Version July 2025
Dosage guidance:
Clinical considerations: Select patients for the treatment of grade 2 astrocytoma or oligodendroglioma based on the presence of IDH1 or IDH2 mutations in tumor specimens.
Astrocytoma or oligodendroglioma, grade 2, IDH1 or IDH2 mutated: Oral: 40 mg once daily; continue until disease progression or unacceptable toxicity (Ref).
Missed dose: If a dose is missed, administer the missed dose as soon as possible within 6 hours of the scheduled administration time. If a dose is missed by >6 hours from the scheduled administration time, skip the missed dose and administer the next dose at the scheduled time. If a dose is vomited, do not administer a replacement dose (wait until the next scheduled dose is due).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function calculated using Cockcroft-Gault equation.
Kidney impairment prior to treatment initiation:
CrCl >40 mL/minute: No dosage adjustment is necessary.
CrCl ≤40 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Monitor for increased adverse reactions; modify dosing for adverse reactions as recommended.
End-stage kidney disease requiring dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Monitor for increased adverse reactions; modify dosing for adverse reactions as recommended.
Hepatic impairment prior to treatment initiation:
Mild or moderate impairment (Child-Turcotte-Pugh class A, B): No dosage adjustment is necessary.
Severe impairment (Child-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Monitor for increased adverse reactions; modify dosing for adverse reactions as recommended.
Acute hepatotoxicity during treatment:
Grade 1 (AST or ALT > ULN to 3 times ULN without concurrent total bilirubin >2 times ULN): Continue vorasidenib at current dose. Monitor liver function tests weekly until recovery to < grade 1.
Grade 2 (AST or ALT >3 to 5 times ULN without concurrent total bilirubin >2 times ULN):
First occurrence: Withhold vorasidenib until recovery to ≤ grade 1 or baseline. If recovery occurs in ≤28 days, resume vorasidenib at the same dose. If recovery occurs in >28 days, resume vorasidenib at a reduced dose.
Recurrence: Withhold vorasidenib until recovery to ≤ grade 1 or baseline; then resume vorasidenib at a reduced dose.
Grade 3 (AST or ALT >5 to 20 times ULN without concurrent total bilirubin >2 times ULN):
First occurrence: Withhold vorasidenib until recovery to ≤ grade 1 or baseline. If recovery occurs in ≤28 days, resume vorasidenib at a reduced dose. If recovery does not occur in ≤28 days, permanently discontinue vorasidenib.
Recurrence: Permanently discontinue vorasidenib.
Grade 2 or 3 (AST or ALT >3 to 20 times ULN with concurrent total bilirubin >2 times ULN):
First occurrence: Withhold vorasidenib until recovery to ≤ grade 1 or baseline; then resume vorasidenib at a reduced dose.
Recurrence: Permanently discontinue vorasidenib.
Grade 4 (AST or ALT >20 times ULN): Permanently discontinue vorasidenib.
|
a Permanently discontinue vorasidenib if unable to tolerate 10 mg once daily. | |
|
Usual (initial) dose |
40 mg once daily |
|
First dose reduction level |
20 mg once daily |
|
Second dose reduction levela |
10 mg once daily |
|
Adverse reaction |
Severity |
Vorasidenib dosage modification |
|---|---|---|
|
General adverse reactions (except hepatotoxicity) |
Grade 3 |
First occurrence: Withhold vorasidenib until recovery to ≤ grade 1 or baseline; then resume vorasidenib at a reduced dose. Recurrence: Permanently discontinue vorasidenib. |
|
Grade 4 |
Permanently discontinue vorasidenib. |
Refer to adult dosing.
(For additional information see "Vorasidenib: Pediatric drug information")
Astrocytoma or oligodendroglioma, grade 2, IDH1 or IDH2 mutated:
Children ≥12 years and Adolescents:
<40 kg: Oral: 20 mg once daily; continue until disease progression or unacceptable toxicity.
≥40 kg: Oral: 40 mg once daily; continue until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity:
Children ≥12 years and Adolescents: Oral:
Dose reduction levels:
|
Patient weight |
Usual dose |
First dose reduction |
Second dose reduction |
|---|---|---|---|
|
a Permanently discontinue therapy if patient unable to tolerate 10 mg once-daily dose. | |||
|
<40 kg |
20 mg once daily |
10 mg once daily |
Permanently discontinuea |
|
≥40 kg |
40 mg once daily |
20 mg once daily |
10 mg once dailya |
Dosage adjustments:
|
Adverse reaction |
Description/severity |
Vorasidenib dosage modification |
|---|---|---|
|
Any adverse reactions |
Grade 3 (first occurrence) |
Withhold vorasidenib until toxicity resolves to ≤ grade 1 or baseline; resume vorasidenib at a reduced dose based on dosage level reduction table. |
|
Grade 3 (recurrent) |
Permanently discontinue vorasidenib. | |
|
Grade 4 |
Permanently discontinue vorasidenib. |
Children ≥12 years and Adolescents: Oral:
CrCl >40 mL/minute: No adjustment necessary.
CrCl ≤40 mL/minute: Has not been studied; monitor closely for adverse effects; if adverse effects occur, adjust dose based on dosage reduction and dosage adjustment for toxicity tables.
End-stage kidney disease requiring dialysis: Has not been studied; monitor closely for adverse effects; if adverse effects occur, adjust dose based on dosage reduction and dosage adjustment for toxicity tables.
Children ≥12 years and Adolescents: Oral:
|
Adverse reaction |
Description/severity |
Vorasidenib dosage modification |
|---|---|---|
|
Baseline liver impairment |
Mild liver impairment |
No dosage adjustment necessary; monitor closely for adverse effects. |
|
Moderate liver impairment |
No dosage adjustment necessary; monitor closely for adverse effects. | |
|
Severe liver impairment |
Has not been studied; monitor closely for adverse effects; if adverse effects occur, adjust dose based on dosage reduction and dosage adjustment for toxicity tables. | |
|
Liver toxicity during therapy |
Grade 1: ALT or AST > ULN to >3 × ULN without total bilirubin >2 × ULN |
No dosage adjustment necessary; monitor liver function weekly until resolution to < grade 1. |
|
Grade 2 (first occurrence): ALT or AST >3 to 5 × ULN without total bilirubin >2 × ULN |
Withhold vorasidenib until resolution to ≤ grade 1 or baseline. • If resolution time ≤28 days, resume at same dose. • If resolution time >28 days, resume at a reduced dose based on dosage reduction tables. | |
|
Grade 2 (recurrence): ALT or AST >3 to 5 × ULN without total bilirubin >2 × ULN |
Withhold vorasidenib until resolution to ≤ grade 1 or baseline; resume at a reduced dose based on dosage reduction tables. | |
|
Grade 3 (first occurrence): ALT or AST >5 to 20 × ULN without total bilirubin >2 × ULN |
Withhold vorasidenib until resolution to ≤ grade 1 or baseline. • If resolution time ≤28 days, resume at a reduced dose based on dosage reduction tables. • If no recovery by ≤28 days, permanently discontinue therapy. | |
|
Grade 3 (recurrence): ALT or AST >5 to 20 × ULN without total bilirubin >2 × ULN |
Permanently discontinue therapy. | |
|
Grade 2 or 3 (first occurrence): Any ALT or AST >3 to 20 × ULN with total bilirubin >2 × ULN |
Withhold vorasidenib until resolution to ≤ grade 1 or baseline; resume at a reduced dose based on dosage reduction tables. | |
|
Grade 2 or 3 (recurrence): Any ALT or AST >3 to 20 × ULN with total bilirubin >2 × ULN |
Permanently discontinue therapy. | |
|
Grade 4: Any ALT or AST >20 × ULN |
Permanently discontinue therapy. |
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Endocrine & metabolic: Increased serum potassium (23%)
Gastrointestinal: Abdominal pain (13%), constipation (13%), diarrhea (25%; grades 3/4: <1%)
Hematologic & oncologic: Decreased neutrophils (14%; grades 3/4: 2%), decreased platelet count (12%), increased hemoglobin (13%), leukopenia (13%; grades 3/4: <1%), lymphocytopenia (11%; grades 3/4: 2%)
Hepatic: Increased gamma-glutamyl transferase (38%), increased serum alanine aminotransferase (59%), increased serum aspartate aminotransferase (46%)
Nervous system: Fatigue (37%; including asthenia), seizure (16%)
Neuromuscular & skeletal: Musculoskeletal pain (26%)
Renal: Increased serum creatinine (11%)
1% to 10%:
Endocrine & metabolic: Decreased serum calcium (10%), decreased serum phosphate (8%), increased serum glucose (10%)
Gastrointestinal: Decreased appetite (9%)
Hepatic: Increased serum alkaline phosphatase (10%)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to vorasidenib or any component of the formulation.
Concerns related to adverse effects:
• Hepatotoxicity: Elevations in hepatic transaminases, which can lead to hepatic failure, hepatic necrosis, and/or autoimmune hepatitis, have occurred with vorasidenib. Approximately one-half of vorasidenib-treated patients experienced increased AST or ALT; grade 3 or 4 elevations also occurred. One-third of patients had elevations in gamma-glutamyl transpeptidase (GGT), including grade 3 or 4 increases in a small number of patients. Elevations in alkaline phosphatase and total bilirubin were also observed. Two patients treated with vorasidenib met criteria for Hy’s law (AST or ALT >3 times ULN and total bilirubin >2 times ULN); these events were associated with autoimmune hepatitis and hepatic failure. The median time to onset of increased AST or ALT was 57 days (range: 1 day to ~2.9 years).
Other warnings/precautions:
• Appropriate use: Select patients for the treatment of grade 2 astrocytoma or oligodendroglioma based on the presence of IDH1 or IDH2 mutations in tumor specimens. Information on approved tests is available at http://www.FDA.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Voranigo: 10 mg, 40 mg
No
Tablets (Voranigo Oral)
10 mg (per each): $797.62
40 mg (per each): $1,595.24
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Voranigo: 10 mg, 40 mg
Vorasidenib is available through specialty pharmacies and various specialty institutions/accounts. Examples from the manufacturer may be found at: https://www.voranigohcp.com.
Oral: Administer at approximately the same time each day, with water, and with or without food. The Canadian labeling recommends that patients avoid food at least 2 hours before and 1 hour after administration. Swallow whole; do not split, crush, or chew tablets.
Oral: Administer tablet with water at the same time each day. May administer without regard to food; however, the Canadian labeling recommends patients avoid food at least 2 hours before and 1 hour after administration. Do not split, crush, or chew tablets. If a dose is vomited, do not administer a replacement dose; continue with therapy the next day.
Missed dose: Administer the missed dose as soon as possible if ≤6 hours from when dose is normally administered; if >6 hours, skip the missed dose and resume therapy the following day.
Astrocytoma or oligodendroglioma, grade 2, IDH1 or IDH2 mutated: Treatment of grade 2 astrocytoma or oligodendroglioma in adult and pediatric patients ≥12 years of age with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, as detected by an approved test, following surgery, including biopsy, subtotal resection, or gross total resection.
Vorasidenib may be confused with enasidenib, ivosidenib, olutasidenib, vandetinib, vemurafenib, vismodegib, vorapaxar, vorinostat.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP1A2 (Major), CYP2B6 (Minor), CYP2C19 (Minor), CYP2C8 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
CYP1A2 Inducers (Moderate): May decrease serum concentration of Vorasidenib. Risk X: Avoid
CYP1A2 Inhibitors (Moderate): May increase serum concentration of Vorasidenib. Management: Avoid concurrent use with moderate CYP1A2 inhibitors when possible. If combined use cannot be avoided, monitor for evidence of adverse effects and adjust vorasidenib dose accordingly if necessary. Risk D: Consider Therapy Modification
CYP1A2 Inhibitors (Strong): May increase serum concentration of Vorasidenib. Risk X: Avoid
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Vorasidenib may decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk X: Avoid
Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid
Fosphenytoin-Phenytoin: May decrease serum concentration of Vorasidenib. Risk X: Avoid
Hormonal Contraceptives: Vorasidenib may decrease serum concentration of Hormonal Contraceptives. Management: Avoid combined use when possible, but if this combination cannot be avoided, use of an alternative, nonhormonal means of contraception is recommended during treatment with vorasidenib and for 3 months after the last dose. Risk D: Consider Therapy Modification
Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor
RifAMPin: May decrease serum concentration of Vorasidenib. Risk X: Avoid
Tobacco (Smoked): May decrease serum concentration of Vorasidenib. Risk X: Avoid
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who could become pregnant should use effective nonhormonal contraception during treatment and for 3 months after the last dose of vorasidenib. Patients with partners who may become pregnant should also use effective contraception during therapy and for 3 months after the last vorasidenib dose.
Vorasidenib may cause some hormonal contraceptives to be ineffective. Consult drug interactions database for more detailed information related to the use of vorasidenib and specific contraceptives.
Adverse effects to fertility were observed in animal toxicology studies; data are lacking on possible fertility effects in humans.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to vorasidenib may cause fetal harm.
It is not known if vorasidenib is present in breast milk.
Due to the potential for adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 2 months after the last dose of vorasidenib.
IDH1 and IDH2 mutation status (from tumor specimen) prior to therapy initiation. Monitor blood chemistry (prior to therapy). Monitor liver function tests (AST, ALT, gamma-glutamyl transpeptidase [GGT], total bilirubin, and alkaline phosphatase) prior to initiation, every 2 weeks during the first 2 months of treatment, then monthly for the first 2 years of treatment, and as clinically indicated (more frequent testing [eg, weekly] in patients who develop transaminase elevations). Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Monitor for signs/symptoms of hepatotoxicity. Monitor for increased adverse reactions in patients with kidney or liver dysfunction. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Vorasidenib is a dual, small molecule inhibitor of mutant (and wild type [in vitro]) isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) enzymes. Mutations in IDH1 or IDH2 result in the production of 2-hydroxyglutarate (2-HG), accumulating in glioma tissue, and competitively inhibiting α-ketoglutarate-dependent enzymes. This inhibition results in changes to DNA hydroxymethylation, gene expression, cellular differentiation, and the tumor microenvironment (Ref). Through inhibition of IDH1 and IDH2, vorasidenib decreases production of 2-HG and partially restores cellular differentiation.
Note: In children ≥12 years and adolescents, pharmacokinetic parameters were similar to adults.
Absorption: A high-fat and high-calorie (total 800 to 1,000 calories, 500 to 600 from fat) meal increased vorasidenib Cmax 3.1-fold and AUC 1.4-fold, compared to the fasting conditions. A low-fat and low-calorie (total 400 to 500 calories, 100 to 125 from fat) meal increased vorasidenib Cmax 2.3-fold and AUC 1.4-fold, compared to the fasting conditions.
Distribution: Vdss: 3,930 L; brain tumor:plasma concentration ratio: 1:6.
Protein binding: 97%.
Metabolism: Primarily hepatic via CYP1A2; minor contributions via CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A. Non-CYP pathways may contribute to up to 30% of metabolism.
Bioavailability: 34%.
Half-life elimination: 10 days.
Time to peak: 2 hours (range: 0.5 to 4 hours).
Excretion: Feces (85%; 56% as unchanged drug); urine (4.5%).
Clearance: 14 L/hour.
