Ivosidenib
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-IVOSIDENIB |
|---|---|
| Type | Drug |
| Aliases | TibsovoІвосиденіб |
| Status | reviewed 2026-05-07 | pending_clinical_signoff |
| Diseases | DIS-CHOLANGIOCARCINOMA |
| Sources | SRC-CLARIDHY-ABOU-ALFA-2020 SRC-ESMO-BTC-2023 SRC-NCCN-HEPATOBILIARY |
Drug Facts
| Class | Mutant-selective IDH1 inhibitor (small-molecule, oral) |
|---|---|
| Mechanism | Orally bioavailable small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1) — selective for the neomorphic R132 hotspot variants (R132H, R132C, R132G, R132L, R132S). Wild-type IDH1 catalyzes oxidative decarboxylation of isocitrate to α-ketoglutarate (αKG); R132 mutations confer a neomorphic gain-of-function activity reducing αKG to the oncometabolite 2-hydroxyglutarate (2-HG). Pathologic 2-HG accumulation competitively inhibits αKG-dependent dioxygenases (TET2, KDM histone demethylases, prolyl hydroxylases), leading to hypermethylation of DNA and histones and a block in cellular differentiation. Ivosidenib binds the mutant-IDH1 active site, suppresses 2-HG production by ~95–98%, restores αKG-dependent enzyme activity, and re-enables terminal differentiation of malignant clones — producing a differentiation response in IDH1- mutant AML and an antiproliferative / disease-con... |
| Typical dosing | Standard adult dose: 500 mg PO once daily, continuous, with or without food (avoid high-fat meals — increase exposure ~25%). Treatment continued until disease progression or unacceptable toxicity. Indication-specific notes: - Cholangiocarcinoma: 500 mg PO once daily continuous (28-day cycle for accounting; no scheduled break). - AML monotherapy (R/R or 1L unfit): 500 mg PO once daily continuous; minimum 6 months of therapy recommended to allow differentiation response (median time-to-CR ~2 months). - AML + azacitidine (AGILE): ivosidenib 500 mg PO daily + azacitidine 75 mg/m² SC/IV days 1–7 of each 28-day cycle. Dose modifications: - QTc >480 ms: hold ivosidenib until QTc ≤480 ms; resume at... |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-05-07 |
Warnings
- Differentiation syndrome (in IDH1-mutant AML) — potentially fatal; manifests within 1 day to 3 months of therapy start; symptoms include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural / pericardial effusion, rapid weight gain, peripheral edema, hepatic / renal / multi-organ dysfunction. Initiate corticosteroids (dexamethasone 10 mg IV q12h) and hemodynamic monitoring at first suspicion; do not wait for confirmation. Boxed warning applies to AML indication; clinically relevant in cholangiocarcinoma at much lower frequency
Notes
Mutant-selective IDH1 inhibitor (Servier; formerly Agios Pharmaceuticals, development code AG-120; transferred to Servier in 2021 with the Agios oncology divestiture). FDA-approved July 2018 for relapsed/refractory IDH1-mutant AML on the basis of AG120-C-001 phase 1 (DiNardo et al. NEJM 2018 — ORR 41.6%, CR+CRh 30.4%). FDA-approved August 2021 for previously-treated IDH1-mutant locally advanced / metastatic cholangiocarcinoma on the basis of ClarIDHy phase 3 (Abou-Alfa et al. Lancet Oncol 2020 — ivosidenib vs placebo: mPFS 2.7 vs 1.4 mo, HR 0.37, p<0.0001; OS HR 0.79 with 70.5% placebo-arm crossover, RPSFT-adjusted OS HR 0.49). FDA-approved May 2022 for newly-diagnosed IDH1-mutant AML in combination with azacitidine on the basis of AGILE phase 3 (Montesinos et al. NEJM 2022 — ivosidenib+aza vs placebo+aza: mOS 24.0 vs 7.9 mo, HR 0.44). FDA-approved October 2023 for r/r IDH1-mutant MDS. EMA approved 2023 for cholangiocarcinoma + AML. IDH1 R132 mutations are mutually exclusive with FGFR2 fusions in intrahepatic cholangiocarcinoma (~13–20% prevalence) and with FLT3 / NPM1 mutations in AML at lower mutual-exclusivity rates. IDH1 R132C is the dominant variant in cholangio (~70% of IDH1...
Used By
Drug
DRUG-OLUTASIDENIB- Olutasidenib
Regimens
REG-IVOSIDENIB-CHOLANGIO- Ivosidenib monotherapy (ClarIDHy) — 2L+ IDH1-mutated cholangiocarcinoma