Leaflet: information for the user

Votubia 1mg dispersible tablets

Votubia 2mg dispersible tablets

Votubia 3mg dispersible tablets

Votubia 5mg dispersible tablets

everolimus

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

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section4.

1.What Votubia is and for what it is used

2.What you need to know before starting to take Votubia

3.How to take Votubia

4.Possible side effects

5.Storage of Votubia

6.Contents of the pack and additional information

Votubia dispersible tablets contain an active ingredient called everolimus. It is used to treat children aged 2 years and older and adults with partial epileptic seizures with or without secondary generalization (epilepsy) associated with a genetic alteration called tuberous sclerosis complex (TSC) that are not controlled with other antiepileptic medications. Partial epileptic seizures begin affecting only one side of the brain, but can spread and extend to larger areas on both sides of the brain (called "secondary generalization"). Votubia dispersible tablets are administered in conjunction with other epilepsy medications.

Votubia is also an antitumoral medication that may block the growth of some cells in the body. It may reduce the size of some brain tumors called subependymal giant cell astrocytomas (SEGA, by its English acronym) that are caused by TSC.

Votubia dispersible tablets are used to treat SEGA associated with TSC in adults and children for whom surgery is not suitable.

If you are being treated for TSC with renal angiomyolipoma, only a doctor experienced in treating TSC patients will prescribe Votubia for you.

If you are being treated for SEGA associated with TSC, Votubia will only be prescribed by a doctor experienced in treating SEGA patients and who can perform blood tests to measure the amount of Votubia in your blood.

Follow carefully all the instructions given by your doctor. They may be different from the general information contained in this leaflet. If you have any doubts about Votubia or the reason why you have been prescribed this medicine, consult your doctor.

Do not take Votubia

• if you are allergicto everolimus, related substances such as sirolimus or temsirolimus, or to any of the other ingredients of this medicine (listed in section6).

If you have had allergic reactions previously, consult your doctor.

Warnings and precautions

Consult your doctor before starting to take Votubia:

• if you have liver problems or if you have had any disease that may have affected your liver. In this case, your doctor may prescribe a different dose of Votubia or interrupt treatment, either for a short period of time 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 drugs. Inform your doctor if you notice excessive thirst or if you need to urinate more frequently.
• if you need to be administered a vaccine while taking Votubia, as vaccination may be less effective. For children with SEGA, it is essential to discuss the infant vaccination program with your doctor before starting treatment with Votubia.
• if you have high cholesterol levels. Votubia may increase cholesterol and/or other blood fats.
• if you have recently undergone major surgery, or if you still have an open wound after surgery. Votubia may increase the risk of wound healing problems.
• if you have an infection. You may need to treat your infection before starting treatment with Votubia.
• if you have previously had hepatitisB, as this may recur during treatment with Votubia (see section4«Adverse reactions»).
• if you have received or are about to receive radiation therapy.

Votubia may also:

• cause mouth sores (oral ulcers).
• weaken your immune system. Therefore, you may be at risk of infection while taking Votubia. If you have a fever or other signs of infection, consult your doctor. Some infections can be serious and fatal in adults and children.
• affect kidney function. Therefore, your doctor will monitor your kidney function while you are taking Votubia.
• cause difficulty breathing, cough, and fever (see section4«Adverse reactions»).
• cause radiation therapy complications. Severe radiation therapy complications (such as difficulty breathing, nausea, diarrhea, skin rash, and mouth, gum, and throat pain), including fatal cases, have been observed in some patients taking everolimus at the same time as receiving radiation therapy or taking everolimus shortly after receiving radiation therapy. Radiation recall syndrome (which presents with skin redness or lung inflammation at the site of previous radiation therapy) has also been reported in patients who had received radiation therapy in the past.

Inform your doctor if you are scheduled to receive radiation therapy soon, or if you have received radiation therapy previously.

Inform your doctorimmediatelyif you experience these symptoms.

During treatment, blood tests will be performed before and periodically. These tests will determine the number of blood cells (white blood cells, red blood cells, and platelets) to check if Votubia is having an undesirable effect on these cells. Blood tests will also be performed to monitor kidney function (creatinine levels, blood urea nitrogen, or protein in urine), liver function (transaminase levels), and blood sugar and lipid levels. These tests are performed because these may be affected by Votubia treatment.

If you are taking Votubia for the treatment of SEGA associated with TSC, periodic blood tests are also necessary to measure the amount of Votubia in the blood, as this will help your doctor decide how much Votubia you need to 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 renal angiomyolipoma in the absence of SEGA, as it has not been studied in these patients.

Use of Votubia with other medicines

Votubia may affect how other medicines work. If you are taking other medicines at the same time as Votubia, your doctor may change the dose of Votubia or the other medicines.

Inform your doctor or pharmacistif you are using, have used recently, or may need to use any other medicine.

The following may increase the risk of adverse reactions with Votubia:

• ketoconazole, itraconazole, voriconazole, or fluconazole and other antifungal medicines used to treat fungal infections.
• clarithromycin, telithromycin, or erythromycin, antibiotics used to treat bacterial infections.
• ritonavir and other medicines used to treat HIV/AIDS.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate your heart rhythm.
• ciclosporin, a medicine used to prevent the body from rejecting transplanted organs.
• imatinib, used to inhibit the growth of abnormal cells.
• ACE inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• cannabidiol (its use includes, among others, the treatment of epilepsy).

The following may reduce the effectiveness of Votubia:

• rifampicin, used to treat tuberculosis (TB).
• efavirenz or nevirapine, used to treat HIV/AIDS.
• 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 situations including inflammatory or immune problems.
• phenytoin, carbamazepine, or phenobarbital and other antiepileptic medicines used to control seizures.

It is essential to avoid the use of all the medicines listed above during Votubia treatment. If you are taking any of them, your doctor may prescribe a different medicine, or may change your Votubia dose.

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 needed. Your doctor will make the decision. If you change the dose of your antiepileptic medicine, inform your doctor.

Taking Votubia with food and drinks

Do not take grapefruit, grapefruit juice while taking Votubia. It may increase the amount of Votubia in your blood, possibly to a harmful level.

Pregnancy, breastfeeding, and fertility

Pregnancy

Votubia may cause harm to the fetus and is not recommended during pregnancy. Inform your doctor if you are pregnant or think you may be pregnant.

Women who may become pregnant should use a very effective contraceptive method during treatment and for 8weeks after completing treatment. If, despite these measures, you think you may be pregnant, consult your doctorbeforetaking more Votubia.

Breastfeeding

Votubia may harm a baby who receives breast milk. Do not breastfeed during treatment and for 2weeks after the last dose of Votubia. Inform your doctor if you are breastfeeding.

Fertility

Votubia may affect male and female fertility. Consult your doctor if you want to have children.

Driving and operating machines

If you feel abnormally tired (fatigue is a common adverse reaction), be extra careful when driving or operating machines.

Votubia contains lactose

Votubia contains lactose (milk sugar). If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medicine.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. Votubia is available as tablets and as dispersible tablets. Take always only the tablets or only the dispersible tablets, and never a combination of both. In case of doubt, consult your doctor or pharmacist again.

How much Votubia to take

If you receive Votubia for the treatment of CET with renal angiomyolipoma, the usual dose is 10 mg, once a day.

Your doctor may recommend a higher or lower dose based on your individual treatment needs, for example if you have kidney problems or if you are taking some other medications in addition to Votubia.

If you receive Votubia for the treatment of CET with SEGA, your doctor will determine the dose of Votubia you need to take based on:

• your age
• your body size
• your liver condition
• other medications you are taking.

You will have blood tests during treatment with Votubia. This is done to determine the amount of Votubia in the blood and to find the most suitable daily dose.

If you experience some adverse effects (see section 4) while taking Votubia, your doctor may reduce the dose you take or interrupt treatment for a short period of time or definitively.

How to take this medication

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

Swallow the tablets whole with a glass of water. The tablets should not be chewed or crushed. If you are taking Votubia tablets for the treatment of CET with SEGA and you cannot swallow the tablets, you can dissolve them in a glass of water:

• Put the required number of tablets in a glass of water (approximately 30 ml).
• Mix the contents of the glass gently until the tablets break down (approximately 7 minutes) and drink the contents immediately.
• Fill the glass with the same amount of water (approximately 30 ml), mix the remaining contents gently and drink all the contents to ensure that the full dose of Votubia tablets is taken.
• If necessary, drink more water to rinse the mouth.

Special information for caregivers

It is recommended that caregivers avoid contact with the Votubia tablet suspension. Wash your hands carefully before and after preparing the suspension.

If you take more Votubia than you should

• If you have taken too much Votubia, or if someone has taken your tablets by mistake, consult your doctor or go to the hospital immediately. Urgent treatment may be necessary.
• Bring the packaging and this leaflet so that the doctor knows what you have taken.

If you forget to take Votubia

If you have forgotten a dose, take the next dose at the time it is due. Do not take a double dose to make up for the missed doses.

If you interrupt treatment with Votubia

Do not stop treatment with Votubia tablets unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

STOP treatment with Votubia and seek medical help 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)
• Intense itching of the skin, with red rash or blisters on the skin

The serious side effects of Votubia include:

Frequent 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 pneumonia)

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

• Swelling, feeling of heaviness or tension, pain, limited mobility of parts of the body (this can appear anywhere in the body and is a potential sign of abnormal fluid accumulation in soft tissue due to lymphatic blockage, also known as lymphedema)
• Rash, itching, acne, 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)

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

• Rash with small blisters filled with fluid, appearing on red skin (signs of potentially severe infection, also known as herpes zoster)
• Fever, chills, rapid breathing and heart rate, rash, and possibility of confusion and disorientation (signs of severe infection, also known as sepsis)

If you experience any of these side effects, report them to your doctor immediately as they may be fatal.

Other possible side effects of Votubia include:

Frequent side effects(may affect more than 1 in 10 people)

• Upper respiratory tract infection
• Sore throat and nasal discharge (nasopharyngitis)
• Headache, pressure in the eyes, nose, or cheek area (signs of sinus and nasal duct inflammation, also known as sinusitis)
• Upper urinary tract infection
• High levels of lipids (fats) in the blood (hypercholesterolemia)
• Loss of appetite
• Headache
• Cough
• Mouth ulcers
• Diarrhea
• Dizziness (nausea)
• Acne
• Rash on the skin
• Feeling tired
• Fever
• Irregular menstrual periods, such as absence of periods (amenorrhea) or irregular periods
• Sore throat (pharyngitis)
• Headache, dizziness, signs of high blood pressure (hypertension)

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

• Middle ear infection
• Swollen gums, with blood (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 levels of sugar in the blood (hyperglycemia)
• Tiredness, difficulty breathing, dizziness, pale skin (signs of low red blood cell count, also known as anemia)
• Fever, sore throat, or mouth ulcers due to infections (signs of low white blood cell count, also known as leucopenia, lymphopenia, neutropenia)
• Spontaneous bleeding or hematomas (signs of low platelet count, also known as thrombocytopenia)
• Mouth pain
• Nasal bleeding (epistaxis)
• Stomach discomfort, feeling of dizziness (nausea)
• Abdominal pain
• Severe pain in the lower abdomen and pelvic area, with irregular menstrual periods (ovarian cyst)
• Excessive gas in the intestines (flatulence)
• Constipation
• Abdominal pain, nausea, vomiting, diarrhea, swelling, and increased gas in the abdomen (signs of stomach mucosa inflammation, also known as gastritis or viral gastroenteritis)
• Dry skin, itching (pruritus)
• Skin inflammation characterized by redness, itching, blisters filled with fluid that become scaly, crusty, and hardened (acneiform dermatitis)
• Hair loss (alopecia)
• Protein in the urine
• Irregular menstrual periods, such as heavy periods (menorrhagia) or vaginal bleeding
• Sleep problems (insomnia)
• Irritability
• Aggression
• High levels of an enzyme called lactate dehydrogenase in the blood that provides information about the health of certain organs
• High levels of a hormone that causes ovulation (increased luteinizing hormone in the blood)
• Weight loss

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

• Muscle spasms, fever, red or brown urine that may be symptoms of muscle damage (rhabdomyolysis)
• Cough with phlegm, chest pain, fever (signs of respiratory tract inflammation, also known as viral bronchitis)
• Alteration of the sense of taste (dysgeusia)
• Irregular menstrual periods, such as delayed periods
• High levels of female reproductive hormone (increased follicle-stimulating hormone)

Unknown frequency(cannot be estimated from available data)

• Reaction at the site of previous radiation therapy (for example, skin redness or lung inflammation) (known as radiation recall syndrome)
• Worsening of radiation therapy side effects

Report side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

The following side effects have been reported in patients taking everolimus for the treatment of other pathologies different from CET:

• Renal alterations: altered or absent urination may be symptoms of renal insufficiency and have been observed in some patients receiving everolimus. Other symptoms may include altered renal function tests (increased creatinine).
• Signs of heart failure, such as shortness of breath, difficulty breathing when lying down, swelling of the feet or 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 levels of sugar in the blood (hyperglycemia).

In some patients taking everolimus, reactivation of hepatitis B has been observed. Inform your doctor if you experience symptoms of hepatitis B during treatment with everolimus. Initial symptoms may include fever, skin rash, inflammation, and joint pain. Other symptoms may include fatigue, loss of appetite, nausea, jaundice (yellow skin), and pain in the upper right abdomen. Other signs of hepatitis may include clear stools or dark urine.

Reporting side effects

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the packaging and on the blister. The expiration date is the last day of the month indicated.
• This medication does not require any special storage temperature..
• Store in the original packaging to protect it from light and moisture.
• Open the blister just before taking Votubia dispersible tablets.
• The suspension prepared for use has been shown to be stable for 60minutes. The suspension should be used immediately after preparation. If it is not used within 60minutes, it should be discarded and a new suspension should be prepared.
• Do not use this medication if the packaging is damaged or shows signs of manipulation.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of empty packaging and unused medications. This will help protect the environment.

Composition of Votubia tablets

• 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 components are hydroxytoluene butylate (E321), magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, and anhydrous lactose (see section 2 “Votubia contains lactose”).

Appearance of Votubia tablets and packaging

Votubia 2.5 mg tablets are white to light yellow elongated tablets. They have the inscription “LCL” on one face and “NVR” on the other.

Votubia 5 mg tablets are white to light yellow elongated tablets. They have the inscription “5” on one face and “NVR” on the other.

Votubia 10 mg tablets are white to light yellow elongated tablets. They have the inscription “UHE” on one face 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 perforated unit dose blisters of 10 x 1 tablets each.

Votubia 5 mg tablets are available in packs containing 30 x 1 or 100 x 1 tablets in perforated unit dose blisters 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 perforated unit dose blisters of 10 x 1 tablets each.

Only some pack sizes may be marketed.

Marketing authorisation holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

Responsible manufacturer

Novartis Farmacéutica SA

Gran Via de les Corts Catalanes, 764

08013 Barcelona

Spain

Novartis Pharma GmbH

Roonstraße 25

D-90429 Nürnberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of this leaflet: 06/2022

Other sources of information

The information provided in this leaflet is available on the website of the European Medicines Agency:http://www.ema.europa.eu