Tolnexa

Leaflet attached to the packaging: patient information

Tolnexa, 20 mg/ml, concentrate for solution for infusion
Docetaxel

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• You should consult a doctor or nurse if you have any further doubts.
• If any of the side effects worsen or if any side effects not mentioned in the leaflet occur, you should tell your doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Tolnexa and what is it used for
• 2. Important information before using Tolnexa
• 3. How to use Tolnexa
• 4. Possible side effects
• 5. How to store Tolnexa
• 6. Contents of the packaging and other information

1. What is Tolnexa and what is it used for

The name of the medicine is Tolnexa, and its common name is docetaxel. Docetaxel is
a substance obtained from yew needles.
Docetaxel belongs to a group of anticancer medicines called taxoids.
Tolnexa is prescribed by a doctor to treat 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, Tolnexa may be given alone or in combination with doxorubicin or trastuzumab, or capecitabine,
• in the treatment of early-stage breast cancer with or without lymph node metastases, Tolnexa may be given in combination with doxorubicin and cyclophosphamide,
• in the treatment of lung cancer, Tolnexa may be given alone or in combination with cisplatin,
• in the treatment of prostate cancer, Tolnexa is given in combination with prednisone or prednisolone,
• in the treatment of metastatic stomach cancer, Tolnexa is given in combination with cisplatin and 5-fluorouracil,
• in the treatment of head and neck cancer, Tolnexa is given in combination with cisplatin and 5-fluorouracil.

2. Important information before using Tolnexa

When not to use Tolnexa:

• if the patient is allergic (hypersensitive) to docetaxel or any of the other ingredients of this medicine (listed in section 6),
• if the patient has a low white blood cell count,
• in severe liver dysfunction.

Warnings and precautions

Before each administration of Tolnexa, blood tests will be performed to check if
the number of blood cells and liver function are suitable for the administration of Tolnexa. In case
of disorders of the white blood cell count, fever or infections may occur.
You should immediately inform your doctor, hospital pharmacist or nurse if you experience
abdominal pain or tenderness, diarrhea, rectal bleeding, blood in the stool or fever.
These symptoms may be the first signs of severe gastrointestinal toxicity, which can
lead to death. The attending physician should diagnose them immediately.
If you experience vision disorders, you should tell your doctor, hospital pharmacist or nurse. In case
of vision disorders, especially blurred vision, eye exams and vision tests should be performed
immediately.
If you have had an allergic reaction during previous treatment with paclitaxel, you should tell your
doctor, hospital pharmacist or nurse. If you experience heart problems, you should tell your doctor or nurse.
In case of acute symptoms or worsening of symptoms from the lungs (fever, shortness of breath or cough),
you should immediately inform your doctor, hospital pharmacist or nurse.
The doctor may decide to stop the treatment immediately.
One day before and one to two days after the administration of Tolnexa, preventive treatment consisting
of oral corticosteroids, such as dexamethasone, will be administered to reduce the severity of side effects.
Side effects that may occur after intravenous infusion of Tolnexa include allergic reactions and fluid retention
(manifested by itching of the hands, feet, legs or weight gain).
During treatment, it may be necessary to take medications that maintain a normal blood cell count.
Tolnexa contains alcohol. In case of alcohol dependence, epilepsy or liver dysfunction, this fact should be
discussed with the doctor. See the section "Tolnexa contains ethanol (alcohol)" below.

Tolnexa and other medicines

You should tell your doctor or nurse about all the medicines you are currently taking or have recently taken,
as well as about the medicines you plan to take, including those that are available without a prescription.
This is because Tolnexa or other medicines may not work as expected or may increase the risk of side effects.
The amount of alcohol present in the medicine may affect the action of other medicines.

Pregnancy, breastfeeding and fertility

You should consult a doctor before using any medicine.
Tolnexa should NOT be given during pregnancy unless the patient's clinical condition requires it.
During treatment, women should not become pregnant and must use an effective method of contraception,
as Tolnexa may be harmful to the unborn child. If you become pregnant during treatment, you should immediately
inform your doctor.
You should not breastfeed while using Tolnexa.
If a man is taking Tolnexa, it is recommended that he does not father a child during and up to 6 months
after the treatment period. Before starting treatment, he should also consult about storing his sperm,
as docetaxel may impair fertility in men.

Driving and using machines

The amount of alcohol present in the medicine may affect the ability to drive and use machines.
Side effects of this medicine may impair the ability to drive, use tools or operate machines (see section 4 Possible side effects).
If this happens, you should not drive, use tools or operate machines before consulting your doctor, nurse or hospital pharmacist.

Tolnexa contains ethanol (alcohol)

This medicine (20 mg/ml concentrate for solution for infusion) contains 50 vol. % ethanol (alcohol), i.e.
up to 0.395 g (0.5 ml) per vial. The amount of alcohol in one vial is equivalent to its content in 10 ml of beer or 4 ml of wine.
This medicine (80 mg/4 ml concentrate for solution for infusion) contains 50 vol. % ethanol (alcohol), i.e.
up to 1.58 g (2 ml) per vial. The amount of alcohol in one vial is equivalent to its content in 40 ml of beer or 17 ml of wine.
This medicine (160 mg/8 ml concentrate for solution for infusion) contains 50 vol. % ethanol (alcohol), i.e.
up to 3.16 g (8 ml) per vial. The amount of alcohol in one vial is equivalent to its content in 80 ml of beer or 33 ml of wine.
Alcohol may have a harmful effect on individuals with alcohol dependence.
The alcohol content should be taken into account in pregnant or breastfeeding women, as well as in children and individuals at high risk, such as patients with liver disease or epilepsy.
The amount of alcohol present in the medicine may affect the central nervous system (part of the nervous system that includes the brain and spinal cord).

3. How to use Tolnexa

Tolnexa is a medicine for administration by medical professionals.

Usually used dose

The dose depends on the patient's body weight and overall condition. The doctor calculates the body surface area in square meters (m2) and determines the dose to be administered based on this.

Method of administration and route of administration

Tolnexa is administered by intravenous infusion into one of the patient's veins. The intravenous infusion,
which lasts about one hour, is performed in a hospital.

Frequency of administration

Intravenous infusions are usually performed every 3 weeks.
The doctor may change the dose and frequency of administration based on the results of blood tests, the patient's overall condition and reaction to Tolnexa.
In particular, you should inform your doctor if you experience diarrhea, mouth sores, numbness, tingling or needle-like sensations, fever, or abnormal blood test results.
This information will allow the doctor to decide whether a dose reduction is necessary.
If you have any further doubts about the use of this medicine, you should consult a doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
You should consult a doctor to explain the possible risk and benefits of the treatment.
The most commonly reported side effects after using docetaxel alone are:
reduced red or white blood cell count, hair loss, nausea, vomiting, mouth sores, diarrhea and fatigue.
When docetaxel is taken in combination with other chemotherapeutic agents, side effects may be more severe.
During intravenous infusion in a hospital, the following allergic reactions may occur (may occur in more than 1 in 10 people):

• redness, skin reactions, itching,
• chest tightness, difficulty breathing,
• fever or chills,
• back pain,
• low blood pressure. More severe reactions may occur.

If you have had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, which may be more severe.
For this reason, your condition will be closely monitored during treatment. You should immediately inform the hospital staff if you observe any of these symptoms.
Between intravenous infusions of docetaxel, the following side effects may occur, and their frequency may vary depending on the treatment regimen:

• Very common(may occur in more than 1 in 10 people):
• infections, reduced red blood cell count (anemia) or white blood cell count (which are necessary to fight infections) and reduced platelet count
• fever: in case of increased temperature, you should immediately inform your doctor
• allergic reactions as described above
• loss of appetite (anorexia)
• insomnia
• numbness or tingling and joint or muscle pain
• headache
• change in taste
• eye inflammation or increased tearing
• swelling caused by abnormal lymphatic drainage
• shortness of breath
• impaired nasal patency; pharyngitis and rhinitis; cough
• nasal bleeding
• mouth sores
• gastrointestinal disorders including nausea, vomiting and diarrhea, constipation
• abdominal pain
• indigestion
• hair loss: in most cases, hair grows back after the end of treatment. In some patients, permanent hair loss has been observed (frequency unknown).
• redness and swelling of the palms and soles, which may cause skin peeling (this can also occur on the arms, face or torso)
• change in nail color, which may subsequently separate from the nail bed
• muscle pain, back pain or bone pain
• change in menstrual cycle or absence of menstruation
• swelling of the hands, feet, lower limbs
• fatigue or flu-like symptoms
• weight gain or weight loss

Common(may occur in up to 1 in 10 people):

• oral thrush
• dehydration
• dizziness
• hearing disorders
• low blood pressure, irregular or rapid heartbeat
• heart failure
• esophagitis
• dry mouth
• difficulty or pain when swallowing
• bleeding
• increased liver enzyme activity (regular blood tests are necessary)

Uncommon(may occur in up to 1 in 100 people):

• fainting
• skin reactions, vein inflammation or swelling at the injection site
• blood clots

Rare(may affect up to 1 in 1000 people):

• colitis, small intestine inflammation, which can lead to death (frequency unknown); intestinal perforation

Frequency not known(cannot be estimated from the available data):

• interstitial lung disease (inflammatory condition of the lungs causing cough and breathing difficulties. Lung inflammation can also occur in patients undergoing docetaxel therapy in combination with radiotherapy)
• pneumonia (lung infection)
• pulmonary fibrosis (scarring and thickening in the lungs with shortness of breath)
• blurred vision due to retinal edema (cystoid macular edema)
• reduced sodium, potassium, magnesium and/or calcium levels 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 can be very serious. If such symptoms occur, you should immediately inform your doctor
• reactions at the injection site of a previous reaction

Reporting side effects

If you experience any side effects, including those not mentioned in the leaflet, you should tell your doctor or pharmacist.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Jerozolimskie Avenue 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: ndl@urpl.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 Tolnexa

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 label on the vial after "EXP".
The expiry date refers to the last day of the month.
Do not store above 25°C.
Store in the original packaging to protect from light.
The medicine should be used immediately after addition to the infusion bag. If the medicine is not used immediately,
the user is responsible for the storage conditions and time; usually, it should not be longer than 24 hours at a temperature below 25°C, including 1 hour for infusion to the patient.
Physical and chemical stability of the prepared infusion solution has been demonstrated for up to 7 days when stored in non-PVC infusion bags at a temperature between 2°C and 8°C.
Docetaxel in the form of an infusion solution is a supersaturated solution and may crystallize over time.
If crystals appear, the solution should not be used and should be discarded.
Medicines should not be disposed of via wastewater or household waste. You should ask your 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 Tolnexa contains

• The active substance of the medicine is docetaxel. 1 ml of the concentrate for solution for infusion contains 20 mg of docetaxel. Each vial of 1 ml of the concentrate for solution for infusion contains 20 mg of docetaxel. Each vial of 4 ml of the concentrate for solution for infusion contains 80 mg of docetaxel. Each vial of 8 ml of the concentrate for solution for infusion contains 160 mg of docetaxel.
• The other ingredients are: polysorbate 80, anhydrous ethanol and anhydrous citric acid.

What Tolnexa looks like and contents of the pack

The concentrate for solution for infusion is a clear, pale yellow to brownish-yellow solution.

Pack size:

20 mg/ml: 1 vial of 5 ml capacity made of colorless glass type I with a rubber stopper coated with a fluorotec layer, an aluminum seal and an orange flip-off cap, containing 1 ml of the concentrate for solution for infusion in a cardboard box.
80 mg/4 ml: 1 vial of 5 ml capacity made of colorless glass type I with a rubber stopper coated with a fluorotec layer, an aluminum seal and a red flip-off cap, containing 4 ml of the concentrate for solution for infusion in a cardboard box.
160 mg/8 ml: 1 vial of 10 ml capacity made of colorless glass type I with a rubber stopper coated with a fluorotec layer, an aluminum seal and a red flip-off cap, containing 8 ml of the concentrate for solution for infusion in a cardboard box.
Not all pack sizes may be marketed.

Marketing authorization holder:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

Date of last revision of the leaflet: ---------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:

INSTRUCTIONS FOR PREPARATION OF TOLNEXA, 20 mg/ml, CONCENTRATE FOR SOLUTION FOR INFUSION

__________________________________________________________________________________
Before preparing the infusion solution of Tolnexa, you should read the entire contents of these instructions.
Recommendations for safe handling of the medicine
Docetaxel is an anticancer medicine and, like other potentially toxic substances, it should be handled with caution and its solutions should be prepared with caution. It is recommended to wear gloves.
In case of contact with the skin of Tolnexa concentrate or infusion solution, the contaminated area should be immediately rinsed with a large amount of water and soap. In case of contact with the mucous membrane, the contaminated area should be immediately rinsed with water.
Preparation of the solution for intravenous administration
Preparation of the infusion solution

Of Tolnexa, 20 mg/ml, concentrate for solution for infusion, containing only

1 vial (20 mg/1 ml, 80 mg/4 ml, 160 mg/8 ml), DO NOT USE with other medicines containing docetaxel in 2 vials (concentrate and solvent).

Tolnexa, 20 mg/ml, concentrate for solution for infusion DOES NOT require prior dilution with a solvent and is ready for addition to the infusion solution.

• Each vial is intended for single use and should be used immediately after opening. If the vial is not used immediately, the user is responsible for the storage time and conditions. To obtain the required dose for the patient, more than one vial of the concentrate for solution for infusion may be needed. For example: to obtain a dose of 140 mg of docetaxel, 7 ml of docetaxel in the form of a concentrate for solution for infusion should be used.
• The required amount of the concentrate for solution for infusion should be drawn up in aseptic conditions using a scaled syringe with a needle.

The concentration of docetaxel in the Tolnexa vial is 20 mg/ml.

• Then, the concentrate should be injected as a single injection (one-shot method) into a bag or bottle of infusion fluid containing 250 ml of 5% glucose solution or 9 mg/ml (0.9%) sodium chloride infusion solution. If a dose greater than 190 mg of docetaxel is required, a larger volume of infusion fluid should be used so that the concentration of docetaxel does not exceed 0.74 mg/ml.
• The bag or bottle of infusion fluid should be manually mixed by rotating it.
• From a microbiological point of view, the dilution of the medicine should be performed in controlled and aseptic conditions, and the infusion solution should be used immediately after preparation. If the solution is not used immediately, the user is responsible for the storage time and conditions.

After addition to the infusion bag as recommended, the docetaxel infusion solution, stored at a temperature below 25°C, is stable for 24 hours. It should be used within 24 hours (including the 1-hour infusion time).
Additionally, physical and chemical stability of the prepared infusion solution has been demonstrated for up to 7 days when stored in non-PVC infusion bags at a temperature between 2°C and 8°C.
Avoid excessive shaking of the infusion bag.
Docetaxel in the form of an infusion solution is a supersaturated solution and may crystallize over time.
If crystals appear, the solution should not be used and should be discarded.
As with all medicines for parenteral administration, the infusion solution should be inspected before use - solutions containing sediment should be discarded.

• Similarly, as with all medicines for parenteral administration, the infusion solution should be inspected before use - solutions containing sediment should be discarded.

Disposal of residues
All medical materials used during the dilution and administration of the medicine should be disposed of in accordance with the applicable standard procedures. Medicines should not be disposed of via wastewater. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.