Paclitaxel-ebeve

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

Paclitaxel-Ebewe is used to treat:
ovarian cancer
In first-line chemotherapy for ovarian cancer, paclitaxel is indicated in combination with cisplatin for the treatment of advanced ovarian cancer or residual tumor (>1 cm) after prior laparotomy.
In second-line chemotherapy for ovarian cancer, paclitaxel is indicated for the treatment of patients with ovarian cancer with metastases, in whom standard treatment with platinum-based regimens has been ineffective.
breast cancer
In adjuvant treatment, paclitaxel is indicated for patients with node-positive breast cancer after anthracycline and cyclophosphamide therapy (AC). Adjuvant treatment with paclitaxel should be considered as an alternative to prolonged AC therapy.
Paclitaxel is indicated for the initial treatment of locally advanced or metastatic breast cancer, either in combination with an anthracycline in patients for whom anthracycline therapy is suitable or in combination with trastuzumab in patients with HER2 receptor overexpression (3+ as determined by immunohistochemistry), for whom anthracycline therapy is not suitable.
Monotherapy with paclitaxel is indicated for the treatment of metastatic breast cancer in patients in whom standard anthracycline therapy has been ineffective or is not suitable.
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.
Kaposi's sarcoma in AIDS
Paclitaxel is indicated for the treatment of advanced Kaposi's sarcoma in AIDS patients in whom previous treatment with liposomal anthracyclines has been ineffective.

2. Important information before using Paclitaxel-Ebewe

When not to use Paclitaxel-Ebewe

• if the patient is hypersensitive to paclitaxel or any of the other ingredients of this medicine (listed in section 6), particularly polyoxyethylated castor oil (macrogolglycerol ricinoleate).
• if the patient is pregnant or breastfeeding.
• if the patient has a low white blood cell count (neutrophils). The white blood cell count is determined 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, the patient should discuss the following with their doctor, pharmacist, or nurse:

• if the patient has liver disease;
• if the patient has any uncontrolled infections;
• if the patient is taking other medicines;
• if the patient experiences hypersensitivity reactions (allergies), such as low blood pressure, respiratory failure, rash;
• if the patient has experienced neurological symptoms in the hands or feet (peripheral neuropathy) in the past;
• if severe or persistent diarrhea occurs during treatment with paclitaxel or shortly after its completion;
• if the patient has heart disease;
• since the medicine contains alcohol and polyoxyethylated castor oil (see "Paclitaxel-Ebewe contains alcohol and polyoxyethylated castor oil");
• if changes in the patient's blood count have been detected;
• if Paclitaxel-Ebewe is used in combination with radiotherapy (radiation) of the lungs;
• if the patient with Kaposi's sarcoma experiences severe mucositis.

Paclitaxel-Ebewe and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Paclitaxel-Ebewe should be used:

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

If the patient is taking paclitaxel with any of the following medicines, they should discuss this with their doctor:

• antibiotics (e.g., erythromycin, rifampicin; if the patient is unsure whether their medicine is an antibiotic, they should ask their doctor, nurse, or pharmacist); including medicines used to treat fungal infections (e.g., ketoconazole);
• medicines used to stabilize mood, also known as antidepressants (e.g., fluoxetine);
• medicines used to treat seizures (e.g., carbamazepine, phenytoin);
• medicines used to reduce blood lipid levels (e.g., gemfibrozil);
• medicines used to treat 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.

Paclitaxel-Ebewe with food and drink

Paclitaxel-Ebewe can be used with food and drink. However, the patient should ask their doctor if they can consume alcohol during treatment.

Pregnancy, breastfeeding, and fertility

If the patient is pregnant or breastfeeding, or thinks they may be pregnant or plans to have a child, they should consult their doctor or pharmacist before using this medicine.
Pregnancy
Paclitaxel-Ebewe should not be used during pregnancy.
Breastfeeding
Paclitaxel-Ebewe should not be used during breastfeeding. Breastfeeding should not be resumed until the doctor considers it safe.
The patient should avoid becoming pregnant while using Paclitaxel-Ebewe. If the patient becomes pregnant, they should inform their doctor immediately. Breastfeeding should be discontinued during treatment with Paclitaxel-Ebewe.

Driving and using machines

There is no reason why the patient should not be able to drive between courses of treatment. However, the patient should remember that Paclitaxel-Ebewe contains a certain amount of alcohol and driving a vehicle immediately after taking the medicine is not recommended. As with all cases, the patient should not drive if they experience dizziness or fainting.

Paclitaxel-Ebewe contains alcohol

Paclitaxel-Ebewe contains ethanol (alcohol) and polyoxyethylated castor oil (macrogolglycerol ricinoleate).
Each 1 ml of Paclitaxel-Ebewe contains 401.7 mg of ethanol (40.2% m/V), which is equivalent to 10 ml of beer or 4 ml of wine.
The alcohol in this medicine may have a harmful effect on children. Effects may include drowsiness and changes in behavior. It may also affect their ability to concentrate and participate in physical activities.
The amount of alcohol in Paclitaxel-Ebewe may affect the patient's ability to drive or operate machines. This is due to the potential effect of the medicine on the patient's judgment and reaction time.
Patients with epilepsy or liver problems should inform their doctor or pharmacist before using the 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 their pharmacist.
If the patient is addicted to alcohol, they should inform their doctor or pharmacist before using the medicine.
The medicine also contains polyoxyethylated castor oil (macrogolglycerol ricinoleate), which may cause severe allergic reactions.

3. How to use Paclitaxel-Ebewe

The doctor decides on the size and number of doses to be given to the patient.
Paclitaxel-Ebewe is administered under the supervision of a doctor, who may provide more detailed information.
The dose of the medicine depends on the type and stage of cancer. Paclitaxel-Ebewe is administered by intravenous infusion over approximately 3 hours. Treatment is usually repeated every 3 weeks (2 weeks for patients with Kaposi's sarcoma).

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.

Using a higher dose of Paclitaxel-Ebewe than recommended

This does not apply to the patient, as Paclitaxel-Ebewe is administered by a doctor or nurse.

Missing a dose of Paclitaxel-Ebewe

This does not apply to the patient, as Paclitaxel-Ebewe is administered by a doctor or nurse.

Stopping treatment with Paclitaxel-Ebewe

The decision to stop treatment with Paclitaxel-Ebewe is made by the doctor.
If the patient has any further questions about using the medicine, they should ask their doctor or pharmacist.

Using Paclitaxel-Ebewe in children and adolescents

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

4. Possible side effects

Like all medicines, Paclitaxel-Ebewe can cause side effects, although not everybody gets them.
If the patient experiences any of the following symptoms of an allergic reaction, they should
immediately contact their doctor.Symptoms may include:
redness of the skin
skin reactions
itching
feeling of pressure in the chest
shortness of breath or difficulty breathing
swelling
All of these reactions may be symptoms of severe side effects.

The patient should immediately contact their doctor if:

they have a fever, severe chills, sore throat, or mouth ulcers(symptoms of bone marrow suppression)
they experience numbness or weakness in their hands and feet(symptoms of peripheral neuropathy)*
they have severe or persistent diarrheawith fever and abdominal pain.
*May persist for more than 6 months after completion of paclitaxel treatment.
Very common side effects (may occur in more than 1 in 10 people)
Hair loss (in most cases, hair loss started before 1 month after starting paclitaxel treatment (in more than 50% of these patients, hair loss was significant), nausea, vomiting, and diarrhea, allergic reactions, such as redness of the skin (mainly on the face), rash on the skin, itching, and general infections. Low blood pressure. Blood disorders (hence the need for regular blood tests), which may cause mild anemia (with feelings of weakness or fatigue), increased risk of infection, or easier bruising. Numbness and/or tingling of the hands and/or feet*, muscle and joint pain, mouth ulcers and tongue ulcers.
*May persist for more than 6 months after completion of paclitaxel treatment.
Common side effects (may occur in less 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 in nail and skin conditions. Symptoms of infusion: sometimes pain, redness of the skin, feeling of heat, swelling, and peeling of the skin at the injection/infusion site. Other skin reactions. Venous inflammation is less common. In patients receiving other chemotherapies and/or radiation therapy, chest pain and/or shortness of breath may occur. Gastrointestinal disorders, abdominal pain, excessive sweating, and limb pain have also been reported.
Uncommon side effects (may occur in less than 1 in 100 people)
Low blood pressure and slow blood flow caused by severe infection, sometimes leading to severe organ dysfunction. Fainting, temporary loss of consciousness. Heart attack.
Rare side effects (may occur in less than 1 in 1000 people)
Fever, dehydration, and anaphylaxis, i.e., an allergic reaction with swelling of the face and/or throat, wheezing, feeling of fainting, and shortness of breath. Chills and back pain associated with an allergic reaction. Pneumonia and other lung disorders, scarring or thickening of lung tissue, causing shortness of breath and cough; pulmonary embolism causing shortness of breath, chest pain, or cough; significant lung function and breathing disorders. Edema and/or weakness of the hands and/or feet have also been reported. Peritonitis (severe abdominal pain); intestinal obstruction with partial or complete blockage of the intestines; perforation (puncture) of the intestines with leakage of intestinal contents into the abdominal cavity; partial inflammatory changes in the intestines caused by poor blood flow to the intestines; pancreatitis; heart disorders that may cause shortness of breath or swelling of the ankles. Other heart disorders have also been reported.
Very rare side effects (may occur in less than 1 in 10,000 people)
Severe infections, vision and hearing disorders, dizziness (also of labyrinthine origin), cough, severe allergic reactions, life-threatening allergic reaction, hives; severe redness of the skin (caused by allergy) with damage to certain skin areas, formation of large blisters, sometimes spreading to large areas of the body and mucous membranes (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), redness of the skin with peeling, often with itching and hair loss.
Detachment of the nail from the nail bed. Sudden drop in blood pressure when changing position from lying down to standing, leading to dizziness. Seizures (convulsions); generalized seizures; confusion and other effects on the brain, up to severe brain dysfunction. Blood clots in blood vessels supplying the abdominal cavity and intestines. Severe intestinal inflammation, causing bloody diarrhea, abdominal pain, or fever.
Esophagitis. Fluid accumulation in the abdominal cavity. Colitis (inflammation of the colon) caused by a low white blood cell count. Liver disorders; partial liver tissue death, causing severe liver dysfunction. Brain and nervous system damage, as a complication of liver dysfunction. Loss of appetite, constipation, headache, difficulty coordinating movements, hearing and/or balance disorders, rapid heart rate, weight loss (anorexia). Blood cell cancer in the bone marrow; various bone marrow disorders, leading to ineffective production of blood cells (which may lead to advanced bone marrow cancer after many years).
Side effects with unknown frequency (which cannot be estimated from available data)
Syndrome of tumor breakdown, which causes:

• high potassium levels in the blood, which may cause irregular heart rhythm (hyperkalemia),
• tetany, seizures, mental retardation, movement disorders, emotional instability, agitation, anxiety, pain, or muscle weakness (hypocalcemia)
• fatigue, loss of appetite, headache, fluid accumulation in the limbs and lungs (kidney failure).

Edema of the macula, distorting central vision.
Photopsia, causing a sensation of flashes of light in the eyes.
Floaters in the vitreous, appearing as spots, streaks, or fragments of a cobweb, floating slowly in front of the eyes.
Phlebitis.
Symmetrical thickening of the skin (scleroderma).
Systemic lupus erythematosus, causing fever, malaise, joint pain, muscle pain, fatigue, and temporary loss of cognitive abilities.
Reports of disseminated intravascular coagulation (DIC); this is a serious condition that causes excessive bleeding or excessive blood clotting, or both.
Redness and swelling of the palms of the hands and soles of the feet, which may cause peeling of the skin.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in the leaflet, they should tell their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, 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
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Paclitaxel-Ebewe

The medicine should be stored 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 month stated.
Vial before opening: Store the vial in the outer packaging (cardboard box) to protect from light. There are no special storage temperature recommendations for the medicine.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Paclitaxel-Ebewe contains

The active substance of the medicine 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.
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 of the medicine are polyoxyethylated castor oil (macrogolglycerol ricinoleate) and ethanol.

What Paclitaxel-Ebewe looks like and contents of the pack

Paclitaxel-Ebewe concentrate for solution for infusion is a clear, colorless to pale yellow, viscous solution.
Packaging:
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
The carton contains 1, 5, or 10 vials with protective packaging (Onco-Safe or Sleeving) or without such packaging. Onco-Safe and Sleeving packaging do not come into contact with the medicine and provide additional protection during transport, increasing the safety of medical and pharmaceutical personnel.

Marketing authorization holder and manufacturer

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

Manufacturer

Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria

For more information about the medicine and its names in the Member States of the European Economic Area, please contact:

Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00
Date of last revision of the leaflet:05/2023
Information intended for healthcare professionals only
CYTOSTATIC

1. Incompatibilities

Polyoxyethylated castor oil (macrogolglycerol ricinoleate) may cause leaching of DEHP [di-(2-ethylhexyl)phthalate] from polyvinyl chloride (PVC) containers in an amount dependent on time and concentration. Therefore, the diluted Paclitaxel-Ebewe product should be prepared, stored, and administered using equipment that does not contain PVC.

2. Instructions for preparation of the medicine

Procedure

As with all anticancer medicines, paclitaxel should be handled with care.
Pregnant women or women of childbearing age should be warned to avoid contact with cytotoxic medicines.
The medicinal product should be diluted by trained personnel in aseptic conditions, in a designated area. Appropriate protective gloves should be worn.
Contact with the skin and mucous membranes should be avoided. If the medicine comes into contact with the skin, it should be washed with soap and water. Local contact with the solution may cause tingling, burning, and redness. If the medicine comes into contact with the mucous membranes, they should be rinsed with plenty of water.
Inhaling the vapors of the solution has caused shortness of breath, chest pain, burning in the throat, and nausea.
If closed vials are stored in the refrigerator, a precipitate may form, which will redissolve upon slight 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 if the precipitate does not redissolve, the vial should be discarded.
After multiple needle insertions and product withdrawals from the vial, the contents of the vials remain stable microbiologically, chemically, and physically for 28 days at 25°C. The user is responsible for other storage conditions and times.
Before dilution
After opening, before dilution, the product can be stored for a maximum of 28 days at 25°C. The user is responsible for other storage times and conditions.
After dilution
After dilution, the medicine remains stable chemically and physically for 48 hours at 25°C and from 2°C to 8°C. From a microbiological point of view, the medicinal product should be used immediately. If it is not used immediately, the user is responsible for the storage time and conditions before administration. In general, this time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution of the solution took place in controlled and validated aseptic conditions.

Preparation of the product for intravenous administration

Before administration by infusion, paclitaxel must be diluted aseptically with 0.9% sodium chloride injection solution or 5% glucose injection solution, or a mixture of 0.9% sodium chloride injection solution and 5% glucose injection solution, to a final concentration of 0.3 to 1.2 mg/ml.
It has been shown that the prepared infusion solution remains stable chemically and physically for 48 hours at 5°C and at 25°C, if diluted with 5% glucose solution or 0.9% sodium chloride injection solution. From a microbiological point of view, the medicinal product should be used immediately. If it is not used immediately, the user is responsible for the storage time and conditions before administration. This time should not normally exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution of the solution took place in controlled and validated aseptic conditions.
The prepared solution is intended for single use only.
During preparation, the solutions may be cloudy due to the solvent contained in the medicine, which cannot be removed by filtration. Paclitaxel-Ebewe should be administered through an infusion set with a built-in filter with a microporous membrane (pore size not larger than 0.22 μm). No significant loss of potency of the product has been observed during simulated administration of the solution through an intravenous infusion set with an internal filter.
There are rare reports of precipitation during paclitaxel administration, usually at the end of a 24-hour infusion. Although the cause of precipitation has not been explained, it is likely due to excessive saturation of the diluted solution. To minimize 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. During infusion, the appearance of the solution should be regularly checked, and if precipitation occurs, the infusion should be discontinued.
To minimize patient exposure to DEHP, which may be leached from infusion bags, sets, or other medical equipment made of polyvinyl chloride (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 filter devices with short inlet and/or outlet tubes made of PVC did not result in significant leaching of DEHP.

Disposal

All equipment used to prepare and administer or that has come into contact with paclitaxel should be disposed of in accordance with local guidelines for the disposal of cytostatics.

3. Shelf life

Unopened vials: 3 years.
After opening, before dilution
After multiple needle insertions and product withdrawals from the vial, the contents of the vials remain stable microbiologically, chemically, and physically for 28 days at 25°C.
From a microbiological point of view, after opening the vial, the product can be stored for a maximum of 28 days at 25°C. The user is responsible for other storage times and conditions.
After dilution
After dilution, the medicine remains stable chemically and physically for 48 hours at 25°C and from 2°C to 8°C. From a microbiological point of view, the medicinal product should be used immediately. If it is not used immediately, the user is responsible for the storage time and conditions before administration. In general, this time should not exceed 24 hours at a temperature of 2°C to 8°C, unless the dilution of the solution took place in controlled and validated aseptic conditions.

4. Special precautions for storage

Vial before opening: Store the vial in the outer packaging (cardboard box) to protect from light.