Docetaxel Teva 80 mg concentrate and solvent for solution forinfusion

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

Docetaxel Teva 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 Teva could 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, Docetaxel Teva could be administered in combination with doxorubicin and cyclophosphamide.
• For the treatment of lung cancer, Docetaxel Teva could be administered either alone or in combination with cisplatin.
• For the treatment of prostate cancer, Docetaxel Teva is administered in combination with prednisone or prednisolone.
• For the treatment of metastatic gastric cancer, Docetaxel Teva is administered in combination with cisplatin and 5-fluorouracil.
• For the treatment of head and neck cancer, Docetaxel Teva is administered in combination with cisplatin and 5-fluorouracil.

You must NOT be given Docetaxel Teva if

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

Take special care with Docetaxel Teva

Before each treatment with Docetaxel Teva, you will have blood tests to check that you have enough blood cells and sufficient liver function to receive Docetaxel Teva. In case of white blood cell 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 Teva 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 Teva 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 medicines, including medicines obtained without a prescription. This is because Docetaxel Teva or other medicines 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 Teva 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 you must use an effective contraception during therapy because Docetaxel Teva 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 Teva 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 Teva.

Driving and using machines

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

Docetaxel Teva 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 Teva 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 Docetaxel Teva. 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 Teva 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 Teva alone are: decrease in the number of red blood cells or white blood cells, hair loss, nausea, vomiting, sores in the mouth, diarrhoea and tiredness.

The severity of adverse events of Docetaxel Teva may be increased when Docetaxel Teva 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 Teva 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 colour 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
• oesophagatis
• 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 Teva should not be used after the expiry date which is stated on the carton and vials.

Do not store above 25°C.
Do not freeze.

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).

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Docetaxel Teva concentrate vial contains:

• The active substance is docetaxel. Each vial of Docetaxel Teva concentrate contains 80 mg of docetaxel. Each ml of concentrate contains 27.73 mg docetaxel.
• The other ingredients are polysorbate 80 and 25.1% (w/w) anhydrous ethanol.

What the solvent vial contains:

Water for injections.

What Docetaxel Teva looks like and contents of the pack:

Docetaxel Teva concentrate for solution for infusion is a clear viscous, yellow to brown-yellow solution.

Each carton contains:

• one 15 ml clear glass vial with a flip-off cap containing 2.88 ml concentrate and,
• one 15 ml clear glass vial with a flip-off cap containing 5.12 ml of solvent.

Marketing Authorisation Holder

Teva Pharma B.V.
Computerweg 10
3542 DR Utrecht
The Netherlands

Manufacturer:

Pharmachemie B.V.
Swensweg 5
PO Box 552
2003 RN Haarlem, The Netherlands

TEVA Pharmaceutical Works Private Limited Company

Táncsics Mihály út 82

H-2100 Gödöll-,

Hungary

Teva Kutno SA

Sienkiewicza 25;

99-300 Kutno

Poland

Teva Czech Industries s.r.o

Ostravská 29
-.p. 305

747 70 Opava-Komárov

Czech Republic

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Teva Pharma Belgium N.V.S.A. TelTél 32 3 820 73 73 LuxembourgLuxemburg Teva Pharma Belgium S.A. Tél 32 3 820 73 73

Te 359 2 489 95 82 Magyarország Teva Magyarország Zrt Tel. 36 1 288 64 00

eská republika Teva Pharmaceuticals CR, s.r.o. Tel 420 251 007 111 Malta Teva .. el 30 210 72 79 099

Danmark Teva Denmark AS Tlf 45 44 98 55 11 Nederland Teva Nederland B.V. Tel 31 0 800 0228400

Deutschland Teva Generics GmbH Tel 49 351 834 0 Norge Teva Sweden AB Tlf 46 42 12 11 00

Österreich Teva Generics GmbH Tel 49 351 834 0 Eesti Teva Eesti esindus UAB Sicor Biotech Eesti filiaal Tel 372 611 2409

Teva .. 30 210 72 79 099 Polska Teva Pharmaceuticals Polska Sp. z o.o. Tel. 48 22 345 93 00

España Teva Genéricos Española, S.L.U. Tél 34 91 387 32 80 Portugal Teva Pharma - Produtos Farmacêuticos Lda Tel 351 214 235 910

France Teva Santé Tél 33 1 55 91 7800 România Teva Pharmaceuticals S.R.L Tel 4021 212 08 90

Ireland Teva Pharmaceuticals Ireland Tel 353 042 9395 892 Slovenija Pliva Ljubljana d.o.o. Tel 386 1 58 90 390

Ísland Teva UK Limited Sími 44 1323 501 111. Slovenská republika Teva Pharmaceuticals Slovakia s.r.o. Tel 421 2 5726 7911

Italia Teva Italia S.r.l. Tel 39 0289179805 SuomiFinland Teva Sweden AB PuhTel 46 42 12 11 00

Teva .. 30 210 72 79 099 Sverige Teva Sweden AB Tel 46 42 12 11 00

Latvija UAB Sicor Biotech filile Latvij Tel 371 67 784 980 United Kingdom Teva UK Limited Tel 44 1323 501 111

Lietuva

UAB ?Sicor Biotech?
Tel: +370 5 266 02 03

This leaflet was last approved in { MM/YYYY}

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

PREPARATION GUIDE FOR USE WITH DOCETAXEL TEVA 80 mg CONCENTRATE AND SOLVENT FOR SOLUTION FOR INFUSION
__________________________________________________________________________

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

1. FORMULATION

Docetaxel Teva 80 mg concentrate for solution for infusion is a clear viscous, yellow to brown-yellow solution containing 27.73 mg/ml docetaxel (anhydrous) in polysorbate 80. The solvent for Docetaxel Teva is water for injections.

2. PRESENTATION

Docetaxel Teva is supplied as single-dose vials.

Each box contains one Docetaxel Teva vial (80 mg) and one corresponding solvent for Docetaxel Teva vial in a carton.

Docetaxel Teva vials should not be stored above 25°C and should be protected from light. Docetaxel Teva should not be used after the expiry date shown on the carton and vials.

2.1 Docetaxel 80 mg vial:

• The Docetaxel 80 mg vial is a 15 ml clear glass vial with a bromobutyl rubber stopper and a flip-off cap.
• The Docetaxel 80 mg vial contains a solution of docetaxel in polysorbate 80 at a concentration of 27.73 mg/ml.

Each vial contains 80 mg/2.88 ml of a 27.73 mg/ml solution of docetaxel in polysorbate 80 (fill volume: 94.4 mg/3.40 ml). This fill volume has been established during the development of docetaxel to compensate for liquid loss during preparation of the premix 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 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 per vial.

2.2 Solvent for Docetaxel 80 mg vial:

• The solvent for Docetaxel 80 mg vial is a 15 ml clear glass vial with a bromobutyl rubber stopper and a flip-off cap.
• The solvent for Docetaxel composition is water for injections.

Each solvent vial contains 5.12 ml of water for injections (fill volume: 6.29 ml). The addition of the entire contents of the solvent vial to the contents of the docetaxel 80 mg concentrate for solution for infusion vial ensures a premix concentration of 10 mg/ml docetaxel.

3. RECOMMENDATIONS FOR THE SAFE HANDLING

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

If Docetaxel Teva concentrate, premix solution or infusion solution should come into contact with skin, wash immediately and thoroughly with soap and water. If Docetaxel Teva 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 Teva premix solution (10 mg docetaxel/ml)

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

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

4.1.3 Inject the entire contents of the syringe into the corresponding Docetaxel Teva 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 25°C) 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 mg/ml 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 +2°C and +8°C or at room temperature (below 25°C).

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 mg/ml 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 non-PVC infusion bag containing either 5%
glucose solution or sodium chloride 9 mg/ml (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 mg/ml docetaxel is not exceeded.

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

4.2.4 The Docetaxel Teva 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 Teva 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.