Temomedac

Patient Information Leaflet: Information for the User

Temomedac 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 this leaflet carefully before 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 give it to other people, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Temomedac is and what it is used for

Temomedac contains a medicine called temozolomide. This medicine is an antitumour agent.
Temomedac is used to treat specific types of brain tumours:

• in adults with newly diagnosed glioblastoma multiforme. Temomedac is initially used in combination with radiotherapy (concomitant treatment phase) and subsequently on its own (monotherapy treatment phase).
• in children aged 3 years and older and in adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temomedac is used in these tumours which have recurred or progressed after standard therapy.

2. What you need to know before taking Temomedac

Do not take Temomedac

• if you are allergic to temozolomide or to any of the other ingredients of this medicine (listed in section 6).
• if you have had a previous allergic reaction to dacarbazine (an anticancer medicine sometimes called DTIC). Signs of an allergic reaction include itching, shortness of breath or wheezing, swelling of the face, lips, tongue, or throat.
• if the number of certain types of blood cells is severely reduced (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 ensure that the number of these cells is adequate before starting treatment.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before taking Temomedac,

• 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 (with glioblastoma multiforme), you may be given Temomedac 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 Temomedac could cause reactivation of hepatitis B, which in some cases may be fatal. Before starting treatment, patients will be carefully checked by the doctor for signs of this infection.
• if you have low levels of red blood cells (anaemia), white blood cells, or platelets, or have blood clotting problems before starting treatment, or if you develop them during treatment. Your doctor may decide to reduce the dose, interrupt, suspend, or change the treatment. You may also require additional treatments. In some cases, administration of Temomedac may need to be suspended.
• blood samples will be frequently analysed during treatment to monitor for unwanted effects of Temomedac on your blood cells.
• because there is a low risk that you may develop other blood cell abnormalities, including leukaemia.
• if you experience nausea (feeling sick) and/or vomiting, which are very common side effects of Temomedac (see section 4), your doctor may prescribe a medicine (an anti-emetic) to help prevent vomiting. If you vomit frequently before or during treatment, ask your doctor about the best time to take Temomedac until vomiting is under control. If you vomit after taking a dose, do not take another dose on the same day.
• if you develop fever or symptoms 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 Temomedac 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. There is limited information available on patients over 3 years of age who have taken Temomedac.

Other medicines and Temomedac
Inform 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, suspect you may be pregnant, or are planning a pregnancy, consult your doctor or pharmacist before taking this medicine. This is because you should not be treated with Temomedac during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be used by female patients of childbearing potential during treatment with Temomedac and for at least 6 months after completion of treatment.

You must stop breastfeeding if you are being treated with Temomedac.

Male fertility
Temomedac 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
Temomedac may cause tiredness or drowsiness. If this occurs, do not drive or operate tools, machinery, or bicycles until you know how this medicine affects you (see section 4).

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

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

Additional information for Temomedac 20 mg hard capsules
The excipient sunset yellow FCF (E 110) present in the capsule shell may cause allergic reactions.

3. How to take Temomedac

Take this medicine exactly as instructed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Dosage and duration of treatment
Your doctor will determine your dose of Temomedac. 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
Temomedac to prevent or control nausea and vomiting.
Patients with newly diagnosed glioblastoma multiforme
If you are a patient who has been diagnosed with the tumour for the first time, treatment will consist of two
phases:

• initially, Temomedac is given in combination with radiotherapy (concomitant phase)
• subsequently, Temomedac is administered alone (monotherapy phase). During the concomitant phase, your doctor will start Temomedac at a dose of 75 mg/m² (usual dose). You will take this dose daily for 42 days (up to a maximum of 49 days) in combination with radiotherapy. The administration of Temomedac may be delayed or interrupted based on your blood cell counts and how well you tolerate the medicine during the concomitant phase. Once radiotherapy is completed, you will stop treatment for 4 weeks. This will allow your body time to recover. Then, you will start monotherapy.

During the monotherapy phase, the dose and method of taking Temomedac will be different.
Your doctor will determine your correct dose. There may be up to 6 treatment periods (cycles).
Each cycle lasts 28 days. You will take your new dose of Temomedac alone once daily
for the first 5 days (“treatment days”) of each cycle. The initial dose will be 150 mg/m². This will be
followed by 23 days without Temomedac. This completes the 28-day treatment cycle.
After Day 28, the next cycle will begin. You will again take Temomedac once daily
for 5 days, followed by 23 days without Temomedac. The dose of Temomedac may be adjusted,
delayed, or interrupted based on your blood counts and how well you tolerate the medicine during
each treatment cycle.
Patients with tumours that have recurred or worsened (malignant gliomas, such as glioblastoma
multiforme or anaplastic astrocytoma) treated with Temomedac alone
A treatment cycle with Temomedac lasts 28 days.
You will take Temomedac alone once daily for the first 5 days. This daily dose
depends on any previous chemotherapy treatments you may have received.
If you have not previously received chemotherapy, your first dose of Temomedac will be
200 mg/m² once daily for the first 5 days. If you have previously received
chemotherapy, your first dose of Temomedac will be 150 mg/m² once daily for the first
5 days.
For the following 23 days, you will not receive Temomedac. This completes the 28-day cycle.
After Day 28, the next cycle will begin. You will again take Temomedac once daily
for five days, followed by 23 days without Temomedac.
Before each new cycle, blood tests will be performed to determine whether the dose of
Temomedac needs to be modified. Based on the results of your blood tests, your doctor may
adjust your dose for the next cycle.
How to take Temomedac
Take the dose of Temomedac prescribed for you once daily, preferably at the same time
each day.
Take the capsules 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 with skin, eyes, or nose. If
powder accidentally comes into contact with eyes or nose, rinse the affected area
with water.
Depending on the prescribed dose, you may need to take more than one capsule
simultaneously, possibly with different strengths (active substance content in mg). The
colour and number on the capsule shell differ for each strength (see table below).

It is important to make sure you fully understand and remember the following:

• how many capsules you need to take for your daily dose. Ask your doctor or pharmacist to write this down for you (including the colour).
• which days you need to take your treatment. Review the dose with your doctor each time you start a new cycle, as it may differ from the previous cycle.

Take Temomedac exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist. Mistakes in taking this medicine could cause serious harm to your health.

If you take more Temomedac than you should
In case of accidental ingestion of more capsules than prescribed, contact your doctor, pharmacist, or nurse immediately.

If you forget to take Temomedac
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 forgotten dose, unless specifically instructed by your doctor.

If you have any doubts about the use of this medicine, consult 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 immediately if you experience:

• a severe allergic reaction (hypersensitivity) (rash, breathlessness or other breathing difficulties),
• uncontrolled bleeding,
• seizures (fits),
• fever,
• chills,
• severe headache that does not go away.

Treatment with Temomedac 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 reduced resistance to infections. The reduction in blood cell count is usually short-lived. In some cases, it 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 Temomedac will be reduced or treatment stopped.

Other side effects 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 blood cell count (neutropenia, lymphopenia, thrombocytopenia)
• allergic reaction
• increased blood sugar levels
• memory loss, depression, anxiety, confusion, inability to fall asleep or stay asleep
• coordination disorders and balance problems
• 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, eye pain
• 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 controlling 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 that have resulted in death
• new or reactivated infections due to cytomegalovirus
• wound infections
• infections caused by reactivated hepatitis B virus
• secondary tumours including leukaemia
• reduction in blood cell count (pancytopenia, anaemia, leucopenia)
• red spots under the skin
• diabetes insipidus (symptoms include increased urination and thirst), low blood potassium levels
• mood changes, hallucinations
• partial paralysis, change in smell perception
• dry eyes
• hearing disorders, middle ear infection
• palpitations (when you can feel your heartbeat), hot flushes
• stomach 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 swelling of the skin (including palms of hands and soles of feet)
• increased sensitivity of the skin to sunlight, urticaria (hives), increased sweating, change in skin colour
• difficulty urinating
• vaginal bleeding, vaginal irritation, absent or heavy menstrual periods, breast pain, sexual impotence
• chills, facial swelling, discolouration of the tongue, thirst, dental disorders

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via 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 Temomedac

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 the packaging. The expiry date refers to the last day of that month.
Do not store above 30°C.
Store in the original packaging to protect the medicine from moisture.
Keep the vial tightly closed.
Inform your pharmacist if you notice any changes in the appearance of the capsules.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What Temomedac contains

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

• The other components are:
  Capsule contents: anhydrous lactose, anhydrous colloidal silica, sodium carboxymethyl starch type A, tartaric acid, stearic acid (see section 2 “Temomedac contains lactose”).
  Capsule shell (including printing ink):
  Temomedac 5 mg hard capsules: gelatin, titanium dioxide (E 171), shellac, glycol propylene, carmine aluminium lake (E 132), yellow iron oxide (E 172).
  Temomedac 20 mg hard capsules: gelatin, titanium dioxide (E 171), shellac, glycol propylene, sunset yellow FCF aluminium lake (E 110).
  Temomedac 100 mg hard capsules: gelatin, titanium dioxide (E 171), red iron oxide (E 172), shellac, glycol propylene, and yellow iron oxide (E 172).
  Temomedac 140 mg hard capsules: gelatin, titanium dioxide (E 171), shellac, glycol propylene, indigo carmine aluminium lake (E 132).
  Temomedac 180 mg hard capsules: gelatin, titanium dioxide (E 171), shellac, glycol propylene, red iron oxide (E 172).
  Temomedac 250 mg hard capsules: gelatin, titanium dioxide (E 171), shellac, glycol propylene, black iron oxide (E 172).

Description of the appearance of Temomedac and contents of the pack
Temomedac 5 mg hard capsules have an opaque white body, a cap with two green ink stripes, and the body of the capsule is printed with “T 5 mg” in green ink.
Temomedac 20 mg hard capsules have an opaque white body, a cap with two orange ink stripes, and the body of the capsule is printed with “T 20 mg” in orange ink.
Temomedac 100 mg hard capsules have an opaque white body, a cap with two pink ink stripes, and the body of the capsule is printed with “T 100 mg” in pink ink.
Temomedac 140 mg hard capsules have an opaque white body, a cap with two blue ink stripes, and the body of the capsule is printed with “T 140 mg” in blue ink.
Temomedac 180 mg hard capsules have an opaque white body, a cap with two red ink stripes, and the body of the capsule is printed with “T 180 mg” in red ink.
Temomedac 250 mg hard capsules have an opaque white body, a cap with two black ink stripes, and the body of the capsule is printed with “T 250 mg” in black ink.

Hard capsules for oral use are supplied in amber glass bottles containing 5 or 20 capsules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
medac
Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany

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