Temozolomide Teva 180 mg hard capsules

Temozolomide Teva is an antitumour agent.

Temozolomide Teva is used for the treatment of patients with specific forms of brain tumours:

• newly-diagnosed glioblastoma multiforme. Temozolomide Teva is first used together with radiotherapy (concomitant phase of treatment) and after that alone (monotherapy phase of treatment).
• malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temozolomide Teva is used in these tumours if they return or get worse after standard treatment.

Do not take Temozolomide Teva

• if you are allergic (hypersensitive) to temozolomide or any of the other ingredients of Temozolomide Teva.
• if you have had an allergic reaction to dacarbazine (an anticancer medicine sometimes called DTIC). Signs of allergic reaction include feeling itchy, breathlessness or wheezing, swelling of the face, lips, tongue or throat.
• if certain kinds of blood cells are severely reduced (myelosuppression), such as your white blood cell count and platelet count. These blood cells are important for fighting infection and for proper blood clotting. Your doctor will check your blood to make sure you have enough of these cells before you begin treatment.

Take special care with Temozolomide Teva

• you should be observed closely for the development of a serious form of pneumonia called Pneumocystis carinii pneumonia (PCP) . If you are a newly-diagnosed patient (glioblastoma multiforme) you may be receiving Temozolomide Teva for 42 days in combination with radiotherapy. In this case, your doctor will also prescribe medicine to help you prevent this type of pneumonia (PCP).
• if you have low counts of red blood cells (anaemia), white blood cells and platelets, or blood clotting problems before starting the treatment, or if you develop them during treatment. Your doctor may decide to reduce the dose, interrupt, stop or change your treatment. You may also

need other treatments. In some cases, it may be necessary to stop treatment with Temozolomide Teva

• Your blood will be tested frequently during treatment to monitor the side effects of Temozolomide Teva on your blood cells.
• you may have a small risk of other changes in blood cells, including leukaemia.
• if you have nausea (feeling sick in your stomach) and/or vomiting which are very common side effects of Temozolomide Teva (see section 4 ?Possible side effects?), your doctor may prescribe you a medicine (an anti-emetic) to help prevent vomiting.
• If you vomit frequently before or during treatment, ask your doctor about the best time to take Temozolomide Teva until the vomiting is under control. If you vomit after taking your dose, do not take a second dose on the same day.
• if you develop fever or symptoms of an infection contact your doctor immediately.
• do not open, crush or chew the capsules. If a capsule is damaged, avoid contact of the powder with your skin, eyes or nose. Avoid inhaling the powder. If you accidentally get some in your eyes or nose, flush the area with water.
• if you are older than 70 years of age, you might be more prone to infection, bruising or bleeding.
• if you have liver or kidney problems, your dose of Temozolomide Teva may need to be adjusted.

Children
Due to lack of experience, Temozolomide Teva should not be used in children younger than 3 years.

Infertility
Temozolomide Teva may cause permanent infertility. Male patients should use effective contraceptions and not father a child for up to 6 months after stopping treatment. It is recommended to seek advice on conservation of sperm prior to treatment.

Using other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Tell your doctor if you are pregnant, think you might be or are planning to get pregnant. You must not be treated with Temozolomide Teva during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be taken by both male and female patients who are taking Temozolomide Teva (see also ?Take special care with Temozolomide Teva, Infertility? above).

You should stop breast-feeding while receiving treatment with Temozolomide Teva.

Driving and using machines

Temozolomide Teva may make you feel tired or sleepy. In this case, do not drive or use any tools or machines.

Important information about some of the ingredients of Temozolomide Teva

Temozolomide Teva hard capsules contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Dosage and duration of treatment

Your doctor will work out your dose of Temozolomide Teva. This is based on your size (height and weight) and if you have a recurrent tumour and have had chemotherapy treatment in the past. You may be given other medicines (anti-emetics) to take before and/or after taking Temozolomide Teva to prevent or control nausea and vomiting.

Patients with newly-diagnosed glioblastoma multiforme If you are a newly-diagnosed patient, treatment will occur in two phases:

• treatment together with radiotherapy (concomitant phase) first
• followed by treatment with only Temozolomide Teva (monotherapy phase).

Concomitant phase
During the concomitant phase, your doctor will start Temozolomide Teva at a dose of 75 mg/m² (usual dose). You will take this dose every day for 42 days (up to 49 days) in combination with radiotherapy. The Temozolomide Teva dose may be delayed or stopped, depending on you blood counts and how you tolerate your medicine during the concomitant phase.
Once the radiotherapy is completed, you will interrupt treatment for 4 weeks. This will give your body a chance to recover.
Then, you will start the monotherapy phase.

Monotherapy phase
During the monotherapy phase, the dose and way you take Temozolomide Teva will be different. Your doctor will work out your exact dose. There may be up to 6 treatment periods (cycles). Each one lasts 28 days. You will take your new dose of Temozolomide Teva alone once daily for the first 5 days (?dosing days?) of each cycle. The first dose will be 150 mg/m². Then you will have 23 days without Temozolomide Teva. This adds up to a 28-day treatment cycle.

After Day 28, the next cycle will begin. You will again take Temozolomide Teva once daily for 5 days followed by 23 days without Temozolomide Teva. The Temozolomide Teva dose may be adjusted, delayed or stopped depending on your blood counts and how you tolerate your medicine during each treatment cycle.

Patients with tumours that have returned or worsened (malignant glioma, such as glioblastoma

multiforme or anaplastic astrocytoma) taking Temozolomide Teva only

A treatment cycle with Temozolomide Teva lasts 28 days.
You will take Temozolomide Teva alone once daily for the first 5 days. This daily dose depends on whether or not you have received chemotherapy before.

If you have not been previously treated with chemotherapy, your first dose of Temozolomide Teva will be 200 mg/m² once daily for the first 5 days. If you have been previously treated with chemotherapy, your first dose of Temozolomide Teva will be 150 mg/m² once daily for the first 5 days.
Then, you will have 23 days without Temozolomide Teva. This adds up to a 28-day treatment cycle.

After Day 28, the next cycle will begin. You will again receive Temozolomide Teva once daily for 5 days, followed by 23 days without Temozolomide Teva.

Before each new treatment cycle, your blood will be tested to see if the Temozolomide Teva dose needs to be adjusted. Depending on your blood test results, your doctor may adjust your dose for the next cycle.

Administration

Take your prescribed dose of Temozolomide Teva once a day, preferably at the same time each day.

Take the capsules on an empty stomach; for example, at least one hour before you plan to eat breakfast.

Swallow the capsule(s) whole with a glass of water. Do not open or chew the capsules. If a capsule is damaged, avoid contact with your skin, eyes or nose. If it occurs, wash the affected area thoroughly.

Depending on the prescribed dose, you may have to take more than one capsule together, eventually with different strengths (content of active substance, in mg). The colour and marking of the capsule is different for each strength (see table below).

Strength Colourmarking Temozolomide Teva 5 mg two stripes in green ink on the cap and T 5 mg in green ink on the body Temozolomide Teva 20 mg two stripes in orange ink on the cap and T 20 mg in orange ink on the body Temozolomide Teva 100 mg two stripes in pink ink on the cap and T 100 mg in pink ink on the body Temozolomide Teva 140 mg two stripes in blue ink on the cap and T 140 mg in blue ink on the body Temozolomide Teva 180 mg two stripes in red ink on the cap and T 180 mg in red ink on the body Temozolomide Teva 250 mg two stripes in black ink on the cap and T 250 mg in black ink on the body

You should make sure you fully understand and remember the following :

• how many capsules you need to take every dosing day. Ask your doctor or pharmacist to write it down (including the colour).
• which days are your dosing days. Review the dose with your doctor each time you start a new cycle, since it may be different from the last cycle.

Always take Temozolomide Teva exactly as your doctor has told you. It is very important to check with your doctor or pharmacist if you are not sure. Errors in how you take this medicine may have serious health consequences.

If you take more Temozolomide Teva than you should

If you accidentally take more Temozolomide Teva capsules than you were told to, contact your doctor or pharmacist immediately.

If you forget to take Temozolomide Teva

Take the missed dose as soon as possible during the same day. If a full day has gone by, check with your doctor. Do not take a double dose to make up for a forgotten dose, unless your doctor tells you to do so.

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

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

Contact your doctorimmediatelyif you have any of the following:

• a severe allergic (hypersensitive) reaction (hives, wheezing or other breathing difficulty),
• uncontrolled bleeding,
• seizures (convulsions),
• fever,
• a severe headache that does not go away.

Temozolomide Teva treatment can cause a reduction in certain kinds of blood cells. This may cause you to have increased bruising or bleeding, anaemia (a shortage of red blood cells), fever, and reduced resistance to infections. The reduction in blood cell counts is usually short-lived. In some cases, it may be prolonged and may lead to a very severe form of anaemia (aplastic anaemia). Your doctor will monitor your blood regularly for any changes, and will decide if any specific treatment is needed. In some cases, your Temozolomide Teva dose will be reduced or treatment stopped.

Side effects from clinical studies:

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.

Temozolomide Teva in combination treatment with radiotherapy in newly-diagnosed glioblastoma

Patients receiving Temozolomide Teva in combination with radiotherapy may experience different side effects than patients taking Temozolomide Teva alone. The following side effects may occur, and may require medical attention.

Very common: loss of appetite, headache, constipation (difficulty passing stools), nausea (feeling sick in your stomach), vomiting, rash, hair loss, tiredness.

Common: oral infections, wound infection, reduced number of blood cells (neutropenia, thrombocytopenia, lymphopenia, leukopenia), increased sugar in the blood, loss of weight, change in mental status or alertness, anxiety/depression, sleepiness, difficulty speaking, impaired balance, dizziness, confusion, forgetfulness, difficulty concentrating, inability to fall asleep or stay asleep, tingling sensation, bruising, shaking, abnormal or blurry vision, double vision, hearing impairment, shortness of breath, cough, blood clot in the legs, fluid retention, swollen legs, diarrhoea, stomach or abdominal pain, heartburn, upset stomach, difficulty swallowing, dry mouth, skin irritation or redness, dry skin, itching, muscle weakness, painful joints, muscle aches and pains, frequent urination, difficulty with holding your urine, allergic reaction, fever, radiation injury, face swelling, pain, abnormal taste, abnormal liver function tests.

Uncommon: flu-like symptoms, red spots under the skin, appearance of a swollen face or muscle weakness, low potassium level in the blood, weight gain, mood swings, hallucination and memory impairment, partial paralysis, impaired coordination, difficulty swallowing, impaired sensations, partial loss of vision, dry or painful eyes, deafness, infection of the middle ear, ringing in the ears, earache, palpitations (when you can feel your heart beat), blood clot in the lung, high blood pressure, pneumonia, inflammation of your sinuses, bronchitis, a cold or the flu, swollen stomach, difficulty controlling your bowel movements, haemorrhoids, peeling skin, increased skin sensitivity to sunlight, change in skin colour, increased sweating, muscle damage, back pain, difficulty in urinating, vaginal bleeding, sexual impotence, absent or heavy menstrual periods, vaginal irritation, breast pain, hot flushes, shivering, discolouration of your tongue, change in your sense of smell, thirst, tooth disorder.

Temozolomide Teva monotherapy in recurrent or progressive glioma

The following side effects may occur, and may require medical attention.

Very common: reduced number of blood cells (neutropenia or lymphopenia, thrombocytopenia), loss of appetite, headache, vomiting, nausea (feeling sick in your stomach), constipation (difficulty passing stools).

Common: loss of weight, tiredness, dizziness, tingling sensation, shortness of breath, diarrhoea, abdominal pain, upset stomach, rash, itching, hair loss, fever, weakness, shivering, feeling unwell, pain, change in taste.

Uncommon: reduced number of blood cell counts (pancytopenia, anaemia, leukopenia).

Rare: cough, infections including pneumonia.

Very rare: skin redness, urticaria (hives), skin eruption, allergic reactions.

Other side effects

Very rare cases of severe rash with skin swelling, including on the palms of the hands and soles of the feet, or painful reddening of the skin and/or blisters on the body or in the mouth have been observed. Tell your doctor immediately if this occurs.

Very rare cases of lung side effects have been observed with Temozolomide Teva. Patients usually present with shortness of breath and cough. Tell your doctor if you notice any of these symptoms.

In very rare cases, patients taking Temozolomide Teva and medicines like it may have a small risk of developing secondary cancers, including leukaemia.

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 pharmacist.

Keep out of the reach and sight of children, preferably in a locked cupboard. Accidental ingestion can be lethal for children.

Do not use Temozolomide Teva after the expiry date which is stated on the label and carton. The expiry date refers to the last day of that month.

Store in the original package.
Keep the bottle tightly closed in order to protect from moisture.

Tell your pharmacist if you notice any change in the appearance of the capsules.

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

What Temozolomide Teva contains

• The active substance is temozolomide. Each capsule contains 180 mg temozolomide.
• The other ingredients are:
• capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• capsule shell (including printing ink): gelatin, titanium dioxide (E171), shellac, propylene glycol, red iron oxide (E172)

What Temozolomide Teva looks like and contents of the pack

Temozolomide Teva180 mg hard capsules have a white opaque body and cap with two stripes in red ink on the cap and with ?T 180 mg? in red ink on the body.

The hard capsules for oral use are dispensed in amber glass bottles containing 5 or 20 capsules.

Not all pack sizes may be marketed.

Marketing Authorization Holder

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

Manufacturer

NerPharMa S.r.l.
Viale Pasteur, 10
20014 Nerviano (MI)
Italy

Pharmachemie BV.

Swensweg 5

2031 GA Haarlem

The Netherlands

TEVA Santé SA

Rue Bellocier

89107 Sens

France

Haupt Pharma Amareg GmbH

Donaustaufer Stra?e 378

93055 Regensburg

Germany

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

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