Tezolamet 20 mg, harde capsules

Tezolamet contains a medicine called temozolomide. This medicine is an antitumour agent.

Tezolamet is used for the treatment with specific forms of brain tumours:

• in adults with newly-diagnosed glioblastoma multiforme. Tezolamet is first used together with radiotherapy (concomitant phase of treatment) and after that alone (monotherapy phase of treatment).
• in children 3 years and older and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Tezolamet is used in these tumours if they return or get worse after standard treatment.

Do not use Tezolamet

• if you are allergic to temozolomide or any of the other ingredients of this medicine (listed in section 6).
• 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.

Warnings and precautionsTalk to your doctor, pharmacist or nurse before taking Tezolamet,

• as you should be observed closely for the development of a serious form of chest infection called Pneumocystis carinii pneumonia (PCP). If you are a newly- diagnosed patient (glioblastoma multiforme) you may be receiving Tezolamet 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 Tezolamet. Your blood will be tested frequently during treatment to monitor the side effects of Tezolamet on your blood cells.
• as 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 Tezolamet (see section 4), 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 Tezolamet 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.
• 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 Tezolamet may need to be adjusted.

Children and adolescents

Do not give this medicine to children under the age of 3 years because it has not been studied. There is limited information in patients over 3 years of age who have taken Tezolamet.

Other medicines and Tezolamet

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

Pregnancy, breast-feeding and fertility

If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. This is because you must not be treated with Tezolamet during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be taken by both male and female patients who are taking Tezolamet (see also “Male fertility” below).

You should stop breast-feeding while receiving treatment with Tezolamet.

Male fertility

Tezolamet 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.

Driving and using machines

Tezolamet may make you feel tired or sleepy. In this case, do not drive or use any tools or machines or cycle until you see how this medicine affects you (see section 4).

Tezolamet contains lactose

Tezolamet hard capsules contain lactose (a kind of sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Dosage and duration of treatment

Your doctor will work out your dose of Tezolamet. 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 Tezolamet 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 Tezolamet (monotherapy phase).

During the concomitant phase, your doctor will start Tezolamet 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 Tezolamet dose may be delayed or stopped, depending on your 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.

During the monotherapy phase, the dose and way you take Tezolamet 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 Tezolamet 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 Tezolamet. This adds up to a 28- day treatment cycle. After Day 28, the next cycle will begin. You will again take Tezolamet once daily for 5 days followed by 23 days without Tezolamet. The Tezolamet 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 Tezolamet only:

A treatment cycle with Tezolamet lasts 28 days. You will take Tezolamet 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 Tezolamet will be 200 mg/m2 once daily for the first 5 days. If you have been previously treated with chemotherapy, your first dose of Tezolamet will be 150 mg/m2 once daily for the first 5 days. Then, you will have 23 days without Tezolamet. This adds up to a 28-day treatment cycle.

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

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

How to take Tezolamet

Take your prescribed dose of Tezolamet 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 crush or chew the capsules. If a capsule is damaged, avoid contact of the powder with your skin, eyes or nose. If you accidentally get some in your eyes or nose, flush the area with water.

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 of the capsule cap is different for each strength (see in the table below).

Strength	Colour of the cap
Tezolamet 5 mg hard capsules	Green
Tezolamet 20 mg hard capsules	Orange
Tezolamet 100 mg hard capsules	Purple
Tezolamet 140 mg hard capsules	Blue
Tezolamet 180 mg hard capsules	Chocolate brown
Tezolamet 250 mg hard capsules	White

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 Tezolamet 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 Tezolamet than you should

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

If you forget to take Tezolamet

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, pharmacist or nurse.

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

Contact your doctor immediately if 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.

Tezolamet 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 Tezolamet dose will be reduced or treatment stopped.

Side effects from clinical studies:

Tezolamet in combination treatment with radiotherapy in newly-diagnosed glioblastoma

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

Very common (may affect more than 1 in 10 people): loss of appetite, headache, constipation (difficulty passing stools), nausea (feeling sick in your stomach), vomiting, rash, hair loss, tiredness.

Common (may affect up to 1 in 10 people): 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 (may affect up to 1 in 100 people): 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, agitation, 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, cerebral hemorrhage (stroke), 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.

Tezolamet monotherapy in recurrent or progressive glioma

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

Very common(may affect more than 1 in 10 people): 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(may affect up to 1 in 10 people): 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 (may affect up to 1 in 100 people): reduced number of blood cell counts (pancytopenia, anaemia, leukopenia).

Rare (may affect up to 1 in 1,000 people): cough, infections including pneumonia.

Very rare (may affect up to 1 in 10,000 people): 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 Tezolamet. 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 Tezolamet and medicines like it may have a small risk of developing secondary cancers, including leukaemia.

There have been cases of hepatic side effects including elevations of liver enzymes, increased bilirubin, problems with bile flow (cholestasis) and hepatitis.

If you get any side effectstalk to your doctor or pharmacist. This includes any side effects not listed in this leaflet.

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

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

HDPE Bottle presentation

Store below 30 °C

Store in the original bottle in order to protect from moisture.

Keep the bottle tightly closed.

Sachet presentation

5mg, 20mg: Store below 25°C

100mg, 140mg, 180mg and 250mg: Store below 30°C

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

What Tezolamet contains

• The active substance is temozolomide. Each capsule contains 5 mg temozolomide.
• The active substance is temozolomide. Each capsule contains 20 mg temozolomide.
• The active substance is temozolomide. Each capsule contains 100 mg temozolomide.
• The active substance is temozolomide. Each capsule contains 140 mg temozolomide.
• The active substance is temozolomide. Each capsule contains 180 mg temozolomide.
• The active substance is temozolomide. Each capsule contains 250 mg temozolomide.
• The other ingredients are: Capsule content Lactose Anhydrous Silica, Colloidal Anhydrous Sodium Starch Glycollate (Type A) Tartaric Acid Stearic Acid Capsule shell, Size 0: 5 mg: Gelatin, Titanium dioxide (E 171). Yellow iron oxide (E 172), Indigotine – FD&C Blue2 (E132) 20 mg: Gelatin, Ttitanium dioxide (E 171) Red iron oxide (E 172) Yellow iron oxide (E 172) 100 mg: Gelatin Titanium dioxide (E 171) Red iron oxide (E 172) Indigotine FD&C blue2 (E 132) 140 mg: Gelatin, Titanium dioxide (E 171) Indigotine FD&C blue 2 (E 132) 180 mg: Gelatin,

Titanium dioxide (E 171)

Red iron oxide (E 172)

Black iron oxide (E 172)

Yellow iron oxide (E 172)

250 mg: Gelatin,

Titanium dioxide (E 171)

Printing ink

Black Ink:

Shellac

Macrogol

Strong ammonia solution

Potassium hydroxide

Black iron oxide (E 172)

What Tezolamet looks like and contents of the pack

5 mg: The hard gelatin capsules are size 0 and have a green opaque cap/white opaque body with 5 printed in black ink on the body.

20 mg: The hard gelatin capsules are size 0 and have an orange opaque cap /white opaque body) with 20 printed in black ink on the body.

100 mg: The hard gelatin capsules are size 0 and have a purple opaque cap /white opaque body with 100 printed in black ink on the body

140 mg: The hard gelatin capsules are size 0 and have a blue opaque cap /white opaque body with 140 printed in black ink on the body

180mg: The hard gelatin capsules are size 0 and have a chocolate brown opaque cap /white opaque body with 180 printed in black ink on the body

250 mg: The hard gelatin capsules are size 0 and have a white opaque cap /white opaque body with 250 printed in black ink on the body

HDPE Bottle presentation

Child proof container, made from white opaque High Density Polyethylene Bottles with Polppropylene child-proof closure, with polyester coil and dessicant desiccant containing 5 capsules.

Sachet presentation

Sachets composed of paper on linear low density polyethylene (outermost layer), aluminium and ethylene acrylic acid co-polymer (innermost layer). Each sachet contains 1 hard capsule and is dispensed in a cardboard carton. The carton contains 5 or 20 hard capsules, individually sealed in sachets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturers

Marketing Authorisation Holder Pharmazac S.A.

31, Naoussis str., Votanikos 10447 Athene Griekenland

Manufacturer

EirGen Pharma Ltd.

64/66 Westside Business Park, Old Kilmeaden Road, Waterford

Ierland

Genepharm S.A.

18th Km. Marathon Ave., 153 51 Pallini

Griekenland

Millmount Healthcare Ltd

Block-7, City North Business Campus, Stamullen, Co. Meath

Ierland

Millmount Healthcare Ltd

Units 5-7, Navan Enterprise Centre, TrimRoad, Co. Meath

Ierland

In het Register ingeschreven onder:

Tezolamet 5 mg harde capsules: RVG 110851

Tezolamet 20 mg harde capsules: RVG 110852

Tezolamet 100 mg harde capsules: RVG 110853

Tezolamet 140 mg harde capsules: RVG 110854

Tezolamet 180 mg harde capsules: RVG 110855

Tezolamet 250 mg harde capsules: RVG 110856

This medicines product is authorised in the Member States of the EEA under the following names:

Griekenland

Tezolamet 5 mg καψάκιο, σκληρό

Tezolamet 20 mg καψάκιο, σκληρό

Tezolamet 100 mg καψάκιο, σκληρό

Tezolamet 140 mg καψάκιο, σκληρό

Tezolamet 180 mg καψάκιο, σκληρό

Tezolamet 250 mg καψάκιο, σκληρό

This leaflet was last approved in oktober 2013