II. Indications
- Acute Myelogenous Leukemia (IDH1/2+ new or advanced/refractory)
III. Mechanism
- Isocitrate Dehydrogenase (IDH)
- Isocitrate Dehydrogenase is a cytoplasmic enzyme that decarboxylating isocitrate to alpha ketoglutarate
- Rate limiting step of the TCA Cycle (Kreb Cycle)
- Isocitrate Dehydrogenase (IDH) has 3 forms with the same activity (the first 2 are associated with cancers)
- IDH1 is found in cytoplasm (and encoded by gene 2q33)
- IDH2 is found in mitochondria (and encoded by gene 15q26)
- IDH2 Mutations
- Associated with Acute Myelogenous Leukemia (similar to IDH1)
IV. Medications
- Enasidenib (Idhifa)
V. Dosing
- See other references for disease specific dosing protocols
VI. Safety
- Avoid in Lactation
- Avoid Breast Feeding for an additional one month after completing Enasidenib
- Avoid in pregnancy (all trimesters, pregnancy category X)
- Use reliable Contraception
VII. Adverse Effects
- Edema
- Hepatotoxicity
- Prolonged QTc
- Myelosuppression
- Differentiation Syndrome
- Presents with fever and Dyspnea
- Signs include Pulmonary Infiltrates, Pleural Effusions, Pericardial Effusions, weight gain, Cardiomyopathy, Hypotension