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Votubia is a brand name for Everolimus. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Renal angiomyolipoma associated with tuberous sclerosis complex (TSC) Votubia is indicated for the treatment of adult patients with renal angiomyolipoma associated with TSC who are at risk of complications (based on factors such as tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but…
Verbatim from this product's EMA label. Tap a section to expand.
Treatment with Votubia should be initiated by a physician experienced in the treatment of patients with TSC and therapeutic drug monitoring. Posology Renal angiomyolipoma associated with TSC The recommended dose is 10 mg of everolimus once daily.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. If a dose is missed, the patient should not take an additional dose, but take the usual prescribed next dose. SEGA associated with TSC Careful titration may be required to obtain the optimal therapeutic effect.
Doses that will be tolerated and effective vary between patients. 5). 5 mg/m2. 2). Different strengths of Votubia tablets can be combined to attain the desired dose. Everolimus whole blood trough concentrations should be assessed at least 1 week after commencing treatment.
Dosing should be titrated to attain trough concentrations of 5 to 15 ng/ml. The dose may be increased to attain a higher trough concentration within the target range to obtain optimal efficacy, subject to tolerability. 5 mg to attain the target trough concentration for optimal clinical response.
Efficacy, safety, concomitant therapy, and the current trough concentration should be considered when planning for dose titration. 5 mg with a steady state concentration of 4 ng/ml. g. 5 mg from the current daily dose). 5 mg, it should be rounded to the next available tablet strength.
2). SEGA volume should be evaluated approximately 3 months after commencing Votubia therapy, with subsequent dose adjustments taking changes in SEGA volume, corresponding trough concentration, and tolerability into consideration. Once a stable dose is attained, trough concentrations should be monitored every 3 to 6 months in patients with changing BSA, or every 6 to 12 months in patients with stable BSA, for the duration of treatment.
Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. If a dose is missed, the patient should not take an additional dose, but take the usual prescribed next dose. Dose adjustments due to adverse reactions Management of severe and/or intolerable suspected adverse reactions may require dose reduction and/or temporary interruption of Votubia therapy.
For adverse reactions of Grade 1, dose adjustment is usually not required. If dose reduction is required, the recommended dose is approximately 50% lower than the daily dose previously administered. For dose reductions below the lowest available strength, alternate day dosing should be considered.
2]). • EXIST-3 (CRAD001M2304): This was a randomised, double-blind, controlled, phase III trial comparing adjunctive treatment of low and high everolimus exposure (low trough [LT] range of 3-7 ng/ml [n=117] and high trough [HT] range of 9-15 ng/ml [n=130]) versus placebo (n=119), in patients with TSC and refractory partial-onset seizures receiving 1 to 3 antiepileptics.
The median duration of the double-blind period was 18 weeks. 8). • EXIST-2 (CRAD001M2302): This was a randomised, double-blind, controlled, phase III trial of everolimus (n=79) versus placebo (n=39) in patients with either TSC plus renal angiomyolipoma (n=113) or sporadic lymphangioleiomyomatosis (LAM) plus renal angiomyolipoma (n=5).
0 weeks (range 9 to 115) for those receiving placebo. 9). • EXIST-1 (CRAD001M2301): This was a randomised, double-blind, controlled, phase III trial of everolimus (n=78) versus placebo (n=39) in patients with TSC who have SEGA, irrespective of age.
6 weeks (range 14 to 88) for those receiving placebo. 3). • CRAD001C2485: This was a prospective, open-label, single-arm phase II study of everolimus in patients with SEGA (n=28). 2). The adverse events considered to be associated with the use of Votubia (adverse reactions), based upon the review and medical assessment of all adverse events reported in the above studies, are described below.
The most frequent adverse reactions (incidence ≥1/10) from the pooled safety data are (in decreasing order): stomatitis, pyrexia, nasopharyngitis, diarrhoea, upper respiratory tract infection, vomiting, cough, rash, headache, amenorrhoea, acne, pneumonia, urinary tract infection, sinusitis, menstruation irregular, pharyngitis, decreased appetite, fatigue, hypercholesterolaemia, and hypertension.
The most frequent grade 3-4 adverse reactions (incidence ≥1%) were pneumonia, stomatitis, amenorrhoea, neutropenia, pyrexia, menstruation irregular, hypophosphataemia, diarrhoea, and cellulitis. 03. Tabulated list of adverse reactions Table 3 shows the incidence of adverse reactions based on pooled data of patients receiving everolimus in the three TSC studies (including both the double-blind and open-label extension phase, where applicable).
Non-infectious pneumonitis Non-infectious pneumonitis is a class effect of rapamycin derivatives, including everolimus. 8). Some cases were severe and on rare occasions, a fatal outcome was observed. A diagnosis of non-infectious pneumonitis should be considered in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough or dyspnoea, and in whom infectious, neoplastic and other non-medicinal causes have been excluded by means of appropriate investigations.
Opportunistic infections such as pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) should be ruled out in the differential diagnosis of non-infectious pneumonitis (see section “Infections” below). Patients should be advised to report promptly any new or worsening respiratory symptoms.
Patients who develop radiological changes suggestive of non-infectious pneumonitis and have few or no symptoms may continue Votubia therapy without dose adjustments. If symptoms are moderate, consideration should be given to interruption of therapy until symptoms improve.
The use of corticosteroids may be indicated. Votubia may be reinitiated at a daily dose approximately 50% lower than the dose previously administered. For cases where symptoms of non-infectious pneumonitis are severe, Votubia therapy should be discontinued and the use of corticosteroids may be indicated until clinical symptoms resolve.
Votubia may be reinitiated at a daily dose approximately 50% lower than the dose previously administered depending on the individual clinical circumstances. For patients who require use of corticosteroids for treatment of non-infectious pneumonitis, prophylaxis for pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) may be considered.
8). Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis, candidiasis or pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) and viral infections including reactivation of hepatitis B virus, have been described in patients taking 8 everolimus.
1.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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4). Table 1 Votubia dose adjustment recommendations Adverse reaction Severity1 Votubia dose adjustment Non-infectious pneumonitis Grade 2 Consider interruption of therapy until symptoms improve to Grade 1. Re-initiate Votubia at approximately 50% lower than the daily dose previously administered.
Discontinue treatment if failure to recover within 4 weeks. Grade 3 Interrupt Votubia until symptoms resolve to Grade 1. Consider re-initiating Votubia at approximately 50% lower than the daily dose previously administered. If toxicity recurs at Grade 3, consider discontinuation.
Grade 4 Discontinue Votubia. 5 Stomatitis Grade 2 Temporary dose interruption until recovery to Grade 1. Re-initiate Votubia at same dose. If stomatitis recurs at Grade 2, interrupt dose until recovery to Grade 1. Re-initiate Votubia at approximately 50% lower than the daily dose previously administered.
Grade 3 Temporary dose interruption until recovery to Grade 1. Re-initiate Votubia at approximately 50% lower than the daily dose previously administered. Grade 4 Discontinue Votubia. Other non-haematological toxicities (excluding metabolic events) Grade 2 If toxicity is tolerable, no dose adjustment required.
If toxicity becomes intolerable, temporary dose interruption until recovery to Grade 1. Re-initiate Votubia at same dose. If toxicity recurs at Grade 2, interrupt Votubia until recovery to Grade 1. Re-initiate Votubia at approximately 50% lower than the daily dose previously administered.
Grade 3 Temporary dose interruption until recovery to Grade 1. Consider re-initiating Votubia at approximately 50% lower than the daily dose previously administered. If toxicity recurs at Grade 3, consider discontinuation. Grade 4 Discontinue Votubia.
g. hyperglycaemia, dyslipidaemia) Grade 2 No dose adjustment required. Grade 3 Temporary dose interruption. Re-initiate Votubia at approximately 50% lower than the daily dose previously administered. Grade 4 Discontinue Votubia. Thrombocytopenia Grade 2 […]
Adverse reactions are listed according to MedDRA system organ class. Frequency categories are defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 16 Table 3 Adverse reactions reported in TSC studies Infections and infestations Very common Nasopharyngitis, upper respiratory tract infection, pneumonia a, urinary tract infection, sinusitis, pharyngitis Common Otitis media, cellulitis, pharyngitis streptococcal, gastroenteritis viral, gingivitis Uncommon Herpes zoster, sepsis, bronchitis viral Blood and lymphatic system disorders Common Anaemia, neutropenia, leucopenia, thrombocytopenia, lymphopenia Immune system disorders Common Hypersensitivity Metabolism and nutrition disorders Very common Decreased appetite, hypercholesterolaemia Common Hypertriglyceridaemia, hyperlipidaemia, hypophosphataemia, hyperglycaemia Psychiatric disorders Common Insomnia, aggression, irritability Nervous system disorders Very common Headache Uncommon Dysgeusia Vascular disorders Very common Hypertension Common Lymphoedema Respiratory, thoracic and mediastinal disorders Very common Cough Common Epistaxis, pneumonitis Gastrointestinal disorders Very common Stomatitis b, diarrhoea, vomiting Common Constipation, nausea, abdominal pain, flatulence, oral pain, gastritis Skin and subcutaneous tissue disorders Very common Rash c, acne Common Dry skin, acneiform dermatitis, pruritus, alopecia Uncommon Angioedema Musculoskeletal and connective tissue disorders Uncommon Rhabdomyolysis Renal and urinary disorders Common Proteinuria Reproductive system and breast disorders Very common Amenorrhoea d, menstruation irregular d Common Menorrhagia, ovarian cyst, vaginal haemorrhage Uncommon Menstruation delayed d General disorders and administration site conditions Very common Pyrexia, fatigue Investigations Common Blood lactate dehydrogenase increased, blood luteinising hormone increased, weight decreased Uncommon Blood follicle stimulating hormone increased 17 Injury, poisoning and procedural complications Not knowne Radiation recall syndrome, potentiation of radiation reaction a Includes pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) b Includes (very common) stomatitis, mouth ulceration, aphthous ulcer; (common) tongue ulceration, lip ulceration and (uncommon) gingival pain, glossitis c Includes (very common) rash; (common) rash erythematous, erythema and (uncommon) rash […]
g. 8). Physicians and patients should be aware of the increased risk of infection with Votubia. Pre-existing infections should be treated appropriately and should have resolved fully before starting treatment with Votubia. While taking Votubia, be vigilant for symptoms and signs of infection; if a diagnosis of infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of Votubia.
If a diagnosis of invasive systemic fungal infection is made, Votubia treatment should be promptly and permanently discontinued and the patient treated with appropriate antifungal therapy. Cases of pneumocystis jirovecii (carinii) pneumonia (PJP, PCP), some with fatal outcome, have been reported in patients who received everolimus.
PJP/PCP may be associated with concomitant use of corticosteroids or other immunosuppressive agents. Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required.
g. 3). g. g. 5). 8). Stomatitis mostly occurs within the first 8 weeks of treatment. 1). Management of stomatitis may therefore include prophylactic (in adults) and/or therapeutic use of topical treatments, such as an alcohol-free corticosteroid oral solution as a mouthwash.
However products containing alcohol, hydrogen peroxide, iodine and thyme derivatives should be avoided as they may exacerbate the condition. Monitoring for and treatment of fungal infection is recommended, especially in patients being treated with steroid-based medicinal products.
5). Haemorrhage Serious cases of haemorrhage, some with a fatal outcome, have been reported in patients treated with everolimus in the oncology setting. No serious cases of renal haemorrhage were reported in the TSC setting. Caution is advised in patients taking Votubia, particularly during concomitant use with active substances known to affect platelet function or that can increase the risk of haemorrhage as well as in patients with a history of bleeding disorders.
Healthcare professionals and patients should be vigilant for signs and symptoms of bleeding throughout the treatment period, especially if risk factors for haemorrhage are combined. 9 […]