Votubia (Everolimus)
mTOR inhibitor for tuberous sclerosis complex (TSC) – seizures and SEGA brain tumors
Quick Facts About Votubia
Key Takeaways About Votubia
- Specialist-only medication: Votubia must be prescribed by a physician experienced in treating TSC, with regular blood level monitoring to adjust the dose
- Two TSC indications: Treats both TSC-associated epilepsy (age 2+) and SEGA brain tumors (when surgery is not suitable)
- Immunosuppressive effects: Votubia weakens the immune system, increasing infection risk – report fever or infection signs to your doctor promptly
- Many drug interactions: Numerous medications affect Votubia blood levels – always inform your doctor of all medicines you take, including herbal products
- Pregnancy contraindicated: Votubia can harm the fetus – highly effective contraception is required during treatment and for 8 weeks afterward
What Is Votubia and What Is It Used For?
Votubia (everolimus) is a targeted medicine that inhibits the mTOR protein pathway. It is used to treat seizures and brain tumors caused by tuberous sclerosis complex (TSC), a rare genetic condition that causes benign tumors to grow in multiple organs throughout the body.
Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in the TSC1 or TSC2 genes. These mutations lead to overactivation of the mTOR signaling pathway, which controls cell growth and proliferation. When mTOR is abnormally active, it promotes the formation of benign tumors (hamartomas) in the brain, kidneys, skin, heart, lungs, and other organs. By inhibiting the mTOR protein, everolimus directly addresses the underlying molecular cause of TSC.
Votubia is approved by the European Medicines Agency (EMA) for two specific conditions associated with TSC:
TSC-Associated Epilepsy
Votubia dispersible tablets are approved for treating partial-onset seizures, with or without secondary generalization, in patients aged 2 years and older with TSC. Partial seizures originate from one side of the brain but may spread to involve both hemispheres (secondary generalization). Votubia is used as an add-on therapy when other anti-epileptic drugs have not provided adequate seizure control. Clinical trials have demonstrated significant reductions in seizure frequency compared to placebo, with approximately 40% of patients experiencing at least a 50% reduction in seizure frequency.
Subependymal Giant Cell Astrocytoma (SEGA)
SEGA is a slow-growing brain tumor that develops near the ventricles (fluid-filled cavities) of the brain. It occurs in approximately 5-20% of people with TSC. While benign, SEGA can grow large enough to block the flow of cerebrospinal fluid, causing dangerous hydrocephalus (fluid buildup) with symptoms such as headache, nausea, vomiting, and visual disturbances. Votubia has been shown to reduce SEGA tumor volume by 30-50% or more in the majority of patients, offering an alternative to brain surgery for patients in whom surgery is not appropriate or is too risky.
Both Votubia and Afinitor contain the same active ingredient (everolimus) and are manufactured by Novartis. Votubia is specifically branded and approved for TSC-related conditions, while Afinitor is approved for certain cancers including advanced renal cell carcinoma and hormone receptor-positive breast cancer. The dosing and monitoring requirements may differ between indications.
What Should You Know Before Taking Votubia?
Before starting Votubia, your doctor must evaluate your liver function, infection status, diabetes risk, cholesterol levels, and current medications. You must not take Votubia if you are allergic to everolimus, sirolimus, temsirolimus, or any of the other ingredients.
Votubia is prescribed only by physicians experienced in treating patients with TSC who can monitor blood levels through laboratory testing. Your doctor will carefully assess whether Votubia is appropriate for you and will adjust the dose based on blood level results, your body size, liver function, and other medications you are taking.
Contraindications
Do not take Votubia if you are allergic (hypersensitive) to everolimus or related substances such as sirolimus (rapamycin) or temsirolimus, or to any of the other ingredients in the formulation. If you have experienced allergic reactions to these substances in the past, discuss this with your doctor before starting treatment.
Warnings and Precautions
Speak with your doctor before taking Votubia if any of the following apply to you:
- Liver problems: Impaired liver function may require dose adjustment or discontinuation of treatment. Your doctor will assess liver function before and during therapy.
- Diabetes: Votubia can increase blood sugar levels and worsen diabetes mellitus, potentially requiring insulin or oral diabetes medications. Report excessive thirst or frequent urination to your doctor.
- Vaccinations: Immunizations may be less effective during Votubia treatment. For children with TSC, discuss the childhood vaccination schedule with your doctor before starting treatment.
- High cholesterol: Votubia may elevate cholesterol and other blood lipid levels, which will be monitored through regular blood tests.
- Recent surgery: Votubia can impair wound healing. If you have recently had major surgery or have unhealed surgical wounds, inform your doctor.
- Active infections: It may be necessary to treat existing infections before beginning Votubia therapy, as the drug suppresses immune function.
- History of hepatitis B: Hepatitis B infection can reactivate during Votubia treatment. Your doctor may test for hepatitis B before starting therapy.
- Radiation therapy: Severe complications of radiation therapy, including fatal outcomes, have been observed in patients taking everolimus during or shortly after radiation treatment. Inform your doctor if you are scheduled for or have recently received radiation therapy.
Votubia weakens the immune system, increasing the risk of infections – some of which can be severe or fatal in both adults and children. If you develop fever, cough, breathing difficulties, or other signs of infection while taking Votubia, contact your doctor immediately. Do not wait for scheduled appointments if you suspect an infection.
Votubia may also cause mouth ulcers (stomatitis), impair kidney function, cause shortness of breath, cough, and fever (signs of pneumonitis), and may worsen radiation side effects. Your doctor will monitor you for these potential effects through regular check-ups and blood tests.
Blood Test Monitoring
Regular blood tests are essential throughout Votubia treatment. These tests serve multiple purposes:
- Therapeutic drug monitoring: Blood level measurements determine the correct dose for you individually
- Blood cell counts: White blood cells, red blood cells, and platelets can be affected by Votubia
- Kidney function: Creatinine, blood urea nitrogen, and urinary protein levels are monitored
- Liver function: Transaminase levels indicate liver health
- Metabolic parameters: Blood sugar and lipid levels may change during treatment
Pregnancy and Breastfeeding
Votubia may cause harm to the developing fetus and is not recommended during pregnancy. Women of childbearing potential must use highly effective contraception during treatment and for up to 8 weeks after the last dose. If you suspect you may be pregnant, consult your doctor before taking any further doses.
Breastfeeding should be avoided during Votubia treatment and for 2 weeks after the last dose, as the drug may pass into breast milk and harm the nursing infant. Votubia may also affect fertility in both women and men; discuss family planning concerns with your doctor before starting treatment.
How Does Votubia Interact with Other Drugs?
Votubia has significant interactions with many common medications. Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir) increase Votubia blood levels and toxicity risk, while strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine) decrease its effectiveness. Grapefruit juice must be avoided.
Everolimus is primarily metabolized by the liver enzyme CYP3A4 and is also a substrate for the drug transporter P-glycoprotein (P-gp). Any medication that significantly inhibits or induces CYP3A4 will affect Votubia blood levels and may require dose adjustment or substitution. Always tell your doctor or pharmacist about all medicines you are taking, including prescription medications, over-the-counter products, and herbal supplements.
| Drug / Class | Effect on Votubia | Clinical Significance | Action Required |
|---|---|---|---|
| Ketoconazole, Itraconazole, Voriconazole | Significantly increases blood levels | High – increased toxicity risk | Avoid or reduce Votubia dose |
| Clarithromycin, Telithromycin, Erythromycin | Increases blood levels | High – increased side effects | Use alternative antibiotic or adjust dose |
| Ritonavir (HIV protease inhibitor) | Significantly increases blood levels | High – increased toxicity risk | Avoid combination; adjust dose if unavoidable |
| Verapamil, Diltiazem | Moderately increases blood levels | Moderate | Monitor and consider dose adjustment |
| Cyclosporine | Increases blood levels | Moderate to High | Monitor blood levels closely |
| Cannabidiol (CBD) | Increases blood levels | Moderate – especially relevant in epilepsy | Monitor and adjust dose |
| Rifampicin (TB treatment) | Significantly decreases blood levels | High – loss of efficacy | Avoid; use alternative or increase Votubia dose |
| Phenytoin, Carbamazepine, Phenobarbital | Decreases blood levels | High – reduced seizure control | Monitor and increase Votubia dose as needed |
| St. John’s Wort (Hypericum) | Decreases blood levels | High – unpredictable reduction | Avoid completely |
| ACE inhibitors (e.g., Ramipril) | Increased risk of angioedema | Moderate | Monitor for swelling; consider alternatives |
Avoid grapefruit and grapefruit juice completely while taking Votubia. Grapefruit inhibits CYP3A4 in the gut wall, which can increase everolimus blood levels to potentially harmful concentrations.
If you are taking any anti-epileptic drug, a change in dose (increase or decrease) of that medication may necessitate a corresponding adjustment to your Votubia dose. Your doctor will determine this based on blood level monitoring. If you are following a ketogenic diet for seizure control, inform your doctor before starting Votubia.
What Is the Correct Dosage of Votubia?
Votubia dosage is individually determined based on body surface area, liver function, concurrent medications, and therapeutic blood level monitoring. It is taken once daily at the same time each day. Dispersible tablets must be mixed with water before administration – they must not be chewed, crushed, or swallowed whole.
Your doctor will determine the appropriate starting dose of Votubia based on several factors, including your age, body size, liver function, and other medications you are taking. Throughout treatment, blood levels are monitored regularly, and the dose is adjusted to achieve the target therapeutic concentration specific to your condition.
Adults
SEGA in Adults
The starting dose is determined by body surface area (BSA). Typical initial doses range from 2.5 mg to 7.5 mg once daily, adjusted based on blood trough levels. The target blood level is 5–15 ng/mL. Dose adjustments are made at intervals of approximately 2 weeks based on blood level results.
TSC-Related Epilepsy in Adults
The starting dose is similarly based on BSA and concurrent anti-epileptic medications. The target trough level is typically 5–15 ng/mL. The dose is adjusted to achieve the desired blood level while balancing efficacy against side effects. Always take Votubia consistently with or without food – do not alternate.
Children (2 years and older)
Pediatric Dosing
Dosing in children is calculated based on body surface area (BSA). The starting dose and subsequent adjustments are guided by therapeutic drug monitoring. Children's doses are typically lower than adult doses but vary widely depending on individual factors. Children under 2 years of age should not receive Votubia for TSC-related seizures. For SEGA, Votubia may be used in children of any age when surgery is not appropriate.
Elderly
No specific dose adjustment is required based on age alone. However, elderly patients may be more sensitive to certain side effects and often have reduced liver or kidney function, which the prescribing physician will take into account. Monitoring is performed as for all other patients.
Liver Impairment
Patients with liver impairment require dose adjustment. Mild liver impairment may not require a change, but moderate to severe impairment generally requires a reduced starting dose with careful blood level monitoring. In some cases, treatment may need to be interrupted or discontinued.
How to Take Votubia
- Take Votubia once daily at the same time each day
- Take it consistently either with or without food – do not alternate
- Dispersible tablets must be mixed with water to create an oral suspension – never chew, crush, or swallow them whole
- Regular tablets should be swallowed whole with a glass of water
- Never mix regular tablets and dispersible tablets in the same dose
Missed Dose
If you miss a dose, take your next scheduled dose at the usual time. Do not take a double dose to make up for the one you missed. Continue with your regular dosing schedule.
Overdose
If you have taken too much Votubia, or if someone else accidentally takes your tablets, contact a doctor or emergency department immediately. Bring the medication packaging and this information so the healthcare provider knows what has been taken. Urgent medical treatment may be necessary.
Do not stop taking Votubia unless your doctor tells you to do so. Stopping treatment abruptly may lead to regrowth of SEGA tumors or worsening seizure control. If you experience troublesome side effects, talk to your doctor about adjusting the dose rather than stopping on your own.
What Are the Side Effects of Votubia?
The most common side effects of Votubia include mouth ulcers (stomatitis), respiratory infections, headache, diarrhea, acne, skin rash, fatigue, and fever. Serious side effects include pneumonia, pneumonitis, severe infections, and blood count changes. Most side effects are mild to moderate and may resolve if treatment is temporarily paused.
Like all medicines, Votubia can cause side effects, although not everybody gets them. Some side effects can be serious and require immediate medical attention. Stop taking Votubia and seek emergency medical help if you experience signs of a severe allergic reaction: difficulty breathing or swallowing, swelling of the face, lips, tongue, or throat (angioedema), or severe skin rash with itching.
Very Common Side Effects
- Upper respiratory tract infections (cold, sore throat, runny nose)
- Mouth ulcers (stomatitis)
- Diarrhea, nausea, vomiting
- Headache
- Cough
- Skin rash and acne
- Fatigue and fever
- Decreased appetite
- High cholesterol (hypercholesterolemia)
- Menstrual irregularities (absent or irregular periods)
- Sinusitis and pharyngitis
- Urinary tract infections
- High blood pressure
- Pneumonia (fever, cough, breathing difficulty)
Common Side Effects
- Ear infections, gum inflammation, skin inflammation (dermatitis)
- High blood triglycerides, low blood phosphate, high blood sugar
- Anemia (low red blood cells), leukopenia (low white blood cells), thrombocytopenia (low platelets)
- Nosebleeds, stomach discomfort, abdominal pain, constipation, bloating
- Ovarian cysts, vaginal bleeding
- Dry skin, itching, hair loss, acneiform dermatitis
- Protein in urine
- Sleep difficulties (insomnia), irritability, aggression
- Lymphedema (swelling from blocked lymph drainage)
- Pneumonitis (lung inflammation – cough, fever, breathing difficulty)
- Hypersensitivity reactions (rash, itching, hives, breathing difficulty)
- Weight loss
Uncommon Side Effects
- Herpes zoster (shingles) – painful blistering rash
- Sepsis (serious bloodstream infection with fever, chills, confusion)
- Rhabdomyolysis (muscle breakdown – muscle cramps, dark urine)
- Viral bronchitis
- Taste changes (dysgeusia)
- Delayed menstruation, hormonal changes (elevated FSH, LH)
Reported (Frequency Unknown)
- Radiation recall syndrome (skin redness or lung inflammation at site of previous radiation)
- Worsening of radiation therapy side effects
- Hepatitis B reactivation
- Heart failure symptoms (breathlessness, leg swelling)
- Deep vein thrombosis (leg swelling, pain, redness)
- Kidney problems (changes in urine output)
- Wound healing complications
Most side effects are mild to moderate and often improve if treatment is temporarily interrupted for a few days. Contact your doctor promptly if side effects become severe. Never stop Votubia without medical guidance. Your doctor can adjust the dose or provide supportive treatment for side effects while maintaining the therapeutic benefit.
How Should You Store Votubia?
Store Votubia in the original packaging, protected from light and moisture, at room temperature. Open the blister pack immediately before use. Prepared oral suspensions must be taken within 60 minutes. Keep out of reach and sight of children.
Proper storage of Votubia is important to maintain the medication's effectiveness and safety:
- No special temperature requirements – store at normal room temperature
- Keep in the original packaging to protect from light and moisture
- Open blister packs only immediately before taking the dispersible tablets
- Prepared oral suspension (dispersible tablets mixed with water) must be taken immediately; discard if not used within 60 minutes and prepare a new one
- When using an oral syringe for preparation, the suspension must be used within 30 minutes
- Do not use the medication if the package appears damaged or previously opened
- Check the expiration date on the carton and blister – do not use after the stated date
- Do not dispose of Votubia in household waste or wastewater – return unused medication to a pharmacy for safe disposal to protect the environment
What Does Votubia Contain?
Votubia contains everolimus as the active ingredient. Inactive ingredients include lactose monohydrate, butylated hydroxytoluene (E321), magnesium stearate, hypromellose, crospovidone, mannitol, microcrystalline cellulose, and colloidal anhydrous silica.
The active substance is everolimus. Votubia dispersible tablets are available in 1 mg, 2 mg, 3 mg, and 5 mg strengths. Regular tablets are available as 2.5 mg. Each tablet contains the corresponding amount of everolimus as the active ingredient.
Inactive Ingredients
The other ingredients (excipients) serve various pharmaceutical functions:
- Lactose monohydrate – filler/binder (important: inform your doctor if you have lactose intolerance)
- Butylated hydroxytoluene (E321) – antioxidant preservative
- Magnesium stearate – lubricant for tablet manufacturing
- Hypromellose – binding agent
- Crospovidone type A – disintegrant (helps tablet break apart)
- Mannitol – sweetener/filler
- Microcrystalline cellulose – filler/binder
- Colloidal anhydrous silica – flow agent
Tablet Appearance
Votubia dispersible tablets are white to slightly yellowish, round, flat tablets with beveled edges. They are imprinted with “D1”, “D2”, “D3”, or “D5” on one side (corresponding to strength) and “NVR” on the other. The dispersible tablets are available in unit-dose blister packs of 10, 30, or 100 tablets.
Votubia contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
Frequently Asked Questions About Votubia
Votubia (everolimus) is used to treat two conditions caused by tuberous sclerosis complex (TSC): partial-onset seizures (epilepsy) that are not adequately controlled by other anti-epileptic drugs in patients aged 2 years and older, and subependymal giant cell astrocytoma (SEGA), a type of brain tumor, when surgery is not appropriate. It works by inhibiting the mTOR protein, which is overactivated in TSC and drives tumor growth and seizure activity.
The most common side effects (affecting more than 1 in 10 people) include mouth ulcers, upper respiratory infections, diarrhea, headache, cough, skin rash, acne, fatigue, fever, decreased appetite, high cholesterol, vomiting, menstrual irregularities, and high blood pressure. Most of these side effects are mild to moderate and may improve if treatment is temporarily interrupted.
No. Votubia may harm the developing fetus and is not recommended during pregnancy. Women who could become pregnant must use highly effective contraception during treatment and for up to 8 weeks after the last dose. Breastfeeding should also be avoided during treatment and for 2 weeks after the final dose. If you suspect pregnancy, consult your doctor immediately before taking any further doses.
Regular blood tests are essential because Votubia requires therapeutic drug monitoring to ensure the dose is correct for each individual patient. Blood levels can be affected by body size, liver function, and other medications. Additionally, Votubia can affect blood cell counts, kidney function, liver function, blood sugar, and cholesterol levels. Monitoring allows your doctor to detect and manage these changes early.
No. Grapefruit and grapefruit juice must be completely avoided during Votubia treatment. Grapefruit contains compounds that inhibit the CYP3A4 enzyme in the intestinal wall, which can significantly increase the absorption of everolimus and raise blood levels to potentially harmful concentrations. This interaction can increase the risk and severity of side effects.
Votubia and Afinitor both contain the same active ingredient, everolimus, and are manufactured by Novartis. The difference lies in their approved indications: Votubia is specifically approved for TSC-related conditions (epilepsy and SEGA), while Afinitor is approved for certain cancers including advanced renal cell carcinoma and hormone receptor-positive breast cancer. The dosing, monitoring targets, and clinical management may differ between these indications.
References
This article is based on the following evidence-based sources:
- European Medicines Agency (EMA). Votubia – Summary of Product Characteristics. Available at: ema.europa.eu/votubia. Last updated 2025.
- Franz DN, Belousova E, Sparagana S, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013;381(9861):125-132. doi:10.1016/S0140-6736(12)61134-9
- French JA, Lawson JA, Yapici Z, et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016;388(10056):2153-2163. doi:10.1016/S0140-6736(16)31419-2
- Curatolo P, Nabbout R, Lagae L, et al. Management of epilepsy associated with tuberous sclerosis complex: Updated clinical recommendations. European Journal of Paediatric Neurology. 2018;22(5):738-748. doi:10.1016/j.ejpn.2018.05.006
- Krueger DA, Northrup H; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatric Neurology. 2013;49(4):255-265. doi:10.1016/j.pediatrneurol.2013.08.002
- World Health Organization (WHO). Model List of Essential Medicines. 23rd List, 2023. Available at: who.int.
- British National Formulary (BNF). Everolimus – Drug monograph. Available at: bnf.nice.org.uk. Accessed 2026.
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