Temodal

Informazzjoni prinċipali

  • Isem kummerċjali:
  • Temodal
  • Dominju tal-mediċina:
  • Bnedmin
  • Tip ta 'mediċina:
  • Droga allopatika

Dokumenti

Lokalizzazzjoni

  • Disponibbli fi:
  • Temodal
    Unjoni Ewropea
  • Lingwa:
  • Ingliż

Informazzjoni terapewtika

  • Grupp terapewtiku:
  • Antineoplastic agents,
  • Żona terapewtika:
  • Glioma, Glioblastoma
  • Indikazzjonijiet terapewtiċi:
  • Temodal hard capsules is indicated for the treatment of: adult patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment;, children from the age of three years, adolescents and adult patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.,
  • Sommarju tal-prodott:
  • Revision: 31

Status

  • Sors:
  • EMA - European Medicines Agency
  • L-istatus ta 'awtorizzazzjoni:
  • Authorised
  • Numru ta 'awtorizzazzjoni:
  • EMEA/H/C/000229
  • Data ta 'l-awtorizzazzjoni:
  • 25-01-1999
  • Kodiċi EMEA:
  • EMEA/H/C/000229
  • L-aħħar aġġornament:
  • 28-03-2019

Rapport ta 'Valutazzjoni Pubblika

7 Westferry Circus

Canary Wharf

London E14 4HB

United Kingdom

Telephone

+44 (0)20 7418 8400

Facsimile

+44 (0)20 7418 8416

E-mail

info@ema.europa.eu

Website

www.ema.europa.eu

An agency of the European Union

© European Medicines Agency, 2012. Reproduction is authorised provided the source is acknowledged.

EMA/84099/2012

EMEA/H/C/000229

EPAR summary for the public

Temodal

temozolomide

This is a summary of the European public assessment report (EPAR) for Temodal. It explains how the

Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in

favour of granting a marketing authorisation and its recommendations on the conditions of use for

Temodal.

What is Temodal?

Temodal is a medicine that contains the active substance temozolomide. It is available as capsules

(5 mg, 20 mg, 100 mg, 140 mg, 180 mg and 250 mg) and as a powder to be made up into a solution

for infusion (drip into a vein).

What is Temodal used for?

Temodal is an anticancer medicine. It is used to treat malignant glioma (brain tumours) in the

following groups of patients:

adults with newly diagnosed glioblastoma multiforme (an aggressive type of brain tumour).

Temodal is used first with radiotherapy and then on its own;

adults and children three years of age and over with malignant glioma such as glioblastoma

multiforme or anaplastic astrocytoma, when the tumour has returned or got worse after standard

treatment. Temodal is used on its own in these patients.

The medicine can only be obtained with a prescription.

How is Temodal used?

Treatment with Temodal should be prescribed by a doctor with experience in the treatment of brain

tumours.

The dose of Temodal depends on body surface area (calculated using the patient’s height and weight)

and ranges from 75 to 200 mg per square metre, once a day. The dose and the number of doses

depend on the type of tumour being treated, whether the patient has been treated before, whether

Temodal is being used alone or with radiotherapy, and how the patient responds to treatment.

Temodal capsules should be taken whole without food. If the solution for infusion is used, it should be

given over a period of 90 minutes. Patients may also need to take medicines to prevent vomiting

before taking Temodal.

For full details, see the summary of product characteristics (also part of the EPAR).

How does Temodal work?

The active substance in Temodal, temozolomide, belongs to a group of anticancer medicines called

alkylating agents. In the body, temozolomide is converted to another compound called MTIC. MTIC

binds to the DNA of cells while they are reproducing, which stops cell division. As a result, the cancer

cells cannot divide, slowing down the growth of tumours.

How has Temodal been studied?

Temodal capsules have been studied in four main studies.

The first study compared the effectiveness of Temodal and radiotherapy with that of radiotherapy on

its own in 573 patients with newly diagnosed glioblastoma multiforme.

The other three main studies involved patients with malignant glioma that had come back or got worse

after previous treatment. Two of these studies involved patients with glioblastoma multiforme: one

looked at the effects of Temodal in 138 patients and the other compared Temodal with procarbazine

(another anticancer medicine) in 225 patients. The final study looked at the safety and effectiveness of

Temodal in the treatment of 162 patients with anaplastic astrocytoma who were in their first relapse.

The main measures of effectiveness were how long the patients survived or the length of time before

the patient’s cancer started to get worse.

A further two studies were carried out in a total of 35 patients with brain tumours to show that the

capsules and solution for infusion produce the same levels of temozolomide in the blood.

What benefit has Temodal shown during the studies?

In the study of newly diagnosed glioblastoma multiforme, patients survived for an average of 14.6

months when they received Temodal and radiotherapy, compared with 12.1 months with radiotherapy

alone.

In the comparative study of glioblastoma multiforme that had come back or got worse after previous

treatment, it took an average of 2.9 months until the cancer got worse in patients taking Temodal,

compared with 1.9 months in the patients taking procarbazine. In anaplastic astrocytoma, it took an

average of 5.4 months for the cancer to get worse in patients taking Temodal.

What is the risk associated with Temodal?

The most common side effects with Temodal (seen in more than 1 patient in 10) are nausea (feeling

sick), vomiting, constipation, loss of appetite, alopecia (hair loss), headache, fatigue (tiredness),

convulsions (fits), rash, neutropenia or lymphopenia (low white blood cell counts), and

thrombocytopenia (low blood platelet counts). Patients receiving the solution for infusion may also

Temodal

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Temodal

Page 3/3

have injection site reactions, such as pain, irritation, itching, warmth, swelling and redness, as well as

bruising. For the full list of all side effects reported with Temodal, see the package leaflet.

Temodal must not be used in people who are hypersensitive (allergic) to temozolomide, any of the

other ingredients or dacarbazine (another anticancer medicine). Temodal must not be used in patients

with severe myelosuppression (a condition in which the bone marrow cannot make enough blood

cells).

Why has Temodal been approved?

The CHMP decided that Temodal’s benefits are greater than its risks and recommended that it be given

marketing authorisation.

Other information about Temodal

The European Commission granted a marketing authorisation valid throughout the European Union for

Temodal on 26 January 1999.

The full EPAR for Temodal can be found on the Agency’s website: ema.europa.eu/Find

medicine/Human medicines/European public assessment reports. For more information about

treatment with Temodal, read the package leaflet (also part of the EPAR) or contact your doctor or

pharmacist.

This summary was last updated in 02-2012.

Fuljett ta 'Informazzjoni għall-Pazjent: prodott - kompożizzjoni, indikazzjonijiet, effetti sekondarji, dożaġġ, interazzjonijiet, reazzjonijiet avversi, tqala, treddigħ

B. PACKAGE LEAFLET

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 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.

What is in this leaflet

What Temodal is and what it is used for

What you need to know before you take Temodal

How to take Temodal

Possible side effects

How to store Temodal

Contents of the pack and other information

1.

What Temodal is and what it is used for

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

Temodal is used for the treatment of specific forms of brain tumours:

in adults with newly-diagnosed glioblastoma multiforme. Temodal is first used together with

radiotherapy (concomitant phase of treatment) and after that alone (monotherapy phase of

treatment).

in children 3 years and older and adult patients with malignant glioma, such as glioblastoma

multiforme or anaplastic astrocytoma. Temodal is used in these tumours if they return or get

worse 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 medicine sometimes called

DTIC). Signs of allergic reaction include feeling itchy, breathlessness or wheezing, swelling of

the face, lips, tongue or throat.

if certain kinds of blood cells are severely reduced (myelosuppression), such as your white

blood cell count and platelet count. These blood cells are important for fighting infection and

for proper blood clotting. Your doctor will check your blood to make sure you have enough of

these cells before you begin treatment.

Warnings and precautions

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

-

as you should be observed closely for the development of a serious form of chest infection

called Pneumocystis jirovecii pneumonia (PCP). If you are a newly-diagnosed patient

(glioblastoma multiforme) you may be receiving Temodal for 42 days in combination with

radiotherapy. In this case, your doctor will also prescribe medicine to help you prevent this type

of pneumonia (PCP).

if you have ever had or might now have a hepatitis B infection. This is because Temodal could

cause hepatitis B to become active again, which can be fatal in some cases. Patients will be

carefully checked by their doctor for signs of this infection before treatment is started.

if you have low counts of red blood cells (anaemia), white blood cells and platelets, or blood

clotting problems before starting the treatment, or if you develop them during treatment. Your

doctor may decide to reduce the dose, interrupt, stop or change your treatment. You may also

need other treatments. In some cases, it may be necessary to stop treatment with Temodal. Your

blood will be tested frequently during treatment to monitor the side effects of Temodal on your

blood cells.

as you may have a small risk of other changes in blood cells, including leukaemia.

if you have nausea (feeling sick in your stomach) and/or vomiting which are very common side

effects of Temodal (see section 4), your doctor may prescribe you 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

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 develop fever or symptoms of an infection, contact your doctor immediately.

if you are older than 70 years of age, you might be more prone to infections, bruising or

bleeding.

if you have liver or kidney problems, your dose of Temodal may need to be adjusted.

Children and adolescents

Do not give this medicine to children under the age of 3 years because it has not been studied. There

is limited information in patients over 3 years of age 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, breast-feeding 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. This is because you must not be treated with

Temodal during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be taken by both male and female patients who are taking

Temodal (see also “Male fertility” below).

You should stop breast-feeding while receiving treatment with Temodal.

Male fertility

Temodal may cause permanent infertility. Male patients should use effective contraception and not

father a child for up to 6 months after stopping treatment. It is recommended to seek advice on

conservation of sperm prior to treatment.

Driving and using machines

Temodal may make you feel tired or sleepy. In this case, do not drive or use any tools or machines or

cycle until you see how this medicine affects you (see section 4).

Temodal contains lactose

Temodal contains lactose (a kind of sugar). If you have been told by your doctor that you have an

intolerance to some sugars, contact your doctor before taking this medicine.

3.

How to take Temodal

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor

or pharmacist if you are not sure.

Dosage and duration of treatment

Your doctor will work out your dose of Temodal. This is based on your size (height and weight) and

if you have a recurrent tumour and have had chemotherapy treatment in the past.

You may be given other medicines (anti-emetics) 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 occur in two phases:

treatment together with radiotherapy (concomitant phase) first

followed by treatment with only Temodal (monotherapy phase).

During the concomitant phase, your doctor will start Temodal at a dose of 75 mg/m

(usual dose).

You will take this dose every day for 42 days (up to 49 days) in combination with radiotherapy. The

Temodal dose may be delayed or stopped, depending on your blood counts and how you tolerate your

medicine during the concomitant phase.

Once the radiotherapy is completed, you will interrupt treatment for 4 weeks. This will give your

body a chance to recover.

Then, you will start the monotherapy phase.

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

will work out your exact dose. There may be up to 6 treatment periods (cycles). Each one lasts

28 days. You will take your new dose of Temodal alone once daily for the first 5 days (“dosing days”)

of each cycle. The first dose will be 150 mg/m

. Then you will have 23 days without Temodal. This

adds up to a 28-day treatment cycle.

After Day 28, the next cycle will begin. You will again take Temodal once daily for 5 days followed

by 23 days without Temodal. The Temodal dose may be adjusted, delayed or stopped depending on

your blood counts and how you tolerate your medicine during each treatment cycle.

Patients with tumours that have returned or worsened (malignant glioma, such as glioblastoma

multiforme or anaplastic astrocytoma) taking Temodal only:

A treatment cycle with Temodal lasts 28 days.

You will take Temodal alone once daily for the first 5 days. This daily dose depends on whether or

not you have received chemotherapy before.

If you have not been previously treated with chemotherapy, your first dose of Temodal will be

200 mg/m

once daily for the first 5 days. If you have been previously treated with chemotherapy,

your first dose of Temodal will be 150 mg/m

once daily for the first 5 days.

Then, you will have 23 days without Temodal. This adds up to a 28-day treatment cycle.

After Day 28, the next cycle will begin. You will again receive Temodal once daily for 5 days,

followed by 23 days without Temodal.

Before each new treatment cycle, your blood will be tested to see if the Temodal dose needs to be

adjusted. Depending on your blood test results, your doctor may adjust your dose 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 on an empty stomach; for example, at least one hour before you plan to eat

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 your skin, eyes or nose. If you

accidentally get some in your eyes or nose, flush the area with water.

Depending on the prescribed dose, you may have to take more than one capsule together, eventually

with different strengths (content of active substance, in mg). The colour of the capsule cap is different

for each strength (see in the table below).

Strength

Colour of the cap

Temodal 5 mg hard capsules

green

Temodal 20 mg hard capsules

yellow

Temodal 100 mg hard capsules

pink

Temodal 140 mg hard capsules

blue

Temodal 180 mg hard capsules

orange

Temodal 250 mg hard capsules

white

You should make sure you fully understand and remember the following:

how many capsules you need to take every dosing day. Ask your doctor or pharmacist to write

it down (including the colour).

which days are your dosing days.

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

last cycle.

Always take Temodal exactly as your doctor has told you. It is very important to check with your

doctor or pharmacist if you are not sure. Errors in how you take this medicine may have serious health

consequences.

If you take more Temodal than you should

If you accidentally take more Temodal capsules than you were told to, contact your doctor,

pharmacist or nurse immediately.

If you forget to take Temodal

Take the missed dose as soon as possible during the same day. If a full day has gone by, check with

your doctor. Do not take a double dose to make up for a forgotten dose, unless your doctor tells you to

do so.

If you have any further questions on 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 immediately if you have any of the following:

a severe allergic (hypersensitive) reaction (hives, wheezing or other breathing difficulty),

uncontrolled bleeding,

seizures (convulsions),

fever,

chills,

severe headache that does not go away.

Temodal treatment can cause a reduction in certain kinds of blood cells. This may cause you to have

increased bruising or bleeding, anaemia (a shortage of red blood cells), fever, and reduced resistance

to infections. The reduction in blood cell counts 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

monitor your blood regularly for any changes, and will decide if any specific treatment is needed. In

some cases, your Temodal dose will be reduced or treatment stopped.

Side effects from clinical studies:

Temodal in combination treatment with radiotherapy in newly-diagnosed glioblastoma

Patients receiving Temodal in combination with radiotherapy may experience different side effects

than patients taking Temodal alone. The following side effects may occur, and may require medical

attention.

Very common (may affect more than 1 in 10 people): loss of appetite, headache, constipation

(difficulty passing stools), nausea (feeling sick in your stomach), vomiting, rash, hair loss, tiredness.

Common (may affect up to 1 in 10 people): oral infections, wound infection, reduced number of

blood cells (neutropenia, thrombocytopenia, lymphopenia, leukopenia), increased sugar in the blood,

loss of weight, change in mental status or alertness, anxiety/depression, sleepiness, difficulty

speaking, impaired balance, dizziness, confusion, forgetfulness, difficulty concentrating, inability to

fall asleep or stay asleep, tingling sensation, bruising, shaking, abnormal or blurry vision, double

vision, hearing impairment, shortness of breath, cough, blood clot in the legs, fluid retention, swollen

legs, diarrhoea, stomach or abdominal pain, heartburn, upset stomach, difficulty swallowing, dry

mouth, skin irritation or redness, dry skin, itching, muscle weakness, painful joints, muscle aches and

pains, frequent urination, difficulty with holding your urine, allergic reaction, fever, radiation injury,

face swelling, pain, abnormal taste, abnormal liver function tests.

Uncommon (may affect up to 1 in 100 people): flu-like symptoms, red spots under the skin, low

potassium level in the blood, weight gain, mood swings, hallucination and memory impairment,

partial paralysis, impaired coordination, impaired sensations, partial loss of vision, dry or painful

eyes, deafness, infection of the middle ear, ringing in the ears, earache, palpitations (when you can

feel your heart beat), blood clot in the lung, high blood pressure, pneumonia, inflammation of your

sinuses, bronchitis, a cold or the flu, swollen stomach, difficulty controlling your bowel movements,

haemorrhoids, peeling skin, increased skin sensitivity to sunlight, change in skin colour, increased

sweating, muscle damage, back pain, difficulty in urinating, vaginal bleeding, sexual impotence,

absent or heavy menstrual periods, vaginal irritation, breast pain, hot flushes, shivering,

discolouration of your tongue, change in your sense of smell, thirst, tooth disorder.

Temodal monotherapy in recurrent or progressive glioma

The following side effects may occur, and may require medical attention.

Very common (may affect more than 1 in 10 people): reduced number of blood cells (neutropenia

or lymphopenia, thrombocytopenia), loss of appetite, headache, vomiting, nausea (feeling sick in your

stomach), constipation (difficulty passing stools), tiredness.

Common (may affect up to 1 in 10 people): loss of weight, sleepiness, dizziness, tingling sensation,

shortness of breath, diarrhoea, abdominal pain, upset stomach, rash, itching, hair loss, fever,

weakness, shivering, feeling unwell, pain, change in taste.

Uncommon (may affect up to 1 in 100 people): reduced blood cell counts (pancytopenia, anaemia,

leukopenia).

Rare (may affect up to 1 in 1,000 people): cough, infections including pneumonia.

Very rare (may affect up to 1 in 10,000 people): skin redness, urticaria (hives), skin eruption,

allergic reactions.

Other side effects:

Cases of elevations of liver enzymes have been commonly reported. Cases of increased bilirubin,

problems with bile flow (cholestasis), hepatitis and injury to the liver, including fatal liver failure,

have been uncommonly reported.

Very rare cases of severe rash with skin swelling, including on the palms of the hands and soles of the

feet, or painful reddening of the skin and/or blisters on the body or in the mouth have been observed.

Tell your doctor immediately if this occurs.

Very rare cases of lung side effects have been observed with Temodal. Patients usually present with

shortness of breath and cough. Tell your doctor if you notice any of these symptoms.

In very rare cases, patients taking Temodal and medicines like it may have a small risk of developing

secondary cancers, including leukaemia.

New or reactivated (recurring) cytomegalovirus infections and reactivated hepatitis B virus infections

have been uncommonly reported. Cases of brain infections caused by herpes virus

(meningoencephalitis herpetic), including fatal cases, have been uncommonly reported. Cases of

sepsis (when bacteria and their toxins circulate in the blood and start to damage the organs) have been

uncommonly reported.

Cases of diabetes insipidus have been uncommonly reported. Symptoms of diabetes insipidus include

passing a lot of urine and feeling thirsty.

Reporting of side effects

If you get 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 via 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.

How to store Temodal

Keep this medicine out of the sight and reach of children, preferably in a locked cupboard. Accidental

ingestion can be lethal for children.

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

refers to the last day of that month.

Bottle presentation

Do not store above 30

Store in the original bottle in order to protect from moisture.

Keep the bottle tightly closed.

Sachet presentation

Do not store above 30

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. These measures will help protect the environment.

6.

Contents of the pack and other information

What Temodal contains

The active substance is temozolomide.

Temodal 5 mg hard capsules: Each capsule contains 5 mg temozolomide.

Temodal 20 mg hard capsules: Each capsule contains 20 mg temozolomide.

Temodal 100 mg hard capsules: Each capsule contains 100 mg temozolomide.

Temodal 140 mg hard capsules: Each capsule contains 140 mg temozolomide.

Temodal 180 mg hard capsules: Each capsule contains 180 mg temozolomide.

Temodal 250 mg hard capsules: Each capsule contains 250 mg temozolomide.

The other ingredients are:

capsule content:

anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, stearic

acid (see section 2 "Temodal contains lactose").

capsule shell:

Temodal 5 mg hard capsules: gelatin, titanium dioxide (E 171), sodium laurilsulfate, yellow iron

oxide (E 172), indigo carmine (E 132).

Temodal 20 mg hard capsules: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron

oxide (E 172),

Temodal 100 mg hard capsules: gelatin, titanium dioxide (E 171), sodium lauril sulfate, red iron

oxide (E 172),

Temodal 140 mg hard capsules: gelatin, titanium dioxide (E 171), sodium lauril sulfate, indigo

carmine (E 132),

Temodal 180 mg hard capsules: gelatin, titanium dioxide (E 171), sodium lauril sulfate, yellow iron

oxide (E 172), and red iron oxide (E 172),

Temodal 250 mg hard capsules: gelatin, titanium dioxide (E 171), sodium lauril sulfate.

printing ink:

shellac, propylene glycol, purified water, ammonium hydroxide, potassium hydroxide, and black iron

oxide (E 172).

What Temodal looks like and contents of the pack

Temodal 5 mg hard capsules have an opaque white body, an opaque green cap, and are imprinted with

black ink.

Temodal 20 mg hard capsules have an opaque white body, an opaque yellow cap, and are imprinted

with black ink.

Temodal 100 mg hard capsules have an opaque white body, an opaque pink cap, and are imprinted

with black ink.

Temodal 140 mg hard capsules have an opaque white body, a blue cap, and are imprinted with black

ink.

Temodal 180 mg hard capsules have an opaque white body, an opaque orange cap, and are imprinted

with black ink.

Temodal 250 mg hard capsules have an opaque white body and cap, and are imprinted with black ink.

Bottle presentation

The hard capsules for oral use are dispensed in amber glass bottles containing 5 or 20 capsules.

The carton contains 1 bottle.

Sachet presentation

The hard capsules (capsules) for oral use are individually sealed in sachets and dispensed in cartons

containing 5 or 20 hard capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

The Netherlands

Manufacturer: SP Labo N.V., Industriepark 30, B-2220 Heist-op-den-Berg, Belgium

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgique/België/Belgien

MSD Belgium BVBA/SPRL

Tél/Tel: 0800 38 693 (+32(0)27766211)

dpoc_belux@merck.com

Lietuva

UAB Merck Sharp & Dohme

Tel.: +370 5 278 02 47

msd_lietuva@merck.com

България

Мерк Шарп и Доум България ЕООД

Тел.: +359 2 819 3737

info-msdbg@merck.com

Luxembourg/Luxemburg

MSD Belgium BVBA/SPRL

Tél/Tel: 0800 38 693 (+32(0)27766211)

dpoc_belux@merck.com

Česká republika

Merck Sharp & Dohme s.r.o.

Tel.: +420 233 010 111

dpoc_czechslovak@merck.com

Magyarország

MSD Pharma Hungary Kft.

Tel.: +36 1 888 53 00

hungary_msd@merck.com

Danmark

MSD Danmark ApS

Tlf: +45 4482 4000

dkmail@merck.com

Malta

Merck Sharp & Dohme Cyprus Limited

Tel: 8007 4433 (+356 99917558)

malta_info@merck.com

Deutschland

MSD SHARP & DOHME GMBH

Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)

e-mail@msd.de

Nederland

Merck Sharp & Dohme BV

Tel: 0800 9999000 (+31 23 5153153)

medicalinfo.nl@merck.com

Eesti

Merck Sharp & Dohme OÜ

Tel.: +372 6144 200

msdeesti@merck.com

Norge

MSD (Norge) AS

Tlf: +47 32 20 73 00

msdnorge@msd.no

Eλλάδα

MSD Α.Φ.Β.Ε.Ε.

Τηλ: +30 210 98 97 300

dpoc_greece@merck.com

Österreich

Merck Sharp & Dohme Ges.m.b.H.

Tel: +43 (0) 1 26 044

msd-medizin@merck.com

España

Merck Sharp & Dohme de España, S.A.

Tel: +34 91 321 06 00

msd_info@merck.com

Polska

MSD Polska Sp. z o.o.

Tel: +48 22 549 51 00

msdpolska@merck.com

France

MSD France

Tél: +33 (0) 1 80 46 40 40

Portugal

Merck Sharp & Dohme, Lda.

Tel: +351 21 446 57 00

clic@merck.com

Hrvatska

Merck Sharp & Dohme d.o.o.

Tel: + 385 1 6611 333

croatia_info@merck.com

România

Merck Sharp & Dohme Romania S.R.L.

Tel: + 4021 529 29 00

msdromania@merck.com

Ireland

Merck Sharp & Dohme Ireland (Human Health)

Limited

Tel: +353 (0)1 2998700

medinfo_ireland@merck.com

Slovenija

Merck Sharp & Dohme, inovativna zdravila

d.o.o.

Tel: +386 1 5204 201

msd_slovenia@merck.com

Ísland

Vistor hf.

Simi: +354 535 7000

Slovenská republika

Merck Sharp & Dohme, s. r. o.

Tel.: +421 2 58282010

dpoc_czechslovak@merck.com

Ιtalia

MSD Italia S.r.l.

Tel: +39 06 361911

medicalinformation.it@merck.com

Suomi/Finland

MSD Finland Oy

Puh/Tel: +358 (0)9 804650

info@msd.fi

Κύπρος

Merck Sharp & Dohme Cyprus Limited

Τηλ: 800 00 673 (+357 22866700)

cyprus_info@merck.com

Sverige

Merck Sharp & Dohme (Sweden) AB

Tel: +46 (0) 77 5700488

medicinskinfo@merck.com

Latvija

SIA Merck Sharp & Dohme Latvija

Tel: +371 67364224

msd_lv@merck.com

United Kingdom

Merck Sharp & Dohme Limited

Tel: +44 (0) 1992 467272

medicalinformationuk@merck.com

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu.

Package Leaflet: Information for the user

Temodal 2.5 mg/ml powder for solution for infusion

temozolomide

Read all of this leaflet carefully before you start using 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.

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.

What is in this leaflet

What Temodal is and what it is used for

What you need to know before you use Temodal

How to use Temodal

Possible side effects

How to store Temodal

Contents of the pack and other information

1.

What Temodal is and what it is used for

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

Temodal is used for the treatment of specific forms of brain tumours:

in adults with newly-diagnosed glioblastoma multiforme. Temodal is first used together with

radiotherapy (concomitant phase of treatment) and after that alone (monotherapy phase of

treatment).

in children 3 years and older and adult patients with malignant glioma, such as glioblastoma

multiforme or anaplastic astrocytoma. Temodal is used in these tumours if they return or get

worse after standard treatment.

2.

What you need to know before you use Temodal

Do not use 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 medicine sometimes called

DTIC). Signs of allergic reaction include feeling itchy, breathlessness or wheezing, swelling of

the face, lips, tongue or throat.

if certain kinds of blood cells are severely reduced (myelosuppression), such as your white

blood cell count and platelet count. These blood cells are important for fighting infection and

for proper blood clotting. Your doctor will check your blood to make sure you have enough of

these cells before you begin treatment.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Temodal,

-

as you should be observed closely for the development of a serious form of chest infection

called Pneumocystis jirovecii pneumonia (PCP). If you are a newly-diagnosed patient

(glioblastoma multiforme) you may be receiving Temodal for 42 days in combination with

radiotherapy. In this case, your doctor will also prescribe medicine to help you prevent this type

of pneumonia (PCP).

if you have ever had or might now have a hepatitis B infection. This is because Temodal could

cause hepatitis B to become active again, which can be fatal in some cases. Patients will be

carefully checked by their doctor for signs of this infection before treatment is started.

if you have low counts of red blood cells (anaemia), white blood cells and platelets, or blood

clotting problems before starting the treatment, or if you develop them during treatment. Your

doctor may decide to reduce the dose, interrupt, stop or change your treatment. You may also

need other treatments. In some cases, it may be necessary to stop treatment with Temodal. Your

blood will be tested frequently during treatment to monitor the side effects of Temodal on your

blood cells.

as you may have a small risk of other changes in blood cells, including leukaemia.

if you have nausea (feeling sick in your stomach) and/or vomiting which are very common side

effects of Temodal (see section 4), your doctor may prescribe you a medicine (an anti-emetic)

to help prevent vomiting.

if you develop fever or symptoms of an infection, contact your doctor immediately.

if you are older than 70 years of age, you might be more prone to infections, bruising or

bleeding.

if you have liver or kidney problems, your dose of Temodal may need to be adjusted.

Children and adolescents

Do not give this medicine to children under the age of 3 years because it has not been studied. There

is limited information in patients over 3 years of age who have used Temodal.

Other medicines and Temodal

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, think you may be pregnant or are planning to have a baby, ask your doctor or

pharmacist for advice before using this medicine. This is because you must not be treated with

Temodal during pregnancy unless clearly indicated by your doctor.

Effective contraceptive precautions must be taken by both male and female patients who are using

Temodal (see also “Male fertility” below).

You should stop breast-feeding while receiving treatment with Temodal.

Male fertility

Temodal may cause permanent infertility. Male patients should use effective contraception and not

father a child for up to 6 months after stopping treatment. It is recommended to seek advice on

conservation of sperm prior to treatment.

Driving and using machines

Temodal may make you feel tired or sleepy. In this case, do not drive or use any tools or machines or

cycle until you see how this medicine affects you (see section 4).

Temodal contains sodium

This medicine contains 2.4 mmol sodium per vial. This should be taken into consideration by patients

on a controlled sodium diet.

3.

How to use Temodal

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor

or pharmacist if you are not sure.

Your doctor will work out your dose of Temodal. This is based on your size (height and weight) and

if you have a recurrent tumour and have had chemotherapy treatment in the past.

You may be given other medicines (anti-emetics) to take before and/or after receiving Temodal to

prevent or control nausea and vomiting.

Patients with newly-diagnosed glioblastoma multiforme:

If you are a newly-diagnosed patient, treatment will occur in two phases:

treatment together with radiotherapy (concomitant phase) first

followed by treatment with only Temodal (monotherapy phase).

During the concomitant phase, your doctor will start Temodal at a dose of 75 mg/m

(usual dose).

You will receive this dose every day for 42 days (up to 49 days) in combination with radiotherapy.

The Temodal dose may be delayed or stopped, depending on your blood counts and how you tolerate

your medicine during the concomitant phase.

Once the radiotherapy is completed, you will interrupt treatment for 4 weeks. This will give your

body a chance to recover.

Then, you will start the monotherapy phase.

During the monotherapy phase, the dose and way you receive Temodal in this phase will be different.

Your doctor will work out your exact dose.

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

You will receive your new dose of Temodal alone once daily for the first 5 days of each cycle. The

first dose will be 150 mg/m

. Then you will have 23 days without Temodal. This adds up to a 28-day

treatment cycle.

After Day 28, the next cycle will begin. You will again receive Temodal once daily for 5 days

followed by 23 days without Temodal.

The Temodal dose may be adjusted, delayed or stopped depending on your blood counts and how you

tolerate your medicine during each treatment cycle.

Patients with tumours that have returned or worsened (malignant glioma, such as glioblastoma

multiforme or anaplastic astrocytoma) receiving Temodal only:

A treatment cycle with Temodal lasts 28 days.

You will receive Temodal alone once daily for the first 5 days. This daily dose depends on whether or

not you have received chemotherapy before.

If you have not been previously treated with chemotherapy, your first dose of Temodal will be

200 mg/m

once daily for the first 5 days. If you have been previously treated with chemotherapy,

your first dose of Temodal will be 150 mg/m

once daily for the first 5 days.

Then, you will have 23 days without Temodal. This adds up to a 28 day treatment cycle.

After Day 28, the next cycle will begin. You will again receive Temodal once daily for 5 days,

followed by 23 days without Temodal.

Before each new treatment cycle, your blood will be tested to see if the Temodal dose needs to be

adjusted. Depending on your blood test results, your doctor may adjust your dose for the next cycle.

How Temodal is given

Temodal will be given to you by your doctor in a drip into a vein (intravenous infusion), only over

approximately 90 minutes. No infusion site other than a vein is acceptable.

If you use more Temodal than you should

Your medicine is given to you by health care professionals. It is therefore unlikely that you will

receive more Temodal than you should. However, if you do, the doctor or nurse will treat you

accordingly.

If you have any further questions on 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 immediately if you have any of the following:

a severe allergic (hypersensitive) reaction (hives, wheezing or other breathing difficulty),

uncontrolled bleeding,

seizures (convulsions),

fever,

chills,

severe headache that does not go away.

Temodal treatment can cause a reduction in certain kinds of blood cells. This may cause you to have

increased bruising or bleeding, anaemia (a shortage of red blood cells), fever, and reduced resistance

to infections. The reduction in blood cell counts 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

monitor your blood regularly for any changes, and will decide if any specific treatment is needed. In

some cases, your Temodal dose will be reduced or treatment stopped.

Side effects from clinical studies:

Temodal powder for solution for infusion

In addition to the side effects listed below, the following may also occur with the use of Temodal

powder for solution for infusion: pain, irritation, itching, warmth, swelling or redness at the injection

site; also bruising (haematoma).

Temodal in combination treatment with radiotherapy in newly-diagnosed glioblastoma

Patients receiving Temodal in combination with radiotherapy may experience different side effects

than patients using Temodal alone. The following side effects may occur, and may require medical

attention.

Very common (may affect more than 1 in 10 people): loss of appetite, headache, constipation

(difficulty passing stools), nausea (feeling sick in your stomach), vomiting, rash, hair loss, tiredness.

Common (may affect up to 1 in 10 people): oral infections, wound infection, reduced number of

blood cells (neutropenia, thrombocytopenia, lymphopenia, leukopenia), increased sugar in the blood,

loss of weight, change in mental status or alertness, anxiety/depression, sleepiness, difficulty

speaking, impaired balance, dizziness, confusion, forgetfulness, difficulty concentrating, inability to

fall asleep or stay asleep, tingling sensation, bruising, shaking, abnormal or blurry vision, double

vision, hearing impairment, shortness of breath, cough, blood clot in the legs, fluid retention, swollen

legs, diarrhoea, stomach or abdominal pain, heartburn, upset stomach, difficulty swallowing, dry

mouth, skin irritation or redness, dry skin, itching, muscle weakness, painful joints, muscle aches and

pains, frequent urination, difficulty with holding your urine, allergic reaction, fever, radiation injury,

face swelling, pain, abnormal taste, abnormal liver function tests.

Uncommon (may affect up to 1 in 100 people): flu-like symptoms, red spots under the skin, low

potassium level in the blood, weight gain, mood swings, hallucination and memory impairment,

partial paralysis, impaired coordination, impaired sensations, partial loss of vision, dry or painful

eyes, deafness, infection of the middle ear, ringing in the ears, earache, palpitations (when you can

feel your heart beat), blood clot in the lung, high blood pressure, pneumonia, inflammation of your

sinuses, bronchitis, a cold or the flu, swollen stomach, difficulty controlling your bowel movements,

haemorrhoids, peeling skin, increased skin sensitivity to sunlight, change in skin colour, increased

sweating, muscle damage, back pain, difficulty in urinating, vaginal bleeding, sexual impotence,

absent or heavy menstrual periods, vaginal irritation, breast pain, hot flushes, shivering,

discolouration of your tongue, change in your sense of smell, thirst, tooth disorder.

Temodal monotherapy in recurrent or progressive glioma

The following side effects may occur, and may require medical attention.

Very common (may affect more than 1 in 10 people): reduced number of blood cells (neutropenia

or lymphopenia, thrombocytopenia), loss of appetite, headache, vomiting, nausea (feeling sick in your

stomach), constipation (difficulty passing stools), tiredness.

Common (may affect up to 1 in 10 people): loss of weight, sleepiness, dizziness, tingling sensation,

shortness of breath, diarrhoea, abdominal pain, upset stomach, rash, itching, hair loss, fever,

weakness, shivering, feeling unwell, pain, change in taste.

Uncommon (may affect up to 1 in 100 people): reduced blood cell counts (pancytopenia, anaemia,

leukopenia).

Rare (may affect up to 1 in 1,000 people): cough, infections including pneumonia.

Very rare (may affect up to 1 in 10,000 people): skin redness, urticaria (hives), skin eruption,

allergic reactions.

Other side effects:

Cases of elevations of liver enzymes have been commonly reported. Cases of increased bilirubin,

problems with bile flow (cholestasis), hepatitis and injury to the liver, including fatal liver failure,

have been uncommonly reported.

Very rare cases of severe rash with skin swelling, including on the palms of the hands and soles of the

feet, or painful reddening of the skin and/or blisters on the body or in the mouth have been observed.

Tell your doctor immediately if this occurs.

Very rare cases of lung side effects have been observed with Temodal. Patients usually present with

shortness of breath and cough. Tell your doctor if you notice any of these symptoms.

In very rare cases, patients receiving Temodal and medicines like it may have a small risk of

developing secondary cancers, including leukaemia.

New or reactivated (recurring) cytomegalovirus infections and reactivated hepatitis B virus infections

have been uncommonly reported. Cases of brain infections caused by herpes virus

(meningoencephalitis herpetic), including fatal cases, have been uncommonly reported. Cases of

sepsis (when bacteria and their toxins circulate in the blood and start to damage the organs) have been

uncommonly reported.

Cases of diabetes insipidus have been uncommonly reported. Symptoms of diabetes insipidus include

passing a lot of urine and feeling thirsty.

Reporting of side effects

If you get 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 via 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.

How to store Temodal

Keep this medicine out of the sight and reach of children.

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

refers to the last day of that month.

Store in a refrigerator (2°C – 8°C).

Once your medicine is prepared for infusion (reconstituted), the solution may be stored at room

temperature (25°C) for up to 14 hours, including infusion time.

The reconstituted solution should not be used if discolouration or particulate matter is observed.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

6.

Contents of the pack and other information

What Temodal contains

The active substance is temozolomide. Each vial contains 100 mg temozolomide. After reconstitution,

each ml solution for infusion contains 2.5 mg of temozolomide.

The other ingredients are mannitol (E421), threonine, polysorbate 80, sodium citrate (for

pH-adjustment) and hydrochloric acid concentrated (for pH-adjustment) (see section 2).

What Temodal looks like and contents of the pack

The powder for solution for infusion is a white powder. Temodal is available in a glass vial, with a

butyl rubber stopper and aluminium seal with a flip-off bonnet.

Each pack contains 1 vial of 100 mg temozolomide.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

The Netherlands

Manufacturer: SP Labo N.V., Industriepark 30, B-2220 Heist-op-den-Berg, Belgium

For any information about this medicine, please contact the local representative of the Marketing

Authorisation Holder:

Belgique/België/Belgien

MSD Belgium BVBA/SPRL

Tél/Tel: 0800 38 693 (+32(0)27766211)

dpoc_belux@merck.com

Lietuva

UAB Merck Sharp & Dohme

Tel.: +370 5 278 02 47

msd_lietuva@merck.com

България

Мерк Шарп и Доум България ЕООД

Тел.: +359 2 819 3737

info-msdbg@merck.com

Luxembourg/Luxemburg

MSD Belgium BVBA/SPRL

Tél/Tel: 0800 38 693 (+32(0)27766211)

dpoc_belux@merck.com

Česká republika

Merck Sharp & Dohme s.r.o.

Tel.: +420 233 010 111

dpoc_czechslovak@merck.com

Magyarország

MSD Pharma Hungary Kft.

Tel.: +36 1 888 53 00

hungary_msd@merck.com

Danmark

MSD Danmark ApS

Tlf: +45 4482 4000

dkmail@merck.com

Malta

Merck Sharp & Dohme Cyprus Limited

Tel: 8007 4433 (+356 99917558)

malta_info@merck.com

Deutschland

MSD SHARP & DOHME GMBH

Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)

e-mail@msd.de

Nederland

Merck Sharp & Dohme BV

Tel: 0800 9999000 (+31 23 5153153)

medicalinfo.nl@merck.com

Eesti

Merck Sharp & Dohme OÜ

Tel.: +372 6144 200

msdeesti@merck.com

Norge

MSD (Norge) AS

Tlf: +47 32 20 73 00

msdnorge@msd.no

Eλλάδα

MSD Α.Φ.Β.Ε.Ε.

Τηλ: +30 210 98 97 300

dpoc_greece@merck.com

Österreich

Merck Sharp & Dohme Ges.m.b.H.

Tel: +43 (0) 1 26 044

msd-medizin@merck.com

España

Merck Sharp & Dohme de España, S.A.

Tel: +34 91 321 06 00

msd_info@merck.com

Polska

MSD Polska Sp. z o.o.

Tel: +48 22 549 51 00

msdpolska@merck.com

France

MSD France

Tél: +33 (0) 1 80 46 40 40

Portugal

Merck Sharp & Dohme, Lda.

Tel: +351 21 446 57 00

clic@merck.com

Hrvatska

Merck Sharp & Dohme d.o.o.

Tel: + 385 1 6611 333

croatia_info@merck.com

România

Merck Sharp & Dohme Romania S.R.L.

Tel: + 4021 529 29 00

msdromania@merck.com

Ireland

Merck Sharp & Dohme Ireland (Human Health)

Limited

Tel: +353 (0)1 2998700

medinfo_ireland@merck.com

Slovenija

Merck Sharp & Dohme, inovativna zdravila

d.o.o.

Tel: +386 1 5204 201

msd_slovenia@merck.com

Ísland

Vistor hf.

Simi: +354 535 7000

Slovenská republika

Merck Sharp & Dohme, s. r. o.

Tel.: +421 2 58282010

dpoc_czechslovak@merck.com

Ιtalia

MSD Italia S.r.l.

Tel: +39 06 361911

medicalinformation.it@merck.com

Suomi/Finland

MSD Finland Oy

Puh/Tel: +358 (0)9 804650

info@msd.fi

Κύπρος

Merck Sharp & Dohme Cyprus Limited

Τηλ: 800 00 673 (+357 22866700)

cyprus_info@merck.com

Sverige

Merck Sharp & Dohme (Sweden) AB

Tel: +46 (0) 77 5700488

medicinskinfo@merck.com

Latvija

SIA Merck Sharp & Dohme Latvija

Tel: +371 67364224

msd_lv@merck.com

United Kingdom

Merck Sharp & Dohme Limited

Tel: +44 (0) 1992 467272

medicalinformationuk@merck.com

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

http://www.ema.europa.eu.

The following information is intended for medical or health care professional use only:

Caution must be exercised in handling Temodal 2.5 mg/ml powder for solution for infusion. The use

of gloves and aseptic technique is required. If Temodal 2.5 mg/ml comes into contact with skin or

mucosa, it should be washed immediately and thoroughly with soap and water.

Each vial must be reconstituted with 41 ml sterilised water for injections. The resulting solution

contains 2.5 mg/ml TMZ. The vials should be gently swirled and not shaken. The solution should be

inspected and any vial containing visible particulate matter should not be used. Reconstituted product

must be used within 14 hours, including infusion time.

A volume up to 40 ml reconstituted solution should be withdrawn, according to the total prescribed

dose and transferred into an empty 250 ml infusion bag (PVC or polyolefin). The pump tubing should

be attached to the bag, the tubing purged and then capped. Temodal 2.5 mg/ml must be administered

by intravenous infusion only over a period of 90 minutes.

Temodal 2.5 mg/ml powder for solution for infusion may be administered in the same IV line with

0.9% Sodium Chloride injection. It is incompatible with dextrose solutions.

In absence of additional data this medicinal product must not be mixed with other medicinal products

or infused simultaneously through the same intravenous line.

This medicinal product is for single use only. Any unused product or waste material should be

disposed of in accordance with local requirements.