1 mg, 2 mg, 3 mg, and 5 mg dispersible tablets
everolimus
What Votubia is and what it is used for
Votubia dispersible tablets contain the active substance everolimus. Votubia is used to treat children from the age of 2 and adults with partial-onset seizures with or without secondary generalization ( epilepsy ) associated with a genetic disease called tuberous sclerosis complex (TSC) and when other anti-epileptic drugs do not work well enough. Partial seizures start from one side of the brain but can spread and extend over larger areas on both sides of the brain (so-called “secondary generalization”). Votubia dispersible tablets are given together with other medicines against epilepsy.
Votubia is also an anti-tumour drug that can prevent the growth of certain cells in the body. It can reduce the size of a type of brain tumor called subependymal giant cell astrocytoma (SEGA), which is also caused by TSC.
Votubia dispersible tablets are used to treat SEGA associated with TSC in adults and children when surgery is not appropriate.
What you need to know before you take Votubia
Votubia is only prescribed by doctors with experience in treating patients with SEGA or seizures and who can measure the amount of Votubia in the blood through a blood test.
Follow your doctor’s instructions carefully. They may differ from the general information contained in this leaflet. If you have any questions about Votubia or why you have been prescribed it, ask your doctor.
Do not take Votubia
- if you are allergic to everolimus or related substances, such as sirolimus, temsirolimus, or any other ingredient in this medicine (listed in section 6).
If you have had allergic reactions before, ask your doctor for advice.
Warnings and precautions
Talk to your doctor before taking Votubia:
- if you have problems with your liver or if you have ever had any disease that may have affected your liver. In that case, the doctor may need to prescribe another dose of Votubia or stop the treatment, either for a shorter period or permanently.
- if you have diabetes (high blood sugar). Votubia can increase blood sugar levels and worsen diabetes mellitus. This may result in the need for insulin and/or oral diabetes medication. Tell your doctor if you experience any abnormal thirst or need to urinate more often.
- if you need to be vaccinated while you are receiving treatment with Votubia, as the vaccination may then be less effective. For children with SEGA or seizures, it is important to discuss the childhood vaccination program with the doctor before starting treatment with Votubia.
- if you have high cholesterol levels, as Votubia can increase cholesterol levels and/or other blood fats.
- if you have recently had major surgery or if you still have an unhealed wound after surgery. Votubia may increase the risk of problems with wound healing.
- if you have an infection, it may be necessary to treat the infection before starting treatment with Votubia.
- if you previously had hepatitis B, as the infection may reoccur during treatment with Votubia (see section 4, Possible side effects ).
- if you have received or will receive radiotherapy.
Votubia can also:
- cause mouth ulcers
- weaken your immune system. There is therefore a risk that you will get an infection while you are taking Votubia. If you develop a fever or other signs of an infection, consult your doctor. Some infections can be severe and can lead to death in adults and children.
- affect kidney function. Therefore, your doctor will check your kidney function while you are taking Votubia.
- cause shortness of breath, cough, and fever (see section 4, Possible side effects ).
- cause complications of radiotherapy. Severe complications of radiotherapy (such as shortness of breath, nausea, diarrhea, skin rash, and soreness of the mouth, gums, and throat), including death, have been observed in some patients taking everolimus at the same time or shortly after they received radiotherapy at. So-called radiation-induced skin reaction (including reddening of the skin or pneumonia at the site of the previous radiotherapy) has also been reported in patients who have received the previous radiotherapy. Tell the doctor if you are planning to have radiation therapy shortly or if you have had radiation therapy in the past.
Contact your doctor immediately if you experience these symptoms.
Blood samples will be taken before and regularly during the treatment. With the help of these, you can check the number of blood cells ( white blood cells, red blood cells, and platelets ) in the body and see if Votubia has any unwanted effect on these cells. Blood samples are also taken to check your kidney function (creatinine level, blood urea or protein in urine), liver function (transaminase levels), and blood sugar and blood lipid levels. This is because these can also be affected by Votubia.
Regular blood tests are also necessary to measure how much Votubia is in the blood, as this helps the doctor decide how much Votubia you need to take.
Children and young people
Votubia can be used in children and adolescents with SEGA associated with TSC.
Votubia should not be used in children under 2 years of age with TSC and seizures.
Other medicines and Votubia
Votubia can affect the way some other medicines work. If you take other medicines simultaneously as Votubia, the doctor may need to change the dose of Votubia or the other medicines.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
The following may increase the risk of side effects with Votubia:
- ketoconazole, itraconazole, voriconazole, or fluconazole, and other medicines used to treat fungal infections
- clarithromycin, telithromycin, or erythromycin – antibiotics used to treat bacterial infections
- ritonavir or other medicines used to treat HIV infection/AIDS
- verapamil or diltiazem used to treat heart conditions or high blood pressure
- dronedarone, a medicine that regulates heart rhythm
- ciclosporin, a medicine used to prevent the body from rejecting transplanted organs
- imatinib, a drug that inhibits the growth of tumor cells
- ACE inhibitors (eg ramipril), used to treat high blood pressure and other cardiovascular diseases
- cannabidiol (used, among other things, for the treatment of epileptic seizures)
The following may reduce the effect of Votubia:
- rifampicin ‑ used to treat tuberculosis (TB)
- efavirenz or nevirapine used to treat HIV infection/AIDS
- St. John’s wort ( Hypericum perforatum ), an herbal remedy used to treat depression and other conditions
- dexamethasone, a corticosteroid used to treat several conditions, including inflammation and immune disorders
- phenytoin, carbamazepine or phenobarbital, and other antiepileptics – used to stop seizures.
All medicines listed above should be avoided during treatment with Votubia. If you are taking any of these medicines, your doctor may switch you to another drug or change the dose of Votubia.
If you are taking any medicine for epilepsy, a change in the dose of that medicine (increase or decrease) may make it necessary to change the dose of Votubia. Your doctor will decide this. If the dose of one of your epilepsy medicines is changed, inform your doctor.
Before taking Votubia, tell your doctor if you follow a certain diet to reduce the number of seizures.
Votubia with food and drink
Avoid grapefruit and grapefruit juice while you are being treated with Votubia. They can increase the amount of Votubia in the blood to a potentially harmful level.
Pregnancy, breastfeeding, and fertility
Pregnancy
Votubia can hurt the fetus and is not recommended during pregnancy. Tell the doctor if you are pregnant or if you think you may be pregnant.
Women who could become pregnant must use a highly effective method of contraception during treatment and up to 8 weeks after stopping treatment. If, despite these measures, you think you may have become pregnant, consult your doctor before taking any more Votubia.
Breast-feeding
Votubia can hurt children who are breastfed. You should not breastfeed during treatment and up to 2 weeks after the last dose of Votubia. Tell the doctor if you are breastfeeding.
Fertility
Votubia can affect fertility in women and men. Talk to your doctor if you want to have children.
Driving ability and use of machinery
If you feel unusually tired (fatigue is a common side effect), take special care when driving or using machinery.
Votubia contains lactose
Votubia contains lactose (milk sugar). If you have an intolerance to certain sugars, you should consult your doctor before taking this medication.
How to take Votubia
Always take this medicine as directed by your doctor or pharmacist. Votubia is available as tablets and dispersible tablets. Always take either the tablets or the dispersible tablets and never a combination of both. Ask your doctor or pharmacist if you are unsure.
What dose of Votubia you should take
Your doctor will decide which dose of Votubia you need based on:
- your age
- your body size
- liver function
- what other medicines you are taking.
During treatment with Votubia, blood samples will be taken to measure the amount of Votubia in the blood so that the dose is adapted specifically for you.
If you experience particular side effects (see section 4) while taking Votubia, your doctor may lower your dose or stop treatment, either for a short time or permanently
How to take this medicine
- Take Votubia dispersible tablets once a day.
- Take them at the same time each day.
- You can either take them with food and drink or without food and drink, but you should take them the same way every day.
Only take Votubia dispersible tablets as an oral suspension
Do not chew or crush the dispersible tablets. Do not swallow them whole. You must mix the dispersible tablets with water to form a cloudy liquid (a so-called oral suspension ).
How to prepare and take the oral suspension a
Prepare the oral suspension by mixing the dispersible tablets with water, either in an oral syringe or in a small glass. After preparation, you must drink the suspension immediately. If not taken within 30 minutes when using an oral syringe or within 60 minutes when using a small glass, discard the suspension and prepare a new one. Read the detailed instructions at the end of this leaflet on how to do this. Ask your doctor or pharmacist if you are unsure
Important information for caregivers
Caregivers should avoid direct contact with the suspension of one of the Votubia tablets. Wash your hands thoroughly before and after preparing the suspension.
If you have taken too much Votubia
- If you have taken too much Votubia, or if someone else accidentally takes your dispersible tablets, contact your doctor or hospital immediately. Urgent medical treatment may be necessary.
- Bring the tablet package and this leaflet with you, so that the doctor knows what you have taken.
If you forget to take Votubia
If you miss a dose, take the next dose as planned. Do not take a double dose to make up for a forgotten dispersible tablet.
If you stop taking Votubia
Do not stop taking Votubia dispersible tablets unless your doctor tells you to.
If you have any further questions about this medicine, ask your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
STOP taking 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 )
- severe skin itching with red or raised rashes.
Serious side effects of Votubia can be:
Very common side effects ( may affect more than 1 in 10 people)
- fever, cough, difficulty breathing, wheezing (signs of pneumonia due to infection – pneumonia ).
Common side effects ( may affect up to 1 in 10 people)
- swelling, the feeling of heaviness or tension, pain, limited movement of body parts (this can occur anywhere in the body and is a possible sign of an abnormal accumulation of fluid in soft tissue due to a blockage in the lymphatic system, called lymphoedema)
- rash, itching, hives, difficulty breathing or swallowing, dizziness (signs of severe allergic reaction – hypersensitivity reaction )
- fever, cough, difficulty breathing, and wheezing (signs of pneumonia – pneumonitis ).
Uncommon side effects ( may affect up to 1 in 100 people)
- rash with small fluid-filled blisters on reddened skin (a sign of viral disease which may be severe – shingles )
- fever, chills, rapid breathing and heart rate, skin rash, and possible confusion and disorientation (signs of serious infection – sepsis ).
If you experience any of these side effects, talk to your doctor immediately as they can have life-threatening consequences.
Other possible side effects of Votubia can be:
Very common side effects ( may affect more than 1 in 10 people)
- upper respiratory tract infection
- sore throat and runny nose
- headache, pressure over eyes, nose, and cheeks (signs of sinusitis)
- urinary tract infection
- high blood fats ( hypercholesterolemia )
- decreased appetite
- headache
- cough
- mouth ulcers
- diarrhea
- vomiting
- acne
- rash
- feeling of fatigue
- fever
- menstrual disorders such as missed periods ( amenorrhea ) or irregular periods
- sore throat ( pharyngitis )
- headache, dizziness – signs of high blood pressure.
Common side effects ( may affect up to 1 in 10 people)
- otitis
- swollen and bleeding gums or signs of inflamed gums
- skin inflammation
- high blood fats and triglycerides
- low phosphate levels in the blood
- high blood sugar
- tiredness, shortness of breath, pale skin (signs of low levels of red blood cells – anemia)
- fever, sore throat, mouth ulcers due to infection (signs of low levels of white blood cells – leukopenia, lymphopenia, neutropenia )
- bleeding or bruising that occurs without reason (signs of low levels of platelets – thrombocytopenia )
- mouth pain
- nosebleed
- stomach upset e.g. nausea
- abdominal pain
- severe pain, which may be sharp, in the abdomen and pelvic floor along with irregular periods (ovarian cysts)
- the increased amount of gases in the intestines, tension
- constipation
- abdominal pain, nausea, vomiting, diarrhea, swollen and bloated abdomen (signs of inflammation of the stomach lining – gastritis or viral gastroenteritis )
- dry skin, itching
- inflammation of the skin characterized by redness, itching, and fluid-filled cysts that are scaly, scaly, or hard ( dermatitis acneiform)
- hair loss
- protein in the urine
- menstrual disturbances such as heavy bleeding or vaginal bleeding
- sleep difficulties
- irritability
- aggressiveness
- high blood levels of lactate dehydrogenase, an enzyme that provides information about the condition of certain organs
- elevated levels of the hormone that triggers ovulation ( luteinizing hormone )
- weight loss.
Uncommon side effects ( may affect up to 1 in 100 people)
- muscle cramps, fever, dark colored urine, which may be symptoms of muscle damage ( rhabdomyolysis )
- mucus cough, chest pain, fever (signs of inflammation of the respiratory tract – viral bronchitis )
- taste changes
- menstrual disorders such as delayed menstruation
- elevated levels of female sex hormones (follicle-stimulating hormone )
Has been reported ( occurs in an unknown number of users )
- reaction at the area of previous radiation treatment, e.g. redness of the skin or pneumonia (so-called radiation-induced skin reaction (radiation recall syndrome))
worsening of side effects from radiotherapy
If these side effects become severe, contact a doctor and/or pharmacist. Most side effects are mild to moderate and generally disappear if treatment is discontinued for a few days.
The following side effects have been reported in patients using everolimus for conditions other than TSC:
- Kidney problems: altered frequency or absence of urination may be a sign of kidney failure and has been observed in some patients treated with everolimus. Other symptoms may be altered kidney function tests (elevated creatinine ).
- Symptoms of heart failure, e.g. shortness of breath, difficulty breathing when lying down, and swelling in the feet or legs.
- Blockage or narrowing of a blood vessel (vein) in the leg (deep vein thrombosis ) – symptoms of this can be swelling and/or pain in one of the legs, usually in the calf, as well as redness or feeling of warmth in the affected area.
- Problems with wound healing.
- High blood sugar.
Recurrence (reactivation) of hepatitis B has been observed in several patients receiving everolimus. Tell your doctor if you experience any symptoms of hepatitis B during treatment with everolimus. Examples of early symptoms are fever, skin rash, joint pain, and inflammation. Other symptoms may include fatigue, decreased appetite, nausea, jaundice (yellowing of the skin), and pain in the upper, right side of the abdomen. Pale stools or dark urine can also be signs of hepatitis.
How to store Votubia
- Keep this medicine out of the sight and reach of children.
- Use before the expiry date stated on the carton and blister pack. The expiration date is the last day of the specified month.
- No special temperature instructions.
- Store in the original packaging. Light sensitive. Moisture sensitive.
- Open the blister just before using Votubia dispersible tablets.
- The durability of suspension one is 60 minutes. The suspension must be taken immediately after preparation. If not used within 60 minutes, it must be discarded and a new suspension prepared.
- Do not use the medicine if you see that the package is damaged or appears to have been opened before.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
- The active substance is everolimus.One Votubia 1 mg dispersible tablet contains 1 mg everolimus.One Votubia 2 mg dispersible tablet contains 2 mg everolimus.One Votubia 3 mg dispersible tablet contains 3 mg everolimus.One Votubia 5 mg dispersible tablet contains 5 mg everolimus.
- Other ingredients are butyl hydroxytoluene (E321), magnesium stearate, lactose monohydrate, hypromellose, crospovidone type A, mannitol, microcrystalline cellulose and colloidal silicon dioxide, anhydrous (see section 2 “Votubia contains lactose”).
Appearance and package sizes of the medicine
Votubia 1 mg dispersible tablets are white to yellowish, round, flat tablets with beveled edges and no score. They are stamped with “D1” on one side and “NVR” on the other.
Votubia 2 mg dispersible tablets are white to yellowish, round, flat tablets with beveled edges and no score. They are stamped with “D2” on one side and “NVR” on the other.
Votubia 3 mg dispersible tablets are white to yellowish, round, flat tablets with beveled edges and no score. They are stamped with “D3” on one side and “NVR” on the other.
Votubia 5 mg dispersible tablets are white to yellowish, round, flat tablets. They are stamped with “D5” on one side and “NVR” on the other
Votubia 1 mg dispersible tablets are available in packages containing 30 dispersible tablets in perforated single-dose blisters of 10 x 1 tablet each.
Votubia 2 mg dispersible tablets are available in packs containing 10 x 1, 30 x 1, or 100 x 1 dispersible tablets in perforated single-dose blisters of 10 x 1 tablet each.
Votubia 3 mg and 5 mg dispersible tablets are available in packs containing 30 x 1 or 100 x 1 dispersible tablet in perforated unit dose blisters of 10 x 1 tablet each
Not all pack sizes may be marketed.
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
Contact the representative of the Marketing Authorization Holder if you would like to know more about this medicine:
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