TAXOTERE 80 mg/4 ml CONCENTRATE FOR INFUSION SOLUTION

1. What is TAXOTERE and what is it used for

The name of this medicine is TAXOTERE. Its common name is docetaxel. Docetaxel is a substance derived from the needles (leaves) of the yew tree.

Docetaxel belongs to a group of anticancer medicines called taxoids.

TAXOTERE has been prescribed by your doctor for the treatment of breast cancer, certain types of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer, or head and neck cancer:

• For the treatment of advanced breast cancer, TAXOTERE may be administered either alone or in combination with doxorubicin, or trastuzumab or capecitabine.
  • For the treatment of early breast cancer with or without lymph node involvement, TAXOTERE may be administered in combination with doxorubicin and cyclophosphamide.
  • For the treatment of lung cancer, TAXOTERE may be administered either alone or in combination with cisplatin.
  • For the treatment of prostate cancer, TAXOTERE is administered in combination with prednisone or prednisolone.
  • For the treatment of metastatic gastric cancer, TAXOTERE is administered in combination with cisplatin and 5-fluorouracil.
  • For the treatment of head and neck cancer, TAXOTERE is administered in combination with cisplatin and 5-fluorouracil.

2. What you need to know before you use TAXOTERE

TAXOTERE must not be administered:

• if you are allergic (hypersensitive) to docetaxel or to any of the other ingredients of TAXOTERE (listed in section 6).
• if your white blood cell count is too low.
• if you have severe liver disease.

Warnings and precautions

Before each treatment with TAXOTERE, you will have a blood test to check that you have a sufficient number of blood cells and sufficient liver function to receive TAXOTERE. In case of alterations in white blood cells, you may suffer from fever or infections.

Inform your doctor, pharmacist, or nurse immediately if you have abdominal pain or tenderness, diarrhea, rectal bleeding, blood in your stools, or fever. These symptoms could be the first signs of severe gastrointestinal toxicity, which can be fatal. Your doctor must address this immediately.

Inform your doctor, pharmacist, or nurse if you have vision problems. In case of vision problems, particularly blurred vision, an eye examination and vision test must be performed immediately.

Inform your doctor, pharmacist, or nurse if you have heart problems.

Inform your doctor, pharmacist, or nurse if you have previously experienced allergic reactions to paclitaxel.

If you develop acute or worsening problems in your lungs (fever, difficulty breathing, cough), inform your doctor, pharmacist, or nurse immediately. Your doctor may interrupt your treatment immediately.

Your doctor will recommend that you take premedication, consisting of an oral corticosteroid such as dexamethasone, one day before the administration of TAXOTERE and that you continue for one or two days after to minimize some side effects that may occur after the infusion of TAXOTERE, in particular allergic reactions and fluid retention (swelling of the hands, feet, legs, or weight gain).

During treatment, you may receive other medicines to maintain your blood cell count.

Severe skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported with TAXOTERE:

• SJS/TEN symptoms may include blisters, peeling, or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands, or feet) with or without a rash. You may also have symptoms similar to flu at the same time, such as fever, chills, or muscle pain.
• AGEP symptoms may include a red, scaly, and widespread rash with bumps under the inflamed skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever.

If you develop severe skin reactions or any of the reactions mentioned above, contact your doctor or healthcare professional immediately.

Inform your doctor, pharmacist, or nurse before starting TAXOTERE if you have kidney problems or high blood levels of uric acid.

TAXOTERE contains alcohol. Consult your doctor if you have a history of alcoholism, epilepsy, or liver disorders. See also the section below “TAXOTERE contains ethanol (alcohol)”.

Using TAXOTERE with other medicines

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription. The reason is that TAXOTERE or the other medicine may not work as well as expected, and you may have a greater chance of experiencing a side effect.

The alcohol content of this medicine may alter the effects of other medicines.

Pregnancy, breastfeeding, and fertility

Consult your doctor before using any medicine.

TAXOTERE must not be administered if you are pregnant, unless clearly indicated by your doctor.

You must not become pregnant while being treated with this medicine and for 2 months after the end of your treatment. You must use an effective method of contraception during treatment and for 2 months after the end of your treatment, as TAXOTERE may be harmful to the fetus. If you become pregnant during treatment, you must inform your doctor immediately.

TAXOTERE must not be used during breastfeeding.

If you are a man being treated with TAXOTERE, you must not father a child and must use an effective method of contraception during treatment and for 4 months after the end of your treatment. It is recommended that you be informed about sperm preservation before treatment, as docetaxel may affect male fertility.

Driving and using machines

The alcohol content of this medicine may affect your ability to drive and use machines.

You may experience side effects of this medicine that could affect your ability to drive, use tools, or operate machinery (see section 4 Possible side effects). If this happens, do not drive or use any tools or machinery before consulting your doctor, nurse, or pharmacist.

TAXOTERE contains ethanol (alcohol)

This medicine contains 50% v/v anhydrous ethanol (alcohol), which is equivalent to 1.58 g of anhydrous ethanol per vial, corresponding to 40 ml of beer or 17 ml of wine.

This medicine is harmful to individuals with alcohol dependence.

The alcohol content should be taken into account in pregnant or breastfeeding women, children, and high-risk populations, such as patients with liver disease or epilepsy.

The alcohol content of this medicine may have effects on the central nervous system (part of the nervous system that includes the brain and spinal cord).

3. How to use TAXOTERE

TAXOTERE will be administered to you by a healthcare professional.

Usual dose

The dose will depend on your weight and general condition. Your doctor will calculate your body surface area in square meters (m2) and determine the dose you should receive.

Form and method of administration

TAXOTERE will be administered by infusion into one of your veins (intravenous route). The infusion will last approximately one hour, during which you will be in the hospital.

Frequency of administration

You will receive the treatment, by intravenous infusion, once every 3 weeks.

Your doctor may change the dose and frequency of administration depending on your blood tests, your general condition, and your response to TAXOTERE. In particular, inform your doctor if you experience diarrhea, mouth sores, numbness or tingling, fever, and provide the results of your blood tests. This information will allow your doctor to decide whether a dose reduction is necessary. If you have any other questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Your doctor will discuss the possible risks and benefits of your treatment with you.

The most common side effects of TAXOTERE, when used alone, are: a decrease in the number of red or white blood cells, hair loss, nausea, vomiting, mouth sores, diarrhea, and fatigue.

The severity of the side effects of TAXOTERE may increase when used in combination with other chemotherapy agents.

During the infusion in the hospital, the following allergic reactions may occur (may affect more than 1 in 10 patients):

• flushing, skin reactions, itching,
• chest tightness, difficulty breathing,
• fever or chills,
• back pain,
• low blood pressure.

More severe reactions may occur.

If you had an allergic reaction to paclitaxel, you may also experience an allergic reaction to docetaxel, which may be more severe.

The hospital staff will closely monitor your condition during treatment. If you notice any of these effects, inform them immediately.

Between infusions of TAXOTERE, the following may occur, and their frequency may vary depending on the combination of medicines you receive:

Very common(may affect more than 1 in 10 patients):

• infections, decrease in the number of red or white blood cells, or platelets
• fever: if this happens, you must inform your doctor immediately
• allergic reactions, such as those described above
• loss of appetite (anorexia)
• insomnia
• numbness or tingling, or pain in the joints
• headache
• taste disturbance
• eye inflammation or excessive tearing
• swelling caused by defective lymphatic drainage
• shortness of breath
• nasal discharge; inflammation of the throat and nose; cough
• nasal bleeding
• mouth sores
• stomach upset, including nausea, vomiting, and diarrhea, constipation
• abdominal pain
• indigestion
• hair loss (in most cases, your hair will grow back normally). In some cases (frequency not known), permanent hair loss has been observed
• redness and swelling of the palms of your hands or the soles of your feet, which may cause skin peeling (this may also occur on the arms, face, or body)
• change in nail color, which may cause nail detachment
• muscle pain; back pain or bone pain
• changes or absence of menstrual period
• swelling of hands, feet, legs
• fatigue; or cold-like symptoms
• weight gain or loss
• upper respiratory tract infection.

Common(may affect up to 1 in 10 patients):

• oral candidiasis
• dehydration
• dizziness
• impaired hearing
• decreased blood pressure, irregular or rapid heartbeats
• heart failure
• esophagitis
• dry mouth
• difficulty or pain when swallowing
• bleeding
• elevation of liver enzymes (hence the need for regular blood tests)
• increase in blood sugar levels (diabetes)
• decrease in potassium, calcium, and/or phosphate in your blood.

Uncommon(may affect up to 1 in 100 patients):

• fainting
• skin reactions, phlebitis (inflammation of the vein), or swelling at the infusion site
• blood clots
• acute myeloid leukemia and myelodysplastic syndrome (types of blood cancer) may occur in patients treated with docetaxel in combination with other anticancer treatments.

Rare(may affect up to 1 in 1,000 patients)

• inflammation of the colon, small intestine, which may be fatal (frequency not known); intestinal perforation.

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

• interstitial lung disease (inflammation of the lungs that causes cough and difficulty breathing. Lung inflammation may also occur when treatment with docetaxel is used with radiotherapy)
• pneumonia (lung infection)
• pulmonary fibrosis (scarring and thickening in the lungs with difficulty breathing)
• blurred vision due to inflammation of the retina within the eye (cystoid macular edema)
• decrease in sodium and/or magnesium in your blood (electrolyte imbalance disorders)
• ventricular arrhythmia or ventricular tachycardia (which may manifest as irregular and/or rapid heartbeats, severe shortness of breath, dizziness, and/or fainting). Some of these symptoms may be severe. If this happens, inform your doctor immediately
• reactions at the injection site, at the site of a previous reaction
• non-Hodgkin's lymphoma (a cancer that affects the immune system) and other types of cancer may occur in patients receiving treatment with docetaxel in combination with other anticancer treatments
• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (blisters, peeling, or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands, or feet) with or without a rash. You may also have symptoms similar to flu at the same time, such as fever, chills, or muscle pain)
• acute generalized exanthematous pustulosis (AGEP) (red, scaly, and widespread rash with bumps under the inflamed skin (including skin folds, trunk, and upper limbs) and blisters accompanied by fever).
• tumor lysis syndrome, a serious condition that manifests as changes in blood tests, such as increased uric acid, potassium, phosphorus, and decreased calcium levels; and results in symptoms such as seizures, kidney failure (reduced or darkened urine), and heart rhythm disturbances. If this happens, you must inform your doctor immediately.
• myositis (inflammation of the muscles - heat, redness, and swelling - that causes muscle pain and weakness).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of TAXOTERE

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the outer packaging and on the label of the vial after EXP. The expiry date is the last day of the month shown.

Do not store above 25°C.

Store in the original packaging to protect from light.

Use the vial immediately after opening. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

From a microbiological point of view, it should be reconstituted/diluted under controlled and aseptic conditions.

The medicine should be used immediately after it has been added to the infusion bag. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 6 hours below 25°C, including the infusion time to the patient.

The physical and chemical stability of the prepared infusion solution has been demonstrated for 48 hours when stored between 2 and 8°C in non-PVC bags.

The docetaxel infusion solution is supersaturated, and therefore may crystallize over time. If crystals appear, the solution must not be used and should be discarded.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Container Contents and Additional Information

What TAXOTERE contains

• The active ingredient is docetaxel (as trihydrate). Each ml of concentrate for solution for infusion contains 20 mg of docetaxel.
• The other ingredients are polysorbate 80, anhydrous ethanol (see section 2), and citric acid.

Appearance of TAXOTERE and container contents

TAXOTERE concentrate for solution for infusion is a solution between yellow and yellow-brown.

The concentrate is provided in a 7 ml clear and colorless glass vial, with a purple aluminum seal and a magenta plastic flip-off cap.

Each container contains a 4 ml vial of concentrate (80 mg of docetaxel).

Marketing Authorization Holder

Sanofi Winthrop Industrie

82 Avenue Raspail

94250 Gentilly

France

Manufacturer(s)

Sanofi-Aventis Deutschland GmbH

Industriepark Höchst

65926 Frankfurt am Main

Germany

or

Sanofi-aventis Zrt.

(Harbor Park) 1, Campona utca

Budapest 1225

Hungary

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

This information is intended only for healthcare professionals:

PREPARATION GUIDE FOR THE USE OF TAXOTERE 80 mg/4 ml CONCENTRATE FOR SOLUTION FOR INFUSION

It is important that you carefully read the contents of this guide before preparing the infusion solution of TAXOTERE.

Recommendations for safe handling

Docetaxel is an antineoplastic agent and, as with other potentially toxic compounds, precautions should be taken when handling and preparing TAXOTERE solutions. The use of gloves is recommended.

If TAXOTERE concentrate or infusion solution comes into contact with the skin, wash the skin immediately and thoroughly with water and soap. If the concentrate or infusion solution comes into contact with the mucous membranes, rinse immediately and thoroughly with water.

Preparation for intravenous administration

Preparation of the infusion solution

DO NOT USE this medicine (TAXOTERE 80 mg/4 ml concentrate for solution for infusion, in a single vial) with other medicines that contain docetaxel in 2 vials (concentrate and solvent).

TAXOTERE 80 mg/4 ml concentrate for solution for infusion DOES NOT require prior dilution with a solvent and is ready to be added to the infusion solution.

• Each vial is for single use and should be used immediately after opening. If not used immediately, the time and conditions of storage are the responsibility of the user. It may be necessary to use more than 1 vial of TAXOTERE concentrate for solution for infusion to obtain the required dose for the patient. For example, for a dose of 140 mg of docetaxel, 7 ml of docetaxel concentrate for solution would be needed.

• Aseptically withdraw the required amount of TAXOTERE concentrate for solution for infusion using a calibrated syringe with a 21G needle.

The concentration of docetaxel in the vial of TAXOTERE 80 mg/4 ml is 20 mg/ml.

• Then, inject it in a single injection into a 250 ml infusion bag or bottle containing either a 5% glucose solution or a 9 mg/ml (0.9%) sodium chloride solution. If a dose greater than 190 mg of docetaxel is required, use a larger volume of infusion fluid to avoid exceeding a concentration of 0.74 mg/ml of docetaxel.
• Manually mix the infusion bag or bottle by rotating it.
• From a microbiological point of view, the reconstitution/dilution should be carried out under aseptic conditions and the medicine should be used immediately. If not used immediately, the periods and conditions of storage are the responsibility of the user.

Once added to the infusion bag as recommended, the docetaxel infusion solution is stable for 6 hours if stored below 25°C. It should be used within this 6-hour period (including the hour of intravenous infusion administration).

In addition, the physical and chemical stability of the prepared infusion solution as recommended is demonstrated for up to 48 hours if stored between 2 and 8°C in non-PVC bags.

The docetaxel infusion solution is supersaturated and may crystallize over time. If crystals appear, the solution should not be used and should be discarded.

• Like all parenteral products, the TAXOTERE infusion solution should be visually inspected before use; solutions where precipitation is observed should be discarded.

Disposal

Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations. Do not throw medicines down the drain. Ask your pharmacist where to dispose of medicines that are no longer needed. This will help protect the environment.