Package leaflet: Information for the user

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

everolimus
Please read all of this leaflet carefully before taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Votubia is and what it is used for
What you need to know before taking Votubia
How to take Votubia
Possible side effects
How to store Votubia
Contents of the pack and other information

1. What Votubia is and what it is used for

Votubia is an anticancer 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 tumours known as renal angiomyolipomas and brain tumours known as subependymal giant cell astrocytomas (SEGA). These tumours are caused by a genetic disorder called tuberous sclerosis complex (TSC).
Votubia tablets are used to treat:

TSC-associated 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 be prescribed to you only by a physician experienced in the treatment of patients with TSC.
If you are being treated for SEGA associated with TSC, Votubia will be prescribed only by a physician experienced in the management of patients with SEGA and with access to blood tests to measure Votubia levels in the blood.
Carefully follow all instructions provided by your doctor. These instructions may differ from the general information contained in this leaflet. If you have any questions about Votubia or why it has been prescribed to you, consult your doctor.

Do not take Votubia

if you are allergic to 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 previously experienced allergic reactions, consult your doctor.

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 such cases, your doctor may need to prescribe a different dose of Votubia or interrupt treatment temporarily or permanently.
if you have diabetes (high blood sugar levels). Votubia may increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic agents. Inform your doctor if you experience excessive thirst or increased frequency of urination.
if you need to receive a vaccine while taking Votubia, as vaccination may be less effective. For children with SEGA, it is important to discuss the pediatric vaccination schedule with your doctor before starting treatment with Votubia.
if you have high cholesterol levels. Votubia may increase cholesterol levels and/or other fats in the blood.
if you have recently undergone surgery or have an unhealed surgical wound. Votubia may increase the risk of wound-healing complications.
if you have an infection. The infection may need to be treated before starting Votubia.
if you have previously had hepatitis B, as it may reactivate during treatment with Votubia (see section 4 “Possible side effects”).
if you have received or are about to receive radiotherapy.

Votubia may also:

cause mouth ulcers (oral mucositis).
weaken the immune system. Therefore, you may be at increased risk of developing infections during treatment with Votubia. If you develop fever or other signs of infection, contact your doctor immediately. Some infections may be severe and potentially fatal in both adults and children.
impair kidney function. Therefore, your doctor will monitor your kidney function during treatment with Votubia.
cause shortness of breath, cough, and fever (see section 4 “Possible side effects”).
cause complications related to radiotherapy. Severe radiation reactions (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 concurrently with or shortly after radiotherapy. Additionally, in patients who previously received radiotherapy, radiation recall syndrome (including skin redness or lung inflammation at the site of prior radiotherapy) has been reported. Inform your doctor if you are planning to receive radiotherapy in the near future or have previously received radiotherapy.

Contact your doctor immediately if you experience any of these symptoms.
You will undergo blood tests before and periodically during treatment. These tests will monitor your blood cell counts (white blood cells, red blood cells, and platelets) to determine whether Votubia is having any adverse effects on these cells. Blood tests will also be performed to monitor kidney function (creatinine, blood urea nitrogen, or protein in urine), liver function (transaminase levels), and blood glucose and lipid levels. These levels may also be affected by Votubia.
If you are receiving Votubia for the treatment of SEGA associated with TSC, regular blood tests are also necessary to measure Votubia blood levels, as this will help your doctor determine the appropriate dose for you.

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 renal angiomyolipoma without SEGA, as it has not been studied in such patients.

Other medicines and Votubia
Votubia may affect the action of certain medicines. If you are taking other medications while on Votubia, your doctor may need to adjust the dose of Votubia or the other medications.
Inform your doctor or pharmacist if you are taking, have recently taken, or might start taking any other medicines.

The following may increase the risk of side effects with Votubia:

ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal agents 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 heart rhythm.
cyclosporine, a medicine used to prevent organ transplant rejection.
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, among others, 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 disorders.
phenytoin, carbamazepine, or phenobarbital and other antiepileptic drugs used to prevent 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 alternative medications or adjust your Votubia dose.
If you are taking an antiepileptic medicine, a change in its dose (increase or decrease) may necessitate an adjustment in your Votubia dose. Your doctor will assess whether such an adjustment is needed. If your antiepileptic medicine dose is changed, inform your doctor.

Votubia with food and drink
Avoid grapefruit and grapefruit juice while taking Votubia. These may increase the amount of Votubia in your blood, even to harmful levels.

Pregnancy, breastfeeding, and fertility
Pregnancy
Votubia may harm the unborn baby and is not recommended during pregnancy. Inform your doctor if you are pregnant or think you may be pregnant.
Women of childbearing potential must use highly effective contraception during treatment and for 8 weeks after the end of treatment. If, despite these precautions, you suspect you are pregnant, consult your doctor before taking any further doses of Votubia.

Breastfeeding
Votubia may harm the breastfed infant. You must not breastfeed during treatment and for 2 weeks after the last dose of Votubia. Inform your doctor if you are breastfeeding.

Fertility
Votubia may affect male and female fertility. Speak with your doctor if you wish to have children.

Driving and using machines
If you feel unusually tired (fatigue is a common side effect), exercise particular caution when driving or operating machinery.

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

3. How to take Votubia

Take this medicine exactly as directed by your doctor or pharmacist.
Votubia is available as tablets and dispersible tablets. Always take only tablets or only dispersible tablets—never a combination of both. If you have any doubts, consult your doctor or pharmacist.

How much Votubia to take
If you are receiving Votubia for the treatment of TSC with renal angiomyolipoma, the usual dose is 10 mg, taken once daily.

Higher or lower doses may be prescribed by your doctor based on individual treatment needs, for example if you have liver problems or are taking other medicines in addition to Votubia.

If you are receiving Votubia for the treatment of TSC with SEGA, your doctor will determine the dose of Votubia you should take based on:

age
body surface area
liver function
concomitant use of other medications.

You will undergo blood tests during treatment with Votubia. These tests are performed to measure the amount of Votubia in your blood and to determine the optimal dose for you.

If certain adverse events occur while you are taking Votubia (see section 4), your doctor may reduce your dose, or temporarily or permanently discontinue treatment.

How to take this medicine

Take Votubia tablets once daily.
Take them at the same time each day.
Take them with or without food, but always in the same manner 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 are unable to swallow them, dissolve the tablets in a glass of water:

Place the required number of tablets in a glass of water (approximately 30 ml).
Gently stir the contents of the glass until the tablets dissolve (approximately 7 minutes), then drink the solution immediately.
Refill the glass with the same amount of water (approximately 30 ml), gently stir the remaining contents, and drink all of it to ensure you have taken the full dose of Votubia tablets.
If necessary, drink additional water to remove any residue from your mouth.

Special information for healthcare providers
Healthcare providers should avoid contact with the Votubia tablet suspension. Wash hands thoroughly before and after preparing the suspension.

If you take more Votubia than you should

If you have taken more Votubia than prescribed, or if someone else has accidentally taken your tablets, contact a doctor immediately or go to the hospital. Emergency treatment may be required.
Keep the packaging and this patient information leaflet available so the doctor knows what has been taken.

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

If you stop taking Votubia
Do not stop treatment with Votubia tablets unless instructed by your doctor.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
STOP taking 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 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 due to 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 in certain parts of the body (this may occur in any part of the body and may indicate abnormal fluid accumulation in soft tissues due to blockage in the lymphatic system, also known as lymphoedema)
Rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of 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 fluid-filled blisters appearing on red skin (signs of viral infection which may potentially be severe, also known as herpes zoster)
Fever, chills, rapid breathing and heart rate, rash, and possible confusion and disorientation (signs of severe infection, also known as sepsis)

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

Upper respiratory tract 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
Increased levels of lipids (fats) in the blood (hypercholesterolemia)
Decreased appetite
Headache
Cough
Mouth ulcers
Diarrhoea
Malaise (vomiting)
Acne
Skin rash
Feeling of tiredness
Fever
Menstrual disorders such as absence of periods (amenorrhoea) or irregularities
Sore throat (pharyngitis)
Headache, dizziness, signs of elevated blood pressure (hypertension)

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

Middle ear infection
Swelling, bleeding of the gums (signs of gum inflammation, also known as gingivitis)
Skin inflammation (cellulitis)
Increased levels of lipids (fats) in the blood (hyperlipidaemia, increased triglycerides)
Low levels of phosphates in the blood (hypophosphataemia)
High blood sugar levels (hyperglycaemia)
Fatigue, shortness of breath, dizziness, pale skin (signs of reduced red blood cells, also known as anaemia)
Fever, sore throat or mouth ulcers due to infections (signs of reduced white blood cells, also known as leucopenia, lymphopenia, neutropenia)
Spontaneous bleeding or bruising (signs of reduced platelets, also known as thrombocytopenia)
Mouth pain
Nosebleeds (epistaxis)
Stomach disturbances such as feeling unwell (nausea)
Abdominal pain
Severe pain in the lower abdominal and pelvic area which may be sharp, with menstrual irregularities (ovarian cyst)
Excess gas in the intestine (flatulence)
Constipation
Abdominal pain, nausea, vomiting, diarrhoea, bloating and abdominal distension, signs of inflammation of the stomach wall, also known as gastritis or viral gastroenteritis)
Dry skin, itching
An inflammatory skin condition characterised by redness, itching and fluid leakage from blisters that become scaly, crusted or hardened (acneiform dermatitis)
Hair loss (alopecia)
Protein in the urine
Menstrual disorders such as excessive bleeding (menorrhagia) or vaginal bleeding
Sleep disturbances (insomnia)
Irritability
Aggressiveness
Increased blood levels of an enzyme called lactate dehydrogenase, a marker of organ health
High levels of the hormone regulating ovulation (increased blood luteinising hormone)
Weight loss

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

Muscle spasms, fever, red-brown urine which may be symptoms of a muscle disorder (rhabdomyolysis)
Cough with phlegm, chest pain, fever (signs of inflammation of the respiratory tract, also known as viral bronchitis)
Altered taste (dysgeusia)
Menstrual disorders such as delays
Increased levels of the female reproductive hormone (increased blood follicle-stimulating hormone)

Not known (frequency cannot be estimated from the available data)

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

If these side effects worsen, inform your doctor and/or pharmacist. Most of the side effects are mild or moderate in severity and usually resolve 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: 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 blood sugar levels (hyperglycaemia)

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via 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 stated on the carton and blister pack. The expiry date refers to the last day of that month.
Do not store above 25°C.
Store in the original packaging to protect the medicine from light and moisture.
Open the blister pack immediately before taking the Votubia dispersible tablets.
Do not use this medicine if the packaging is damaged or shows any signs of deterioration.

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

6. Package contents and other information

What Votubia tablets contain

The active substance 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 components are butylated hydroxytoluene (E321), magnesium stearate, monohydrate lactose, 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 white to yellowish, elongated tablets. They are engraved with
“LCL” on one side and “NVR” on the other.
Votubia 5 mg tablets are white to yellowish, elongated tablets. They are engraved with
“5” on one side and “NVR” on the other.
Votubia 10 mg tablets are white to yellowish, elongated tablets. They are engraved with
“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 blisters divisible into unit doses of 10 x 1 tablets each.
Votubia 5 mg tablets are available in packs containing 30 x 1 or 100 x 1 tablets in blisters divisible into unit doses of 10 x 1 tablets each.
Votubia 10 mg tablets are available in packs containing 10 x 1, 30 x 1 or 100 x 1 tablets in blisters divisible into unit doses of 10 x 1 tablets 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
Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nuremberg
Germany
Novartis Pharmaceuticals S.R.L.
Str. Livezeni nr. 7A
540472 Targu Mures
Romania

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52 555

Eesti Norge
SIA Novartis Baltics Eesti filiaal Novartis Norge AS
Tel: +372 66 30 810 Tlf: +47 23 05 20 00

Ελλάδα Österreich
Novartis (Hellas) A.E.B.E. Novartis Pharma GmbH
Τηλ: +30 210 281 17 12 Tel: +43 1 86 6570

España Polska
Novartis Farmacéutica, S.A. Novartis Poland Sp. z o.o.
Tel: +34 93 306 42 00 Tel.: +48 22 375 4888

France Portugal
Novartis Pharma S.A.S. Novartis Farma - Produtos Farmacêuticos, S.A.
Tél: +33 1 55 47 66 00 Tel: +351 21 000 8600

Hrvatska România
Novartis Hrvatska d.o.o. Novartis Pharma Services Romania SRL
Tel. +385 1 6274 220 Tel: +40 21 31299 01

Ireland Slovenija
Novartis Ireland Limited Novartis Pharma Services Inc.
Tel: +353 1 260 12 55 Tel: +386 1 300 75 50

Ísland Slovenská republika
Vistor hf. Novartis Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 5542 5439

Italia Suomi/Finland
Novartis Farma S.p.A. Novartis Finland Oy
Tel: +39 02 96 54 1 Puh/Tel: +358 (0)10 6133 200

Κύπρος Sverige
Novartis Pharma Services Inc. Novartis Sverige AB
Τηλ: +357 22 690 690 Tel: +46 8 732 32 00

Latvija
SIA Novartis Baltics
Tel: +371 67 887 070

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

Package leaflet: information for the user

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

everolimus
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as yours, because it may be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet

What Votubia is and what it is used for
What you need to know before taking Votubia
How to take Votubia
Possible side effects
How to store Votubia
Contents of the pack and other information

1. What Votubia is and what it is used for

Votubia dispersible tablets contain an active substance called everolimus. It is used in children from 2 years of age and in adults to treat 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 epileptic seizures start in only one side of the brain, but may spread and extend to broader areas on both sides of the brain (a phenomenon known as "secondary generalization"). Votubia dispersible tablets are used in combination with other epilepsy medicines.
Votubia is also an anticancer medicine that can block the growth of certain cells in the body. It may reduce the size of brain tumours called subependymal giant cell astrocytomas (SEGA), which are also caused by TSC.
Votubia dispersible tablets are used to treat SEGA associated with TSC in adults and children for whom surgery is not appropriate.

2. What you should know before taking Votubia

Votubia will only be prescribed by a physician experienced in the treatment of patients with SEGA or epileptic seizures and who has access to blood tests to measure the amount of Votubia in the blood.
Carefully follow all instructions given by your doctor. These instructions may differ from the general information contained in this leaflet. If you have any questions about Votubia or why it has been prescribed to you, consult your doctor.

Do not take Votubia

if you are allergic to everolimus, to substances similar to sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section 6). If you have previously experienced allergic reactions, consult your doctor.

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 such cases, your doctor may need to prescribe a different dose of Votubia or temporarily or permanently discontinue treatment.
if you have diabetes (high blood sugar levels). Votubia may increase blood sugar levels and worsen diabetes mellitus. This may require treatment with insulin and/or oral antidiabetic agents. Inform your doctor if you experience excessive thirst or increased frequency of urination.
if you need to receive 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 Votubia treatment.
if you have high cholesterol levels. Votubia may increase cholesterol levels and/or other blood fats.
if you have recently undergone surgery, or if you have an unhealed surgical wound. Votubia may increase the risk of wound-healing complications.
if you have an infection. It may be necessary to treat the infection before starting Votubia.
if you have previously had hepatitis B, as it may reactivate during treatment with Votubia (see section 4 “Possible side effects”).
if you have received or are about to receive radiotherapy.

Votubia may also:

cause mouth ulcers (oral cavity ulcerations).
weaken the immune system. Therefore, you may be at increased risk of developing an infection during treatment with Votubia. If you develop fever or other signs of infection, consult your doctor.
some infections may be severe and may be fatal in both adults and children.
impair kidney function. Therefore, your doctor will monitor your kidney function during treatment with Votubia.
cause shortness of breath, cough, and fever (see section 4 “Possible side effects”).
cause complications related to radiotherapy. Severe radiation reactions (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 concurrently with radiotherapy or shortly after radiotherapy. Additionally, in patients who have previously undergone radiotherapy, radiation recall syndrome (including skin redness or lung inflammation at the site of prior radiotherapy) has been reported. Inform your doctor if you are planning to receive radiotherapy in the near future or have received radiotherapy in the past.

Contact your doctor immediately if you experience any of these symptoms.
You will have blood tests before and periodically during treatment. These tests will monitor the number of blood cells in your body (white blood cells, red blood cells, and platelets) to determine whether Votubia is having any adverse effects on these cells. Blood tests will also be performed to monitor kidney function (creatinine, blood urea nitrogen, or protein in urine), liver function (transaminase levels), and blood glucose and lipid levels. These levels may also be affected by Votubia.
Regular blood tests are also necessary to measure the amount of Votubia in your blood, as this will help your doctor determine the appropriate dose of Votubia for you.

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

Other medicines and Votubia
Votubia may affect the action of certain medicines. If you are taking other medicines while taking Votubia, your doctor may need to adjust the dose of Votubia or of the other medicines.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

The following may increase the risk of side effects with Votubia:

ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal agents 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 heart rhythm.
cyclosporine, a medicine used to prevent rejection of transplanted organs.
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, among others, 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 disorders.
phenytoin, carbamazepine, or phenobarbital and other antiepileptic medicines used to prevent 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 alternative medicines or adjust your dose of Votubia.
If you are taking an antiepileptic medicine, a change in the dose of the antiepileptic medicine (increase or decrease) may necessitate a change in the dose of Votubia. Your doctor will assess whether such a change is needed. If the dose of your antiepileptic medicine is changed, inform 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 may harm the unborn baby and is not recommended during pregnancy. Inform your doctor if you are pregnant or think you might be pregnant.
Women of childbearing potential must use highly effective contraception during treatment and for 8 weeks after the end of treatment. If, despite these precautions, you suspect you are pregnant, consult your doctor before taking any further doses of Votubia.

Breastfeeding
Votubia may harm the breastfed infant. You must not breastfeed during treatment and for 2 weeks after the last dose of Votubia. Inform your doctor if you are breastfeeding.

Fertility
Votubia may affect male and female fertility. Talk to your doctor if you wish to have children.

Driving and using machines
If you feel unusually tired (fatigue is a common side effect), exercise particular caution when driving or operating machinery.

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

3. How to take Votubia

Take this medicine exactly as instructed by your doctor or pharmacist.
Votubia is available as tablets and dispersible tablets. Always take either tablets or dispersible tablets, but never a combination of both. If you have any doubts, consult your doctor or pharmacist.
How much Votubia to take
Your doctor will determine the dose of Votubia you should take based on:

age
body surface area
liver function
concomitant use of other medicines.

You will undergo blood tests during treatment with Votubia. These tests measure the amount of Votubia in your blood and help determine the best dose for you.
If certain adverse events occur while you are taking Votubia (see section 4), your doctor may reduce your dose, or interrupt or permanently stop treatment.
How to take this medicine

Take the Votubia dispersible tablets once daily.
Take them at the same time each day.
Take them with or without food, but take them the same way every day.

Take Votubia dispersible tablets 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 take the oral suspension
Prepare the oral suspension by mixing the dispersible tablets with water in an oral syringe or a small glass. You must drink the suspension immediately after preparation. 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. See the detailed instructions at the end of this leaflet for how to do this. Ask your doctor or pharmacist if you are unsure.
Special information for handlers
Handlers should avoid contact with the oral suspension. Wash hands thoroughly before and after preparing the suspension.
If you take more Votubia than you should

If you have taken more Votubia than prescribed, or if someone else has accidentally taken your dispersible tablets, contact a doctor immediately or go to hospital. Emergency treatment may be required.
Keep the packaging and this leaflet with you so the doctor knows what has been taken.

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 the forgotten dose.
If you stop taking Votubia
Do not stop treatment with Votubia dispersible tablets unless instructed by your doctor.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone 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 skin itching, with 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 due to 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 in certain body parts (this may occur in any part of the body and may indicate abnormal fluid accumulation in soft tissues due to blockage in the lymphatic system, also known as lymphoedema)
Skin rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of 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)

Skin rash with small fluid-filled blisters 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 severe infection, also known as sepsis)

Upper respiratory tract infections
Sore throat and runny nose (nasopharyngitis)
Headache, pressure in the eyes, nose or cheek areas (signs of inflammation of the sinuses and nasal passages, also known as sinusitis)
Urinary tract infections
Elevated levels of lipids (fats) in the blood (hypercholesterolemia)
Decreased appetite
Headache
Cough
Mouth ulcers
Diarrhoea
Malaise (vomiting)
Acne
Skin rash
Feeling of tiredness
Fever
Menstrual disorders such as absence of periods (amenorrhea) or irregularities
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 gum inflammation, 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 blood sugar levels (hyperglycaemia)
Fatigue, shortness of breath, dizziness, pale skin (signs of low red blood cells, also known as anaemia)
Fever, sore throat or mouth ulcers due to infections (signs of low white blood cells, also known as leucopenia, lymphopenia, neutropenia)
Spontaneous bleeding or bruising (signs of low platelets, also known as thrombocytopenia)
Mouth pain
Nosebleeds (epistaxis)
Stomach disturbances such as feeling unwell (nausea)
Abdominal pain
Severe pain in the abdominal and lower pelvic area that may be sharp, with menstrual irregularities (ovarian cyst)
Excess gas in the intestine (flatulence)
Constipation
Abdominal pain, nausea, vomiting, diarrhoea, bloating and abdominal distension, signs of inflammation of the stomach wall, also known as gastritis or viral gastroenteritis)
Dry skin, itching
An inflammatory skin condition characterised by redness, itching and fluid leakage from blisters that become scaly, crusted or hardened (acneiform dermatitis)
Hair loss (alopecia)
Protein in the urine
Menstrual disorders such as excessive bleeding (menorrhagia) or vaginal bleeding
Sleep disturbances (insomnia)
Irritability
Aggressiveness
Elevated blood levels of an enzyme called lactate dehydrogenase, a marker of organ health
Elevated levels of the hormone regulating ovulation (increased blood luteinizing hormone)
Weight loss

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

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

Not known (frequency cannot be determined from available data)

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

If these side effects worsen, inform your doctor and/or pharmacist. Most of these side effects are mild or moderate in severity and usually resolve 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: 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 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 leg, usually in the calf, redness or warmth of the skin in the affected area
Problems with wound healing
High blood sugar levels (hyperglycaemia)

Reactivation of hepatitis B has been observed in some patients treated with everolimus. Inform your doctor if you experience symptoms of hepatitis B during treatment with everolimus. Early symptoms may include fever, skin 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 part of the abdomen. Light-coloured stools or dark urine may also be signs of hepatitis.

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 stated on the carton and blister. The expiry date refers to the last day of that month.
This medicine does not require any special storage temperature.
Store in the original packaging to protect the medicine from light and moisture.
Open the blister immediately before taking the Votubia dispersible tablets.
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 prepared.
Do not use this medicine if the packaging is damaged or shows any signs of deterioration.

Do not dispose of medicines via 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 dispersible tablets contain

The active substance is everolimus.
Each dispersible tablet of Votubia 1 mg contains 1 mg of everolimus. Each dispersible tablet of Votubia 2 mg contains 2 mg of everolimus. Each dispersible tablet of Votubia 3 mg contains 3 mg of everolimus. Each dispersible tablet of Votubia 5 mg contains 5 mg of everolimus.
The other components are butylated hydroxytoluene (E321), magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, mannitol, microcrystalline cellulose and anhydrous colloidal silicon dioxide (see section 2 “Votubia contains lactose”).

Description of the appearance of Votubia dispersible tablets and package contents
Votubia 1 mg dispersible tablets are white to yellowish-white, round, flat tablets with bevelled edges and no break line. They are marked with “D1” on one side and “NVR” on the other.
Votubia 2 mg dispersible tablets are white to yellowish-white, round, flat tablets with bevelled edges and no break line. They are marked with “D2” on one side and “NVR” on the other.
Votubia 3 mg dispersible tablets are white to yellowish-white, round, flat tablets with bevelled edges and no break line. They are marked with “D3” on one side and “NVR” on the other.
Votubia 5 mg dispersible tablets are white to yellowish-white, round, flat tablets with bevelled edges and no break line. They are marked with “D5” on one side and “NVR” on the other.
Votubia 1 mg dispersible tablets are available in packages containing 30 dispersible tablets in divided blisters for single doses, each containing 10 x 1 tablets.
Votubia 2 mg dispersible tablets are available in packages containing 10 x 1, 30 x 1 or 100 x 1 dispersible tablets in divided blisters for single doses, each containing 10 x 1 tablets.
Votubia 3 mg and Votubia 5 mg dispersible tablets are available in packages containing 30 x 1 or 100 x 1 dispersible tablets in divided blisters for single doses, each containing 10 x 1 tablets.
It is possible that not all pack sizes or strengths are marketed in your country.

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Novartis Pharma N.V. SIA Novartis Baltics Lietuvos filialas
Tél/Tel: +32 2 246 16 11 Tel: +370 5 269 16 50

България Luxembourg/Luxemburg
Novartis Bulgaria EOOD Novartis Pharma N.V.
Тел.: +359 2 489 98 28 Tél/Tel: +32 2 246 16 11

Česká republika Magyarország
Novartis s.r.o. Novartis Hungária Kft
Tel: +420 225 775 111 Tel.: +36 1 457 65 00

Danmark Malta
Novartis Healthcare A/S Novartis Pharma Services Inc.
Tlf: +45 39 16 84 00 Tel: +356 2122 2872

Deutschland Nederland
Novartis Pharma GmbH Novartis Pharma B.V.
Tel: +49 911 273 0 Tel: +31 88 04 52.555