Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Les Laboratoires Servier, 50, rue Carnot, 92284 Suresnes cedex, France
Voranigo as monotherapy is indicated for the treatment of predominantly non-enhancing Grade 2 astrocytoma or oligodendroglioma with an IDH1 R132 or IDH2 R172 mutation in adult and adolescent patients aged 12 years and older and weighing at least 40 kg who only had surgical intervention and are not in immediate need of radiotherapy or chemotherapy (see section 5.1).
Treatment should be initiated and supervised by a physician experienced in the use of anti-cancer medicinal products.
Before taking Voranigo, patients must have confirmation of an isocitrate dehydrogenase-1 (IDH1) R132 or isocitrate dehydrogenase-2 (IDH2) R172 mutation using an appropriate diagnostic test. The presence of an IDH1 R132 or IDH2 R172 mutation should be asessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose. If the CE-marked IVD is not available, IDH1 R132 or IDH2 R172 mutation should be assessed by an alternative validated test.
The recommended dose of Voranigo in adults and adolescents 12 years of age and older is 40 mg once daily for patients weighing at least 40 kg. No dose recommendation can be made in patients weighing less than 40 kg because of the lack of clinical data in this population.
Treatment should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient.
If a dose is missed or not taken at the usual time, it should be taken as soon as possible within 6 hours after the missed dose. The next dose should be taken at the regularly scheduled time.
If a dose is missed by more than 6 hours, it should be skipped and the next dose should be taken at the regularly scheduled time.
If a dose is vomited, replacement tablets should not be taken. The tablets should be taken as usual the following day.
Complete blood counts and blood chemistries, including liver enzymes, should be assessed prior to starting treatment, every 2 weeks during the first 2 months and then once monthly for the first 2 years of treatment, and as clinically indicated thereafter. Certain patients may require more frequent and ongoing monitoring (see section 4.4).
Dose interruption or dose reduction may be required based on individual safety and tolerability. The recommended dose reduction levels are provided in Table 1.
Table 1. Recommended dose reduction levels:
| Dose level | Dose and schedule | Number and strength of tablets |
|---|---|---|
| Starting dose | 40 mg once daily | One 40 mg tablet / once daily |
| First dose reduction | 20 mg once daily | Two 10 mg tablets / once daily |
| Second dose reduction | 10 mg once daily | One 10 mg tablet / once daily |
The recommended Voranigo dose modifications and management for adverse reactions are provided in Table 2.
Table 2. Recommended Voranigo dose modifications and management for adverse reactions:
| Adverse reaction | Severitya | Management and dose modifications |
|---|---|---|
| Hepatotoxicity (Elevation of ALT or AST) (see section 4.4) | Grade 1 ALT or AST increase >ULN to 3 x ULN without concurrent total bilirubin >2 x ULN | Continue Voranigo at current dose. Monitor liver enzymes weekly until recovery to < Grade 1. |
| Grade 2 ALT or AST >3 to 5 x ULN without concurrent total bilirubin >2 x ULN | First occurrence: Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤Grade 1 or baseline. • Recovery in ≤28 days, resume Voranigo at the same dose. • Recovery in >28 days, resume Voranigo at reduced dose (see Table 1). Recurrence: Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤ Grade 1 or baseline, and resume Voranigo at reduced dose (see Table 1). | |
| Grade 3 ALT or AST >5 to 20 x ULN without concurrent total bilirubin >2 x ULN | First occurrence: Withhold Voranigo and monitor liver enzymes twice per week until recovery to ≤ Grade 1 or baseline. • Recovery in ≤28 days, resume Voranigo at reduced dose (see Table 1). • If not recovered in ≤28 days, permanently discontinue Voranigo. Recurrence: Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤ Grade 1 or baseline. | |
| Grade 2 or 3 Any ALT or AST >3 to 20 x ULN with concurrent total bilirubin >2 x ULN in absence of clear alternative explanation.b | Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤ Grade 1 or baseline. | |
| Grade 4 Any ALT or AST >20 x ULN | Permanently discontinue Voranigo and monitor liver enzymes twice per week until recovery to ≤ Grade 1 or baseline. | |
| Other adverse reactions | Grade 3 | First occurrence: Withhold Voranigo until recovery to ≤ Grade 1 or baseline. • Resume Voranigo at reduced dose (see Table 1). Recurrence: Permanently discontinue Voranigo. |
| Grade 4 | Permanently discontinue Voranigo. |
Abbreviations: ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; ULN = Upper limit of normal
a Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
b If an alternative aetiology is identified, consider resuming Voranigo at reduced dose (see Table 1) following resolution to Grade 1 or baseline.
No dose adjustment is recommended for patients ≥65 years of age (see section 5.2).
No starting dose adjustment is recommended for patients with renal impairment (estimated glomerular filtration rate [eGFR] >40 mL/min/1.73 m²). The pharmacokinetics of vorasidenib and metabolite AGI-69460 have not been studied in patients with eGFR ≤40 mL/min/1.73 m² or renal impairment requiring dialysis. Vorasidenib should not be used in patients with eGFR ≤40 mL/min/1.73 m² or who require dialysis (see sections 4.4 and 5.2).
No starting dose adjustment is recommended for patients with mild or moderate (Child-Pugh class A or B) hepatic impairment. The pharmacokinetics of vorasidenib and AGI-69460 have not been studied in patients with severe hepatic impairment (Child-Pugh class C). Vorasidenib should be used with caution in patients with severe hepatic impairment and this patient population should be closely monitored (see sections 4.4 and 5.2).
No clinical data are available in children aged 12 years to <18 years (see section 5.1).
Voranigo is for oral use.
The tablets should be taken once daily at about the same time each day. Patients should not eat food at least 2 hours before and 1 hour after taking Voranigo (see section 5.2). The tablets are to be swallowed whole with a glass of water and should not be split, crushed or chewed as no data are available to confirm similar bioavailability of the drug product when tablet manipulations are applied.
In the event of overdose, toxicity is likely to manifest as exacerbation of the adverse reactions associated with vorasidenib (see section 4.8). Patients should be closely monitored and provided with appropriate supportive care (see sections 4.2 and 4.4). There is no specific antidote for vorasidenib overdose.
30 months.
This medicinal product does not require any special storage conditions.
White HDPE bottle with a polypropylene (PP) child-resistant closure and polyethylene (PE) faced induction heat seal liner including three silica gel desiccants in HDPE canisters. Pack-size of 30 film-coated tablets.
Patients should be advised not to swallow the silica gel desiccant found in the tablet bottle.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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