Taxotere 80 mg/4 ml concentrate for infusion solution

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

TAXOTERE 80 mg/4 ml concentrate for solution for infusion

Docetaxel

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, hospital pharmacist, or nurse.
• If you experience any side effects, consult your doctor, hospital pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Package leaflet contents:

1. What TAXOTERE is and what it is used for
2. What you need to know before you start using TAXOTERE
3. How to use TAXOTERE
4. Possible side effects
5. Storage of TAXOTERE
6. Contents of the pack and other information

1. What TAXOTERE is and what it is used for

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

Docetaxel belongs to a group of anticancer agents known as 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 given either alone or in combination with doxorubicin, trastuzumab, or capecitabine.
  • For the treatment of early breast cancer with or without lymph node involvement, TAXOTERE may be given in combination with doxorubicin and cyclophosphamide.
  • For the treatment of lung cancer, TAXOTERE may be given 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 using TAXOTERE

Do not use TAXOTERE:

• if you are allergic (hypersensitive) to docetaxel or to any of the other components 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 an adequate number of blood cells and sufficient liver function to receive TAXOTERE. If your white blood cells are abnormal, you may develop fever or infections.

Immediately inform your doctor, hospital pharmacist, or nurse if you experience abdominal pain or tenderness, diarrhoea, rectal bleeding, blood in the stool, or fever. These symptoms could be the first signs of severe gastrointestinal toxicity, which may be fatal. Your doctor must address this immediately.

Inform your doctor, hospital pharmacist, or nurse if you have vision problems. If you experience vision problems, especially blurred vision, you should have an immediate eye and vision examination.

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

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

If you develop acute problems or worsening of lung symptoms (fever, difficulty breathing, cough), inform your doctor, hospital pharmacist, or nurse immediately. Your doctor may need to stop your treatment immediately.

Your doctor will recommend that you take premedication consisting of an oral corticosteroid such as dexamethasone, starting one day before administration of TAXOTERE and continuing for one or two days afterwards, to minimize certain adverse effects that may occur after infusion of TAXOTERE, particularly allergic reactions and fluid retention (swelling of hands, feet, legs, or weight gain).

During treatment, you may receive other medications to maintain your blood cell counts.

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

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

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

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

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

Use of TAXOTERE with other medicines

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other medicine, including those obtained without a prescription. This is because TAXOTERE or the other medicine may not work as expected, and you may have an increased risk of side effects.

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

Pregnancy, breast-feeding, and fertility

Talk to your doctor before using any medicine.

TAXOTERE must not be given during pregnancy unless clearly indicated by your doctor.

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

TAXOTERE must not be used during breast-feeding.

If you are a man receiving treatment with TAXOTERE, you must not father a child and should use an effective method of contraception during treatment and for 4 months after stopping treatment with this medicine. You are advised to seek information about sperm preservation before starting treatment, as docetaxel may impair male fertility.

Driving and using machines

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

You may experience adverse effects from this medicine that could affect your ability to drive, use tools, or operate machinery (see section 4 Possible side effects). If this occurs, do not drive or use any tools or machinery until you have consulted your doctor, nurse, or hospital pharmacist.

TAXOTERE contains ethanol (alcohol)

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

This medicine is harmful for people suffering from alcoholism.

The alcohol content should be taken into account in pregnant or breast-feeding 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 (the 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 body weight and general condition. Your doctor will calculate your body surface area in square meters (m²) and determine the dose you should receive.

Method and route of administration

TAXOTERE will be given by intravenous infusion into one of your veins. The infusion will last approximately one hour, during which time you will remain in the hospital.

Frequency of administration

The treatment will be administered by intravenous infusion once every 3 weeks.

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

4. Possible adverse effects

Like all medicines, TAXOTERE may cause adverse effects, although not everyone experiences them.

Your doctor will discuss these with you and explain the potential risks and benefits of your treatment.

The most common adverse effects of TAXOTERE when given alone are: decrease in red or white blood cells, alopecia, nausea, vomiting, mouth sores, diarrhoea, and fatigue.

The severity of adverse effects of TAXOTERE may increase when it is administered in combination with other chemotherapeutic agents.

During the infusion in 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,
• decreased blood pressure.

Other more serious reactions may also occur.

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

Hospital staff will closely monitor your health during treatment. If you notice any of these effects, inform them immediately.

Between TAXOTERE infusions, 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 red blood cells (anaemia) or white blood cells (which are important for fighting infections) and platelets
• fever: if this occurs, you must inform your doctor immediately
• allergic reactions as described above
• loss of appetite (anorexia)
• insomnia
• sensation of numbness, tingling, or pain in joints
• headache
• altered taste
• eye inflammation or excessive tearing
• swelling caused by defective lymphatic drainage
• shortness of breath
• nasal discharge; inflammation of throat and nose; cough
• nosebleeds
• mouth sores
• stomach discomfort including nausea, vomiting, diarrhoea, constipation
• abdominal pain
• indigestion
• hair loss (in most cases, your hair will regrow normally). In some cases (frequency not known), permanent hair loss has been observed
• redness and swelling of the palms of the hands or soles of the feet, which may lead to skin peeling (this may also occur in arms, face or body)
• change in nail colour, which may become detached
• muscle pain; back or bone pain
• changes or absence of menstrual periods
• swelling of hands, feet, legs
• fatigue; or cold-like symptoms
• weight gain or weight loss
• upper respiratory tract infection.

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

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

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

• fainting
• skin reactions, phlebitis (vein inflammation) or swelling at the infusion site
• blood clot formation
• acute myeloid leukaemia 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 or small intestine, which could be fatal (frequency not known); intestinal perforation.

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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, hospital pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse 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 stated on the outer packaging and on the label of the vial following EXP. The expiry date refers to the last day of the month indicated.

Do not store above 25°C.

Keep in the original packaging to protect from light.

Use the vial immediately after opening. If not used immediately, the storage periods and conditions are the responsibility of the user.

From a microbiological standpoint, reconstitution/dilution must be performed under controlled aseptic conditions.

The medicine should be used immediately once added to the infusion bag. If not used immediately, the storage periods and conditions are the responsibility of the user and should normally not exceed 6 hours below 25°C, including the time of infusion to the patient.

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

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

Do not dispose of medicines via wastewater. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What TAXOTERE contains

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

What TAXOTERE looks like and contents of the pack

TAXOTERE concentrate for solution for infusion is a solution ranging from yellow to brownish-yellow.

The concentrate is supplied in a 7 ml vial made of colourless, transparent glass, with a purple aluminium seal and a magenta flip-off plastic cap.

Each pack contains one 4 ml vial of concentrate (80 mg of docetaxel).

Marketing Authorisation 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

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorisation Holder.

Date of the most recent review of this leaflet:

Other sources of information

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

This information is intended for healthcare professionals only:

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

It is important to read this guide carefully before preparing the TAXOTERE infusion solution.

Recommendations for safe handling

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

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

Preparation for intravenous administration

Preparation of the infusion solution

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

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

• Each vial is for single use only and should be used immediately after opening. If not used immediately, the storage periods and conditions are the responsibility of the user. More than one vial of TAXOTERE concentrate for infusion solution may be required to achieve the patient's required dose. For example, a dose of 140 mg of docetaxel would require 7 ml of concentrated docetaxel solution.

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

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

• Then, inject it all at once (in a single injection) into a 250 ml infusion bag or bottle containing either 5% glucose solution or 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 docetaxel concentration of 0.74 mg/ml.
• Mix the infusion bag or bottle manually by gentle rotation.
• From a microbiological standpoint, reconstitution/dilution should be performed under controlled aseptic conditions and the medicine should be used immediately. If not used immediately, the storage periods and conditions are the responsibility of the user.

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

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

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

• As with all parenteral products, the TAXOTERE infusion solution should be inspected visually before use; solutions in which precipitate formation is observed should be discarded.

Disposal

The disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations. Do not dispose of medicines via wastewater. Ask your pharmacist where to dispose of medicines you no longer use. This will help protect the environment.