VOTUBIA 10 mg Tabletki

Treść ulotki

1. Votubia 2.5 mg tablets, 5 mg tablets, 10 mg tablets
   1. What is Votubia and what is it used for
   2. What you need to know before taking Votubia
   3. How to take Votubia
   4. Possible side effects
   5. How to store Votubia
   6. Package contents and other information
2. Votubia 1 mg dispersible tablets, 2 mg dispersible tablets, 3 mg dispersible tablets, 5 mg dispersible tablets
   1. What is Votubia and what is it used for
   2. What you need to know before taking Votubia
   3. How to take Votubia
   4. Possible side effects
   5. How to store Votubia
   6. Content of the pack and other information

Votubia 2.5 mg tablets, 5 mg tablets, 10 mg tablets

everolimus

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Votubia and what is it used for

Votubia is an anti-cancer medicine that can block the growth of certain cells in the body. It contains
an active substance called everolimus which can reduce the size of kidney tumors called
renal angiomyolipomas and brain tumors called subependymal giant cell astrocytomas
(SEGA). These tumors are caused by a genetic disorder called tuberous sclerosis complex
(TSC).
Votubia tablets is used for the treatment of:

• TSC with renal angiomyolipoma in adults who do not require immediate surgery.
• SEGA associated with TSC in adults and children for whom surgery is not appropriate.

2. What you need to know before taking Votubia

If you are being treated for TSC with renal angiomyolipoma, Votubia will only be prescribed to you by a doctor
experienced in the treatment of patients with TSC.
If you are being treated for SEGA associated with TSC, Votubia will only be prescribed to you by a doctor experienced in the
treatment of patients with SEGA and with access to blood tests to measure the amount of
Votubia in the blood.
Follow all of your doctor's instructions carefully. These instructions may be different from the
ones in this leaflet, so speak to your doctor.

Do not take Votubia

• if you are allergicto everolimus, to similar substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6). If you have had allergic reactions in the past, ask your doctor for advice.

Warnings and precautions
Talk to your doctor before taking Votubia:

• if you have liver problems or have had any illness that may have affected your liver. In this case, your doctor may need to prescribe a different dose of Votubia or stop treatment, for a short period or permanently.
• if you have diabetes (high blood sugar levels). Votubia can increase blood sugar levels and worsen diabetes mellitus. This may require the use of insulin and/or oral antidiabetic agents. Tell your doctor if you experience excessive thirst or increased frequency of urination.
• if you need to get a vaccine while taking Votubia, as vaccination may be less effective. For children with SEGA, it is important to talk to your doctor about the pediatric vaccination schedule before starting treatment with Votubia.
• if you have high cholesterol levels. Votubia can raise cholesterol and/or other fat levels in the blood.
• if you have recently had surgery, or if you have a wound that has not yet healed following surgery. Votubia may increase the risk of problems related to wound healing.
• if you have an infection. The infection may need to be treated before starting Votubia.
• if you have had hepatitis B in the past, as it may recur during treatment with Votubia (see section 4 “Possible side effects”).
• if you have received or are about to receive radiotherapy.

Votubia can also:

• cause mouth sores (ulcers in the oral cavity).
• weaken the immune system. Therefore, you may be at risk of contracting an infection during treatment with Votubia. If you have a fever or other signs of infection, see your doctor. Some infections can be serious and can be fatal in adults and children.
• impair kidney function. Therefore, your doctor will check your kidney function during treatment with Votubia.
• cause shortness of breath, cough and fever (see section 4 “Possible side effects”).
• cause complications from radiotherapy. Serious reactions to radiation (such as shortness of breath, nausea, diarrhea, skin rashes and irritation of the mouth, gums and throat), including fatal cases, have been observed in some patients who were taking everolimus at the same time as radiotherapy or who were taking everolimus shortly after radiotherapy. In addition, so-called radiation recall syndrome (including skin redness or lung inflammation at the site of previous radiotherapy) has been reported in patients who had previously undergone radiotherapy. Tell your doctor if you are planning to receive radiotherapy in the near future or have received radiotherapy in the past.

Tell your doctor immediatelyif you experience these symptoms.
You will have blood tests before and periodically during treatment. These tests will check the amount of blood cells in your body (white blood cells, red blood cells and
platelets) to see if Votubia has an undesirable effect on these cells. You will also have blood tests to check kidney function (creatinine levels, blood urea nitrogen, or
protein in urine), liver function (transaminase levels) and blood sugar and
lipid levels. These levels can also be affected by Votubia.
If you receive Votubia for the treatment of SEGA associated with TSC, regular blood tests are also
necessary to measure how much Votubia is in the blood, as this will help your doctor decide
how much Votubia you should take.

Children and adolescents
Votubia can be used in children and adolescents with SEGA associated with TSC.
Votubia should not be used in children or adolescents with TSC who have a renal angiomyolipoma
without SEGA, as it has not been studied in these patients.

Other medicines and Votubia
Votubia can affect the action of some medicines. If you are taking other medicines while
taking Votubia, your doctor may need to change the dose of Votubia or the other medicines.
Tell your doctor or pharmacist if you are taking, have recently taken or might start taking any other medicine.
The following may increase the risk of side effects with Votubia:

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungals used to treat fungal infections.
• clarithromycin, telithromycin or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medicines used to treat HIV/AIDS infection.
• verapamil or diltiazem used to treat heart disease or high blood pressure.
• dronedarone, used to help regulate the heartbeat.
• cyclosporine, a medicine used to prevent organ rejection in transplant patients.
• imatinib, used to block the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• cannabidiol (uses include, also, the treatment of seizures).

The following may reduce the effectiveness of Votubia:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine used to treat HIV/AIDS infection.
• St John's wort ( Hypericum perforatum), a herbal remedy used to treat depression and other conditions.
• dexamethasone corticosteroid used to treat a wide range of conditions including inflammatory or immune problems.
• phenytoin, carbamazepine or phenobarbital and other anti-epileptics used to block seizures.

All of the medicines listed above should be avoided during treatment with Votubia. If you are
taking any of these medicines, your doctor may prescribe different medicines, or may
change your dose of Votubia.
If you are taking an anti-epileptic medicine, a change in the dose of the anti-epileptic medicine
(increase or decrease) may require a change in the dose of Votubia. Your doctor
will assess the need for this change. If the dose of your anti-epileptic medicine is changed,
tell your doctor.

Votubia with food and drink
Avoid grapefruit and grapefruit juice while being treated with Votubia. This could
increase the amount of Votubia in the blood, even to a harmful level.

Pregnancy, breastfeeding and fertility
Pregnancy
Votubia can cause harm to the fetus and is not recommended during pregnancy. Tell your doctor if you are
pregnant or think you may be.
Women who can become pregnant should use very effective contraception
during treatment and for 8 weeks after the end of treatment. If, despite these measures,
you suspect you are pregnant, ask your doctor for advice beforetaking Votubia any further.
Breastfeeding
Votubia can cause harm to the infant. Do not breastfeed during treatment and for
2 weeks after the last dose of Votubia. Tell your doctor if you are breastfeeding.
Fertility
Votubia may affect male and female fertility. Talk to your doctor if you wish to become
pregnant.

Driving and using machines
If you feel unusually tired (fatigue is a common side effect), be particularly
careful when driving vehicles or using machines.

Votubia contains lactose
Votubia contains lactose (milk sugar). If your doctor has told you that you have an intolerance to
some sugars, contact your doctor before taking this medicine.

3. How to take Votubia

Take this medicine following exactly the instructions of your doctor or pharmacist.
Votubia exists as tablets and dispersible tablets. Always take only the tablets or only the
dispersible tablets and never a combination of both. If you have any doubts, consult your doctor or
pharmacist.

How much Votubia to take
If you receive Votubia for the treatment of TSC with renal angiomyolipoma, the usual dose is 10 mg,
to be taken once a day.
Higher or lower doses may be prescribed by your doctor based on individual treatment needs,
for example if you have liver problems or need to take other medicines in addition to Votubia.
If you receive Votubia for the treatment of TSC with SEGA, the doctor will determine the dose of Votubia that you
must take based on:

• age
• body surface area
• liver status
• taking other medicines.

You will undergo blood tests during treatment with Votubia. This is to measure the
amount of Votubia in the blood and find the best dose for you.
If certain undesirable events (see section 4) occur while you are taking Votubia, your
doctor may reduce your dose or interrupt treatment for a short period of time or
permanently.

How to take this medicine

• Take Votubia tablets once a day.
• Take them at the same time each day.
• Take them with or without food, but you must take them the same way every day.

Swallow the tablets whole with a glass of water. Do not chew or crush the tablets. If you are
taking Votubia tablets for the treatment of TSC with SEGA and if you are unable to
swallow them, dissolve the tablets in a glass of water:

• Place the necessary number of tablets in a glass of water (about 30 ml).
• Gently stir the contents of the glass until the tablets dissolve and (about 7 minutes) then drink the contents immediately.
• Refill the glass with the same amount of water (about 30 ml), gently stir the remaining contents and drink all the contents to be sure you have taken the entire dose of Votubia tablets.
• If necessary, drink more water to remove any residue from the mouth.

Particular information for healthcare professionals
Healthcare professionals should try to avoid contact with the suspension of Votubia tablets. Wash
your hands thoroughly before and after preparing the suspension

If you take more Votubia than you should

• If you have taken more Votubia than you should, or if someone else has accidentally taken your tablets, contact a doctor immediately or go to hospital. Emergency treatment may be necessary.

If you forget to take Votubia
If you forget to take a dose, take the next dose as scheduled. Do not take a
double dose to make up for a missed dose.

If you stop taking Votubia
Do not stop treatment with Votubia tablets unless your doctor tells you to do so.
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
STOP treatment with Votubia and contact your doctor immediately if you or your child
experience any of the following signs of an allergic reaction:

• difficulty breathing or swallowing
• swelling of the face, lips, tongue or throat (signs of angioedema)
• severe itching of the skin, with a red rash or skin swellings

Serious side effects of Votubia include:
Very common side effects(may affect more than 1 in 10 people)

• Fever, cough, difficulty breathing, wheezing (signs of lung inflammation caused by infection, also known as infectious pneumonia)

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

• Swelling, feeling of heaviness or tightness, pain, limited mobility of some parts of the body (this can occur in any part of the body and is a potential sign of abnormal fluid accumulation in the soft tissues due to a blockage in the lymphatic system, also known as lymphedema)
• Rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of a severe allergic reaction, also known as hypersensitivity)
• Fever, cough, difficulty breathing, wheezing (signs of lung inflammation, also known as pneumonia)

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

• Rash with small blisters filled with fluid appearing on red skin (signs of a viral infection that may potentially be serious, also known as herpes zoster)
• Fever, chills, rapid breathing and heart rate, rash and possible confusion and disorientation (signs of a serious infection, also known as sepsis)

If any of these side effects occur, tell your doctor immediately, as
this may be life-threatening.
Other possible side effects of Votubia include:
Very common side effects( may affect more than 1 in 10 people)

• Upper airway infections
• Sore throat and runny nose (rhinopharyngitis)
• Headache, pressure in the eyes, nose or cheek area (signs of inflammation of the sinuses and nasal passages, also known as sinusitis)
• Urinary tract infection
• High levels of lipids (fats) in the blood (hypercholesterolemia)
• Decreased appetite
• Headache
• Cough
• Mouth ulcers
• Diarrhea
• Feeling unwell (vomiting)
• Acne
• Skin rash
• Feeling tired
• Fever
• Menstrual disorders such as absence of periods (amenorrhea) or irregularity
• Sore throat (pharyngitis)
• Headache, dizziness, signs of increased blood pressure (hypertension)

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

• Middle ear infection
• Swelling, bleeding of the gums (signs of inflammation of the gums, also known as gingivitis)
• Skin inflammation (cellulitis)
• High levels of lipids (fats) in the blood (hyperlipidemia, increased triglycerides)
• Low levels of phosphates in the blood (hypophosphatemia)
• High levels of sugar in the blood (hyperglycemia)
• Fatigue, shortness of breath, dizziness, pale skin (signs of a decrease in red blood cells, also known as anemia)
• Fever, sore throat or mouth ulcers due to infections (sign of a decrease in white blood cells, also known as leucopenia, lymphopenia, neutropenia)
• Spontaneous bleeding or bruising (signs of a decrease in platelets, also known as thrombocytopenia)
• Pain in the mouth
• Nosebleeds (epistaxis)
• Stomach disorders such as feeling unwell (nausea)
• Abdominal pain
• Severe pain in the lower abdomen and pelvic area that may be sharp, with irregular periods (ovarian cyst)
• Excess gas in the intestines (flatulence)
• Constipation
• Abdominal pain, nausea, vomiting, diarrhea, swelling and distension of the abdomen, signs of inflammation of the stomach wall, also known as gastritis or viral gastroenteritis)
• Dry skin, itching
• An inflammatory skin condition characterized by redness, itching and leakage of fluid from blisters that become scaly, crusty, or hardened (acneiform dermatitis)
• Hair loss (alopecia)
• Protein in the urine
• Menstrual disorders such as heavy bleeding (menorrhagia) or vaginal bleeding
• Sleep disorders (insomnia)
• Irritability
• Aggression
• High levels in the blood of an enzyme called lactate dehydrogenase, a signal of the health of some organs
• High levels of the hormone that regulates ovulation (increased blood luteinizing hormone)
• Weight loss

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

• Muscle spasms, fever, reddish-brown urine which may be symptoms of a muscle disorder (rhabdomyolysis)
• Cough with mucus, chest pain, fever (signs of inflammation of the airways, also known as viral bronchitis)
• Altered taste (dysgeusia)
• Menstrual disorders such as delays
• High levels of the female hormone for reproduction (increased blood follicle stimulating hormone)

Not known(frequency cannot be estimated based on available data)

• Reaction at the site of previous radiotherapy, e.g. skin redness or lung inflammation (so-called radiation recall syndrome)
• Increased side effects of radiation treatment

If these side effects worsen, tell your doctor and/or pharmacist. Most
side effects are mild or moderate in intensity and usually disappear if treatment
is interrupted for a few days.
The following side effects have been reported in patients treated with everolimus for
conditions other than TSC:

• Kidney problems: an altered frequency or absence of the need to urinate may be symptoms of kidney failure and have been observed in some patients treated with everolimus. Other symptoms may include changes in kidney function tests (increased creatinine).
• Symptoms of heart failure such as shortness of breath, difficulty breathing when lying down, swelling of the feet and legs
• Blockage or obstruction of a blood vessel (vein) in the leg (deep vein thrombosis). Symptoms may include swelling and/or pain in one of the legs, usually the calf, redness or warmth of the skin in the affected area
• Problems with wound healing
• High levels of sugar in the blood (hyperglycemia)

Reactivation of hepatitis B has been observed in some patients treated with everolimus. Tell your
doctor if you develop symptoms of hepatitis B during treatment with everolimus. Early symptoms
may include fever, rash, pain and inflammation of the joints. Other symptoms
may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain
in the upper right abdomen. Pale stools or dark urine can also be signs of hepatitis.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through the national reporting system reported in
Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Votubia

• 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 package and blister. The expiry date refers to the last day of that month.
• Do not store at a temperature above 25°C.
• Store in the original package to protect the medicine from light and moisture.
• Open the blister immediately before taking the dispersible tablets of Votubia.
• Do not use this medicine if the package is damaged or shows signs of deterioration.

Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Votubia tablets contain

• The active ingredient is everolimus. Each Votubia 2.5 mg tablet contains 2.5 mg of everolimus. Each Votubia 5 mg tablet contains 5 mg of everolimus. Each Votubia 10 mg tablet contains 10 mg of everolimus.
• The other ingredients are butylhydroxytoluene (E321), magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A and anhydrous lactose (see section 2 “Votubia contains lactose”).

Description of the appearance of Votubia tablets and package contents
Votubia 2.5 mg tablets are off-white to yellowish tablets, elongated in shape. They are imprinted
“LCL” on one side and “NVR” on the other.
Votubia 5 mg tablets are off-white to yellowish tablets, elongated in shape. They are imprinted
“5” on one side and “NVR” on the other.
Votubia 10 mg tablets are off-white to yellowish tablets, elongated in shape. They are imprinted
“UHE” on one side and “NVR” on the other.
Votubia 2.5 mg tablets are available in packs containing 10 x 1, 30 x 1 or 100 x 1 tablets
in divisible blister packs with 10 x 1 tablet each.
Votubia 5 mg tablets are available in packs containing 30 x 1 or 100 x 1 tablets in blister
packs divisible with 10 x 1 tablet each.
Votubia 10 mg tablets are available in packs containing 10 x 1, 30 x 1 or 100 x 1 tablets in
blister packs divisible with 10 x 1 tablet each.
Not all pack sizes or strengths may be marketed in your country.

Marketing authorisation holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Farmacéutica SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел.: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52 555

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

United Kingdom (Northern Ireland)
Novartis Ireland Limited
Tel: +44 1276 698370

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

Votubia 1 mg dispersible tablets, 2 mg dispersible tablets, 3 mg dispersible tablets, 5 mg dispersible tablets

everolimus

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

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Votubia and what is it used for

Votubia dispersible tablets contain an active substance called everolimus. It is used in children
from 2 years of age and in adults for the treatment of focal seizures with or without
secondary generalization (epilepsy) associated with a genetic disease called tuberous sclerosis complex (TSC) and which are not controlled by other antiepileptic medicines. Focal seizures
begin by affecting only one side of the brain, but can spread and extend to larger areas
on both sides of the brain (a phenomenon called "secondary generalization"). Votubia dispersible tablets
are used together with other medicines for epilepsy.
Votubia is also an anti-cancer medicine that can block the growth of certain cells in the body. It can
reduce the size of brain tumors called subependymal giant cell astrocytomas
(SEGAs) which are also caused by TSC.
Votubia dispersible tablets are used for the treatment of SEGAs associated with TSC in adults and
in children for whom surgery is not appropriate.

2. What you need to know before taking Votubia

Votubia will only be prescribed by a doctor experienced in the treatment of patients with SEGA or epileptic seizures and with access to blood tests to measure the amount of Votubia in the blood.
Follow all the doctor's instructions carefully. These instructions may be different from the ones in this leaflet because they have been prescribed for you, consult your doctor.

Do not take Votubia

• if you are allergicto everolimus, to similar substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6). If you have had allergic reactions in the past, ask your doctor for advice.

Warnings and precautions
Talk to your doctor before taking Votubia:

• if you have liver problems or have had any disease that may have affected the liver. In this case, your doctor may need to prescribe a different dose of Votubia or stop treatment, for a short period or permanently.
• if you have diabetes (high blood sugar levels). Votubia can increase blood sugar levels and worsen diabetes mellitus. This may require the use of insulin and/or oral antidiabetic agents. Tell your doctor if you experience excessive thirst or increased frequency of urination.
• if you need to get a vaccine while taking Votubia, as vaccination may be less effective. For children with SEGA or epileptic seizures, it is important to discuss the pediatric vaccination schedule with your doctor before starting treatment with Votubia.
• if you have high cholesterol levels. Votubia can raise cholesterol and/or other fat levels in the blood.
• if you have recently had surgery, or if you have a wound that has not yet healed following surgery. Votubia may increase the risk of problems related to wound healing.
• if you have an infection. It may be necessary to treat the infection before starting Votubia.
• if you have previously had hepatitis B, because it may recur during treatment with Votubia (see section 4 “Possible side effects”).
• if you have received or are about to receive radiation therapy.

Votubia can also:

• cause mouth sores (ulcerations in the oral cavity).
• weaken the immune system. Therefore, you may be at risk of contracting an infection during treatment with Votubia. If you have a fever or other signs of infection, consult your doctor.
• some infections can be serious and can be fatal in adults and children.
• impair kidney function. Therefore, your doctor will check kidney function during treatment with Votubia.
• cause shortness of breath, cough and fever (see section 4 “Possible side effects”).
• cause complications from radiation therapy. Serious reactions to radiation (such as shortness of breath, nausea, diarrhea, skin rashes and irritation of the mouth, gums and throat), including fatal cases, have been observed in some patients who were taking everolimus at the same time as radiation therapy or who were taking everolimus shortly after radiation therapy. In addition, a condition called radiation recall syndrome (including skin redness or lung inflammation at the site of previous radiation therapy) has been reported in patients who have undergone radiotherapy in the past. Tell your doctor if you are planning to receive radiation therapy in the near future or have received radiation therapy in the past.

Tell your doctor immediatelyif you experience these symptoms.
You will have blood tests before and periodically during treatment. These tests will check the amount of blood cells in your body (white blood cells, red blood cells and platelets) to see if Votubia has an undesirable effect on these cells. You will also have blood tests to check kidney function (creatinine levels, blood urea nitrogen, or protein in the urine), liver function (transaminase levels) and blood sugar and lipid levels. These levels can also be affected by Votubia.
Regular blood tests are also necessary to measure how much Votubia is in your blood, as this will help your doctor decide how much Votubia you should take.

Children and adolescents
Votubia can be used in children and adolescents with SEGA associated with TSC.
Votubia should not be used in children under 2 years of age with TSC and epileptic seizures.

Other medicines and Votubia
Votubia can affect the action of some medicines. If you are taking other medicines while taking Votubia, your doctor may need to change the dose of Votubia or the other medicines.

Tell your doctor or pharmacistif you are taking, have recently taken or might take any other medicine.
The following may increase the risk of side effects with Votubia:

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungals used to treat fungal infections.
• clarithromycin, telithromycin or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medicines used to treat HIV/AIDS infection.
• verapamil or diltiazem used to treat heart conditions or high blood pressure.
• dronedarone, used to help regulate the heartbeat.
• cyclosporine, a medicine used to prevent organ rejection in transplant patients.
• imatinib, used to block the growth of abnormal cells.
• angiotensin converting enzyme (ACE) inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• cannabidiol (uses also include the treatment of seizures).

The following may reduce the effectiveness of Votubia:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine, used to treat HIV/AIDS infection.
• St John's wort ( Hypericum perforatum), a herbal product used to treat depression and other conditions.
• dexamethasone, a corticosteroid used to treat a wide range of conditions including inflammatory or immune problems.
• phenytoin, carbamazepine or phenobarbital and other antiepileptics used to block epileptic seizures.

All of the medicines listed above should be avoided during treatment with Votubia. If you are taking any of these medicines, your doctor may prescribe different medicines, or may change your dose of Votubia.
If you are taking an antiepileptic medicine, a change in the dose of the antiepileptic medicine (increase or decrease) may require a change in the dose of Votubia. The doctor will assess the need for this change. If the dose of your antiepileptic medicine is changed, tell your doctor.
If you are following a specific diet to reduce the frequency of epileptic seizures, please inform your doctor before taking Votubia.

Votubia with food and drink
Avoid grapefruit and grapefruit juice while being treated with Votubia. This could increase the amount of Votubia in the blood, even to a harmful level.

Pregnancy, breastfeeding and fertility
Pregnancy
Votubia can cause harm to the fetus and is not recommended during pregnancy. Tell your doctor if you are pregnant or think you might be.
Women who can become pregnant must use very effective contraception during treatment and for 8 weeks after the end of treatment. If, despite these measures, you suspect pregnancy, ask your doctor for advice beforetaking Votubia again.
Breastfeeding
Votubia can cause harm to the infant. You should not breastfeed during treatment and for 2 weeks after the last dose of Votubia. Tell your doctor if you are breastfeeding.
Fertility
Votubia may affect male and female fertility. Talk to your doctor if you wish to become pregnant.

Driving and operating machinery
If you feel unusually tired (fatigue is a common side effect), be particularly careful when driving vehicles or using machinery.

Votubia contains lactose
Votubia contains lactose (milk sugar). If your doctor has diagnosed you with intolerance to some sugars, contact him before taking this medicine.

3. How to take Votubia

Take this medicine following exactly the instructions of your doctor or pharmacist.
Votubia exists as tablets and dispersible tablets. Always take only the tablets or only the
dispersible tablets and never a combination of both. If you have doubts, consult your doctor or
pharmacist.

How much Votubia to take
The doctor will determine the dose of Votubia that you must take based on:

• age
• body surface area
• liver status
• taking of other medicines.

You will undergo blood tests during treatment with Votubia. This is to measure the
amount of Votubia in the blood and find the best dose for you.
If certain undesirable events (see section 4) occur while you are taking Votubia, your
doctor may reduce your dose or interrupt treatment for a short period of time or
permanently.

How to take this medicine

• Take the dispersible tablets of Votubia once a day.
• Take them at the same time each day.
• Take them with or without food but you must take them the same way every day.

Take the dispersible tablets of Votubia only as an oral suspension
Do not chew or crush the dispersible tablets. Do not swallow the dispersible tablets whole. The
dispersible tablets must be mixed with water to form a cloudy liquid
(oral suspension).

How to prepare and how to take the oral suspension
Prepare the oral suspension by mixing the dispersible tablets with water in an oral
syringe or in a small glass. You must drink the suspension immediately after preparing it. If
you do not drink it within 30 minutes when using an oral syringe or within 60 minutes when using
a small glass, discard it and prepare a new suspension. Read the detailed instructions at the end
of this leaflet to know how to do it. Ask your doctor or pharmacist if you are not sure.

Particular information for healthcare professionals
Healthcare professionals should try to avoid contact with the oral suspension. Wash your hands
thoroughly before and after preparing the suspension.

If you take more Votubia than you should

• If you have taken more Votubia than you should, or if someone else has accidentally taken your dispersible tablets, contact a doctor immediately or go to hospital. Emergency treatment may be necessary.

If you forget to take Votubia
If you forget to take a dose, take the next dose as scheduled. Do not take a
double dose to make up for a missed dose.

If you stop taking Votubia
Do not stop treatment with Votubia dispersible tablets unless your
doctor tells you to.
If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
STOP treatment with Votubia and contact your doctor immediately if you or your child
experience any of the following signs of an allergic reaction:

• difficulty breathing or swallowing
• swelling of the face, lips, tongue or throat (signs of angioedema)
• severe itching of the skin, with red rash or skin bumps

Serious side effects of Votubia include:
Very common side effects(may affect more than 1 in 10 people)

• Fever, cough, difficulty breathing, wheezing, (signs of lung inflammation caused by infection, also known as infectious pneumonia)

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

• Swelling, feeling of heaviness or tightness, pain, limited mobility of some parts of the body (this can occur in any part of the body and is a potential sign of abnormal fluid accumulation in the soft tissues due to a blockage in the lymphatic system, also known as lymphedema)
• Rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of a severe allergic reaction, also known as hypersensitivity)
• Fever, cough, difficulty breathing, wheezing (signs of lung inflammation, also known as pneumonia)

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

• Rash with small blisters filled with fluid that appear on reddened skin (signs of a viral infection that may potentially be serious, also known as shingles)
• Fever, chills, rapid breathing and heart rate, rash and possible confusion and disorientation (signs of a serious infection, also known as sepsis)

If any of these side effects occur, tell your doctor immediately, as
this may be life-threatening.
Other possible side effects of Votubia include:
Very common side effects( may affect more than 1 in 10 people)

• Upper airway infections
• Sore throat and runny nose (rhinopharyngitis)
• Headache, pressure in the eyes, nose or cheek areas (signs of inflammation of the sinuses and nasal passages, also known as sinusitis)
• Urinary tract infection
• High levels of lipids (fats) in the blood (hypercholesterolemia)
• Decreased appetite
• Headache
• Cough
• Mouth ulcers
• Diarrhea
• Feeling unwell (vomiting)
• Acne
• Skin rash
• Feeling tired
• Fever
• Menstrual disorders such as missed periods (amenorrhea) or irregularity
• Sore throat (pharyngitis)
• Headache, dizziness, signs of increased blood pressure (hypertension)

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

• Middle ear infection
• Swelling, bleeding of the gums (signs of inflammation of the gums, also known as gingivitis)
• Skin inflammation (cellulitis)
• High levels of lipids (fats) in the blood (hyperlipidemia, increased triglycerides)
• Low levels of phosphates in the blood (hypophosphatemia)
• High levels of sugar in the blood (hyperglycemia)
• Fatigue, shortness of breath, dizziness, pale skin (signs of a decrease in red blood cells, also known as anemia)
• Fever, sore throat or mouth ulcers due to infections (sign of a decrease in white blood cells, also known as leukopenia, lymphopenia, neutropenia)
• Spontaneous bleeding or bruising (signs of a decrease in platelets, also known as thrombocytopenia)
• Pain in the mouth
• Nosebleed (epistaxis)
• Stomach discomfort such as feeling unwell (nausea)
• Abdominal pain
• Severe pain in the lower abdomen and pelvic area that may be sharp, with irregular periods (ovarian cyst)
• Excess gas in the intestines (flatulence)
• Constipation
• Abdominal pain, nausea, vomiting, diarrhea, bloating and distension of the abdomen, signs of inflammation of the stomach wall, also known as gastritis or viral gastroenteritis)
• Dry skin, itching
• An inflammatory skin condition characterized by redness, itching and leakage of fluid from blisters that become scaly, crusty, or hardened (acneiform dermatitis)
• Hair loss (alopecia)
• Protein in the urine
• Menstrual disorders such as heavy bleeding (menorrhagia) or vaginal bleeding
• Sleep disorders (insomnia)
• Irritability
• Aggression
• High levels in the blood of an enzyme called lactate dehydrogenase, a signal of the health of some organs
• High levels of the hormone that regulates ovulation (increased blood luteinizing hormone)
• Weight loss

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

• Muscle spasms, fever, reddish-brown urine which may be symptoms of a muscle disorder (rhabdomyolysis)
• Cough with mucus, chest pain, fever (signs of inflammation of the airways also known as viral bronchitis)
• Altered taste (dysgeusia)
• Menstrual disorders such as delays
• High levels of the female hormone for reproduction (increased blood follicle stimulating hormone)

Not known(frequency cannot be estimated based on available data)

• Reaction at the site of previous radiotherapy, e.g. skin redness or lung inflammation (so-called radiation recall syndrome)
• Increased side effects of radiation treatment

If these side effects worsen tell your doctor and/or pharmacist. Most
side effects are mild or moderate in intensity and usually disappear if treatment
is interrupted for a few days.
The following side effects have been reported in patients treated with everolimus for
conditions other than TSC:

• Kidney problems: an altered frequency or absence of the need to urinate may be symptoms of kidney failure and have been observed in some patients treated with everolimus. Other symptoms may include changes in kidney function tests (increased creatinine).
• Symptoms of heart failure such as shortness of breath, difficulty breathing when lying down, swelling of the feet and legs
• Blockage or obstruction of a blood vessel (vein) in the leg (deep vein thrombosis). Symptoms may include swelling and/or pain in one of the legs, usually in the calf, redness or warmth of the skin in the affected area
• Problems with wound healing
• High levels of sugar in the blood (hyperglycemia)

Reactivation of hepatitis B has been observed in some patients treated with everolimus. Tell your
doctor if you develop symptoms of hepatitis B during treatment with everolimus. Early symptoms
may include fever, rash, joint pain and inflammation. Other symptoms
may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain
in the upper right side of the abdomen. Pale stools or dark urine can also be signs of hepatitis.

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

5. How to store Votubia

• 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 package and blister. The expiry date refers to the last day of that month.
• This medicine does not require any particular storage temperature.
• Store in the original package to protect the medicine from light and moisture.
• Open the blister immediately before taking the dispersible tablets of Votubia.
• The stability of the ready-to-use suspension has been demonstrated for 60 minutes. The suspension must be administered immediately after preparation. If not administered within 60 minutes of preparation, the suspension must be discarded and a new suspension must be prepared.
• Do not use this medicine if the package is damaged or shows signs of deterioration.

Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What Votubia dispersible tablets contains

• The active ingredient is everolimus.
• Each Votubia 1 mg dispersible tablet contains 1 mg of everolimus. Each Votubia 2 mg dispersible tablet contains 2 mg of everolimus. Each Votubia 3 mg dispersible tablet contains 3 mg of everolimus. Each Votubia 5 mg dispersible tablet contains 5 mg of everolimus.
• The other ingredients are butylhydroxytoluene (E321), magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, mannitol, microcrystalline cellulose and anhydrous colloidal silica (see section 2 “Votubia contains lactose”).

Description of the appearance of Votubia dispersible tablets and pack contents
Votubia 1 mg dispersible tablets are off-white to yellowish-white, round, flat tablets with a bevelled
edge and no fracture line. They have “D1” imprinted on one side and “NVR” on the other.
Votubia 2 mg dispersible tablets are off-white to yellowish-white, round, flat tablets with a bevelled
edge and no fracture line. They have “D2” imprinted on one side and “NVR” on the other.
Votubia 3 mg dispersible tablets are off-white to yellowish-white, round, flat tablets with a bevelled
edge and no fracture line. They have “D3” imprinted on one side and “NVR” on the other.
Votubia 5 mg dispersible tablets are off-white to yellowish-white, round, flat tablets with a bevelled
edge and no fracture line. They have “D5” imprinted on one side and “NVR” on the other.
Votubia 1 mg dispersible tablets are available in packs containing 30 dispersible tablets
in divisible blisters for single doses of 10 x 1 tablet each.
Votubia 2 mg dispersible tablets are available in packs containing 10 x 1, 30 x 1 or
100 x 1 dispersible tablets in divisible blisters for single doses of 10 x 1 tablet each.
Votubia 3 mg and Votubia 5 mg dispersible tablets are available in packs containing 30 x 1 or
100 x 1 dispersible tablets in divisible blisters for single doses of 10 x 1 tablet each.
Not all pack sizes or strengths may be marketed in your country.

Marketing Authorisation Holder
Novartis Europharm Limited
Vista Building
Elm Park, Merrion Road
Dublin 4
Ireland

Manufacturer
Novartis Farmacéutica SA
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain
Novartis Pharma GmbH
Roonstraße 25
D-90429 Nuremberg
Germany
For further information on this medicine, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Lietuva
SIA Novartis Baltics Lietuvos filialas
Tel: +370 5 269 16 50

България
Novartis Bulgaria EOOD
Тел.: +359 2 489 98 28

Luxembourg/Luxemburg
Novartis Pharma N.V.
Tél/Tel: +32 2 246 16 11

Česká republika
Novartis s.r.o.
Tel: +420 225 775 111

Magyarország
Novartis Hungária Kft
Tel.: +36 1 457 65 00

Danmark
Novartis Healthcare A/S
Tlf: +45 39 16 84 00

Malta
Novartis Pharma Services Inc.
Tel: +356 2122 2872

Deutschland
Novartis Pharma GmbH
Tel: +49 911 273 0

Nederland
Novartis Pharma B.V.
Tel: +31 88 04 52.555

Eesti
SIA Novartis Baltics Eesti filiaal
Tel: +372 66 30 810

Norge
Novartis Norge AS
Tlf: +47 23 05 20 00

Ελλάδα
Novartis (Hellas) A.E.B.E.
Τηλ: +30 210 281 17 12

Österreich
Novartis Pharma GmbH
Tel: +43 1 86 6570

España
Novartis Farmacéutica, S.A.
Tel: +34 93 306 42 00

Polska
Novartis Poland Sp. z o.o.
Tel.: +48 22 375 4888

France
Novartis Pharma S.A.S.
Tél: +33 1 55 47 66 00

Portugal
Novartis Farma - Produtos Farmacêuticos, S.A.
Tel: +351 21 000 8600

România
Novartis Pharma Services Romania SRL
Tel: +40 21 31299 01

Hrvatska
Novartis Hrvatska d.o.o.
Tel. +385 1 6274 220

Ireland
Novartis Ireland Limited
Tel: +353 1 260 12 55

Slovenija
Novartis Pharma Services Inc.
Tel: +386 1 300 75 50

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Novartis Slovakia s.r.o.
Tel: +421 2 5542 5439

Italia
Novartis Farma S.p.A.
Tel: +39 02 96 54 1

Suomi/Finland
Novartis Finland Oy
Puh/Tel: +358 (0)10 6133 200

Κύπρος
Novartis Pharma Services Inc.
Τηλ: +357 22 690 690

Sverige
Novartis Sverige AB
Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

United Kingdom (Northern Ireland)
Novartis Ireland Limited
Tel: +44 1276 698370

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

INSTRUCTIONS FOR USE
Read and follow these instructions carefully so that you can prepare the medicine correctly.
This will become a cloudy liquid (oral suspension).
Use an oral syringe or a small glass only to prepare and take
Votubia suspension – do not use them for any other purpose.
Important information:
Take Votubia dispersible tablets only as a suspension.
These instructions are for taking doses between 1 mg and 10 mg.
The maximum amount you can take at one time using the syringe or small glass is
10 mg, using a maximum of 5 dispersible tablets.

• If you need to take a higher dose or need to use more than 5 dispersible tablets, divide the dose and repeat the operations using the same syringe or small glass.
• Ask your doctor or pharmacist how to divide the dose if you are not sure.

Healthcare professionals should try to avoid contact of the oral suspension with the skin. Keep
the medicine out of the reach of children.
Use only water (tap water or non-carbonated bottled water) to prepare the
oral suspension. Do not use fruit juice or other liquids.
The patient should drink the suspension immediately after it has been prepared. If the patient does not
drink it within 30 minutes if a syringe was used or within 60 minutes if a
small glass was used, discard it and prepare a new suspension.

Instructions for healthcare professionals to prepare the suspension using a syringe:
You will need:

• blister pack with Votubia dispersible tablets
• Scissors to open the blister
• 10 ml syringe with 1 ml increments (for single use): see figure below
• 2 clean glasses
• Approximately 30 ml of water

Plunger
Cylinder
Volume
indicators
Tip

Preparation

• 1. Wash and dry your hands.
• 2. Take the 10 ml syringe and pull out the plunger, removing it completely from the syringe cylinder.

Add the dispersible tablets

• 3. Use the scissors to open the blister along the dotted line. Remove the dispersible tablets from the blister. Immediately insert them into the syringe cylinder.

• 4. Reinsert the plunger into the syringe cylinder. Push the plunger down until it touches the dispersible tablets.

Add water

• 5. Fill a small glass with water (tap water or non-carbonated bottled water). Place the tip of the syringe in water. Draw up approximately 5 ml of water by slowly pulling the plunger up to the 5 ml mark on the syringe.

Note: The amount of water in the syringe does not need to be
exact but all the tablets must be covered. If
some tablets get stuck in the dry upper
part of the syringe, gently tap the syringe until
they fall into the water.

Mix the medicine

• 6. Hold the syringe with the tip pointing upwards. Slowly pull the plunger up to the 9 ml mark on the syringe to draw in air.

• 7. Place the filled syringe in the empty, clean glass, with the tip pointing upwards. Wait for 3 minutes - until the dispersible tablets are completely dissolved.

3

• 8. Mix the medicine by gently inverting the syringe five times before administering the dose. Do not shake. Use the oral suspension immediately. If not used within 30 minutes, it must be discarded and prepared again.

5x
Remove the air

• 9. Hold the syringe with the tip pointing upwards. Slowly push the plunger to remove most of the air (it is okay if a small amount of air remains in the tip).

Take the medicine

• 10. Place the syringe in the patient's mouth. Slowly push the plunger to administer the entire contents of the syringe.

• 11. Carefully remove the syringe from the patient's mouth.

Make sure all the medicine is taken

• 12. Insert the tip of the syringe into a glass filled with water. Draw up 5 ml of water by slowly pulling the plunger.

• 13. Hold the syringe with the tip pointing upwards. Slowly pull the plunger up to the 9 ml mark on the syringe to draw in air.

• 14. With the tip of the syringe pointing upwards, move the water to collect any medicine remaining inside.
• 15. Hold the syringe with the tip pointing upwards. Slowly push the plunger to remove most of the air.

• 16. Place the syringe in the patient's mouth. Slowly push the plunger to administer the entire contents of the syringe
• 17. Carefully remove the syringe from the patient's mouth.

If the total prescribed dose is greater than 10 mg or
needs to be prepared using more than 5 dispersible
tablets, repeat the operations from 2 to 17 to
finish taking the dose.
Cleaning

• 18. Ask your pharmacist where to dispose of the syringe.
• 19. Wash and dry your hands.

Instructions for patients or healthcare professionals to prepare the suspension using a small
glass
You will need:

• Blister pack with Votubia dispersible tablets
• Scissors to open the blister
• 1 small glass (maximum volume 100 ml)
• 30 ml graduated cup to measure the water
• Approximately 50 ml of water to prepare the suspension
• Spoon for stirring

Preparation

• 1. Wash and dry your hands.

Prepare the water

• 2. Pour approximately 25 ml of water into the 30 ml graduated cup. The amount of water does not need to be exact.

25 ml of

water

• 3. Pour the water from the graduated cup into the small glass.

Add the dispersible tablets

• 4. Use scissors to open the blister pack along the dotted line. Remove the dispersible tablets from the blister pack.

• 5. Place the dispersible tablets into the water.

Mix the medicine

• 6. Wait for 3 minutes until the dispersible tablets are completely dissolved.

3Min

• 7. Gently stir the contents of the glass with a spoon and proceed to step 8.

Take the medicine

• 8. The patient must immediately drink all the oral suspension from the glass. If the suspension is not used within 60 minutes, it must be discarded and prepared again.

Ensure all the medicine is taken

• 9. Refill the glass with the same amount of water (approximately 25 ml). Stir the contents with the spoon to remove any medicine remaining in the glass and on the spoon.

• 10. The patient must drink all the oral suspension from the glass. If the total prescribed dose is greater than 10 mg or ifit needs to be prepared using more than 5 dispersible tablets, repeat steps 2 to 10 tofinish taking the dose.

Cleaning

• 11. Wash the glass and spoon thoroughly with clean water. Dry the glass and spoon with a clean paper towel. Store them in a dry and clean place for next time.

• 12. Wash and dry your hands.