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 (temozolomide)

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse. See section 4.

Contents of thePackage Leaflet

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

Temodal contains a medication called temozolomida. This medication is an antitumoral agent.

Temodal is indicated for the treatment of specific forms of brain tumors:

• in adults with newly diagnosed glioblastoma multiforme. Temodal is used initially in combination with radiation therapy (concomitant phase of treatment) and subsequently 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 indicated in these tumors if they recur or worsen after standard treatment.

Do not take Temodal

• if you are allergic to temozolomida or any of the other components of this medication (listed in section 6).
• if you have had a reaction to dacarbazina (a cancer drug, sometimes called DTIC). Symptoms of a reaction include itching, feeling of lack of air or hissing, swelling of the face, lips, tongue, or throat.
• if you have a significant reduction in certain types of blood cells (myelosuppression), including white blood cell count and platelet count. These blood cells are important in fighting infections and for proper blood clotting. Your doctor will ask for blood tests to check that you have enough of these cells before starting treatment.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Temodal.

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

• if you have low red blood cell, white blood cell, and platelet counts, or blood clotting problems before treatment, or if you develop them during treatment. Your doctor may reduce the dose of the medication or interrupt it, or you may need another treatment. In some cases, it may be necessary to discontinue Temodal treatment. You will be subjected to frequent blood tests to monitor the side effects of Temodal on your blood cells.
• since you may have a low risk of other blood cell abnormalities, including leukemia.

• if you have nausea (urge to vomit) and/or vomiting, which are very frequent side effects with Temodal (see section 4), your doctor may prescribe an antiemetic medication for you.

If you frequently vomit 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 susceptible to infection and more prone to bruising and bleeding.

-if you have liver or kidney problems, your Temodal dose will be adjusted.

Children and adolescents

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

Other medications and Temodal

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication, as you should not be treated with Temodal during pregnancy unless clearly indicated by your doctor.

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

You should stop breastfeeding while taking Temodal treatment.

Male fertility

Temodal may cause permanent infertility. Male patients should use an effective contraceptive method and not leave their partner pregnant for at least 3 months after completing treatment. It is recommended to consult about sperm conservation before treatment.

Driving and operating machinery

Temodal may make you feel tired or sleepy. In this case, do not drive, operate tools or machines, or ride a bike until you see how this medication affects you (see section 4).

Temodal contains lactose

This medication contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Temodal contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per capsule; it is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist.In case of doubt, consult your doctor or pharmacist again.

Dose and treatment duration

Your doctor will determine your correct dose of Temodal. Based on your build (height and weight), if you have a recurrent tumor and if you have been previously treated with chemotherapy.

You may be prescribed another medication (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 performed in two phases:

• First, combined treatment with radiation therapy (concomitant phase)
• Followed by treatment only with Temodal (monotherapy phase).

During the concomitant phase, your doctor will start with Temodal at a dose of 75 mg/m2 (normal dose). This dose will be taken daily for 42 days (up to a maximum of 49 days) in combination with radiation therapy. The Temodal dose may be delayed or interrupted, depending on your blood counts and how you tolerate the medication during the concomitant phase.

Once radiation therapy is complete, you will interrupt treatment for 4 weeks to give your body the opportunity to recover.

Then, you will start the monotherapy phase.

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

You may have up to 6 treatment periods (cycles). Each cycle lasts 28 days.

You will take your new Temodal dose only once a day during 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 totals 28 days per treatment cycle.

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

The Temodal dose may be adjusted, delayed, or suppressed, depending on your blood test results and how you tolerate the medication during each treatment cycle.

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

A treatment cycle with Temodal is 28 days.

You will take Temodal only once a day during the first 5 days. This daily dose will depend on whether you have been previously treated with chemotherapy or not.

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

Then there will be 23 days without Temodal. This totals 28 days per treatment cycle.

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

Each time you start a new treatment cycle, your blood will be analyzed to verify if your Temodal dose should be adjusted. Depending on the results, your doctor may adjust your medication 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 with an empty stomach; for example, at least one hour before you plan to have breakfast. Swallow the entire capsule with a glass of water. Do not open, crush, or chew the capsules. If the capsule is damaged, avoid contact with the powder with the skin, eyes, or nose. If it accidentally gets into your eyes or nose, rinse the area with water.

You may need to take more than one capsule at a time, with different concentrations (active ingredient content, in mg). The color of the capsule cap is different for each concentration (see table below).

Make sure you understand and remember the following:

• How many capsules you need to take each day of dosing. Tell your doctor or pharmacist to note it down (including the color).
• Your dosing days.

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

Follow exactly the administration instructions of Temodal indicated by your doctor. Consult your doctor or pharmacist if you have doubts.The errors in taking this medication can have serious consequences for your health.

If you take more Temodal than you should

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

If you forget to take Temodal

Take the dose you forgot as soon as possible during the same day. If a whole day has passed, consult your doctor. Do not take a double dose to compensate for the missed doses, unless your doctor tells you to do so.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Contactyour doctor immediatelyif you have any of the following:

• severe allergic reaction (urticaria, wheezing, or other breathing difficulties),
• uncontrolled bleeding,
• seizures,
• fever,
• chills,
• intense 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 experience bruising or bleeding, anemia (reduction in red blood cell count), fever, and decreased resistance to infections. The reduction in blood cell count is usually temporary. In some cases, it can be prolonged and may cause a very severe form of anemia (aplastic anemia). Your doctor will have you undergo frequent blood tests to detect any changes that may occur, and will decide if you need specific treatment. In some cases, the dose of Temodal will be reduced or discontinued.

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, diarrhea, constipation
• skin rash, hair loss
• fatigue

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

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

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

• herpetic encephalitis (brain infection), including fatal cases
• wound infections
• new or reactivated cytomegalovirus infections
• reactivated hepatitis B virus infections
• secondary cancers, including leukemia
• reduced red blood cell count (pancytopenia, anemia, 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 disability, middle ear infection
• palpitations (can feel heartbeats), hot flashes
• swollen stomach, difficulty controlling bowel movements, hemorrhoids, dry mouth
• hepatitis and liver damage (including fatal liver failure), cholestasis, increased bilirubin
• blistering on the body or in the mouth, skin peeling, skin rash, painful skin inflammation (including palms of hands and soles of feet)
• sensitivity to sunlight, urticaria (hives), increased sweating, skin color changes
• difficulty urinating
• vaginal bleeding, vaginal irritation, absent or intense menstrual periods, breast pain, impotence
• chills, facial swelling, tongue discoloration, thirst, dental problems
• dry eyes

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keepthis medicationout of sightand out of reachof children, preferably in a locked cabinet. Accidental ingestion can be fatal in children.

Do notusethis medicationafterthe expiration date that appears on the packaging and box.The expiration date is the last day of the month indicated.

Do not store at a temperature above 30?°C.

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of Temodal

The active ingredient is temozolomida.

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

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

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

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

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

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

The other components are:

Capule content:

anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic acid (see section2 "Temodal contains lactose").

Capule body:

Temodal 5mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate, iron oxide yellow (E172), indigo carmine (E132).

Temodal 20mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate, iron oxide yellow (E172).

Temodal 100mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate, iron oxide red (E172).

Temodal 140mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate, indigo carmine (E132).

Temodal 180mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate, iron oxide yellow (E172) and iron oxide red (E172).

Temodal 250mg hard capsules:gelatine, titanium dioxide (E171), sodium lauryl sulfate.

Printing ink:

shellac, propylene glycol (E1520), purified water, ammonia hydroxide, potassium hydroxide and iron oxide black (E172).

Appearance of the product and contents of the pack

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 “5mg”, the Schering‑Plough logo and two bars.

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 “20mg”, the Schering‑Plough logo and two bars.

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 “100mg”, the Schering‑Plough logo and two bars.

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

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 “180mg”, the Schering‑Plough logo and two bars.

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 “250mg”, the Schering‑Plough logo and two bars.

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

Only some pack sizes may be marketed.

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.