TEMODAL 20 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 experience 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 further information

1. What is Temodal and what is it used for

Temodal contains a medicine called temozolomide. This medicine is an antitumoral agent.

Temodal is used in the treatment of specific forms of brain tumors:

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

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 (an anticancer drug, sometimes called DTIC). Signs of an allergic reaction include itching, shortness of breath or wheezing, swelling of the face, lips, tongue, or throat.
• if you have significantly reduced certain types of blood cells (myelosuppression), as well as a low white blood cell count and low platelet count. These blood cells are important for fighting infections 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 possible development of a severe 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 you avoid this type of pneumonia (PCP).
• if you have ever had or may have hepatitis B infection, as Temodal could reactivate hepatitis B, which in some cases can be fatal. Before starting treatment, your doctor will carefully examine you for signs of this infection.

• if you have low red blood cell counts (anemia), low white blood cell counts, and low platelet counts, or blood clotting problems before treatment, or if you develop them during treatment. Your doctor may reduce your dose of Temodal or interrupt it, or you may need other treatment. In some cases, it may be necessary to stop treatment with Temodal. You will be frequently subjected to blood tests to monitor the side effects of Temodal on your blood cells.
• as you may have a low risk of other blood cell disorders, including leukemia.

• 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 of age, you may be more susceptible to infection and more prone to infections, bruising, and bleeding.
• if you have liver or kidney problems, your dose of Temodal will be adjusted.

Children and adolescents

Do not give this medicine to children under 3 years of age, 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, breastfeeding, 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, as you should not be treated with Temodal during pregnancy unless clearly indicated by your doctor.

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

You must stop breastfeeding while being treated with Temodal.

Male fertility

Temodal may cause permanent infertility. Male patients should use effective contraceptive methods and not get their partner pregnant during and for at least 3 months after finishing treatment. It is recommended to consult about sperm preservation before treatment.

Driving and using machines

Temodal may make you feel tired or sleepy. In this case, do not drive or use tools or machines, or ride a bicycle until you see 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, consult them before taking this medicine.

Temodal contains sodium

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

3. How to take Temodal

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

Dose and duration of treatment

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

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 carried out in two phases:

• first, concomitant treatment with radiotherapy
• 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). This dose will be taken 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 cell counts and how you tolerate the medication during the concomitant phase.

Once radiotherapy is completed, treatment will be interrupted for 4 weeks to give your body a chance to recover.

Then, the monotherapy phase will begin.

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

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

You will take your new dose of Temodal 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 adds up to a total treatment cycle of 28 days.

After day 28, the next cycle will begin. You will take Temodal again once a day for 5 days, followed by 23 days without Temodal. The dose of Temodal may be adjusted, delayed, or skipped, depending on your blood cell counts and how you tolerate your 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 adds up to a total treatment cycle of 28 days.

After day 28, a new cycle will begin. 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 check if your dose of Temodal needs to 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 every 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 the capsule is damaged, avoid contact of the powder with the skin, eyes, or nose. If it accidentally gets into your eyes or nose, rinse the area with water.

Depending on the prescribed dose, 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).

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

• how many capsules you need to take each day of dosing. Tell your doctor or pharmacist to write it down for you (including the color).
• what your dosing days are.

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. 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 or 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 missed doses, unless your doctor tells you to do so.

If you have any other questions about 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 breathing difficulties,
• 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 have bleeding or bruising, anemia (reduced red blood cell count), fever, and a reduced ability to fight 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 frequently subject you to blood tests to detect any changes, and decide if you need specific treatment. In some cases, the dose of Temodal will be reduced or interrupted.

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 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 state 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, nasal inflammation
• stomach or abdominal pain, stomach upset/acid reflux, difficulty swallowing
• dry skin, itching
• muscle damage, muscle weakness, muscle pain
• joint pain, back pain
• frequent urination, 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 leukemia
• reduced red blood cell counts (pancytopenia, anemia, leukopenia)
• 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 flashes
• bloated stomach, difficulty controlling bowel movements, hemorrhoids, 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, skin color changes
• difficulty urinating
• vaginal bleeding, vaginal irritation, absent or heavy menstrual periods, breast pain, impotence
• chills, facial swelling, tongue discoloration, thirst, tooth disorder
• dry eyes

Reporting of side effects

If you experience 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 through 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. The expiry date is the last day of the month stated.

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. This 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 components are:

Capsule content:

anhydrous lactose, anhydrous colloidal 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 individually sealed in blisters and dispensed in boxes containing 5 or 20 hard capsules.

Only some pack sizes may be marketed.

You can request more information about this medicinal product by contacting 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: https://www.ema.europa.eu.