Vorasidenib

VORANIGO is indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible isocitrate dehydrogenase-1 (IDH1) or isocitrate dehydrogenase-2 (IDH2) mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection. VORANIGO is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation, as detected by an FDA-approved test, following surgery including biopsy, sub-total resection, or gross total resection.

Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants. In cell-based and in vivo tumor models expressing IDH1 or IDH2 mutated proteins, vorasidenib decreased production of 2-hydroxyglutarate (2-HG) and partially restored cellular differentiation.

Recommended dosage in adults: 40 mg orally once daily Recommended dosage in pediatric patients 12 years of age and older based on body weight: ≥40 kg: 40 mg orally once daily <40 kg: 20 mg orally once daily Take with or without food.

None. None.

Hepatotoxicity: VORANIGO can cause hepatic transaminase elevations, which can lead to hepatic failure, hepatic necrosis, and autoimmune hepatitis. Monitor liver function tests every 2 weeks during the first 2 months of treatment, then monthly for the first 2 years of treatment, and as clinically indicated. Withhold, reduce the dose or discontinue VORANIGO based on severity. Embryo-Fetal Toxicity: VORANIGO can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective nonhormonal contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity The most common (≥15%) adverse reactions include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. Grade 3 or 4 (≥2%) laboratory abnormalities were ALT increased, AST increased, GGT increased, and neutrophils decreased.

CYP1A2 Inhibitors: Avoid concomitant use of strong and moderate CYP1A2 inhibitors. CYP1A2 Inducers: Avoid concomitant use of moderate CYP1A2 inducers and smoking tobacco. Certain CYP3A Substrates: Avoid concomitant use with CYP3A substrates, where a minimal concentration change can reduce efficacy. Hormonal Contraception: If concomitant use cannot be avoided, use with nonhormonal contraception methods.

Storage Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F).