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Common name: ivosidenib
Trade name: Tibsovo
All names: ivosidenib, ivosidenib, ivosidenib, Tibsovo
Indications:
Relapsed or refractory acute myeloid leukemia
Usage and Dosage:
500 mg orally daily with or without food until disease progression or unacceptable toxicity.
Avoid high-fat meals.
Adverse Reactions:
The most common adverse reactions (≥20%) are fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, ECG QT prolongation, rash, pyrexia, cough, and constipation.
Contraindications:
Not clear yet.
Precautions:
QTc interval prolongation: Monitor ECG and electrolytes. If QTc interval prolongation occurs, reduce or withhold Tbsovo, then resume dosing or discontinue Tbsovo.
Guillain-Barré Syndrome: Monitor for signs and symptoms of new movements and/or sensations. Tibsovo was terminated after being diagnosed with Guillain-Barré syndrome.
Breastfeeding: Breastfeeding is not recommended.
Storage:
Store at 20°C to 25°C (68°F to 77°F); Allowed deviation is between 15°C and 30°C (59°F and 86°F)
Mechanism of Action:
Ivosidenib is a small molecule inhibitor that targets mutant isocitrate dehydrogenase 1 (IDH1) enzyme.
Susceptible IDH1 mutations are defined as those that result in elevated 2-hydroxyglutarate (2-HG) levels in leukemia cells, for which efficacy is predicted by 1) clinically recommended doses of ivosidenib and/or 2) inhibition of mutant IDH1 enzymatic activity. ivosidenib concentrations are sustainable at recommended doses based on validated methods.
The most common of such mutations are R132H and R132Cs substitutions.
Ivosidenib inhibits selected IDH1 R132 mutants in vitro at much lower concentrations than wild-type IDH1. In a mouse xenograft model, inhibition of the mutant IDH1 enzyme by ivosidenib resulted in reduced 2HG levels and induction of myeloid differentiation in vitro and in vivo.