Temozolomide Sandoz - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: information for the user

Temozolomide Sandoz 5 mg hard capsules

Temozolomide Sandoz 20 mg hard capsules

Temozolomide Sandoz 100 mg hard capsules

Temozolomide Sandoz 140 mg hard capsules

Temozolomide Sandoz 180 mg hard capsules

Temozolomide Sandoz 250 mg hard capsules

temozolomide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Temozolomide Sandoz is and what it is used for

• 2. What you need to know before you take Temozolomide Sandoz

• 3. How to take Temozolomide Sandoz

• 4. Possible side effects

• 5. How to store Temozolomide Sandoz

• 6. Contents of the pack and other information

1. What Temozolomide Sandoz is and what it is used for

Temozolomide Sandoz contains a medicine called temozolomide. This medicine is an antitumour agent.

Temozolomide Sandoz is used for the treatment of specific forms of brain tumours:

• in adults with newly-diagnosed glioblastoma multiforme. Temozolomide Sandoz 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. Temozolomide Sandoz is used in these tumours if they return or get worse after standard treatment.

2. What you need to know before you take Temozolomide Sandoz

Do not take Temozolomide Sandoz

• 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 precautions

Talk to your doctor, pharmacist or nurse before taking Temozolomide Sandoz

• as you should be observed closely for the development of a serious form of chest infection called Pneumocystis jirovecii pneumonia (PCP). If you are a newly-diagnosed patient (glioblastoma multiforme) you may be receiving Temozolomide Sandoz 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 ever had or might now have a hepatitis B infection. This is because temozolomide could cause hepatitis B to become active again, which can be fatal in some cases. Patients will be carefully checked by their doctor for signs of this infection before treatment is started.
• 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 Sandoz. Your blood will be tested frequently during treatment to monitor the side effects of Temozolomide Sandoz 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 both very common

side effects of Temozolomide Sandoz (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 Temozolomide Sandoz 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 infections, bruising or

bleeding.

• if you have liver or kidney problems. Your dose of Temozolomide Sandoz 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 Temozolomide Sandoz.

Other medicines and Temozolomide Sandoz

Tell your doctor or pharmacist if you are taking, have recently taken or might take 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 Temozolomide Sandoz during pregnancy unless clearly indicated by your doctor.

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

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

Male fertility

Temozolomide Sandoz may cause permanent infertility. Male patients should use effective contraception 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

Temozolomide Sandoz 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).

Temozolomide Sandoz contains lactose

Temozolomide Sandoz contains 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.

3. How to take Temozolomide Sandoz

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 Temozolomide Sandoz. 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 Sandoz 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 Sandoz (monotherapy phase).

During the concomitant phase, your doctor will start Temozolomide Sandoz 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 Sandoz 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 Temozolomide Sandoz 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 Sandoz 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 Sandoz. This adds up to a 28-day treatment cycle.

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

A treatment cycle with Temozolomide Sandoz lasts 28 days.

You will take Temozolomide Sandoz 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 Sandoz 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 Sandoz will be 150 mg/m2 once daily for the first 5 days.

Then, you will have 23 days without Temozolomide Sandoz. This adds up to a 28-day treatment cycle.

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

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 Sandoz

Take your prescribed dose of Temozolomide Sandoz 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
Temozolomide Sandoz 5 mg hard capsules	green
Temozolomide Sandoz 20 mg hard capsules	yellow
Temozolomide Sandoz 100 mg hard capsules	pink
Temozolomide Sandoz 140 mg hard capsules	blue
Temozolomide Sandoz 180 mg hard capsules	maroon
Temozolomide Sandoz 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 Temozolomide Sandoz 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 Sandoz than you should

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

If you forget to take Temozolomide Sandoz

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.

4. Possible side effects

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,
• chills
• severe headache that does not go away.

Temozolomide Sandoz 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 Sandoz dose will be reduced or treatment stopped.

Side effects from clinical studies:

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 (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
• low potassium level in the blood
• weight gain
• mood swings
• hallucination and memory impairment
• partial paralysis
• impaired coordination
• 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 irriation
• breast pain
• hot flushes
• shivering
• discolouration of your tongue
• change in your sense of smell
• thirst
• tooth disorder.

Temozolomide 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)
• tiredness.

Common (may affect up to 1 in 10 people ):

• loss of weight
• sleepiness
• 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 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:

Cases of elevations of liver enzymes have been commonly reported. Cases of increased bilirubin, problems with bile flow (cholestasis), hepatitis and injury to the liver, including fatal liver failure, have been uncommonly reported.

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. 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 and medicines like it may have a small risk of developing secondary cancers, including leukaemia.

New or reactivated (recurring) cytomegalovirus infections and reactivated hepatitis B virus infections have been uncommonly reported. Cases of brain infections caused by herpes virus (meningoencep­halitis herpetic), including fatal cases, have been uncommonly reportedX’ases of sepsis (when bacteria and their toxins circulate in the blood and start to damage the organs) have been uncommonly reported.

Cases of diabetes insipidus have been uncommonly reported. Symptoms of diabetes insipidus include passing a lot of urine and feeling thirsty.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Temozolomide Sandoz

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.

Bottle

Do not store above 25°C

Store in the original package.

Keep the bottles tightly closed in order to protect from moisture.

Sachet

Do not store above 25°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.

6. Contents of the pack and other information

What Temozolomide Sandoz contains

• The active substance is temozolomide.

Temozolomide Sandoz 5 mg hard capsules

Each capsule contains 5 mg temozolomide.

Temozolomide Sandoz 20 mg hard capsules

Each capsule contains 20 mg temozolomide.

Temozolomide Sandoz 100 mg hard capsules

Each capsule contains 100 mg temozolomide.

Temozolomide Sandoz 140 mg hard capsules

Each capsule contains 140 mg temozolomide.

Temozolomide Sandoz 180 mg hard capsules

Each capsule contains 180 mg temozolomide.

Temozolomide Sandoz 250 mg hard capsules

Each capsule contains 250 mg temozolomide.

• The other ingredients of the capsule are

Temozolomide Sandoz 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 Sandoz 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 Sandoz 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 Sandoz 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 Sandoz 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 Sandoz 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), water.

• - Printing ink: contains shellac, black iron oxide (E 172), potassium hydroxide.

What Temozolomide Sandoz looks like and contents of the pack

Bottle

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

Sachet

Each hard capsule (capsule) is individually packed in a sachet. Each carton contains 5 or 20 hard capsules.

Not all pack sizes may be marketed.

Temozolomide Sandoz 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”.

Each capsule is approximately 15.8 mm in length.

Temozolomide Sandoz 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”.

Each capsule is approximately 11.4 mm in length.

Temozolomide Sandoz 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”.

Each capsule is approximately 15.8 mm in length.

Temozolomide Sandoz 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”.

Each capsule is approximately 19.3 mm in length.

Temozolomide Sandoz 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”.

Each capsule is approximately 19.3 mm in length.

Temozolomide Sandoz 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”.

Each capsule is approximately 21.4 mm in length.

Marketing Authorisation Holder

Sandoz GmbH

Biochemiestraße 10

A-6250 Kundl

Austria

Manufacturer

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1 D-39179 Barleben

Germany

Lek Pharmaceuticals d.d

Verovskova 57

SL-1526 Ljubljana Slovenia

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

Efc^rapufl

Sandoz Bulgaria Branch Office

• 55 Nikola Vaptzarov blvd.