Docetaxel Winthrop 80 mg/2 ml concentrate and solvent forsolution for infusion

The name of this medicine is Docetaxel Winthrop. Its common name is docetaxel. Docetaxel is a substance derived from the needles of yew trees.
Docetaxel belongs to the group of anti-cancer medicines called taxoids.

Docetaxel Winthrop has been prescribed by your doctor for the treatment of breast cancer, special forms of lung cancer (non-small cell lung cancer), prostate cancer, gastric cancer or head and neck cancer:

• For the treatment of advanced breast cancer, Docetaxel Winthrop could be administered either aloneor in combination with doxorubicin, or trastuzumab, or capecitabine.
• For the treatment of early breast cancer with or without lymph node involvement, DocetaxelWinthrop could be administered in combination with doxorubicin and cyclophosphamide.
• For the treatment of lung cancer, Docetaxel Winthrop could be administered either alone or incombination with cisplatin.
• For the treatment of prostate cancer, Docetaxel Winthrop is administered in combination withprednisone or prednisolone.
• For the treatment of metastatic gastric cancer, Docetaxel Winthrop is administered in combinationwith cisplatin and 5-fluorouracil.
• For the treatment of head and neck cancer, Docetaxel Winthrop is administered in combination withcisplatin and 5-fluorouracil.

You must not be given Docetaxel Winthrop if

• you are allergic (hypersensitive) to docetaxel or any of the other ingredients of Docetaxel Winthrop.
• the number of white blood cells is too low.
• you have a severe liver disease.

Take special care with Docetaxel Winthrop

Before each treatment with Docetaxel Winthrop, you will have blood tests to check that you have enough blood cells and sufficient liver function to receive Docetaxel Winthrop. In case of white blood cells disturbances, you may experience associated fever or infections.

You will be asked to take premedication consisting of an oral corticosteroid such as dexamethasone, one day prior to Docetaxel Winthrop administration and to continue for one or two days after it in order to minimise certain undesirable effects which may occur after the infusion of Docetaxel Winthrop in particular allergic reactions and fluid retention (swelling of the hands, feet, legs or weight gain).

During treatment, you may be given other medicines to maintain the number of your blood cells.

Taking other medicines

Please tell your doctor or hospital pharmacist if you are taking or have recently taken any other medicine, including medicines obtained without a prescription. This is because Docetaxel Winthrop or the other medicine may not work as well as expected and you may be more likely to get a side effect.

Pregnancy

Ask your doctor for advice before being given any medicine.

Docetaxel Winthrop must NOT be administered if you are pregnant unless clearly indicated by your doctor.

You must not become pregnant during treatment with this medicine and must use an effective method of contraception during therapy , because Docetaxel Winthrop may be harmful for the unborn baby. If pregnancy occurs during your treatment, you must immediately inform your doctor.

If you are a man being treated with Docetaxel Winthrop you are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment because docetaxel may alter male fertility.

Breast-feeding

You must not breast-feed while you are treated with Docetaxel Winthrop.

Driving and using machines

There is no reason why you cannot drive between courses of Docetaxel Winthrop except if you feel dizzy or are unsure of yourself.

Docetaxel Winthrop will be administered to you by a healthcare professional.

Usual dose

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

Method and route of administration

Docetaxel Winthrop will be given by infusion into one of your veins (intravenous use). The infusion will last approximately one hour during which you will be in the hospital.

Frequency of administration

You should usually receive your infusion once every 3 weeks.

Your doctor may change the dose and frequency of dosing depending on your blood tests, your general condition and your response to TAXOTERE. In particular, please inform your doctor in case of diarrhoea, sores in the mouth, feeling of numbness or pins and needles, fever and give her/him results of your blood tests. Such information will allow her/him to decide whether a dose reduction is needed. If you have any further questions on the use of this medicine, ask your doctor, or hospital pharmacist.

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

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

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10); common (affects 1 to 10 users in 100); uncommon (affects 1 to 10 users in 1,000); rare (affects 1 to 10 users in 10,000); very rare (affects less than 1 user in 10,000); not known (frequency cannot be estimated from the available data).

The most commonly reported adverse reactions of Docetaxel Winthrop alone are: decrease in the number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, diarrhoea and tiredness.

The severity of adverse events of Docetaxel Winthrop may be increased when Docetaxel Winthrop is given in combination with other chemotherapeutic agents.

During the infusion at the hospital the following allergic reactions (experienced in more than 1 person in 10) may occur:

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

The hospital staff will monitor your condition closely during treatment. Tell them immediately if you notice any of these effects.

Between infusions of Docetaxel Winthrop the following may occur, and the frequency may vary with the combinations of medicines that are received:

Very common (experienced in more than 1 in 10 patients):

• infections, decrease in the number of red (anaemia), or white blood cells (which are important in fighting infection) and platelets
• fever: if this happens you must tell your doctor immediately
• allergic reactions as described above
• loss of appetite (anorexia)
• insomnia
• feeling of numbness or pins and needles or pain in the joints or muscles
• headache
• alteration in sense of taste
• inflammation of the eye or increased tearing of the eyes
• swelling caused by faulty lymphatic drainage
• shortness of breath
• nasal drainage; inflammation of the throat and nose; cough
• bleeding from the nose
• sores in the mouth
• stomach upsets including nausea, vomiting and diarrhoea, constipation
• abdominal pain
• indigestion
• short term hair loss (in most cases normal hair growth should return)
• redness and swelling of the palms of your hands or soles of your feet which may cause your skin to peel (this may also occur on the arms, face, or body)
• change in the color of your nails, which may detach
• muscle aches and pains; back pain or bone pain
• change or absence of menstrual period
• swelling of the hands, feet, legs
• tiredness; or flu-like symptoms
• weight gain or loss.

Common (experienced in less than 1 in 10 but more than 1 in 100 patients):

• oral candidiasis
• dehydration
• dizziness
• hearing impaired
• decrease in blood pressure; irregular or rapid heart beat
• heart failure
• oesophagitis
• dry mouth
• difficulty or painful swallowing
• haemorrhage
• raised liver enzymes (hence the need for regular blood tests).

Uncommon (experienced in more than 1 in 1,000 but less than 1 in 100 patients):

• fainting
• at the injection site, skin reactions, phlebitis (inflammation of the vein) or swelling
• inflammation of the colon, small intestine; intestinal perforation
• blood clots

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or hospital pharmacist.

Keep out of the reach and sight of children.

Docetaxel Winthrop should not be used after the expiry date shown on the carton, blister pack and vials.

Do not store above 25°C or below 2°C.
Store in the original package in order to protect from light.

The premix solution should be used immediately after preparation. However the chemical and physical stability of the premix solution has been demonstrated for 8 hours when stored either between 2°C and 8°C or at room temperature (below 25°C).

The infusion solution should be used within 4 hours at room temperature (below 25°C).

What Docetaxel Winthrop concentrate vial contains

• The active substance is docetaxel. Each ml of docetaxel solution contains 40 mg of docetaxel anhydrous. One vial contains 80 mg/2 ml docetaxel.
• The other ingredients are polysorbate 80 and citric acid.

What solvent vial contains

13% (w/w) ethanol 95% in water for injections.

What Docetaxel Winthrop looks like and contents of the pack

Docetaxel Winthrop 80 mg/2 ml concentrate for solution for infusion is a clear viscous, yellow to brown-yellow solution.

Each blister pack contains:

• one single-dose vial of concentrate and,
• one single-dose vial of solvent.

Marketing Authorisation Holder

Aventis Pharma S.A.
20 avenue Raymond Aron
92165 Antony Cedex
France

Manufacturer

Aventis Pharma, Dagenham
Rainham Road South
Dagenham
Essex RM10 7XS
United Kingdom

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

BelgiëBelgiqueBelgien sanofi-aventis Belgium TélTel 32 02 710 54 00 LuxembourgLuxemburg sanofi-aventis Belgium TélTel 32 02 710 54 00 BelgiqueBelgien

sanofi-aventis Bulgaria EOOD . 359 02 970 53 00 Magyarország sanofi-aventis zrt., Magyarország Tel. 36 1 505 0050

eská republika sanofi-aventis, s.r.o. Tel 420 233 086 111 Malta sanofi-aventis Malta Ltd. Tel 356 21493022

Danmark sanofi-aventis Denmark AS Tlf 45 45 16 70 00 Nederland sanofi-aventis Netherlands B.V. Tel 31 0182 557 755

Deutschland Winthrop Arzneimittel GmbH Tel 49 0180 2 222010 Norge sanofi-aventis Norge AS Tlf 47 67 10 71 00

Eesti sanofi-aventis Estonia OÜ Tel 372 627 34 88 Österreich sanofi-aventis GmbH Tel 43 1 80 185 0

sanofi-aventis AEBE 30 210 900 16 00 Polska sanofi-aventis Sp. z o.o. Tel. 48 22 280 00 00

España sanofi-aventis, S.A. Tel 34 93 485 94 00 Portugal sanofi-aventis - Produtos Farmacêuticos, S.A. Tel 351 21 35 89 400

România sanofi-aventis România S.R.L. Tel 40 0 21 317 31 36 France sanofi-aventis France Tél 0 800 222 555 Appel depuis létranger 33 1 57 63 23 23

Ireland sanofi-aventis Ireland Ltd. Tel 353 0 1 403 56 00 Slovenija sanofi-aventis d.o.o. Tel 386 1 560 48 00

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika sanofi-aventis Pharma Slovakia s.r.o. Tel 421 2 33 100 100

Italia sanofi-aventis S.p.A. Tel 39 02 393 91 SuomiFinland sanofi-aventis Oy PuhTel 358 0 201 200 300

sanofi-aventis Cyprus Ltd. 357 22 871600 Sverige sanofi-aventis AB Tel 46 08 634 50 00

Latvija sanofi-aventis Latvia SIA Tel 371 67 33 24 51 United Kingdom sanofi-aventis Tel 44 0 1483 505 515

Lietuva

UAB sanofi-aventis Lietuva
Tel: +370 5 2755224

This leaflet was last approved in {MM/YYYY}.

The following information is intended for medical or healthcare professionals only:

PREPARATION GUIDE FOR USE WITH DOCETAXEL WINTHROP 80 mg/2 ml CONCENTRATE FOR SOLUTION FOR INFUSION AND SOLVENT FOR DOCETAXEL WINTHROP

It is important that you read the entire contents of this procedure prior to the preparation of either the Docetaxel Winthrop premix solution or the Docetaxel Winthrop infusion solution

1. FORMULATION

Docetaxel Winthrop 80 mg/2 ml concentrate for solution for infusion is a clear viscous, yellow to brown-yellow solution containing 40 mg/ml docetaxel (anhydrous) in polysorbate 80 and citric acid. The solvent for Docetaxel Winthrop is a 13% w/w solution of ethanol 95% in water for injections.

2. PRESENTATION

Docetaxel Winthrop is supplied as single-dose vials.

Each box contains one Docetaxel Winthrop vial (80 mg/2 ml) and one corresponding solvent for Docetaxel Winthrop vial in a blister pack.

Docetaxel Winthrop vials should be stored between 2°C and 25°C and protected from light. Docetaxel Winthrop should not be used after the expiry date shown on the carton, blister pack and vials.

2.1 Docetaxel Winthrop 80 mg/2 ml vial

• The Docetaxel Winthrop 80 mg/2 ml vial is a 15 ml clear glass vial with a red flip-off cap.
• The Docetaxel Winthrop 80 mg/2 ml vial contains a solution of docetaxel in polysorbate 80 at a concentration of 40 mg/ml.
• Each Docetaxel Winthrop 80 mg/2 ml vial contains 2.0 ml of a 40 mg/ml solution of docetaxel in polysorbate 80 (fill volume: 94.4 mg/2.36 ml). This volume has been established during the development of Docetaxel Winthrop to compensate for liquid loss during preparation of the premix (see section 4) due to foaming, adhesion to the walls of the vial and "dead-volume". This overfill ensures that after dilution with the entire contents of the accompanying solvent for Docetaxel Winthrop vial, there is a minimal extractable premix volume of 8 ml containing 10 mg/ml docetaxel which corresponds to the labelled amount of 80 mg/2 ml per vial.

2.2 Solvent for Docetaxel Winthrop 80 mg/2 ml vial

• The solvent for Docetaxel Winthrop 80 mg/2 ml vial is a 15 ml clear glass vial with a transparent colourless flip-off cap.
• The solvent for Docetaxel Winthrop composition is a 13% w/w solution of ethanol 95% in water for injections.
• Each solvent for Docetaxel Winthrop 80 mg/2 ml vial contains 7.33 ml. This volume has been established based on the fill volume of the Docetaxel Winthrop 80 mg/2 ml vial. The addition of the entire contents of the solvent vial to the contents of the Docetaxel Winthrop 80 mg/2 ml vial ensures a premix concentration of 10 mg/ml docetaxel.

3. RECOMMENDATIONS FOR THE SAFE HANDLING

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

If Docetaxel Winthrop concentrate, premix solution or infusion solution should come into contact with skin, wash immediately and thoroughly with soap and water. If Docetaxel Winthrop concentrate, premix solution or infusion solution should come into contact with mucous membranes, wash immediately and thoroughly with water.

4. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION

4.1 Preparation of the Docetaxel Winthroppremix solution (10 mg docetaxel/ml)

4.1.1 If the vials are stored under refrigeration, allow the required number of Docetaxel Winthrop boxes to stand at room temperature below 25C for 5 minutes.

4.1.2 Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for Docetaxel Winthrop vial by partially inverting the vial.

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Winthrop vial.

4.1.4 Remove the syringe and needle and mix manually by repeated inversions for at least 45 seconds. Do not shake.

4.1.5 Allow the premix vial to stand for 5 minutes at room temperature below 25C and then check that the solution is homogenous and clear foaming is normal even after 5 minutes due to the presence of polysorbate 80 in the formulation. The premix solution contains 10 mgml docetaxel and should be used immediately after preparation. However the chemical and physical stability of the premix solution has been demonstrated for 8 hours when stored either between 2C and 8C or at room temperature below 25C.

4.2 Preparation of the infusion solution

4.2.1 More than one premix vial may be necessary to obtain the required dose for the patient. Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding premix volume containing 10 mgml docetaxel from the appropriate number of premix vials using graduated syringes fitted with a needle. For example, a dose of 140 mg docetaxel would require 14 ml docetaxel premix solution.

4.2.2 Inject the required premix volume into a 250 ml infusion bag or bottle containing either 5 glucose solution or sodium chloride 9 mgml 0.9 solution for infusion. If a dose greater than 200 mg of docetaxel is required, use a larger volume of the infusion vehicle so that a concentration of 0.74 mgml docetaxel is not exceeded.

4.2.3 Mix the infusion bag or bottle manually using a rocking motion.

4.2.4 The Docetaxel Winthrop infusion solution should be used within 4 hours and should be

aseptically administered as a 1-hour infusion under room temperature (below 25°C) and normal lighting conditions.

4.2.5 As with all parenteral products, Docetaxel Winthrop premix solution and infusion solution should be visually inspected prior to use, solutions containing a precipitate should be discarded.

5. DISPOSAL

All materials that have been utilised for dilution and administration should be disposed of according to standard procedures.