Docetaxel-ebewe

Package leaflet: Information for the user

Docetaxel-Ebewe, 10 mg/ml, concentrate for solution for infusion
Docetaxelum
Please read all of this leaflet carefully before this medicine is given, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, hospital pharmacist, or nurse.
• If you get any side effects, talk to your doctor, hospital pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Docetaxel-Ebewe is and what it is used for
2. What you need to know before you are given Docetaxel-Ebewe
3. How Docetaxel-Ebewe is given
4. Possible side effects
5. How to store Docetaxel-Ebewe
6. Contents of the pack and other information

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

Docetaxel-Ebewe contains the active substance docetaxel. Docetaxel is a substance derived from the needles of the yew tree. Docetaxel-Ebewe belongs to a group of anticancer medicines called taxoids. Docetaxel-Ebewe is prescribed by your doctor for the treatment of breast cancer, certain types of lung cancer (non-small cell lung cancer), prostate cancer, stomach cancer, or head and neck cancer:

• In the treatment of advanced breast cancer, Docetaxel-Ebewe may be given either alone (as monotherapy) or in combination with doxorubicin or trastuzumab, or capecitabine;
• In the treatment of early-stage breast cancer, with or without lymph node involvement, Docetaxel-Ebewe may be given in combination with doxorubicin and cyclophosphamide;
• In the treatment of lung cancer, Docetaxel-Ebewe may be given either as monotherapy or in combination with cisplatin;
• In the treatment of prostate cancer, Docetaxel-Ebewe is given in combination with prednisone or prednisolone;
• In the treatment of metastatic stomach cancer, Docetaxel-Ebewe is given with cisplatin and 5-fluorouracil;
• In the treatment of head and neck cancer, Docetaxel-Ebewe is given in combination with cisplatin and 5-fluorouracil.

2. Important information before using Docetaxel-Ebewe

When Docetaxel-Ebewe must not be given
if the patient is allergic (hypersensitive) to docetaxel or to any of the other
ingredients of this medicine (listed in section 6);
if the patient has too low a number of white blood cells;
if the patient has severe liver disease.

Warnings and precautions
Before each administration of Docetaxel-Ebewe, blood tests will be performed to check whether the blood cell count is adequate and whether liver function allows for administration of the drug. If disturbances in the number of white blood cells occur, fever or infections may develop.
If the patient experiences abdominal pain or tenderness, diarrhea, bleeding from the rectum, blood in the stool, or fever, they should immediately inform the doctor, hospital pharmacist, or nurse. These may be the first symptoms of severe gastrointestinal toxicity, which can be fatal. The physician should promptly initiate appropriate management.
If visual disturbances occur, the patient should inform the doctor, hospital pharmacist, or nurse. Visual disturbances, especially blurred vision, require immediate ophthalmological examination.
If the patient previously experienced an allergic reaction during treatment with paclitaxel, they should inform the doctor, hospital pharmacist, or nurse.
If the patient has heart problems, they should inform the doctor, hospital pharmacist, or nurse.
If the patient develops acute symptoms or worsening of pre-existing lung symptoms (fever, shortness of breath, or cough), they should immediately inform the doctor, hospital pharmacist, or nurse. The physician may decide to immediately discontinue treatment.
The physician will advise the patient to take oral corticosteroids prophylactically (such as dexamethasone) one day before and for one to two days after administration of Docetaxel-Ebewe to reduce the severity of adverse reactions that may occur after administration of Docetaxel-Ebewe, particularly allergic reactions and fluid retention symptoms (swelling of hands, feet, legs, or weight gain).
During treatment, the physician may administer medications to maintain normal blood cell counts.
Severe skin reactions have been reported during docetaxel treatment, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Acute Generalized Exanthematous Pustulosis (AGEP):

• Symptoms of SJS/TEN may include blistering, peeling, or bleeding of the skin at any body site (including mouth, eyes, oral cavity, nose, genital organs, palms, or soles), with or without rash. Influenza-like symptoms such as fever, chills, or muscle pain may also occur simultaneously.
• Symptoms of AGEP may include widespread red, peeling rash with small pustules under swollen skin (including skin folds, trunk, and upper limbs), accompanied by fever. If severe skin reactions or any of the reactions listed above occur, the patient should immediately contact their physician or healthcare provider.

If the patient has kidney problems or high levels of uric acid in the blood, they should inform the doctor, hospital pharmacist, or nurse before starting treatment with Docetaxel-Ebewe.
Docetaxel-Ebewe contains alcohol. Patients with alcohol dependence, epilepsy, or liver impairment should discuss this with their physician. See also section "Docetaxel-Ebewe contains ethanol (alcohol)."

Docetaxel-Ebewe and other medicines
The patient should inform their doctor or hospital pharmacist about all medicines currently used, recently used, or planned for use, including over-the-counter medicines.
Docetaxel-Ebewe or other medicines may not work as expected, or the risk of adverse reactions may increase.
The amount of alcohol present in this medicine may affect the action of other medicines.

Pregnancy, breastfeeding, and effects on fertility
Before taking any medicine, consult a physician.
Docetaxel-Ebewe MUST NOT be given to pregnant women unless the physician considers it necessary.
During treatment and for 2 months after treatment ends, the patient must avoid becoming pregnant.
The patient must use an effective method of contraception during treatment and for 2 months after treatment ends, as docetaxel may harm the unborn child. If the patient becomes pregnant during treatment, they should immediately inform the doctor.
Breastfeeding must not be performed during treatment with Docetaxel-Ebewe.
Men receiving Docetaxel-Ebewe must avoid fathering a child and must use an effective method of contraception during treatment and for 4 months after treatment ends. Before starting treatment, advice should be sought regarding the possibility of sperm storage, as docetaxel may impair male fertility.

Driving and operating machinery
The amount of alcohol present in this medicine may impair the ability to drive or operate machinery.
Adverse reactions may occur that affect the ability to drive or operate tools or machines (see section 4 "Possible side effects"). In such cases, the patient should not drive or operate any tools or machinery until they have consulted with their doctor, nurse, or hospital pharmacist.

Docetaxel-Ebewe contains ethanol (alcohol)
This medicine contains 265 mg of alcohol (ethanol) per ml of concentrate for infusion solution, equivalent to 26% w/w. The amount of alcohol in 1 ml of this medicine is equivalent to 7 ml of beer or 3 ml of wine.
Alcohol may have adverse effects in patients with alcohol-related disorders.
The amount of alcohol in this medicine is unlikely to affect adults and adolescents, and its effects in children are likely to be negligible. However, it may cause some effects in younger children, such as drowsiness.
Alcohol in this medicine may alter the effects of other medicines. If the patient is taking other medicines, they should consult their doctor or pharmacist.
The alcohol content should be considered in pregnant or breastfeeding women, children, and patients at high risk, such as those with liver disease or epilepsy.
If the patient is alcohol-dependent, they should consult their doctor or pharmacist before using this medicine.
The amount of alcohol present in this medicine may affect the central nervous system (the part of the nervous system comprising the brain and spinal cord).

3. How to use Docetaxel-Ebewe

Docetaxel-Ebewe is a medicine administered by medical personnel.
Recommended dose
The dose depends on body weight and the patient's general condition. The doctor will calculate the body surface area in square meters (m²) and determine the dose accordingly.
Method and route of administration
Docetaxel-Ebewe is given as an intravenous infusion into one of the patient's veins. The intravenous infusion, which lasts about one hour, is administered in a hospital.
Frequency of administration
The infusion is usually given every 3 weeks.
The doctor may adjust the dose and frequency of administration depending on blood test results, the patient's general condition, and the patient's response to treatment with Docetaxel-Ebewe. The doctor should be informed, in particular, about the occurrence of diarrhea, mouth ulcers, sensations of numbness, tingling, fever, and should be shown blood test results. Such information will enable the doctor to decide whether the dose should be reduced.
If you have any further doubts regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should consult your doctor to discuss the possible risks and benefits of treatment.
The most commonly reported adverse reactions following administration of Docetaxel-Ebewe alone are:
decreased number of red or white blood cells, hair loss, nausea, vomiting, mouth ulcers,
diarrhea, and fatigue.
The severity of adverse reactions with Docetaxel-Ebewe may be greater when it is administered
in combination with other chemotherapeutic agents.
During hospital infusion, the following hypersensitivity reactions may occur (may affect
more than 1 in 10 people):
skin redness, skin reactions, skin itching
chest tightness, difficulty breathing
fever or chills
back pain
low blood pressure
More severe reactions may also occur.
If a patient has had hypersensitivity reactions to paclitaxel, they may also experience an allergic
reaction to docetaxel, which could be more severe.
Medical staff will closely monitor the patient during treatment. You MUST IMMEDIATELY
inform hospital personnel if any of these symptoms occur.
Between successive infusions of Docetaxel-Ebewe, the following adverse reactions may occur,
and their frequency may vary depending on the treatment regimen used:

Very common (may affect more than 1 in 10 people)
infections, decreased number of red blood cells (anaemia) or white blood cells (important for
fighting infections) and platelets
fever: if body temperature rises, inform your doctor immediately
allergic reactions, as described above
loss of appetite (anorexia)
insomnia
tingling, numbness, or pain in joints or muscles
headache
change in taste perception
eye inflammation or excessive tearing
swelling due to abnormal lymphatic drainage (lymphoedema)
shortness of breath
nasal congestion; throat and nose inflammation; cough
nosebleeds
mouth ulcers
gastrointestinal disturbances, including nausea, vomiting, diarrhoea, constipation
abdominal pain
indigestion
hair loss (in most cases, hair regrows after treatment ends); cases of permanent hair loss have
been observed (frequency unknown)
redness and swelling of the palms and soles, possibly with skin peeling (may also affect arms,
face or other body parts)
change in nail colour, which may separate from the nail bed
muscle pain (including persistent pain), back or bone pain
changes in menstrual cycle or absence of menstruation
swelling of hands, feet, legs
fatigue or flu-like symptoms
increase or decrease in body weight
upper respiratory tract infection

Common (may affect less than 1 in 10 people)
oral fungal infection (thrush)
dehydration
dizziness
hearing disturbances
low blood pressure, irregular or rapid heartbeat
oesophagitis
dry mouth
difficulty or pain when swallowing
bleeding
increased liver enzyme activity (blood tests required)
increased blood glucose levels (hyperglycaemia)
decreased levels of potassium, calcium, and (or) phosphate in the blood

Uncommon (may affect less than 1 in 100 people)
fainting
skin reactions, phlebitis or swelling at the injection site
blood clots
acute myeloid leukaemia and myelodysplastic syndrome (types of blood cancer) may occur
in patients treated with docetaxel in combination with certain other anticancer therapies

Rare (may affect less than 1 in 1000 people)
inflammation of the large or small intestine, possibly leading to death (frequency unknown); intestinal perforation

Frequency not known (frequency cannot be estimated from available data)
interstitial lung disease (lung inflammation causing cough and difficulty breathing. Lung inflammation may also develop when docetaxel is used concurrently with radiotherapy)
pneumonia
pulmonary fibrosis (scarring and thickening of lung tissue causing shortness of breath)
blurred vision due to retinal swelling in the eye (macular oedema)
decreased levels of sodium, potassium, magnesium, and (or) calcium in the blood (electrolyte imbalance)
ventricular arrhythmias or ventricular tachycardia (manifested by irregular and/or rapid heartbeat, severe shortness of breath, dizziness and/or fainting). Some of these symptoms may be severe. In such cases, seek immediate medical attention.
injection site reactions at the site of a previous reaction
non-Hodgkin's lymphoma (a cancer affecting the immune system) and other tumours may occur in patients treated with docetaxel in combination with certain other anticancer therapies
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (formation of blisters, skin peeling or bleeding from any body surface (including mouth, eyes, oral cavity, nose, genital organs, palms or soles), with or without rash. Flu-like symptoms such as fever, chills or muscle pain may also occur simultaneously)
acute generalized exanthematous pustulosis (AGEP) (red, widespread peeling rash with pustules under swollen skin (including skin folds, trunk, and upper limbs) and blisters, accompanied by fever)
tumour lysis syndrome is a serious condition characterized by changes in blood test results, including elevated levels of uric acid, potassium, phosphate, and decreased calcium; leading to symptoms such as seizures, kidney failure (reduced urine output or dark urine) and cardiac arrhythmias. In such cases, inform your doctor immediately
myositis (muscle inflammation – hot, red, and swollen – causing muscle pain and weakness)

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, hospital pharmacist, or nurse. Adverse reactions can also be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products 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 may 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 Docetaxel-Ebewe

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and outer carton,
following EXP. The expiry date refers to the last day of the specified month.
Do not store above 25°C.
Do not freeze.
Keep the vial in the outer carton to protect from light.
Storage conditions after first opening
The medicine should be used within 28 days. Do not store above 25°C.
Storage conditions after dilution
The infusion solution should be used within 4 hours, including the 1-hour infusion.
Chemical and physical in-use stability has been demonstrated for the solution stored at room temperature (below 25°C) or in a refrigerator (from 2°C to 8°C).
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Docetaxel-Ebewe contains
The active substance is docetaxel. One ml of concentrate for solution for infusion contains
10 mg of docetaxel.
The other ingredients are: anhydrous citric acid, macrogol 300, polysorbate 80, 96% ethanol.

What Docetaxel-Ebewe looks like and contents of the pack
Docetaxel-Ebewe is a clear, colourless to pale yellow solution, free from visible particles, with pH 3.0–4.5.
Docetaxel-Ebewe is available in single packs containing 1 vial (20 mg/2 ml,
80 mg/8 ml, 160 mg/16 ml).
Vials may be placed in transparent protective packaging made of plastic material
(Onko-Safe or "Sleeving"). The "Onko-Safe" and "Sleeving" packaging does not come into contact with the medicinal product and provides additional protection during transport, thereby increasing safety for medical and pharmaceutical personnel.

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

Manufacturer
Fareva Unterach GmbH
Mondseestraße 11
4866 Unterach, Austria

For further information about the medicinal product and its names in other 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 exclusively for professional medical personnel

Instructions for drug preparation and waste disposal

Control prior to use
Docetaxel-Ebewe concentrate should be visually inspected before use for precipitation or discoloration. If particulate matter is present in the solution, the solution must be discarded.

Preparation of infusion solution
The concentrate must be diluted before use.
Infusion solutions should be prepared using 0.9% sodium chloride solution or 5% glucose solution and administered as intravenous infusion.

If vials of Docetaxel-Ebewe concentrate for infusion preparation have been stored in a refrigerator, remove the required number of vials and allow them to reach room temperature (below 25°C) before use.

The required volume may be drawn directly from the vial.
To achieve the dose required for a given patient, more than one vial may be necessary.
Under aseptic conditions, using syringes with graduated scales fitted with needles, draw the appropriate volume of liquid containing 10 mg of docetaxel per 1 mL from the appropriate number of vials, depending on the required dose (expressed in mg). For example, a 140 mg dose of docetaxel requires withdrawal of 14 mL of concentrate for infusion solution preparation.

The required volume of Docetaxel-Ebewe concentrate for infusion solution preparation should be added in a single injection into a 250 mL infusion bag or bottle containing 5% glucose solution or 0.9% sodium chloride solution for infusion.

If a docetaxel dose greater than 200 mg is required, a larger volume of diluent should be used so that the docetaxel concentration does not exceed 0.74 mg/mL.

Mix the contents of the infusion bag or bottle manually by gentle inversion and rotation, avoiding foaming. During preparation and transfer of the solution for administration to the patient, shaking or vigorous mixing should also be avoided.

The prepared docetaxel infusion solution is stable for 4 hours and must be used within this time (this period includes both storage and the 1-hour intravenous infusion). The infusion should be administered under aseptic conditions, at room temperature (below 25°C), under normal lighting.

The infusion solution prepared from Docetaxel-Ebewe concentrate should be carefully inspected before administration for the presence of particulate matter. If the solution is not clear or contains particulates, it must be discarded.

From a microbiological standpoint, the product should be used immediately.

Contact between Docetaxel-Ebewe concentrate and equipment or devices made of polyvinyl chloride (PVC) containing plasticizers should be avoided. To minimize patient exposure to DEHP (di-2-ethylhexyl phthalate), which may leach from PVC infusion bags or sets, the final diluted Docetaxel-Ebewe infusion solution should be stored in bottles or bags made of plastic material (polypropylene or polyolefin) and administered using infusion sets lined with polyethylene.

To minimize the potential for precipitation in the infusion solution, the use of infusion bags is recommended. The use of glass bottles is not recommended.

pH and osmolality of the diluted solution
0.3 mg/mL in 5% glucose solution: pH ≈ 3.6; 517 mOsm/kg
0.74 mg/mL in 0.9% NaCl solution: pH ≈ 3.3 – 3.6; 849 mOsm/kg

Guidelines for safe handling of cytotoxic substances
Pregnant women should not handle cytotoxic substances. Injection solutions should be prepared only by appropriately trained personnel in a designated area. The work surface should be covered with absorbent paper mats covered on the outer side with a plastic layer.

Personnel must wear protective gloves, masks, and protective gowns. Appropriate precautions should be taken to avoid accidental contact of the drug with skin or mucous membranes. If such contact occurs, the skin or mucous membranes should be immediately and thoroughly washed with soap and water. In case of accidental eye contamination, the eyes should be immediately and thoroughly rinsed with water.

Syringes and systems with Luer-lock connectors should be used. Use of needles with a large bore is recommended to minimize pressure and potential aerosolization. Aerosol formation can also be reduced by using vented needles. Any unused portions of the product should be disposed of. Appropriate precautions should be taken when disposing of materials used in the preparation of Docetaxel-Ebewe. All unused remnants of the product or contaminated materials should be placed in special bags for hazardous waste. Sharp objects (needles, syringes, vials, etc.) should be placed in appropriate rigid containers. Personnel involved in waste collection and disposal should be informed of the associated risks. All unused remnants of the product or waste should be disposed of in accordance with standard procedures for cytotoxic agents. Excess solution should be poured directly into the drain with a large amount of water.

This medicinal product may be used multiple times; see "Storage conditions and shelf life".

Incompatibilities
This medicinal product must not be mixed with other medicinal products.

Method of administration
Docetaxel-Ebewe is intended for intravenous use only.

Storage conditions and shelf life
Shelf life of the factory-sealed package
Unopened: 2 years
After first opening: 28 days. Do not store above 25°C.

Shelf life after dilution
Physicochemical stability of the solution diluted with 5% glucose solution or 0.9% sodium chloride solution has been demonstrated for 4 hours when stored between 2°C and 8°C protected from light, or at temperatures below 25°C without protection from light.

From a microbiological standpoint, the product should be used immediately. If the medicinal product is not used immediately, the responsibility for storage duration and conditions prior to use lies with the user.

Special precautions for storage
Factory-sealed packaging
Do not store above 25°C.
Do not freeze.
Store the vial in its outer cardboard packaging to protect from light. For information on storage conditions of the diluted medicinal product, see section "Shelf life after dilution".