Votubia 5 mg tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Votubia 2.5 mg tablets

Votubia 5 mg tablets

Votubia 10 mg tablets

everolimus

Read the entire 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Votubia is and what it is 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. Contents of the pack and other information

1. What Votubia is and what it is used for

Votubia is an antitumour 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 certain kidney tumours known as renal angiomyolipomas, and certain 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 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 starting to take Votubia

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

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

Carefully follow all instructions from your doctor. These may differ from the general information contained in this leaflet. If you have any questions about Votubia or why this medicine has been prescribed for you, consult your doctor.

Do not take Votubia

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

Warnings and precautions

Consult your doctor before starting to take Votubia:

• if you have liver problems or have had any illness that may have affected your liver. In this case, your doctor may 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 medicines. Inform your doctor if you notice 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 childhood vaccination schedule with your doctor before starting treatment with Votubia.
• if you have high cholesterol. Votubia may increase cholesterol and/or other blood fats.
• if you have recently undergone 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. It may be necessary to treat your infection before starting Votubia treatment.
• 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 sores (oral ulcers).
• weaken your immune system. Therefore, you may be at risk of developing an infection while taking Votubia. If you develop fever or other signs of infection, consult your doctor. Some infections may be severe and potentially 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 section 4 "Possible side effects").
• cause complications related to radiotherapy. Serious complications of radiotherapy (such as difficulty breathing, nausea, diarrhea, skin rash, and pain in the mouth, gums, and throat), including fatal cases, have been observed in some patients who were taking everolimus at the same time as receiving radiotherapy or shortly after completing radiotherapy. The so-called radiation recall syndrome (characterized by skin redness or lung inflammation at the site of previous radiotherapy) has also been reported in patients who previously received radiotherapy.

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

Contact your doctor immediately if you experience these symptoms.

During treatment, you will undergo blood tests before and periodically throughout treatment. These tests will measure blood cell counts (white blood cells, red blood cells, and platelets) to check whether Votubia is having any unwanted effects on these cells. Blood tests will also be performed to monitor kidney function (levels of creatinine, blood urea nitrogen, or protein in urine), liver function (transaminase levels), and blood sugar and lipid levels. These tests are necessary because these parameters may be affected by treatment with Votubia.

If you are receiving Votubia for the treatment of SEGA associated with TSC, periodic blood tests to measure the amount of Votubia in your blood are also required, as this will help your doctor determine the appropriate dose of Votubia 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 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 adjust the dose of Votubia or of the other medicines.

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

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

• ketoconazole, itraconazole, voriconazole, 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 infection.
• verapamil or diltiazem, used to treat heart problems or high blood pressure.
• dronedarone, a medicine used to help regulate heart rhythm.
• cyclosporine, a medicine used to prevent organ transplant rejection.
• 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 (used, among other things, for 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 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 control seizures.

The use of all the medicines listed above should be avoided during treatment with Votubia. If you are taking any of them, your doctor may prescribe a different medicine 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 require a change in the dose of Votubia. Your doctor will make this decision. If your antiepileptic medicine dose is changed, inform your doctor.

Taking Votubia with food and drinks

Do not consume grapefruit or grapefruit juice while taking Votubia. It may increase the amount of Votubia in the blood, possibly to harmful levels.

Pregnancy, breastfeeding, and fertility

Pregnancy

Votubia may harm the unborn baby and its use is not recommended during pregnancy. Inform your doctor if you are pregnant or think you may be pregnant.

Women who can become pregnant must use a highly effective method of contraception during treatment and for 8 weeks after stopping treatment. If, despite these precautions, you suspect you may be pregnant, consult your doctor before taking any further doses of Votubia.

Breastfeeding

Votubia may harm a 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 fertility in both men and women. Consult your doctor if you wish to have children.

Driving and using machines

If you feel unusually tired (fatigue is a common side effect), take special care when driving or operating machinery.

Votubia contains lactose

Votubia contains lactose (milk sugar). If your doctor has informed you that you have an intolerance to certain sugars, consult him before taking this medicine.

3. How to take Votubia

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

How much Votubia should you take

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

Your doctor may recommend a higher or lower dose depending on your individual treatment needs, for example if you have kidney problems or if you are taking certain 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 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. These are performed to measure the amount of Votubia in your blood and to determine the most appropriate daily dose.

If you experience any adverse effects (see section 4) while taking Votubia, your doctor may reduce your dose, or interrupt treatment temporarily or permanently.

How to take this medicine

• Take Votubia tablets once daily.
• Take them at the same time each day.
• You may take them with or without food, but you should do so consistently every 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 are unable to swallow the tablets, you may disperse them 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 break apart (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 of it to ensure you receive the full dose of Votubia tablets.
• If needed, drink additional water to rinse any residue from your mouth.

Special information for caregivers

Caregivers are advised to avoid contact with the Votubia tablet suspension. Wash your hands thoroughly 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 accidentally taken your tablets, contact your doctor or go to a hospital immediately. Urgent treatment may be necessary.
• Take the container and this leaflet with you so the doctor knows what you have taken.

If you forget to take Votubia

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

If you stop taking Votubia

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

If you have any further questions about 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 everyone will experience them.

STOP taking Votubia and seek immediate medical help 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 lumps on the skin

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 tightness, pain, limited mobility in parts of the body (this may occur anywhere in the body and is a potential sign of abnormal fluid accumulation in soft tissue due to blockage of the lymphatic system, also known as lymphoedema)
• Rash, itching, pimples, 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 appearing on red skin (signs of an infection that may be potentially serious, also known as herpes zoster)
• Fever, chills, rapid breathing and rapid heartbeat, rash, and possible confusion and disorientation (signs of a serious infection, also known as sepsis)

If you experience any of these adverse effects, inform your doctor immediately, as they could be life-threatening.

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 discharge (nasopharyngitis)
• Headache, pressure in the eyes, nose, or cheek area (signs of inflammation of the sinuses and nasal passages, 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 tiredness
• Fever
• Menstrual disorders such as absence of 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, bleeding 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 phosphate in the blood (hypophosphatemia)
• High blood sugar levels (hyperglycemia)
• Tiredness, 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 leukopenia, lymphopenia, neutropenia)
• Spontaneous bleeding or bruising (signs of low platelet count, also known as thrombocytopenia)
• Mouth pain
• Nosebleeds (epistaxis)
• Stomach discomfort such as a feeling of dizziness (nausea)
• Abdominal pain
• Severe pain in the lower abdomen and pelvic area that may be acute, with menstrual irregularities (ovarian cyst)
• Excessive gas in the intestines (flatulence)
• Constipation
• Abdominal pain, nausea, vomiting, diarrhea, bloating, and increased gas in the abdomen (signs of inflammation of the stomach lining, also known as gastritis or viral gastroenteritis)
• Dry skin, itching (pruritus)
• Skin inflammation characterized by redness, itching, fluid-filled cysts that become scaly, crusted, and hardened (acneiform dermatitis)
• Hair loss (alopecia)
• Protein in the urine
• Menstrual disorders such as heavy periods (menorrhagia) or vaginal bleeding
• Sleep problems (insomnia)
• Irritability
• Aggressiveness
• High levels of an enzyme called lactate dehydrogenase in the blood, which provides information about the health of certain organs
• High levels of a hormone that triggers ovulation (increased luteinizing hormone in the blood)
• Weight loss

Uncommon adverse 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 airways, also known as viral bronchitis)
• Altered sense of taste (dysgeusia)
• Menstrual disorders, such as delayed periods
• High levels of female reproductive hormone (increased follicle-stimulating hormone)

Frequency not known (cannot be estimated from available data)

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

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

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

• Kidney problems: altered or absent urination may be symptoms of kidney failure and have been observed in some patients receiving everolimus. Other symptoms may include abnormal 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 warmth of the skin in the affected area.
• Problems with wound healing.
• High blood sugar levels (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. Early symptoms may include fever, skin rash, joint swelling and pain. Other symptoms may include fatigue, loss of appetite, nausea, jaundice (yellowing of the skin), and pain in the upper right part of the abdomen. Pale stools or dark urine may also be signs of hepatitis.

Reporting of adverse effects

If you experience any adverse effect, talk to 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 help provide 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 expiry date stated on the packaging and blister. The expiry date refers to 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 immediately before taking Votubia tablets.
• Do not use this medicine if the packaging is damaged or shows signs of tampering.

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

6. Contents of the pack and other information

Composition of Votubia tablets

• 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”).

Appearance of Votubia tablets and contents of the pack

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

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

Votubia 10 mg tablets are white to slightly yellowish, elongated tablets. They are marked with the inscription “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 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.

Some pack sizes may not be marketed.

Marketing Authorization Holder

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

Manufacturer

Novartis Farmacéutica S.A.
Gran Via de les Corts Catalanes, 764
08013 Barcelona
Spain

Novartis Pharma GmbH
Sophie-Germain-Strasse 10
90443 Nürnberg
Germany

Novartis Pharmaceuticals S.R.L.
Str. Livezeni nr. 7A
540472 Târgu Mureș
Romania

For more information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet:

Other sources of information

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