TEMODAL 180 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Temodal 5 mg hard capsules

Temodal 20 mg hard capsules

Temodal 100 mg hard capsules

Temodal 140 mg hard capsules

Temodal 180 mg hard capsules

Temodal 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.

Contents of thepackage leaflet

1. What is Temodal and what is it used for
2. What you need to know before you take Temodal
3. How to take Temodal
4. Possible side effects
5. Storage of Temodal
6. Contents of the pack and other information

1. What is Temodal and what is it used for

Temodal contains a medicine called temozolomide. This medicine is an anti-tumour agent.

Temodal is used to treat specific forms of brain tumours:

• in adults with newly diagnosed glioblastoma multiforme. Temodal is used initially in combination with radiotherapy (concomitant phase of treatment) and then alone (monotherapy phase of treatment).

• in children aged 3 years and older and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temodal is used for these tumours if they come back or get worse after standard treatment.

2. What you need to know before you take Temodal

Do not take Temodal

• 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 (a cancer medicine, sometimes called DTIC). Signs of allergic reaction include itching, shortness of breath or wheezing, swelling of the face, lips, tongue or throat.
• if you have a severely reduced number of certain types of blood cells (myelosuppression), including a low white blood cell count and low platelet count. These blood cells are important for fighting infection and for proper blood clotting. Your doctor will ask for blood tests to check that you have a sufficient number of these cells before starting treatment.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting Temodal.

• as you will need to be closely monitored for the development of a serious respiratory infection called Pneumocystis jirovecii pneumonia (PCP). If you are a newly diagnosed patient (glioblastoma multiforme) you may be receiving Temodal in the 42-day regimen, in combination with radiotherapy. In this case, your doctor will also prescribe a medicine to help prevent this type of pneumonia (PCP).
• if you have ever had or might have hepatitis B infection, as Temodal could reactivate hepatitis B, which can be fatal in some cases. Before starting treatment, your doctor will carefully examine you for signs of this infection.

• if you have low red blood cell count (anaemia), low white blood cell count and low platelet count, or blood clotting problems before treatment, or if you develop them during treatment. Your doctor may reduce your dose or stop it, or you may need other treatment. In some cases, it may be necessary to stop treatment with Temodal. You will have frequent blood tests to monitor the effects of Temodal on your blood cells.
• as you may have a low risk of other changes in your blood cells, including leukaemia.

• if you have nausea (feeling sick) and/or vomiting, which are very common side effects with Temodal (see section 4), your doctor may prescribe you a medicine to prevent vomiting (antiemetic).

If you vomit frequently before or during treatment, ask your doctor about the best time to take Temodal 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 have a fever or symptoms of an infection, contact your doctor immediately.
• if you are over 70 years old, you may be more prone to infection and more likely to get infections, bruising and bleeding.
• if you have liver or kidney problems, your dose of Temodal may need to be adjusted.

Children and adolescents

Do not give this medicine to children under 3 years old, as its effect in this age group has not been studied. There is limited information available in patients over 3 years who have taken Temodal.

Other medicines and Temodal

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. You should not be treated with Temodal during pregnancy unless clearly indicated by your doctor.

Effective contraceptive methods are recommended for female patients who could become pregnant during treatment with Temodal and for at least 6 months after completing treatment.

You must stop breast-feeding while you are taking Temodal.

Male fertility

Temodal may cause permanent infertility. Male patients should use effective contraceptive methods and not father a child during and for up to 3 months after treatment. It is recommended that you consult about sperm preservation before treatment.

Driving and using machines

Temodal may make you feel tired or sleepy. If this happens, do not drive or use any tools or machines, or ride a bicycle until you know how this medicine affects you (see section 4).

Temodal contains lactose

This medicine contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

Temodal contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per capsule, which is essentially ‘sodium-free’.

3. How to take Temodal

Follow exactly the instructions that your doctor or pharmacist has given you. If you are unsure, ask your doctor or pharmacist.

Dose and duration of treatment

Your doctor will decide the correct dose of Temodal for you. This will depend on your body size (height and weight), whether you have a recurrent tumour and whether you have been treated with chemotherapy before.

You may be prescribed another medicine (antiemetic) to take before and/or after taking Temodal to prevent or control nausea and vomiting.

Patients with newly diagnosed glioblastoma multiforme:

If you are a newly diagnosed patient, treatment will be in two phases:

• first, treatment in combination with radiotherapy (concomitant phase)
• followed by treatment with Temodal alone (monotherapy phase).

During the concomitant phase, your doctor will start Temodal at a dose of 75 mg/m2 (standard dose). You will take this dose every day for 42 days (up to a maximum of 49 days) in combination with radiotherapy. The dose of Temodal may be delayed or interrupted, depending on your blood counts and how well you tolerate the medicine during the concomitant phase.

Once the radiotherapy is completed, treatment will be interrupted for 4 weeks to allow your body to recover.

After this, the monotherapy phase will start.

During the monotherapy phase, the dose and the way you take Temodal will be different. Your doctor will tell you the exact dose.

There may be up to 6 treatment cycles. Each cycle lasts 28 days.

You will take your new dose of Temodal once a day for the first 5 days of each cycle (“dosing days”). The first dose will be 150 mg/m2. Then there will be 23 days without Temodal. This adds up to a total treatment cycle of 28 days.

After day 28, the next cycle will start. You will take Temodal once a day for 5 days, followed by 23 days without Temodal. The dose of Temodal may be adjusted, delayed, or stopped, depending on your blood tests and how well you tolerate your medicine during each treatment cycle.

Patients with recurrent or progressive tumours (malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma) taking Temodal alone:

A treatment cycle with Temodal is 28 days.

You will take Temodal once a day for the first 5 days. The daily dose will depend on whether you have been treated with chemotherapy before or not.

If you have not been treated with chemotherapy before, your first dose of Temodal will be 200 mg/m2 once a day for the first 5 days. If you have been treated with chemotherapy before, your first dose of Temodal will be 150 mg/m2 once a day for the first 5 days.

Then there will be 23 days without Temodal. This adds up to a total treatment cycle of 28 days.

After day 28, a new cycle will start. You will take Temodal once a day for 5 days, followed by 23 days without Temodal.

Each time you start a new treatment cycle, your blood will be tested to check if your dose of Temodal needs to be adjusted. Depending on the results, your doctor may adjust your medicine for the next cycle.

How to take Temodal

Take your prescribed dose of Temodal 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 have 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 it in your eyes or nose, rinse the area with water.

Depending on the prescribed dose, you may need to take more than one capsule at the same time, with different strengths (active ingredient content, in mg). The colour of the capsule cap is different for each strength (see the table below).

You must be sure that you understand and remember the following:

• how many capsules you need to take each dosing day. Ask your doctor or pharmacist to write it down for you (including the colour).
• which are your dosing days.

Review your dose with your doctor each time you start a new cycle, as it may be different from the previous cycle.

Follow exactly the instructions that your doctor has given you. If you are unsure, ask your doctor or pharmacist. Errors in the way you take this medicine can have serious consequences for your health.

If you take more Temodal than you should

If you accidentally take more Temodal capsules than you should, contact your doctor, pharmacist, or nurse immediately.

If you forget to take Temodal

Take the missed dose as soon as possible on the same day. If a whole day has passed, consult 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 other 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 immediatelyif you have any of the following:

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

Treatment with Temodal may cause a reduction in certain types of blood cells. This can make you more likely to get infections, bruising or bleeding. The reduction in blood cells is usually temporary. In some cases, it can be prolonged and can cause a very severe form of anaemia (aplastic anaemia). Your doctor will ask for frequent blood tests to check for any changes and to decide if you need specific treatment. In some cases, the dose of Temodal may be reduced or stopped.

The following are other side effects that have been reported:

Very common side effects (may affect more than 1 in 10 people) are:

• loss of appetite, difficulty speaking, headache
• vomiting, nausea, diarrhoea, constipation
• skin rash, hair loss
• fatigue

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

• infections, oral infections
• low blood cell counts (neutropenia, lymphopenia, thrombocytopenia)
• allergic reaction
• increased blood sugar
• memory changes, depression, anxiety, confusion, inability to sleep or stay asleep
• coordination and balance changes
• difficulty concentrating, changes in mental status or alertness, tingling sensation
• dizziness, altered sensations, tingling, tremors, abnormal taste
• partial loss of vision, abnormal vision, double vision, painful eyes
• hearing loss, ringing in the ears, ear pain
• blood clots in the lungs or legs, high blood pressure
• pneumonia, shortness of breath, bronchitis, cough, inflammation of the nasal passages
• stomach pain or abdominal pain, stomach upset/indigestion, difficulty swallowing
• dry skin, itching
• muscle damage, muscle weakness, muscle pain
• joint pain, back pain
• urinary frequency, difficulty holding urine
• fever, flu-like symptoms, pain, discomfort, cold or flu
• fluid retention, swollen legs
• elevated liver enzymes
• weight loss, weight gain
• radiation injury

Uncommon side effects (may affect up to 1 in 100 people) are:

• brain infections (herpetic meningoencephalitis), including fatal cases
• wound infections
• new or reactivated cytomegalovirus infections
• reactivated hepatitis B virus infections
• secondary cancers, including leukaemia
• reduced blood cell counts (pancytopenia, anaemia, leucopenia)
• red spots under the skin
• diabetes insipidus (symptoms include increased urination and thirst), low potassium levels in the blood
• mood changes, hallucinations
• partial paralysis, change in sense of smell
• hearing impairment, middle ear infection
• palpitations (when you can feel your heart beating), hot flushes
• swollen stomach, difficulty controlling bowel movements, haemorrhoids, dry mouth
• hepatitis and liver damage (including fatal liver failure), cholestasis, increased bilirubin
• blisters on the body or in the mouth, skin peeling, skin rash, painful red skin, severe skin rash with skin peeling (including on the palms of the hands and soles of the feet)
• increased sensitivity to sunlight, hives (urticaria), increased sweating, changes in skin colour
• difficulty urinating
• vaginal bleeding, vaginal irritation, absent or heavy menstrual periods, breast pain, impotence
• chills, swollen face, discolouration of the tongue, thirst, tooth disorder
• dry eyes

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 Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Temodal

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

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

Do not store above 30 ?C.

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

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

6. Container contents and additional information

Composition of Temodal

The active ingredient is temozolomide.

Temodal 5mg hard capsules: Each capsule contains 5 mg of temozolomide.

Temodal 20mg hard capsules: Each capsule contains 20 mg of temozolomide.

Temodal 100mg hard capsules: Each capsule contains 100 mg of temozolomide.

Temodal 140mg hard capsules: Each capsule contains 140 mg of temozolomide.

Temodal 180mg hard capsules: Each capsule contains 180 mg of temozolomide.

Temodal 250mg hard capsules: Each capsule contains 250 mg of temozolomide.

The other ingredients are:

Capsule content:

anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid (see section 2 "Temodal contains lactose").

Capsule body:

Temodal 5mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate, yellow iron oxide (E 172), indigo carmine (E 132).

Temodal 20mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate, yellow iron oxide (E 172).

Temodal 100mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate, red iron oxide (E 172).

Temodal 140mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate, indigo carmine (E 132).

Temodal 180mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate, yellow iron oxide (E 172) and red iron oxide (E 172).

Temodal 250mg hard capsules:gelatin, titanium dioxide (E 171), sodium lauryl sulfate.

Printing ink:

shellac, propylene glycol (E 1520), purified water, ammonium hydroxide, potassium hydroxide, and black iron oxide (E 172).

Appearance of the product and container contents

Temodal 5mg hard capsuleshave a white opaque body, a green opaque cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “5 mg”, the Schering-Plough logo, and two lines.

Temodal 20mg hard capsuleshave a white opaque body, a yellow opaque cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “20 mg”, the Schering-Plough logo, and two lines.

Temodal 100mg hard capsuleshave a white opaque body, a pink opaque cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “100 mg”, the Schering-Plough logo, and two lines.

Temodal 140mg hard capsuleshave a white opaque body, a blue cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “140 mg”, the Schering-Plough logo, and two lines.

Temodal 180mg hard capsuleshave a white opaque body, an orange opaque cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “180 mg”, the Schering-Plough logo, and two lines.

Temodal 250mg hard capsuleshave a white opaque body and cap, and are printed with black ink. The cap is printed with “TEMODAL”. The body is printed with “250 mg”, the Schering-Plough logo, and two lines.

The hard capsules (capsules) for oral administration are sealed individually in blisters and dispensed in boxes containing 5 or 20 hard capsules.

Only some pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Manufacturer: Organon Heist bv, Industriepark 30, 2220 Heist-op-den-Berg, Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.