Overview
11 DESCRIPTION VORANIGO tablets contain vorasidenib, an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor. Vorasidenib is present as the hemicitric acid hemihydrate co-crystal. The chemical name of the co-crystal is 6-(6-chloropyridin-2-yl)- N 2 , N 4 -bis[(2 R )-1,1,1-trifluoropropan-2-yl]-1,3,5-triazine-2,4-diamine, 2-hydroxypropane-1,2,3-tricarboxylic acid,...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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. 12.2 Pharmacodynamics Exposure-Response Relationships Vorasidenib decreases 2-HG tumor concentrations in patients with IDH1 or IDH2 mutated glioma.
Indications
- 1 INDICATIONS AND USAGE 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 [see Dosage and Administration (2.1) , Clinical Pharmacology (12.1) and Clinical Studies (14) ] .
Common Doses
- 40 mg
- 20 mg
- 10 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage in adults: ( 2.3 ) 40 mg orally once daily Recommended dosage in pediatric patients 12 years of age and older based on body weight: ( 2.3 ) ≥40 kg : 40 mg orally once daily ULN to 3 × ULN without concurrent total bilirubin >2 × ULN Continue VORANIGO at current dose. Monitor liver laboratory tests weekly until recovery to 3 to 5 × ULN without concurrent total bilirubin >2 × ULN First Occurrence: Withhold VORANIGO until recovery to ≤Grade 1 or baseline. Recovery in ≤28 days, resume VORANIGO at the same dose.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hepatotoxicity [see Warnings and Precautions (5.1) ] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Servier Pharmaceuticals at 1-800-807-6124 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS CYP1A2 Inhibitors : Avoid concomitant use of strong and moderate CYP1A2 inhibitors. ( 7.1 ) CYP1A2 Inducers : Avoid concomitant use of moderate CYP1A2 inducers and smoking tobacco. ( 7.1 ) Certain CYP3A Substrates : Avoid concomitant use with CYP3A substrates, where a minimal concentration change can reduce efficacy. ( 7.2 ) Hormonal Contraception : If concomitant use cannot be avoided, use with nonhormonal contraception methods. ( 7.2 ) 7.