Temozolomide HEXAL 250 mg hard capsules

Temozolomide HEXAL is an antitumour agent.

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

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

Do not take Temozolomide HEXAL

• if you are allergic (hypersensitive) to
• temozolomide or any of the other ingredients of Temozolomide HEXAL.
• dacarbazine (an anticancer medicine). 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. Therefore, your doctor will check your blood to make sure you have enough of these cells before you begin treatment.

Take special care with Temozolomide HEXAL

• you should be observed closely for the development of a serious form of pneumonia called Pneumocystis carinii pneumonia. If you are a newly-diagnosed patient (glioblastoma multiforme) you may be receiving Temozolomide HEXAL for 42 days in combination with radiotherapy. In this case, your doctor will also prescribe medicine to help you prevent this type of pneumonia.
• 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. In severe cases your doctor may interrupt, stop or change your treatment (see also ?Do not take Temozolomide HEXAL?). You may also need other treatments. Additionally, your blood will be tested frequently during treatment to monitor the side effects of Temozolomide HEXAL on your blood cells.
• you may have a small risk of other changes in blood cells, including leukaemia.
• if you have nausea (feeling sick) and/or vomiting, both very common side effects of Temozolomide HEXAL (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 HEXAL. 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 HEXAL may need to be adjusted.

Temozolomide HEXAL 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.

Children under 3 years

Temozolomide should not be used in children younger than 3 years due to lack of experience.

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

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

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

• Breast-feeding You should stop breast-feeding while receiving treatment with Temozolomide HEXAL.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Temozolomide HEXAL 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 HEXAL

Temozolomide HEXAL hard capsules contains 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.

Dosage and duration of treatment

Your doctor will work out your exact dose of Temozolomide HEXAL, based on

• your body surface, calculated from your height and weight
• if you have a recurrent tumour and
• if you have had chemotherapy treatment in the past.

You may be given other medicines (anti-emetics) to take before and/or after Temozolomide HEXAL to prevent or control nausea and vomiting.

Adult patients with a newly-diagnosed glioblastoma multiforme

Your treatment will occur in two phases:

• Temozolomide HEXAL treatment together with radiotherapy (concomitant phase) first
• followed by treatment with Temozolomide HEXAL alone (monotherapy phase).
• The usual starting dose during the concomitant phase is: 75 mg temozolomide per m 2 body surface.

You will take this dose every day for 42 days (up to 49 days) in combination with radiotherapy.

The Temozolomide HEXAL dose may be delayed or stopped, depending on you blood counts and how you tolerate your medicine.

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 Temozolomide HEXAL will be different.

• The usual starting dose during the monotherapy phase is: 150 mg temozolomide per m 2 body surface.

You will take your dose of Temozolomide alone once daily for the first 5 days (?dosing days?). Then you will have 23 days without Temozolomide HEXAL. This adds up to a 28-day treatment cycle.

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

The Temozolomide HEXAL dose may be adjusted, delayed or stopped depending on your blood counts and how you tolerate your medicine during each treatment cycle.

There may be up to 6 treatment cycles.

Children from the age of three years, adolescents and adult patients with tumours that have returned

or worsened (malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma) taking

Temozolomide HEXAL only

Your daily dose depends on whether or not you have received chemotherapy before.

• The usual starting dose, if you have not been previously treated with chemotherapy is: 200 mg temozolomide m 2 body surface.
• The usual first starting dose, if you have been previously treated with chemotherapy is: 150 mg temozolomide per m 2 .

You will take your dose of Temozolomide HEXAL once daily for the first 5 days. Then, you will have 23 days without Temozolomide HEXAL. This adds up to a 28-day treatment cycle.

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

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

How to take Temozolomide HEXAL

Take your prescribed dose of Temozolomide HEXAL 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.

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 section 6).

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 HEXAL 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 HEXAL than you should

Contact your doctor or pharmacist immediately if you accidentally take more Temozolomide HEXAL capsules than you were told to.

If you forget to take Temozolomide HEXAL

Temozolomide HEXAL should preferably be taken at the same time each day. If you notice during the same day that you have forgotten to take Temozolomide HEXAL, take the missed dose as soon as possible on an empty stomach, i.e. at least 2 hours after and/or 1 hour before a meal. If you notice a full day later that you have missed the dose, 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 stop taking Temozolomide HEXAL

Do not stop your treatment cycle with Temozolomide HEXAL, 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 HEXAL can cause side effects, although not everybody gets them.

Contact your doctorimmediatelyif you have any of the following:

• a severe allergic (hypersensitive) reaction Symptoms may be: swellings similar to after an insect bite (hives), wheezing or other breathing difficulty,
• uncontrolled bleeding,
• fits,
• fever,
• a severe headache that does not go away.

Temozolomide HEXAL treatment can cause a reduction in certain kinds of blood cells. This may cause you to have increased bruising or bleeding, a reduction 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 lack of red blood cells (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 HEXAL dose will be reduced or treatment stopped.

Side effects from clinical studies:

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 know: frequency cannot be estimated from the available data.

Temozolomide in combination treatment with radiotherapy in newly-diagnosed glioblastoma

Patients receiving temozolomide in combination with radiotherapy may experience different side effects than patients taking temozolomide 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 urination
• vaginal irritation or bleeding
• sexual impotence
• absent or heavy menstrual periods
• breast pain
• hot flushes
• shivering
• discolouration of your tongue
• change in your sense of smell
• thirst
• tooth disorder.

Patients with aggressive brain tumours that have returned or worsened taking temozolomide only

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
• swellings similar to after an insect bite (hives)
• skin eruption
• allergic reactions.

Other side effects:

Very rare cases of the following side effects were observed:

• 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. Tell your doctor immediately if this occurs
• lung side effects. Patients usually present with shortness of breath and cough. Tell your doctor if you notice any of these symptoms.
• patients taking temozolomide 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 HEXAL 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 bottles 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 HEXAL contains

The active substance is temozolomide.

Temozolomide HEXAL 5 mg hard capsules

Each capsule contains 5 mg temozolomide.

Temozolomide HEXAL 20 mg hard capsules

Each capsule contains 20 mg temozolomide.

Temozolomide HEXAL 100 mg hard capsules

Each capsule contains 100 mg temozolomide.

Temozolomide HEXAL 140 mg hard capsules

Each capsule contains 140 mg temozolomide.

Temozolomide HEXAL 180 mg hard capsules

Each capsule contains 180 mg temozolomide.

Temozolomide HEXAL 250 mg hard capsules

Each capsule contains 250 mg temozolomide.

The other ingredients of the capsule are

Temozolomide HEXAL 5 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), yellow iron oxide (E 172), indigo carmine (E 132), water.
• Printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

Temozolomide HEXAL 20 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), yellow iron oxide (E 172), water.
• Printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

Temozolomide HEXAL 100 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), red iron oxide (E 172), water.
• Printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

Temozolomide HEXAL 140 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), indigo carmine (E 132), water.
• Printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

Temozolomide HEXAL 180 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), water.
• Printing ink: shellac, black iron oxide (E 172), potassium hydroxide.

Temozolomide HEXAL 250 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid.
• Capsule shell: gelatine, titanium dioxide (E 171), sodium laurilsulfate, water.
• Printing ink: contains shellac, black iron oxide (E 172), potassium hydroxide.

What Temozolomide HEXAL looks like and contents of the pack

The hard capsules are dispensed in amber glass bottles (Type 3 glass) or HDPE bottles with polypropylene child-resistant closures. Each bottle contains either 5 or 20 capsules. The bottles also contain a desiccant disc. Keep the desiccant disc in the bottle. Do not swallow it.

Not all pack sizes may be marketed.

Temozolomide HEXAL 5 mg hard capsules

The hard capsules have a white coloured body, a green coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?5?.

Temozolomide HEXAL 20 mg hard capsules

The hard capsules have a white coloured body, a yellow coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?20?.

Temozolomide HEXAL 100 mg hard capsules

The hard capsules have a white coloured body, a pink coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?100?.

Temozolomide HEXAL 140 mg hard capsules

The hard capsules have a white coloured body, a transparent blue coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?140?.

Temozolomide HEXAL 180 mg hard capsules

The hard capsules have a white coloured body, a maroon coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?180?.

Temozolomide HEXAL 250 mg hard capsules

The hard capsules have a white coloured body, a white coloured cap, and are imprinted with black ink. The cap is imprinted with ?TMZ? and the body is imprinted with ?250?.

Marketing Authorisation Holder

HEXAL AG
Industriestrasse 25
D-83607 Holzkirchen
Germany

Manufacturer

Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
D-39179 Barleben
Germany

Lek Pharmaceuticals d.d

Verovskova 57

SL-1526 Ljubljana

Slovenia

This leaflet was last approved in {MM/YYYY}.