TEMOZOLOMIDE ACCORD

Package leaflet: Information for the user

Temozolomide Accord 5 mg hard capsules, 20 mg hard capsules, 100 mg hard capsules, 140 mg hard capsules, 180 mg hard capsules, 250 mg hard capsules

temozolomide
Please 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

What is in this leaflet

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

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

Temozolomide is an antineoplastic medicinal product.
Temozolomide Accord capsules are used for the treatment of specific types of brain tumours:

• in adults with newly diagnosed glioblastoma multiforme. Temozolomide is initially used in combination with radiotherapy (concomitant treatment phase) and subsequently used alone (monotherapy treatment phase).
• in children aged 3 years and older and in adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temozolomide is used in these tumours when relapse or progression occurs after standard therapy.

2. What you need to know before taking Temozolomide Accord

Do not take Temozolomide Accord

• if you are allergic to temozolomide or to any of the other ingredients of Temozolomide Accord (listed in section 6).
• if you have had an allergic reaction to another anti-cancer medicine called dacarbazine. Signs of an allergic reaction include itching, shortness of breath or wheezing, swelling of the face, lips, tongue or throat.
• if your blood cell count is low (myelosuppression), such as white blood cells and platelets. These blood cells are important for fighting infections and for proper blood clotting. Your doctor will perform blood tests to make sure that the number of these cells is adequate before starting treatment.

Warnings and precautions

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

• because you must be closely monitored for the development of a serious chest infection called Pneumocystis jirovecii pneumonia (PCP). If you are a newly diagnosed patient (glioblastoma multiforme), you may be given Temozolomide Accord for 42 days in combination with radiotherapy. In this case, your doctor will also prescribe medicines to help prevent this type of pneumonia (PCP).
• if you have ever had or may currently have hepatitis B infection. This is because Temozolomide Accord could cause reactivation of hepatitis B, which in some cases can be fatal. Before starting treatment, your doctor will carefully check you for signs of this infection.
• if you have a low number of red blood cells (anaemia), white blood cells and platelets, or blood clotting problems before starting treatment, or if you develop them during treatment. Your doctor may decide to reduce your dose. In severe cases, your doctor may stop, suspend or change your treatment. You may also require additional treatments. In some cases, it may be necessary to suspend administration of temozolomide. Furthermore, blood samples will be frequently analysed during treatment to monitor the adverse effects of Temozolomide Accord on your blood cells.
• because you may have a low risk of developing other blood cell abnormalities, including leukaemia.
• if you have nausea (feeling unwell in the stomach) and/or vomiting, which are very common side effects of temozolomide (see section 4). Your doctor may prescribe a medicine to help prevent vomiting. If you vomit frequently before or during treatment, ask your doctor about the best time to take temozolomide until vomiting is under control. If you vomit after taking a dose, do not take a second dose on the same day.
• if you develop fever or signs of infection, contact your doctor immediately.
• if you are over 70 years old, you may be more prone to infections, bruising or bleeding.
• if you have liver or kidney problems, your dose of temozolomide may need to be adjusted.

Children and adolescents
Do not give this medicine to children under 3 years of age, as it has not been studied in this age group.
Limited information is available in patients over 3 years of age who have taken Temozolomide Accord.

Other medicines and Temozolomide Accord
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, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before taking this medicine. This is because you should not be treated with Temozolomide Accord during pregnancy unless clearly indicated by your doctor.
Effective contraceptive precautions must be used by female patients of childbearing age during treatment with Temozolomide Accord and for at least 6 months after completion of treatment.
You must stop breast-feeding if you are being treated with Temozolomide Accord.

Male fertility
Temozolomide Accord may cause permanent infertility. Male patients should use an effective contraceptive method and should not attempt to father a child for at least 3 months after stopping treatment. It is recommended to seek advice on sperm preservation before starting treatment.

Driving and using machines
Temozolomide may cause tiredness or drowsiness. If this occurs, do not drive or operate tools or machinery or ride a bicycle until you know how this medicine affects you (see section 4).

Temozolomide Accord contains lactose
This medicine contains lactose (a type of sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact him or her before taking this medicine.

Temozolomide Accord contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per capsule, i.e. essentially 'sodium-free'.

3. How to take Temozolomide Accord

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

How to open the sachet
Fold and tear the sachet along the perforated line at the corner of the sachet.

Temozolomide should only be prescribed by a specialist experienced in the treatment of brain tumours.

Dosage and duration of treatment
Your doctor will determine your dose of temozolomide. This depends on your body size (height and weight) and, if you have a recurrent tumour, on any previous chemotherapy treatment you may have had. Other medicines (anti-emetics) may be prescribed to be taken before and/or after taking temozolomide to prevent or control nausea and vomiting.

Take the prescribed dose of Temozolomide Accord once daily. Take the medicine on an empty stomach; for example, at least one hour before 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 inside with your skin, eyes, or nose. Avoid inhaling the powder. If any powder accidentally comes into contact with your eyes or nose, rinse the affected area with water.

If you are taking Temozolomide Accord in combination with radiotherapy (newly diagnosed patients):
While undergoing radiotherapy, your doctor will start temozolomide at a dose of 75 mg/m², and your daily dose will depend on your height and weight. You will take this dose every day for 42 days (up to 49 days) in combination with radiotherapy. Depending on your blood cell counts and how well you tolerate temozolomide, the dose may be delayed or interrupted.

Once radiotherapy is completed, you will stop treatment for 4 weeks. This will give your body time to recover.

Then, you will start monotherapy.

During the monotherapy phase, the dose and way of taking Temodal will be different. Your doctor will determine your correct dose. There may be up to 6 treatment cycles, each lasting at least 28 days. You will take your new dose of temozolomide capsules initially at 150 mg/m² once daily for the first 5 days ("treatment days") of each cycle, followed by 23 days without temozolomide; thus completing the 28-day treatment cycle.

After Day 28, the next cycle will begin, during which you will again take this medicine once daily for 5 days, followed by 23 days without temozolomide. The dose of temozolomide may be adjusted, delayed, or interrupted based on your blood counts and how well you tolerate the medicine during each treatment cycle.

If you are taking Temozolomide Accord capsules alone (without radiotherapy):
A treatment cycle with Temozolomide Accord lasts 28 days. You will take the capsules once daily for the first 5 days ("treatment days"), followed by 23 days without temozolomide, thus completing the 28-day treatment cycle.

After Day 28, the next cycle will begin, during which you will again take this medicine once daily for 5 days, followed by 23 days without temozolomide. Before each new cycle, blood tests will be performed to determine whether the dose of temozolomide needs to be modified.

If you have not previously been treated with chemotherapy, your first dose of temozolomide will be 200 mg/m² once daily for the first 5 days ("treatment days"), followed by 23 days without temozolomide. If you have previously received chemotherapy, your first dose of temozolomide will be 150 mg/m² once daily for the first 5 days ("treatment days"), followed by 23 days without temozolomide.

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

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

All patients
Temozolomide is available in capsules of different strengths (shown on the outer label in mg). Each strength is identified by capsules of a different colour. Depending on the dose of temozolomide prescribed by your doctor, you may need to take several capsules each day during the treatment cycle.

• Make sure you clearly understand exactly how many capsules of each strength you need to take. Ask your doctor or pharmacist to write down the number of capsules for each strength (including the colour) that you need to take for each day of treatment.
• Make sure you know precisely which days are your treatment days.
• Make sure you review the dose with your healthcare provider each time you start a new cycle, as the dose or combination of capsules you need to take may differ from the previous cycle.
• When taking the medicine at home, if you are confused or unsure about how to take your dose, call for instructions before starting the treatment cycle. Errors in taking this medicine could cause serious harm to your health.

If you take more Temozolomide Accord than you should
If you accidentally take more capsules than prescribed, contact 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 full day has passed, contact your doctor. Do not take a double dose to make up for a missed dose unless instructed to do so by your doctor.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, Temozolomide Accord can cause side effects, although not everybody gets them.
Patients receiving temozolomide in combination with radiotherapy may experience different side effects than those reported by patients receiving temozolomide alone.
Contact your doctor immediately if you experience any of the following:

• a severe allergic reaction (hypersensitivity) (hives, shortness of breath or other breathing difficulties),
• 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 may lead to increased bruising or bleeding, anaemia (reduced number of red blood cells), fever and/or reduced resistance to infections. Decreased blood cell counts are usually short-lived; however, in some cases they may be prolonged and may lead to a very severe form of anaemia (aplastic anaemia). Your doctor will regularly monitor your blood and decide whether specific treatment is needed. In some cases, the dose of temozolomide may be reduced or treatment stopped.
Other side effects that have been reported are listed below:
Very common side effects (may affect more than 1 in 10 people):

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

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

• infections, mouth infections
• reduction in the number of blood cells (neutropenia, lymphopenia, thrombocytopenia)
• allergic reaction
• increased blood sugar levels
• memory loss, depression, anxiety, confusion, difficulty falling or staying asleep
• coordination problems and balance disorders
• difficulty concentrating, altered mental state or attention, memory loss
• dizziness, sensory disturbances, tingling sensation, tremor, altered taste
• partial loss of vision, abnormal vision, double vision, dry or painful eyes
• deafness, ringing in the ears, earache
• blood clots in the lung or legs, high blood pressure
• pneumonia, shortness of breath, bronchitis, cough, inflammation of the nasal cavities
• stomach or abdominal pain, stomach discomfort/heartburn, difficulty swallowing
• dry skin, itching
• muscle damage, muscle weakness, muscle pain and cramps
• joint pain, back pain
• frequent urination, difficulty holding urine
• fever, flu-like symptoms, pain, feeling unwell, cold or flu
• fluid retention, swollen legs
• increased liver enzymes
• weight loss, weight gain
• radiation injury

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

• brain infections (herpes meningoencephalitis), including cases resulting in death
• wound infections
• new or reactivated cytomegalovirus infections
• infections caused by reactivated hepatitis B virus
• secondary tumours including leukaemia
• reduction in the number of blood cells (pancytopenia, anaemia, leucopenia)
• red spots under the skin
• diabetes insipidus (symptoms include increased urine output and thirst), low blood potassium levels
• mood changes, hallucinations
• partial paralysis, changes in the perception of smells
• hearing disorders, middle ear infection
• palpitations (when you can feel your heartbeat), hot flushes
• abdominal swelling, difficulty controlling bowel movements, haemorrhoids, dry mouth
• hepatitis and liver damage (including liver failure leading to death), cholestasis, increased bilirubin
• blisters on the body or in the mouth, skin peeling, skin rash, painful redness of the skin, severe skin rash with skin swelling (including palms of hands and soles of feet)
• increased skin sensitivity to sunlight, hives (wheals), increased sweating, changes in skin colour
• difficulty urinating
• vaginal bleeding, vaginal irritation, absent or heavy menstrual periods, breast pain, sexual impotence
• chills, facial swelling, discoloured tongue, thirst, dental disorders
• dry eyes

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Temozolomide Accord

Keep this medicine out of the sight and reach of children, preferably in a locked cabinet.
Accidental ingestion may be fatal in children.
Do not use this medicine after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.

Vial
Do not store above 25°C.
Store in the original vial.
Keep the vial tightly closed to protect the medicine from moisture.

Pouch
Do not store above 25°C.
To protect the medicine from moisture, store in the original packaging.

Inform your pharmacist if you notice any signs of deterioration in the appearance of the capsules.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

What Temozolomide Accord contains

• The active substance is temozolomide.
  Temozolomide Accord 5 mg hard capsules: Each capsule contains 5 mg of temozolomide.
  Temozolomide Accord 20 mg hard capsules: Each capsule contains 20 mg of temozolomide.
  Temozolomide Accord 100 mg hard capsules: Each capsule contains 100 mg of temozolomide.
  Temozolomide Accord 140 mg hard capsules: Each capsule contains 140 mg of temozolomide.
  Temozolomide Accord 180 mg hard capsules: Each capsule contains 180 mg of temozolomide.
  Temozolomide Accord 250 mg hard capsules: Each capsule contains 250 mg of temozolomide.

• Other components are:
  Capsule contents: anhydrous lactose, anhydrous colloidal silica, sodium starch glycolate type A, tartaric acid, stearic acid, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), and indigo carmine (E132).

Capsule shell:
Temozolomide Accord 5 mg hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), indigo carmine (E132), water.
Temozolomide Accord 20 mg hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), water.
Temozolomide Accord 100 mg hard capsules: gelatin, titanium dioxide (E171), red iron oxide (E172), water.
Temozolomide Accord 140 mg hard capsules: gelatin, titanium dioxide (E171), indigo carmine (E132), water.
Temozolomide Accord 180 mg hard capsules: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), water.
Temozolomide Accord 250 mg hard capsules: gelatin, titanium dioxide (E171), water.

Printing ink:
Shellac, propylene glycol, black iron oxide (E172), potassium hydroxide.

Description of the appearance of Temozolomide Accord and pack contents

Temozolomide Accord 5 mg hard capsules have a white body and a green cap, with 'TMZ' printed on the cap and '5' on the body in black ink.
Temozolomide Accord 20 mg hard capsules have a white body and a yellow cap, with 'TMZ' printed on the cap and '20' on the body in black ink.
Temozolomide Accord 100 mg hard capsules have a white body and a pink cap, with 'TMZ' printed on the cap and '100' on the body in black ink.
Temozolomide Accord 140 mg hard capsules have a white body and a blue cap, with 'TMZ' printed on the cap and '140' on the body in black ink.
Temozolomide Accord 180 mg hard capsules have a white body and a brown cap, with 'TMZ' printed on the cap and '180' on the body in black ink.
Temozolomide Accord 250 mg hard capsules have a white body and a white cap, with 'TMZ' printed on the cap and '250' on the body in black ink.

The hard capsules are available in amber glass bottles containing 5 or 20 capsules.
Each pack contains 1 bottle.
The hard capsules are also available in blisters containing 1 capsule.
Each pack contains 5 or 20 blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6th floor,
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,
The Netherlands

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.