Temozolomide Polpharma 100 mg harde capsules

1. WHAT IS AND WHAT IT IS USED FOR

<Product name> is an antitumour agent.

<Product name> is used for the treatment of patients with specific forms of brain tumours:

• newly-diagnosed glioblastoma multiforme. <Product name> 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. <Product name> is used in these tumours if they return or get worse after standard treatment.

2. BEFORE YOU TAKE

Do not take <PRODUCT NAME>

• if you are allergic (hypersensitive) to temozolomide or any of the other ingredients of <Product name>.
• 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 <PRODUCT NAME>

• 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 <Product name> 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 <Product name>. Your blood will be tested frequently during treatment to monitor the side effects of <Product name> 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 <Product name> (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
• <Product name> 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 <Product name> may need to be adjusted.

Due to lack of experience, <Product name> should not be used in children younger than 3 years.

<Product name> 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 <Product name> during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be taken by both male and female patients who are taking <Product name> (see also “Take special care with <Product name>” above). You should stop breast-feeding while receiving treatment with <Product name>.

Driving and using machines

<Product name> 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 <Product name>

<Product name> 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 medicinal product.

3. HOW TO TAKE

Dosage and duration of treatment

Your doctor will work out your dose of <Product name>. 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 <Product name> 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 <Product name> (monotherapy phase).

During the concomitant phase, your doctor will start <Product name> 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 <Product name> 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 <Product name> 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 <Product name> 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 <Product name>. This adds up to a 28- day treatment cycle. After Day 28, the next cycle will begin. You will again take <Product name> once daily for 5 days followed by 23 days without <Product name>. The <Product name> 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 <Product name> only:

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

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

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

How to take <Product name>

Take your prescribed dose of <Product name> 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 of the capsule cap is different for each strength (see in the table below).

Strength	Colour of the cap
<Product name> 5 mg hard capsules	Green
<Product name> 20 mg hard capsules	Orange
<Product name> 100 mg hard capsules	Purple
<Product name> 140 mg hard capsules	Blue
<Product name> 180 mg hard capsules	Chocolate brown
<Product name> 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 <Product name> 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 <PRODUCT NAME> than you should

If you accidentally take more <Product name> capsules than you were told to, contact your doctor or pharmacist immediately.

If you forget to take <PRODUCT NAME>

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 product, ask your doctor or pharmacist.

Like all medicines, <Product name> 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.

<Product name> 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 <Product name> 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.

<Product name> in combination treatment with radiotherapy in newly-diagnosed glioblastoma

Patients receiving <Product name> in combination with radiotherapy may experience different side effects than patients taking <Product name> 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, convulsions, 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.

<Product name> 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 <Product name>. 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 <Product name> 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 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.

5. HOW TO STORE

Keep out of the reach and sight of children

Do not use <Product name> after the expiry date which is stated on the label and carton. The expiry date refers to the last day of that month.

HDPE Bottle presentation

Store below 30oC

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

Keep the bottle tightly closed.

Sachet presentation 5mg, 20mg

Store below 25oC

, 100mg, 140mg, 180mg, 250mg

Store below 30oC

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

What <Product name> 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 blue 2 (E132) 20 mg: gelatin, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172) 100 mg: gelatin, titanium dioxide (E 171), red iron oxide (E172), indigotine FD & C blue 2 (E132) 140 mg: Gelatin, titanium dioxide (E 171), indigotine FD&C blue 2 (E 132) 180 mg: Gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), black iron oxide (E 172) 250 mg: gelatin, titanium dioxide (E 171) Printing ink Shellac, , propylene glycol, purified water, sodium ammonia solution, potassium hydroxide, black iron oxide (E 172)

What <PRODUCT NAME> looks like and the contents of the pack

5 mg: Hard gelatin capsules size 0 (green opaque cap/white opaque body) with 5 printed in black ink on the body.

20 mg: Hard gelatin capsules size 0 (orange opaque cap /white opaque body) with 20 printed in black ink on the body.

100 mg: Hard gelatin capsules size 0 (purple opaque cap /white opaque body) with 100 printed in balck ink on the body

140 mg: Hard gelatin capsules size 0 (blue opaque cap /white opaque body) with 140 printed in black ink on the body

180mg: Hard gelatin capsules size 0 (chocolate brown opaque cap /white opaque body) with 180 printed in black ink on the body

250 mg: Hard gelatin capsules size 0 (white opaque cap /white opaque body) with 250 printed in black ink on the body

HDPE Bottle presentation

White opaque High Density Polyethylene Bottles with Polppropylene push lock assembly closure, with polyester coil and dessicant 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.

<To be completed nationally>

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Pharmaceutical Works POLPHARMA S.A.

19, Pelpliñska Str., 83-200 Starogard Gdañski

Poland

In het register ingeschreven onder:

Temozolomide Polpharma 5 mg harde capsules RVG 109631

Temozolomide Polpharma 20 mg harde capsules RVG 109632

Temozolomide Polpharma 100 mg harde capsules RVG 109633

Temozolomide Polpharma 140 mg harde capsules RVG 109634

Temozolomide Polpharma 180 mg harde capsules RVG 109635

Temozolomide Polpharma 250 mg harde capsules RVG 109636

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

This leaflet was last approved in november 2012.