Overview
11 DESCRIPTION Olutasidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor. The chemical name is (S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile. The chemical structure is: The molecular formula is C 18 H 15 ClN 4 O 2 and the molecular weight is 354.79 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations in patients with AML are R132H and R132C substitutions.
Indications
- 1 INDICATIONS AND USAGE Relapsed or Refractory Acute Myeloid Leukemia REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.1 ), and Clinical Studies ( 14.1 )] . REZLIDHIA is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible IDH1 mutation as detected by...
Common Doses
- 150 mg
Dosage
2 DOSAGE AND ADMINISTRATION Select patients based on presence of IDH1 mutation(s). ( 2.1 ) Recommended dosage: 150 mg orally twice daily, until disease progression or unacceptable toxicity. ( 2.2 ) Take on an empty stomach at least 1 hour before or 2 hours after a meal. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of relapsed or refractory AML with REZLIDHIA based on the presence of IDH1 mutations in blood or bone marrow [see Clinical Trials ( 14.1 )] . Information on FDA- approved tests for the detection of IDH1 mutations in AML is available at http://www.fda.
Black Box Warning
WARNING: DIFFERENTIATION SYNDROME Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until symptom resolution [see Warnings and Precautions ( 5.1 )] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Differentiation Syndrome [see Warnings and Precautions ( 5.1 )] Hepatotoxicity [see Warnings and Precautions ( 5.2 )] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS Strong or moderate CYP3A Inducers: Avoid concomitant use. ( 7.1 ) Sensitive CYP3A Substrates: Avoid concomitant use. Monitor if unavoidable. ( 7.1 ) 7.1 Effect of Other Drugs on Olutasidenib Strong or Moderate CYP3A4 Inducers Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Olutasidenib is a CYP3A substrate. Concomitant use of REZLIDHIA with a strong CYP3A inducer decreases olutasidenib Cmax and AUC, which may reduce REZLIDHIA efficacy [see Clinical Pharmacology ( 12.3 )] .