VOTUBIA 2.5 mg TABLETS

Introduction

Package Leaflet: Information for the User

Votubia 2.5mg tablets

Votubia 5mg tablets

Votubia 10mg tablets

everolimus

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

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

Contents of the pack

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

1. What is Votubia and what is it used for

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

Votubia tablets are used to treat:

• 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 suitable.

2. What you need to know before you take Votubia

If you are being treated for TSC with renal angiomyolipoma, Votubia will only be prescribed for you by a doctor who is experienced in the treatment of patients with TSC.

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

Follow your doctor's instructions carefully. They may be different from the general information contained in this leaflet. If you have any questions about Votubia or why you have been prescribed this medicine, ask your doctor.

Do not take Votubia

• if you are allergicto everolimus, to related 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, talk to your doctor.

Warnings and precautions

Talk to your doctor before you start taking Votubia:

• if you have liver problems or if you have had a disease that may have affected your liver. Your doctor may prescribe a different dose of Votubia or stop treatment for a short period or permanently.
• if you have diabetes (high blood sugar). Votubia may increase blood sugar levels and worsen diabetes mellitus. This may mean you need treatment with insulin and/or oral anti-diabetic medicines. Tell your doctor if you notice you are thirstier than usual or need to urinate more often.
• if you need to be vaccinated while taking Votubia, as vaccination may be less effective. For children with SEGA, it is important to discuss the childhood vaccination program with your doctor before treatment with Votubia.
• if you have high cholesterol. Votubia may increase cholesterol and/or other fats in the blood.
• if you have recently had major surgery or if you still have an unhealed wound after surgery. Votubia may increase the risk of wound healing problems.
• if you have an infection. You may need to be treated for the infection before starting treatment with Votubia.
• if you have had hepatitis B in the past, as it may come back 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.
• weaken your immune system. You may be at risk of getting an infection while taking Votubia. If you have a fever or other signs of infection, talk to your doctor. Some infections can be serious and life-threatening in adults and children.
• affect kidney function. Your doctor will monitor your kidney function while you are taking Votubia.
• cause breathing difficulties, cough, and fever (see section 4 "Possible side effects").
• cause radiotherapy complications. Serious radiotherapy complications (such as breathing difficulties, nausea, diarrhea, skin rash, and pain in the mouth, gums, and throat), including fatal cases, have been observed in some patients taking everolimus at the same time as receiving radiotherapy or taking everolimus shortly after receiving radiotherapy. Radiation recall syndrome (which occurs with skin redness or lung inflammation at the site of previous radiotherapy) has also been reported in patients who have received radiotherapy in the past.

Tell your doctor if you are scheduled to receive radiotherapy soon or if you have received radiotherapy in the past.

Tell your doctor immediatelyif you experience these symptoms.

During treatment, you will have blood tests before and periodically. These tests will determine the number of cells in your blood (white blood cells, red blood cells, and platelets) to check if Votubia is having an unwanted effect on these cells. You will also have blood tests to monitor kidney function (creatinine, urea, or protein in urine), liver function (transaminases), and blood sugar and lipid levels. These tests are done because they may be affected by treatment with Votubia.

If you receive Votubia for the treatment of SEGA associated with TSC, you will also need periodic blood tests to measure the amount of Votubia in your blood, as this will help your doctor decide the amount of Votubia you need to take.

Children and adolescents

Votubia can be used in children and adolescents with SEGA associated with TSC.

Votubia must not be used in children or adolescents with TSC who have renal angiomyolipoma without SEGA, as it has not been studied in these patients.

Using 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.

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

The following may increase the risk of side effects 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.
• cyclosporin, a medicine used to prevent the body from rejecting transplanted organs.
• imatinib, used to inhibit the growth of abnormal cells.
• angiotensin-converting enzyme (ACE) inhibitors (such as ramipril) used to treat high blood pressure or other cardiovascular problems.
• cannabidiol (its use includes, among others, the treatment of epileptic seizures).

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 conditions, including inflammatory or immune system disorders.
• phenytoin, carbamazepine, or phenobarbital, and other anti-epileptics used to control seizures.

It is recommended to avoid the use of all the above-mentioned medicines during treatment with Votubia. If you are taking any of them, your doctor may prescribe a different medicine or change the 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 needed. Your doctor will make this decision. If you change the dose of your anti-epileptic medicine, tell 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 to a harmful level.

Pregnancy, breastfeeding, and fertility

Pregnancy

Votubia may harm your unborn baby and should not be used during pregnancy. Tell your doctor if you are pregnant or think you may be pregnant.

Women who can become pregnant must use a very effective method of contraception during treatment and for up to 8 weeks after finishing treatment. If, despite these measures, you think you may be pregnant, talk to your doctor beforetaking more Votubia.

Breastfeeding

Votubia may harm your baby if you are breastfeeding. You must not breastfeed while taking Votubia and for 2 weeks after your last dose of Votubia. Tell your doctor if you are breastfeeding.

Fertility

Votubia may affect the fertility of men and women. Talk to your doctor if you want to have children.

Driving and using machines

If you feel unusually tired (fatigue is a common side effect), be careful while driving 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, talk to your doctor before taking this medicine.

3. How to take Votubia

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. Votubia is available as tablets and as dispersible tablets. Always take either the tablets or the dispersible tablets, and never a combination of both. If in doubt, consult your doctor or pharmacist again.

How much Votubia to take

If you are taking Votubia for the treatment of TSC with renal angiomyolipoma, the usual dose is 10 mg, taken 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 other medicines in addition to Votubia.

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

• your age
• your body size
• your liver function
• other medicines you are taking.

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

If you experience side effects (see section 4) while taking Votubia, your doctor may reduce the dose you take or stop treatment for a short period or permanently.

How to take this medicine

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

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

• Put the required number of tablets in a glass of water (approximately 30 ml).
• Gently stir the contents of the glass until the tablets break up (approximately 7 minutes) and drink the contents immediately.
• Refill the glass with the same amount of water (approximately 30 ml), gently stir the remaining contents, and drink all the contents to ensure you take the full dose of Votubia tablets.
• If necessary, drink more water to rinse any remaining residue from the mouth.

Special information for caregivers

Caregivers are advised to 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 accidentally, talk to your doctor or go to the hospital immediately. You may need urgent treatment.
• Take the pack and this leaflet with you to show the doctor what you have taken.

If you forget to take Votubia

If you miss a dose, take the next dose at the scheduled time. Do not take a double dose to make up for forgotten doses.

If you stop taking Votubia

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

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

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

STOP treatment with Votubia and seek immediate medical attention 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 a red-colored rash or bumps on the skin

The serious adverse effects of Votubia include:

Very Common Adverse 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 Adverse Effects(may affect up to 1 in 10 people)

• Swelling, feeling of heaviness or tension, pain, limited mobility of body parts (this can appear in any part of the body and is a potential sign of abnormal fluid accumulation in soft tissue due to lymphatic system blockage, also known as lymphedema)
• Rash, itching, acne, 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 Adverse Effects(may affect up to 1 in 100 people)

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

If you experience any of these adverse effects, inform your doctor immediately as they could have fatal consequences.

Other Possible Adverse Effects of Votubia Include:

Very Common Adverse Effects(may affect more than 1 in 10 people)

• Upper respiratory tract infection
• Sore throat and nasal secretion (nasopharyngitis)
• Headache, pressure in the eyes, nose, or cheek area (signs of sinus inflammation, also known as sinusitis)
• Upper urinary tract infection
• High levels of lipids (fats) in the blood (hypercholesterolemia)
• Decreased appetite
• Headache
• Cough
• Mouth ulcers
• Diarrhea
• Feeling of dizziness (vomiting)
• Acne
• Skin rash
• Feeling of fatigue
• Fever
• Menstrual disturbances such as absence of menstrual periods (amenorrhea) or irregular menstrual periods
• Sore throat (pharyngitis)
• Headache, dizziness, signs of high blood pressure (hypertension)

Common Adverse Effects(may affect up to 1 in 10 people)

• Middle ear infection
• Swollen gums with bleeding (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 phosphate in the blood (hypophosphatemia)
• High levels of sugar in the blood (hyperglycemia)
• Fatigue, difficulty breathing, dizziness, paleness of the 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 bruising (signs of low platelet count, also known as thrombocytopenia)
• Mouth pain
• Nosebleeds (epistaxis)
• Stomach upset such as a feeling of dizziness (nausea)
• Abdominal pain
• Severe pain in the lower abdomen and pelvic area that can be acute, with irregular menstrual periods (ovarian cyst)
• Excessive gas in the intestines (flatulence)
• Constipation
• Abdominal pain, nausea, vomiting, diarrhea, bloating, and 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, fluid-filled blisters that become scaly, with crust and hardened (acneiform dermatitis)
• Hair loss (alopecia)
• Protein in the urine
• Menstrual disturbances 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 (increase in luteinizing hormone in the blood)
• Weight loss

Uncommon Adverse Effects(may affect up to 1 in 100 people)

• Muscle spasms, fever, reddish-brown urine that can be symptoms of muscle disorder (rhabdomyolysis)
• Cough with phlegm, chest pain, fever (signs of respiratory tract inflammation, also known as viral bronchitis)
• Disturbance of taste (dysgeusia)
• Menstrual disturbances, such as delayed periods
• High levels of female reproductive hormone (increase in follicle-stimulating hormone)

Frequency Not Known(cannot be estimated from available data)

• Reaction at the site of previous radiation therapy (e.g., skin redness or lung inflammation) (called radiation recall syndrome)
• Worsening of radiation therapy adverse effects

If these adverse effects worsen, please inform your doctor and/or pharmacist. Most of these adverse effects are mild to moderate and usually disappear if treatment is interrupted for a few days.

The following adverse effects have been reported in patients taking everolimus for the treatment of conditions other than CET:

• Kidney disorders: altered or absent urine frequency may be symptoms of kidney failure and have been observed in some patients receiving everolimus. Other symptoms may include altered kidney function tests (increased creatinine).
• Symptoms 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 warming 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. The first symptoms may include fever, skin rash, inflammation, and joint pain. Other symptoms may include fatigue, loss of appetite, nausea, yellowing of the skin (jaundice), and pain in the upper right abdomen. Also, pale stools or dark urine may be signs of hepatitis.

Reporting of Adverse Effects

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

5. Storage of Votubia

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date stated on the packaging and blister. The expiration date is the last day of the month indicated.
• Do not store above 25°C.
• Store in the original packaging to protect from light and moisture.
• Open the blister just before taking Votubia tablets.
• Do not use this medicine if the packaging is damaged or shows signs of tampering.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Votubia Tablets

• The active ingredient is everolimus.

Each 2.5 mg Votubia tablet contains 2.5 mg of everolimus.

Each 5 mg Votubia tablet contains 5 mg of everolimus.

Each 10 mg Votubia 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").

Appearance of Votubia Tablets and Package Contents

Votubia 2.5 mg tablets are white to slightly yellowish, elongated tablets. They are marked with "LCL" on one side and "NVR" on the other.

Votubia 5 mg tablets are white to slightly yellowish, elongated tablets. They are marked with "5" on one side and "NVR" on the other.

Votubia 10 mg tablets are white to slightly yellowish, elongated tablets. They are marked with "UHE" on one side and "NVR" on the other.

Votubia 2.5 mg tablets are available in packages 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 packages containing 30 x 1 or 100 x 1 tablets in perforated unit-dose blisters of 10 x 1 tablets each.

Votubia 10 mg is available in packages containing 10 x 1, 30 x 1, or 100 x 1 tablets in perforated unit-dose blisters of 10 x 1 tablets each.

Not all pack sizes may be marketed.

Marketing Authorization 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 Nürnberg

Germany

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Germany

You can obtain further information on this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet: 06/2022

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu