TEMOZOLOMIDE ACCORD 100 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Temozolomide Accord 5 mg hard capsules

Temozolomide Accord 20 mg hard capsules

Temozolomide Accord 100 mg hard capsules

Temozolomide Accord 140 mg hard capsules

Temozolomide Accord 180 mg hard capsules

Temozolomide Accord 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 the pack and other information

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

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

Temozolomide is an anti-cancer medicine

Temozolomide Accord capsules are taken for the treatment of specific forms of brain tumors:

• Adults with newly diagnosed specific forms of brain tumors (glioblastoma multiforme).
• Temozolomide is used first with radiotherapy (concomitant phase of treatment) and then alone (monotherapy phase of treatment)
• in children aged 3 years and older and adults with specific forms of brain tumors (e.g., glioblastoma multiforme or anaplastic astrocytoma) if they recur or spread after standard treatment.

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

Do not take Temozolomide Accord

• 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 another cancer medicine called dacarbazine. Signs of allergic reactions include itching, shortness of breath or wheezing, swelling of the face, lips, tongue, or throat
• if you have a low number of blood cells, such as a low white blood cell count or platelet count. These blood cells are important for fighting infection and for proper blood clotting. Your doctor will perform blood tests to make sure you have enough of these cells before starting treatment.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting Temozolomide Accord

• your doctor will monitor you for the possible development of a severe chest infection called Pneumocystis carinii jirovecii pneumonia (PCP). If you are a newly diagnosed patient with glioblastoma multiforme, you may be given temozolomide for 42 days 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 may currently have a hepatitis B infection, as Temozolomide Accord 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 anemia, low blood cell counts (e.g., white blood cells or platelets), or blood clotting problems before treatment or develop them during treatment. Your doctor may need to reduce your dose, interrupt your treatment, or may need to give you another treatment. Your doctor will decide if it is necessary to make any changes to your treatment. In some cases, it may be necessary to stop treatment with temozolomide. You will have regular blood tests to monitor your condition. If you have a fever or symptoms of infection, contact your doctor immediately.

• You may have a small risk of other changes in blood cells, including leukemia.

• if you have nausea or vomiting, which is a very common side effect of temozolomide (see section 4). If you vomit frequently before or during treatment, ask your doctor about medicines that help prevent vomiting or control vomiting and the best time to take temozolomide until you control the vomiting. If you vomit after taking the 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. Elderly patients are more prone to infections, bruising, and bleeding.

• if you have liver or kidney problems, as your dose 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 Temozolomida.

Taking Temozolomide Accord with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.

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 medicine, as you should not be treated with Temozolomide Accord during pregnancy unless clearly indicated by your doctor.

Effective contraceptive methods should be used in female patients of childbearing potential during treatment with Temozolomide Accord and for at least 6 months after completing treatment.

Do not breastfeed while taking Temozolomide Accord.

Male fertility

Temozolomide may cause permanent infertility. Male patients should use an effective contraceptive method 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.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

When taking temozolomide, you may feel tired or drowsy. 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).

Temozolomide Accord contains lactose

The capsules contain 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.

Temozolomide Accord contains sodium

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

3. How to take Temozolomide Accord

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

How to open the sachet

Open the sachet by folding and tearing it along the perforation line with the notch in the corner of the sachet.

Only specialists with experience in brain tumors should prescribe temozolomide

Dose and duration of treatment.

Your doctor will decide what dose of temozolomide is right for you based on your body size (height and weight) and whether you have received previous chemotherapy treatment. You may be given other medicines to take before and/or after temozolomide to prevent or control vomiting.

Take the prescribed dose of Temozolomide Accord once a day, on an empty stomach; for example, at least one hour before breakfast. Take 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 the skin, eyes, or nose. Avoid inhaling the powder. If something accidentally gets into your eyes or nose, wash the area with water.

If you take Temozolomide Accord in combination with radiotherapy (newly diagnosed patients):

At the same time as you receive radiotherapy, your doctor will start treatment with temozolomide at a dose of 75 mg/m², and the actual dose you take will depend on your height and weight. You will take this dose every day for 42 days (up to a maximum of 49 days) in combination with radiotherapy. Depending on your blood cell counts and how you tolerate temozolomide, the dose may be postponed or suspended.

Once radiotherapy is finished, you will interrupt treatment for 4 weeks to give your body a chance to recover.

There may be up to 6 cycles of treatment, and each cycle lasts 28 days. You will take your new dose of temozolomide capsules initially at a dose of 150 mg/m² once a day for the first 5 days of each cycle ("days of administration"), followed by 23 days without temozolomide. This adds up to a total treatment cycle of 28 days.

After day 28, you will start the next cycle, in which you will take the medicine once a day for 5 days, followed by 23 days without temozolomide. Depending on your blood cell counts and how you tolerate temozolomide during each treatment cycle, the dose may be adjusted, postponed, or suspended.

If you take Temozolomide Accord capsules alone (without radiotherapy):

A treatment cycle with Temozolomide Accord includes 28 days. You will take the capsules once a day for the first 5 days (“days of administration”), followed by 23 days without temozolomide. This adds up to a total treatment cycle of 28 days.

After day 28, you will start the next cycle, in which you will take the medicine once a day for 5 days, followed by 23 days without temozolomide. Before each new treatment cycle, you will have a blood test to see if it is necessary to adjust the dose of temozolomide.

If you have not received previous chemotherapy treatment, your first dose of temozolomide will be 200 mg/m² once a day for the first 5 days ("days of administration"), followed by 23 days without temozolomide. If you have received previous chemotherapy treatment, your first dose of temozolomide will be 150 mg/m² once a day for the first 5 days ("days of administration"), followed by 23 days without temozolomide.

Depending on the results of your blood tests, your doctor may adjust your dose for the next cycle.

Each time you start a new treatment cycle, make sure you understand exactly how many capsules of each strength you should take each day and how many days you should take this dose.

All patients

Temozolomide comes in capsules of different strengths (shown on the label of the box in mg). Each strength has a cap of a different color. Depending on the dose of temozolomide your doctor prescribes, you may need to take several capsules each day of the treatment cycle.

• Make sure you understand exactly how many capsules of each strength you should take. Ask your doctor or pharmacist to write down the number of capsules of each strength (including the color) you need to take each day of administration.
• Make sure you know exactly which are your days of administration.
• Make sure you review the dose with your doctor each time you start a new cycle. Sometimes the dose or the mix of capsules you need to take may be different from the previous cycle.
• Once you have the medicine at home, if you have doubts or need to clarify something about how to take the dose, call to have it explained again before starting the treatment cycle. Mistakes in taking this medicine can have serious consequences for your health.

If you take more Temozolomide Accord than you should

If you accidentally take more capsules than indicated, consult your doctor, pharmacist, or nurse immediately.

If you forget to take Temozolomide Accord

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 the missed dose, 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.

Patients taking temozolomide in combination with radiotherapy may have different side effects than people taking temozolomide alone.

Contact your doctor immediately if you experience:

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

Treatment with temozolomide may cause a reduction in certain types of blood cells. This can make you more likely to get bruising or bleeding, anemia (lack of red blood cells), fever, and/or a reduced ability to fight infections. The decrease in blood cell count is usually temporary, but in some cases, it can be prolonged and cause a very severe form of anemia (aplastic anemia). Your doctor will perform regular blood tests to detect any changes and will decide if you need specific treatment. In some cases, your doctor may reduce or stop your dose of temozolomide.

Other side effects that have been reported are:

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

• Loss of appetite, difficulty speaking, headache
• Vomiting, nausea, diarrhea, constipation
• Rash, hair loss
• Fatigue

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

• Infections, oral infections, wound infections
• Low blood cell count (neutropenia, lymphopenia, thrombocytopenia)
• Allergic reaction
• Increased blood sugar
• Changes in memory, depression, anxiety, confusion, inability to fall asleep or stay asleep
• Changes in balance and coordination
• Difficulty concentrating, changes in mental state or alertness, forgetfulness
• Dizziness, altered sensations, tingling, tremors, abnormal taste
• Partial loss of vision, abnormal vision, double vision, dryness or pain in the eyes
• Deafness, ringing in the ears, ear pain
• Blood clots in the lungs or legs, high blood pressure
• Pneumonia, difficulty breathing, bronchitis, cough, sinusitis
• Stomach or abdominal pain, heartburn, difficulty swallowing
• Dry skin, itching
• Muscle damage, muscle weakness, muscle pain
• Joint pain, back pain
• Frequent urination, difficulty controlling urination
• Fever, flu-like symptoms, pain, feeling unwell, a cold or flu
• Fluid retention, swelling of the legs
• Increased liver enzymes
• Weight loss, weight gain

Radiation injury

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

• Brain infections (herpetic meningoencephalitis) including fatal cases
• New or reactivated cytomegalovirus infections
• Reactivated hepatitis B virus infections
• Secondary cancers including leukemia
• Low blood cell count (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, changes in your sense of smell
• Changes in hearing, middle ear infection
• Palpitations (when you can feel your heartbeat), hot flashes
• Stomach swelling, difficulty controlling bowel movements, hemorrhoids, dry mouth
• Hepatitis and liver damage (including fatal liver failure), cholestasis, increased bilirubin
• Blisters on the body and in the mouth, skin peeling, skin rash, redness, painful redness of the skin, severe skin rash with swelling of the skin (including palms and soles)
• Increased sensitivity to sunlight, hives, increased sweating, changes in skin color
• Difficulty urinating
• Vaginal bleeding, vaginal irritation, absent or heavy menstrual periods, breast pain, sexual impotence
• Chills, swelling of the face, discoloration of the tongue, thirst, dental disorder

Reporting of side effects

If you experience 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 Temozolomide Accord

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

Do not use this medicine after the expiry date which is stated on the label and on the carton. The expiry date is the last day of the month stated.

Bottle

Do not store above 25°C.

Store in the original bottle. Keep the bottle tightly closed to protect from moisture.

Sachet

Do not store above 25°C.

Store in the original packaging to protect from moisture.

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. This will help protect the environment.

6. Container Content and Additional Information

Composition of Temozolomida Accord

The active ingredient is temozolomide.

Temozolomida Accord 5 mg hard capsules: Each capsule contains 5 mg of temozolomide.

Temozolomida Accord 20 mg hard capsules: Each capsule contains 20 mg of temozolomide.

Temozolomida Accord 100 mg hard capsules: Each capsule contains 100 mg of temozolomide.

Temozolomida Accord 140 mg hard capsules: Each capsule contains 140 mg of temozolomide.

Temozolomida Accord 180 mg hard capsules: Each capsule contains 180 mg of temozolomide.

Temozolomida Accord 250 mg 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.

Capsule shell:

Temozolomida Accord 5 mg hard capsules: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), carmine indigo (E 132), water.

Temozolomida Accord 20 mg hard capsules: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), water.

Temozolomida Accord 100 mg hard capsules: gelatin, titanium dioxide (E 171), and red iron oxide (E 172), water.

Temozolomida Accord 140 mg hard capsules: gelatin, titanium dioxide (E 171), carmine indigo (E 132), water.

Temozolomida Accord 180 mg hard capsules: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), water.

Temozolomida Accord 250 mg hard capsules: gelatin, titanium dioxide (E 171), water. Printing ink:

shellac, propylene glycol, black iron oxide (E 172), and potassium hydroxide.

Appearance of the Product and Container Content

Temozolomida Accord 5 mg hard capsules have a white body, a green cap, and are printed with black ink, TMZ on the cap and "5" on the body of the capsule.

Temozolomida Accord 20 mg hard capsules have a white body, a yellow cap, and are printed with black ink, TMZ on the cap and "20" on the body of the capsule.

Temozolomida Accord 100 mg hard capsules have a white body, a pink cap, and are printed with black ink, TMZ on the cap and "100" on the body of the capsule.

Temozolomida Accord 140 mg hard capsules have a white body, a blue cap, and are printed with black ink, TMZ on the cap and "140" on the body of the capsule.

Temozolomida Accord 180 mg hard capsules have a white body, a garnet cap, and are printed with black ink, TMZ on the cap and "180" on the body of the capsule.

Temozolomida Accord 250 mg hard capsules have a white body, a white cap, and are printed with black ink, TMZ on the cap and "250" on the body of the capsule.

The hard capsules are presented in amber glass bottles containing 5 or 20 capsules. Each carton contains one bottle.

The hard capsules are dispensed in sachets containing 1 capsule.

Each box contains 5 or 20 sachets.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center, Moll de Barcelona, s/n,

Edifici Est 6ª planta,

08039 Barcelona, Spain

Manufacturer

Accord Healthcare Polska Sp.z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

Accord Healthcare B.V.,

Winthontlaan 200,

3526 KV Utrecht,

Netherlands

The last revision of this prospectus was in XX/YYYY

Other Sources of Information

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