TEMOZOLOMIDE SANDOZ 100 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

Temozolomide Sandoz 5 mg hard capsules EFG

Temozolomide Sandoz 20 mg hard capsules EFG

Temozolomide Sandoz 100 mg hard capsules EFG

Temozolomide Sandoz 140 mg hard capsules EFG

Temozolomide Sandoz 180 mg hard capsules EFG

Temozolomide Sandoz 250 mg hard capsules EFG

temozolomide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

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

Temozolomide Sandoz contains a medicine called temozolomide. This medicine is an antitumor agent.

Temozolomide Sandoz is used in the treatment of specific forms of brain tumors:

• in adults with newly diagnosed glioblastoma multiforme. Temozolomide Sandoz is initially used in combination with radiotherapy (concomitant phase of treatment) and subsequently alone (monotherapy phase of treatment),

in children aged 3 years and older and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temozolomide Sandoz is indicated in these tumors if they recur or worsen after standard treatment.

• in children aged 3 years and older and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma. Temozolomide Sandoz is indicated in these tumors if they recur or worsen after standard treatment.

2. What you need to know before taking Temozolomide Sandoz

Do not take Temozolomide Sandoz

• if you are allergic to temozolomide or any of the other ingredients of this medicine (listed in section 6),
• if you have had an allergic reaction to dacarbazine (an anticancer drug, sometimes called DTIC). Signs of an allergic reaction include itching, shortness of breath or wheezing, swelling of the face, lips, tongue, or throat,
• if you have significantly reduced certain types of blood cells (myelosuppression), as well as low white blood cell count and low platelet count. These blood cells are important for fighting infections and for proper blood clotting. Your doctor will ask for blood tests to check that you have a sufficient number of these cells before starting treatment.

Warnings and precautions

Talk to your doctor or pharmacist before starting Temozolomide Sandoz

• as you will need to be carefully monitored for the possible development of a severe respiratory infection called Pneumocystis jirovecii pneumonia (PCP). If you are a newly diagnosed patient (glioblastoma multiforme) you may be receiving Temozolomide Sandoz in the 42-day regimen, in combination with radiotherapy. In this case, your doctor will also prescribe a medicine to help prevent this type of pneumonia (PCP).
• if you have or may currently have a hepatitis B infection. This is because temozolomide may cause hepatitis B to become active again, which could be fatal in some cases. Patients will be carefully examined by their doctor for signs of infection before starting treatment,
• if you have low red blood cell count (anemia), low white blood cell count, and low platelet count, or blood clotting problems before treatment, or if you develop them during treatment. Your doctor may reduce the dose of the medicine. In some cases, your doctor may interrupt, stop, or change the treatment (see "Do not take Temozolomide Sandoz"). You may also need other treatment. You will be frequently subjected to blood tests to monitor the side effects of Temozolomide Sandoz on your blood cells.
• as you may have a low risk of other blood cell disorders, including leukemia,
• if you have nausea (feeling sick) and/or vomiting, which are very common side effects with Temozolomide Sandoz (see section 4), your doctor may prescribe an antiemetic medicine to prevent vomiting.

If you vomit frequently before or during treatment, ask your doctor about the best time to take Temozolomide Sandoz until the vomiting is controlled. If you vomit after taking your dose, do not take a second dose on the same day,

• if you have a fever or symptoms of an infection, contact your doctor immediately,
• if you are over 70 years of age, you may be more susceptible to infection and more prone to infections, bruising, and bleeding,
• if you have liver or kidney problems, your dose of Temozolomide Sandoz will be adjusted.

Children and adolescents

Do not give this medicine to children under 3 years of age, as its effect in this age group has not been studied. There is limited information available in patients over 3 years who have taken Temozolomide Sandoz.

Taking Temozolomide Sandoz with other medicines

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

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine, as you should not be treated with Temozolomide Sandoz during pregnancy unless clearly indicated by your doctor.

Effective contraceptive measures are recommended for both male and female patientswho are taking Temozolomide Sandoz (see also "Male fertility" below).

You must stop breastfeeding while being treated with Temozolomide Sandoz.

Male fertility

Temozolomide Sandoz may cause permanent infertility. Male patients must use effective contraceptive methods and not get their partner pregnant until 6 months after finishing treatment. It is recommended to consult about sperm preservation before treatment.

Driving and using machines

Temozolomide Sandoz may make you feel tired or sleepy, in this case, do not drive or use tools or machines, or ride a bicycle until you see how this medicine affects you (see section 4).

Temozolomide Sandoz contains lactose

This medicine contains lactose (a type of sugar). If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Temozolomide Sandoz

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Dose and duration of treatment

Your doctor will determine the correct dose of Temozolomide Sandoz based on your body size (height and weight), whether you have a recurrent tumor, and whether you have been previously treated with chemotherapy. You may be prescribed another medicine (antiemetic) to take before and/or after taking Temozolomide Sandoz to prevent or control nausea and vomiting.

Adult patients with newly diagnosed glioblastoma multiforme:

If you are a newly diagnosed patient, treatment will be carried out in two phases:

• first, concomitant treatment with radiotherapy (concomitant phase),
• followed by treatment with only Temozolomide Sandoz (monotherapy phase).

During the concomitant phase, your doctor will start with Temozolomide Sandoz at a dose of 75 mg/m2 (standard dose). You will take this dose every day for 42 days (up to a maximum of 49 days) in combination with radiotherapy. The dose of Temozolomide Sandoz may be delayed or interrupted, depending on your blood counts and how you tolerate the medication during the concomitant phase.

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

Then, the monotherapy phase will begin.

During the monotherapy phase, the dose and how you take Temozolomide Sandoz will be different.

Your doctor will indicate the exact dose.

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

You will take your new dose of Temozolomide Sandoz once a day for the first 5 days of each cycle ("dosing days"). The first dose will be 150 mg/m2. Then, there will be 23 days without Temozolomide Sandoz. This adds up to a total treatment cycle of 28 days.

After day 28, the next cycle will begin. You will take Temozolomide Sandoz once a day for 5 days, followed by 23 days without Temozolomide Sandoz.

The dose of Temozolomide Sandoz may be adjusted, delayed, or omitted, depending on your blood tests and how you tolerate your medication during each treatment cycle.

Adult patients with recurrent or progressive tumors (malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma) taking only Temozolomide Sandoz:

A treatment cycle with Temozolomide Sandoz is 28 days.

You will take Temozolomide Sandoz once a day for the first 5 days. The daily dose will depend on whether you have been previously treated with chemotherapy or not.

If you have not been previously treated with chemotherapy, your first dose will be 200 mg/m2 once a day for the first 5 days. If you have been previously treated with chemotherapy, your first dose of temozolomide will be 150 mg/m2 once a day for the first 5 days.

Then, there will be 23 days without Temozolomide Sandoz. This adds up to a total treatment cycle of 28 days.

After day 28, a new cycle will begin. You will take Temozolomide Sandoz once a day for 5 days, followed by 23 days without Temozolomide Sandoz.

Each time you start a new treatment cycle, your blood will be tested to check if your dose of temozolomide needs to be adjusted. Depending on the results, your doctor may adjust your medication for the next cycle.

How to take Temozolomide Sandoz

Take your prescribed dose of Temozolomide Sandoz 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 have breakfast. Swallow the capsule(s) whole with a glass of water. Do not open, crush, or chew the capsules. If the capsule is damaged, avoid contact of the powder with the skin, eyes, or nose. If it accidentally gets into your eyes or nose, rinse the area with water.

Depending on the prescribed dose, you may need to take more than one capsule at a time, with different concentrations (active ingredient content, in mg). The color of the capsule cap is different for each concentration (see table below).

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

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

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

Follow exactly the administration instructions of Temozolomide Sandoz given by your doctor. Consult your doctor or pharmacist if you have any doubts. Errors in the way you take this medicine can have serious consequences for your health.

If you take more Temozolomide Sandoz than you should

If you accidentally take more Temozolomide Sandoz capsules than you should, contact your doctor or pharmacist or nurse immediately.

If you forget to take Temozolomide Sandoz

Temozolomide Sandoz should be taken at the same time each day. If a whole day has passed, consult your doctor. Do not take a double dose to make up for the 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 Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Contact your doctor immediatelyif you have any of the following:

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

• uncontrolled bleeding,
• seizures,
• fever,
• chills,
• severe headache that does not go away.

Treatment with Temozolomida Sandoz may cause a reduction in certain types of blood cells. This can increase the likelihood of bruising or bleeding, anemia (reduction in the number of red blood cells), fever, and decreased resistance to infections. The reduction in blood cell count is generally temporary. In some cases, it can be prolonged and may produce a very severe form of anemia (aplastic anemia). Your doctor will frequently perform blood tests to detect any changes that may occur and decide if you need specific treatment.

Adverse effects seen in clinical studies:

Temozolomida in combination with radiotherapy in patients with newly diagnosed glioblastoma

Patients who receive Temozolomida in combination with radiotherapy may experience different adverse reactions than those who receive Temozolomida alone. The following adverse effects may occur and may require medical attention.

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

• loss of appetite,
• headache,
• constipation (difficulty evacuating feces),
• nausea (vomiting urges),
• vomiting,
• skin rash,
• hair loss,
• fatigue.

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

• oral infections,
• wound infections,
• reduced blood cell count (neutropenia, thrombocytopenia, lymphopenia, leucopenia),
• increased blood sugar,
• weight loss,
• changes in mental state or alertness,
• anxiety/depression,
• drowsiness,
• difficulty speaking,
• balance disturbance,
• dizziness,
• confusion,
• memory disturbances,
• difficulty concentrating,
• inability to sleep or stay asleep,
• tingling sensation,
• bruising,
• agitation,
• abnormal or blurred vision,
• double vision,
• hearing loss,
• breathing difficulties,
• cough,
• thrombosis in the legs,
• fluid retention,
• swollen legs,
• diarrhea,
• abdominal or stomach pain,
• heartburn,
• gastric upset,
• difficulty swallowing,
• dry mouth,
• skin irritation or redness,
• dry skin,
• itching,
• muscle weakness,
• joint pain,
• muscle pain,
• frequent urination,
• difficulty controlling urine,
• allergic reaction,
• fever,
• radiation injury,
• facial swelling,
• pain,
• taste disturbance,
• abnormal liver function tests.

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

• pseudogripal symptoms,
• red spots under the skin,
• low potassium levels in the blood,
• weight gain,
• mood changes,
• hallucinations and memory loss,
• partial paralysis,
• coordination failure,
• decreased sensitivity,
• partial loss of vision,
• dry or painful eyes,
• hearing loss,
• middle ear infection,
• ringing in the ears,
• ear pain,
• palpitations (when the heartbeat can be felt),
• pulmonary thrombosis,
• high blood pressure,
• pneumonia,
• nasal passage inflammation,
• bronchitis,
• cold or flu,
• stomach distension,
• difficulty controlling bowel movements,
• hemorrhoids,
• skin peeling,
• increased skin sensitivity to sunlight,
• skin color change,
• increased sweating,
• muscle damage,
• back pain,
• difficulty urinating,
• vaginal bleeding,
• sexual impotence,
• abundant or absent menstrual periods,
• vaginal irritation,
• breast pain,
• hot flashes,
• chills,
• tongue color change,
• change in sense of smell,
• thirst,
• dental disturbances.

Monotherapy with temozolomida in recurrent or progressive brain tumor

The following adverse reactions may occur and may require medical attention.

Very common(may affectmore than 1 in 10 people):

• reduction in blood cell count (neutropenia or lymphopenia, thrombocytopenia),
• loss of appetite,
• headache,
• vomiting,
• nausea (vomiting urges),
• constipation (difficulty evacuating feces),
• fatigue.

Common(mayaffect up to 1 in 10 people):

• weight loss,
• drowsiness,
• fatigue,
• dizziness,
• tingling sensation,
• breathing difficulties,
• diarrhea,
• abdominal pain,
• gastric upset,
• skin rash,
• itching,
• hair loss,
• fever,
• weakness,
• chills,
• feeling unwell,

• pain,
• taste disturbance.

Uncommon (mayaffect up to 1 in 100 people):

• reduction in blood cell count (pancytopenia, anemia, leucopenia).

Rare(mayaffect up to 1 in 1,000 people):

• cough,
• infections including pneumonia.

Very rare(mayaffect up to 1 in 10,000 people

• skin redness,
• hives,
• skin rash,
• allergic reactions.

Other adverse effects:

There have been cases of adverse hepatic effects, including elevations of liver enzymes, increased bilirubin, problems with bile flow (cholestasis), and hepatitis. Liver damage, including fatal liver failure, has been reported.

Very rare cases of severe skin rash with skin swelling, including on the palms of the hands and soles of the feet, or skin redness with pain and/or blisters on the body or in the mouth have been observed. If this occurs, inform your doctor immediately.

Very rare cases of adverse pulmonary effects with Temozolomida Sandoz have been observed. Patients usually present with breathing difficulties and cough. Inform your doctor if you notice any of these symptoms.

Very rarely, patients taking temozolomida and similar medications may have a small risk of developing secondary cancers, including leukemia.

New or reactivated (recurrent) cytomegalovirus infections and reactivated hepatitis B virus infections have been reported infrequently. Infrequent cases of herpes virus-related brain infections (herpetic meningoencephalitis), including fatal cases, have been reported. Sepsis (a situation in which bacteria and their toxins circulate in the blood and begin to damage organs) has been reported infrequently.

Diabetes insipidus has also been reported infrequently. Symptoms of diabetes insipidus include excessive urination and thirst.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Annex V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Temozolomida Sandoz

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

Do not use this medicine after the expiration date stated on the label and outer packaging after "EXP". The expiration date is the last day of the month indicated.

Bottle

Do not store above 25°C.

Store in the original package.

Keep the bottle tightly closed to protect it from moisture.

Blister pack

Do not store above 25°C.

Consult your pharmacist if you notice any change in the appearance of the capsules.

Do not dispose of medicines through wastewater or household waste. Ask your pharmacist where to dispose of medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Temozolomida Sandoz

• The active ingredient is temozolomide.

Temozolomida Sandoz 5 mg hard capsules

Each capsule contains 5 mg of temozolomide

Temozolomida Sandoz 20 mg hard capsules

Each capsule contains 20 mg of temozolomide

Temozolomida Sandoz 100 mg hard capsules

Each capsule contains 100 mg of temozolomide

Temozolomida Sandoz 140 mg hard capsules

Each capsule contains 140 mg of temozolomide

Temozolomida Sandoz 180 mg hard capsules

Each capsule contains 180 mg of temozolomide

Temozolomida Sandoz 250 mg hard capsules

Each capsule contains 250 mg of temozolomide

• The other components of the capsule are:

Temozolomida Sandoz 5 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), indigo carmine (E 132), and water
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Temozolomida Sandoz 20 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), and water
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Temozolomida Sandoz 100 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), red iron oxide (E 172), and water.
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Temozolomida Sandoz 140 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), indigo carmine (E 132), and water.
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Temozolomida Sandoz 180 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), and water.
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Temozolomida Sandoz 250 mg hard capsules

• Capsule content: anhydrous lactose, colloidal anhydrous silica, sodium starch glycolate type A, tartaric acid, and stearic acid.
• Capsule body: gelatin, titanium dioxide (E 171), and water
• Printing ink: shellac, potassium hydroxide, and black iron oxide (E 172).

Product Appearance and Package Contents

Bottle

The hard capsules are presented in amber glass bottles (type 3) with a child-resistant polypropylene closure containing 5 or 20 capsules. Each bottle contains a desiccant sachet. Keep the desiccant sachet in the bottle. Do not swallow.

Blister

Each capsule (capsules) is packaged in individual blisters. Each pack contains 5 or 20 hard capsules.

Temozolomida Sandoz 5 mg hard capsules

The hard capsules have a white body, a green cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “5”.

Each capsule is approximately 15.8 mm in length.

Temozolomida Sandoz 20 mg hard capsules

The hard capsules have a white body, a yellow cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “20”.

Each capsule is approximately 11.4 mm in length.

Temozolomida Sandoz 100 mg hard capsules

The hard capsules have a white body, a pink cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “100”.

Each capsule is approximately 15.8 mm in length.

Temozolomida Sandoz 140 mg hard capsules

The hard capsules have a white body, a blue transparent cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “140”.

Each capsule is approximately 19.3 mm in length.

Temozolomida Sandoz 180 mg hard capsules

The hard capsules have a white body, a maroon cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “180”.

Each capsule is approximately 19.3 mm in length.

Temozolomida Sandoz 250 mg hard capsules

The hard capsules have a white body, a white cap, and are printed with black ink. The cap is printed with “TMZ”. The body is printed with “250”.

Each capsule is approximately 21.4 mm in length.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Sandoz GmbH

Biochemiestraße 10

A-6250 Kundl

Austria

Manufacturer

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1

D-39179 Barleben

Germany

Lek Pharmaceuticals d.d

Verovskova 57

SI-1526 Ljubljana

Slovenia

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:{MM/YYYY}

Other Sources of Information

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

The leaflet for this medicinal product can be found on the European Medicines Agency website in all languages of the European Union/European Economic Area.