Docefrez 80 mg powder and solvent for concentrate for solutionfor infusion

Docefrez contains the active substance docetaxel. Docetaxel, derived from yew-tree needles, belongs to a group of anti-cancer medicines called taxanes.

Docefrez is used, either alone or in combination with other medicines, for the treatment of the following kinds of cancer:

• advanced breast cancer, alone or with doxorubicin, or trastuzumab, or capecitabine
• early breast cancer with or without lymph node involvement, with doxorubicin and cyclophosphamide
• non-small cell lung cancer (NSCLC), alone or with cisplatin
• prostate cancer, with prednisone or prednisolone
• metastatic gastric cancer, with cisplatin and 5-fluorouracil
• head and neck cancer, with cisplatin and 5-fluorouracil.

Do not use Docefrez

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

Take special care with Docefrez

Tell your doctor if you have:

• heart problems
• liver problems
• kidney problems

Before each Docefrez dose, you will have blood tests to check that your blood cell counts and liver function are adequate.

Using other medicines

99

Please tell your doctor or nurse if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
In particular, tell your doctor if you are using medicines containing any of the following active substances:

• ritonavir and other protease inhibitors, used to treat HIV infection/AIDS
• ketoconazole and itraconazole, used to treat fungal infections
• ciclosporin, used to suppress your immune system (e.g. after transplants)
• erythromycin, antibiotic used for bacterial infections

Pregnancy

Ask your doctor for advice before being given any medicine.

You must not use Docefrez 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 Docefrez 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 Docefrez 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 using Docefrez.

Driving and using machines

There are no studies on the effects of Docefrez on the ability to drive and use machines. However, given that it can cause dizziness, tiredness and fainting, you should not drive or use machines if you experience any of these side effects.

Important information about some of the ingredients of Docefrez

The solvent contains small amounts of ethanol (alcohol), less than 100 mg per dose.

Your doctor will calculate your dose according to your body surface area in square metres (depends on weight and height) and your general condition.

You will be given Docefrez by a healthcare professional in the hospital. It is administered through a drip into a vein (intravenous infusion) for about one hour. You should usually receive your Docefrez infusion every three weeks.

Your doctor may change the dose and/or frequency of administration depending on the results of your blood tests, your general condition and the occurence of certain side effects. Tell your doctor or nurse if you have fever, diarrhoea, sores in the mouth, feeling of numbness or pins and needles.

Your doctor may prescribe you other medicines before or during treatment with Docefrez:

• to minimise allergic reactions and fluid retention (pre-treatment with an oral corticoid such asdexamethasone),
• to stimulate your bone marrow to produce more blood cells (e.g. filgrastim).

If you have any further questions on the use of this medicine, ask your doctor or nurse.

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

Side effects may occur with certain frequencies, which are defined as follows:

• 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 frequent side effects of Docefrez, when given alone, are decrease in the number of red blood cells or white blood cells, alopecia, nausea, vomiting, sores in the mouth, diarrhoea and tiredness (all very common).

Tell your doctor or nurse immediately during or shortly after the infusion, you notice any of the following symptoms of allergic reactions (very common):

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

Other very common side effects:

• fever*: tell your doctor or nurse immediately
• infections, including pneumonia and blood poisoning
• decreased number of red bloods cells (anaemia, with symptoms of such as paleness, weakness)
• decreased number of white blood cells (may make you more prone to infections)
• decreased number of platelets (increased risk of unexpected bleedings)
• allergic reactions (see above)
• headache* , insomnia*
• feeling of numbness or pins and needles, taste disturbances (due to nerve damage)
• pain in the joints or muscles
• inflammation of the eye or increased watering of the eyes
• swelling caused by fluids from the lymph nodes spreading to uncommon places
• swelling of the hands, feet, legs
• shortness of breath, cough*
• dripping or running nose; inflammation of the throat and nose*
• bleeding from the nose
• sores in the mouth
• nausea, vomiting, indigestion*, bellyache*
• diarrhoea, constipation*
• hair loss
• redness and swelling of the palms of your hands or soles of your feet which may cause 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*
• tiredness, pain, flu-like symptoms*
• loss of appetite (anorexia), weight gain or loss*

Common side effects:

• fungal infection of the mouth (oral candidiasis)
• dehydration
• dizziness, hearing impaired
• decrease in blood pressure (hypotension), heart failure; irregular heart beat (arrhythmia)
• dry mouth, difficulty or painful swallowing, inflammation of the gullet (oesophagitis)
• bleeding
• raised liver enzymes (in blood tests)

Uncommon side effects:

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

When Docefrez is given in combination with other anti-cancer medicines, the frequency or severity of some side effects may increase. Side effects marked with ?*? have been reported when Docefrez was given in combination.

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 nurse.

Keep out of the reach and sight of children.

Do not use Docefrez after the expiry date which is stated on the carton and vial after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2ºC - 8ºC).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

The reconstituted solution should be used immediately after preparation.

Chemical and physical in-use stability of the reconstituted solution has been demonstrated for 8 hours when stored either between 2°C and 8°C or below 25°C and for the final solution for infusion for 4 hours at room temperature.

The infusion should be used within 4 hours below 25 ºC.

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 Docefrez contains

• The active substance is docetaxel. [Docefrez 80 mg powder and solvent for concentrate for solution for infusion] Each vial contains

80 mg docetaxel (anhydrous). After reconstitution, 1 ml of concentrate contains 24 mg docetaxel. The solvent contains 35.4% w/w ethanol and polysorbate 80.

What Docefrez looks like and contents of the pack

Docefrez 80 mg powder and solvent for concentrate for solution for infusion:
Powder vial: Docefrez is a white lyophilised powder, supplied in a colourless glass vial with a grey non-latex rubber stopper and a red aluminium seal.
Solvent vial: 4 ml clear, colourless solution supplied in a glass vial with a grey non-latex rubber stopper and a brown aluminium seal.

Each pack contains: 1 powder vial and 1 solvent vial.

Marketing Authorisation Holder and Manufacturer

Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands
tel. +31 (0)23 568 5501

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

BelgiëBelgiqueBelgien Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 LuxembourgLuxemburg Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 Magyarország Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

eská republika Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 Malta Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

Danmark Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 Nederland Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

Deutschland SUN Pharmaceuticals Germany GMBH Kandelstrasse 7 Norge Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 103

79199 Kirchzarten Germany tel. 49 0 7661 90 91 58-0 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

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Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 Polska Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

Portugal Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 España SUN Pharmaceuticals Spain S.L. CBobinadora 1-5 Planta 1a Local 13 Mataro, 08302 Barcelona Spain tel. 34 93 798 02 85

France SUN Pharmaceuticals France 34, Rue Jean Mermoz 78600 Maisons Laffitte France tel. 33 6 48 27 05 59 România Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

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Italia SUN Pharmaceuticals Italia S.R.L. Via Luigi Rizzo, 8 I-20151 Milano Italy tel. 39 02 33 49 07 93 SuomiFinland Sun Pharmaceutical Industries Europe B.V. Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

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Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501 Polarisavenue 87 2132 JH Hoofddorp The Netherlands tel. 31 023 568 5501

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Lietuva
Sun Pharmaceutical Industries Europe B.V.
Polarisavenue 87
2132 JH Hoofddorp
The Netherlands
tel. +31 (0)23 568 5501

This leaflet was last approved in

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

PREPARATION GUIDE FOR USE WITH DOCEFREZ 80 MG, POWDER AND SOLVENT FOR

CONCENTRATE FOR SOLUTION FOR INFUSION

It is important that you read the entire contents of this procedure prior to the preparation of either the

Docefrez reconstituted solution or the Docefrez solution for infusion.

1. FORMULATION

The Docefrez 80 mg powder is a white to off white lyophilised powder containing 80 mg (plus 18% overfill:

94.4 mg) of docetaxel (anhydrous). The solvent for Docefrez is a solution of 35.4% w/w Ethanol

(anhydrous) in Polysorbate 80. After reconstitution, 1 ml of concentrate contains 24 mg docetaxel

2. PRESENTATION

Docefrez is supplied as single-dose vials.

Each pack of Docefrez 80 mg powder for concentrate for solution for infusion contains one single-dose vial of docetaxel (anhydrous) (80 mg with corresponding fill of 94.4 mg as lyophilised powder) and a corresponding single-dose vial with 4.0 ml of solvent consisting of 35.4% (w/w) of Ethanol (anhydrous) in Polysorbate 80.

The overfill ensures that after dilution with the entire extractable volume of the accompanying solvent vial for Docefrez, there is a minimal extractable reconstituted solution of 3.36 ml containing 80 mg docetaxel (anhydrous).

Docefrez vials should be stored in a refrigerator. Do not freeze. Docefrez should not be used after the expiry

date shown on the carton and vials.

2.1 Docefrez 80 mg powder vials

Docefrez 80 mg, Powder for Concentrate for Solution for Infusion

• The Docefrez 80 mg vial contains a white to off white lyophilised powder in a 15 ml tubular colourless glass vial with 20 mm grey rubber stopper and sealed with red flip-off aluminium seal.
• Each vial of Docefrez 80 mg contains 80 mg docetaxel (anhydrous) (plus 18% overfill: 94.4 mg docetaxel).

2.2 Docefrez 80 mg solvent vials

The solvent for Docefrez is 35.4% w/w Ethanol in Polysorbate 80.

Solvent for Docefrez 80 mg, Powder for Solution for Infusion

• The solvent vial for Docefrez 80 mg is a 5 ml colourless type 1 tubular glass vial with 20 mm grey bromobutyl rubber stopper sealed with 20 mm brown flip-off aluminium seal.
• Each solvent vial of Docefrez 80 mg contains 4 ml of 35.4% w/w ethanol in Polysorbate 80.

The overfills are included to ensure that, after dilution with the entire volume of the accompanying solvent vial, the minimum extractable volume of reconstituted concentrate containing 20 mg or 80 mg docetaxel, respectively, may be withdrawn from the vial.

3. RECOMMENDATIONS FOR THE SAFE HANDLING

Docefrez is an antineoplastic agent and, as with other potentially toxic compounds, caution should be

exercised when handling it and preparing Docefrez solutions. The use of gloves is recommended.

If Docefrez powder, reconstituted solution or infusion solution should come into contact with skin, wash

immediately and thoroughly with soap and water. If Docefrez powder, reconstituted solution or infusion

solution should come into contact with mucous membranes, wash immediately and thoroughly with water.

4. PREPARATION FOR INTRAVENOUS ADMINISTRATION

Do not use any PVC equipment or device. Docefrez is incompatible with PVC equipment or devices.

Docefrez powder and solvent for concentrate for solution for infusion is for single use only.

4.1 Reconstitution of Docefrez Powder for Solution for Infusion

4.1.1 Allow the required number of Docefrez boxes which are stored in a refrigerator, to stand at room

temperature (below 25ºC) for 5 minutes.

4.1.2 Using a syringe fitted with a needle, aseptically withdraw the entire contents of the solvent for

Docefrez vial by partially inverting the vial.

4.1.3 Inject the entire contents of the syringe into the corresponding Docefrez vial.

4.1.4 Remove the syringe and needle and shake well for complete solubilisation of powder.

4.1.5 Allow the reconstituted vial to stand for 5 minutes at room temperature (below 25ºC) and then check

that the solution is homogenous and clear.

The reconstituted solution contains approximately 24 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 vial of reconstituted solution 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

volume from the appropriate number of reconstituted solutions using graduated syringes fitted with a needle.

For example, a dose of 140 mg docetaxel would require one 80 mg and three 20 mg packs. The reconstituted

solution contains ~ 24 mg/ml docetaxel, corresponding with an extractable volume of approximately

20 mg/0.84 ml and 80 mg/3.36 ml.

4.2.2 Inject the required volume of reconstituted solution into a 250 ml infusion bag or bottle 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 Docefrez 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, Docefrez reconstituted solution and solution for infusion 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 and any unused product should be

disposed of in accordance with local requirements.