Ivosenib 250 mg, containing the active ingredient Ivosidenib, is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH1 mutation as detected by an FDA-approved test. It provides a targeted therapy option for patients who have limited response to conventional treatments. Ivosenib is also approved for newly diagnosed AML patients who are ineligible for intensive chemotherapy and carry an IDH1 mutation.

By specifically targeting the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, Ivosenib helps reduce abnormal cell proliferation and promotes differentiation of leukemic cells, offering an effective precision therapy approach for AML management.

Description

Ivosenib 250 mg is an oral small-molecule inhibitor of mutant IDH1, an enzyme involved in the citric acid cycle. Mutations in IDH1 lead to the accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which interferes with normal cell differentiation and contributes to leukemia progression. Ivosenib inhibits mutant IDH1, reducing 2-HG levels and allowing leukemic cells to mature into normal blood cells.

Pharmacology

Ivosidenib selectively inhibits the mutant IDH1 enzyme without affecting the wild-type enzyme. By blocking mutant IDH1 activity, Ivosenib:

• Reduces intracellular 2-HG accumulation.

• Promotes differentiation of immature leukemic blasts into mature blood cells.

• Suppresses leukemic cell proliferation while preserving normal hematopoiesis.

Ivosenib is metabolized primarily in the liver via CYP3A4, and its oral formulation allows once-daily dosing, providing sustained inhibition of the mutant enzyme.

Dosage & Administration

• Recommended Dose: 500 mg orally once daily until disease progression or unacceptable toxicity.

• Capsules should be swallowed whole with water and taken at approximately the same time each day.

• Food may be taken with the medication, as Ivosenib can be administered with or without meals.

Drug Interactions

• CYP3A4 Inhibitors: Strong inhibitors (e.g., ketoconazole) may increase Ivosenib levels; dose adjustment may be required.

• CYP3A4 Inducers: Strong inducers (e.g., rifampicin, phenytoin) may reduce effectiveness and should be avoided.

Contraindications

• Hypersensitivity to Ivosidenib or any of the formulation components.

Side Effects

Common adverse reactions include diarrhea, nausea, fatigue, febrile neutropenia, leukocytosis, and QT interval prolongation. Serious complications may include differentiation syndrome, which can be life-threatening if not promptly recognized and treated. Regular monitoring of blood counts, electrolytes, and cardiac function is recommended during therapy.

Pregnancy & Lactation

• Pregnancy: Ivosenib can cause fetal harm based on animal studies. Effective contraception is recommended for both male and female patients during and after treatment.

• Lactation: The presence of Ivosenib in human milk is unknown; breastfeeding is not recommended during therapy.

Overdose

Limited clinical data exist on Ivosenib overdose. Supportive care and monitoring of vital signs, electrolytes, and organ function are recommended in case of accidental ingestion of higher-than-prescribed doses.

Special Populations

• Geriatric Use: No significant differences in efficacy have been observed, though older patients may be at higher risk for adverse events.

• Hepatic or Renal Impairment: Dose adjustments may be necessary for moderate to severe impairment; careful monitoring is advised.

• Pediatric Use: Safety and effectiveness in patients under 18 years have not been established.

Therapeutic Class

Targeted Cancer Therapy – IDH1 Inhibitor

Storage Conditions

Store below 30°C in a dry place, protected from light. Keep out of reach of children.