which may lead to peeling of the skin.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301 / Fax: +48 22 49 21 309 / Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Paclitaxel-Ebewe

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP.
The expiry date refers to the last day of the stated month.
Unopened vial: Store the vial in the outer packaging (cardboard box) to protect from light.
There are no special temperature storage requirements for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Paclitaxel-Ebewe contains
The active substance is paclitaxel. Each ml of solution contains 6 mg of paclitaxel.
1 vial of 5 ml contains 30 mg of paclitaxel.
1 vial of 16.7 ml contains 100 mg of paclitaxel.
RMS approved version DK/07.11.2005
1 vial of 25 ml contains 150 mg of paclitaxel.
1 vial of 50 ml contains 300 mg of paclitaxel.
1 vial of 100 ml contains 600 mg of paclitaxel.
The other ingredients are: polyoxyethylated castor oil (macrogol glycerol hydroxystearate) and ethanol.

What Paclitaxel-Ebewe looks like and contents of the pack
Paclitaxel-Ebewe concentrate for solution for infusion is a clear, colourless to pale yellow, viscous solution.
Pack sizes:
1 vial of 5 ml
1 vial of 16.7 ml
1 vial of 25 ml
1 vial of 50 ml
1 vial of 100 ml
Cartons contain 1, 5 or 10 vials, with or without protective packaging (Onco-Safe or Sleeving). Onco-Safe and Sleeving packaging do not come into contact with the medicinal product and provide additional protection during transport, thereby increasing safety for medical and pharmaceutical personnel.

Marketing Authorisation Holder
EBEWE Pharma Ges.m.b.H. Nfg. KG
Mondseestrasse 11
A-4866 Unterach, Austria

Manufacturer
Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria

For further information about the medicinal product and its trade names in the European Economic Area countries, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. 22 209 70 00

Information intended for healthcare professionals only
CYTOSTATIC

1. Pharmaceutical incompatibilities
Polyoxyethylated castor oil (macrogol glycerol hydroxystearate) may leach DEHP [di-(2-ethylhexyl)phthalate] from polyvinyl chloride (PVC) containers in amounts depending on time and concentration. Therefore, diluted Paclitaxel-Ebewe must be prepared, stored, and administered using equipment that does not contain PVC.

2. Instructions for preparation of the medicinal product for administration

Handling
RMS approved version DK/07.11.2005
As with all antineoplastic agents, caution should be exercised when handling paclitaxel.
Pregnant women or women of childbearing potential should be warned to avoid contact with cytotoxic drugs.
The medicinal product should be diluted by trained personnel under aseptic conditions in a designated area. Appropriate protective gloves must be worn. Contact of the medicinal product with skin and mucous membranes should be avoided. If the medicinal product comes into contact with the skin, wash thoroughly with soap and water. Local contact with the solution may cause tingling, burning, and redness. In case of contact with mucous membranes, flush thoroughly with water.
Inhalation of solution vapours has caused shortness of breath, chest pain, burning in the throat, and nausea.

If sealed vials are stored in a refrigerator, a precipitate may form which redissolves upon gentle agitation or even without agitation when the vial reaches room temperature. This does not affect the quality of the product. If the solution remains cloudy or the precipitate does not dissolve, the vial should be discarded.

After multiple needle insertions and withdrawals from the vial, the contents remain microbiologically, chemically, and physically stable for up to 28 days at 25°C. The user is responsible for any other storage conditions and duration.

Preparation of the product for intravenous administration
Before infusion, paclitaxel must be diluted under aseptic conditions with 0.9% sodium chloride solution for injection, 5% glucose solution for injection, or a mixture of 0.9% sodium chloride solution for injection and 5% glucose solution, to a final concentration of 0.3 to 1.2 mg/ml.

It has been demonstrated that the prepared infusion solution maintains chemical and physical stability for 48 hours at 5°C and at 25°C when diluted with 5% glucose solution or 0.9% sodium chloride solution for injection. From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage time and conditions prior to administration. Typically, this should not exceed 24 hours at 2–8°C, unless dilution occurred under controlled and validated aseptic conditions.

The prepared solution is for single use only.
During preparation, solutions may appear slightly cloudy due to the vehicle in the product, which cannot be removed by filtration. Paclitaxel-Ebewe should be administered using an infusion set with an integrated in-line filter with a microporous membrane (pore size not greater than 0.22 µm). No significant loss of potency has been observed during simulated administration through an intravenous infusion set with an in-line filter.

There have been rare reports of precipitation during paclitaxel administration, usually towards the end of a 24-hour infusion. Although the cause of precipitation has not been fully elucidated, it is likely due to excessive saturation of the diluted solution. To reduce the risk of precipitation, the paclitaxel solution should be used as soon as possible after dilution and excessive shaking or agitation should be avoided. The infusion set should be thoroughly flushed before use. The appearance of the solution should be checked regularly during infusion, and if precipitation occurs, the infusion should be discontinued.

To minimize patient exposure to DEHP, which may leach from infusion bags, sets, or other medical equipment made of PVC, diluted Paclitaxel-Ebewe solutions should be stored in containers that do not contain PVC (made of glass, polypropylene) or in plastic bags (polypropylene, polyolefin) and administered through polyethylene infusion sets. The use of filtration devices with short inlet and/or outlet tubing segments made of PVC has not resulted in significant leaching of DEHP.

RMS approved version DK/07.11.2005

Disposal
All equipment used for preparation and administration, or any equipment that has come into contact with paclitaxel, must be disposed of in accordance with local guidelines for handling cytostatic agents.

3. Shelf life
Unopened vials: 3 years.

After opening, before dilution
After multiple needle insertions and withdrawals from the vial, the contents remain microbiologically, chemically, and physically stable for up to 28 days at 25°C.
From a microbiological standpoint, after opening the vial, the product may be stored for up to 28 days at 25°C. The user is responsible for any alternative storage duration and conditions.

After dilution
After dilution, the medicinal product maintains chemical and physical stability for 48 hours at 25°C and at 2–8°C. From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage time and conditions prior to administration. Generally, this should not exceed 24 hours at 2–8°C, unless dilution occurred under controlled and validated aseptic conditions.

4. Special precautions for storage
Before opening, store the vial in its outer packaging (cardboard box) to protect from light.

Paclitaxel-ebewe