Ivosidenib (ivosidenib) Medication Guide

Ivosidenib is a prescription medication. Patients should fully understand the drug information before use. The Ivosidenib Medication Guide covers key aspects such as patient selection, dosage regimen, and management of adverse reactions.

Patient Selection

Patients receiving treatment with ivosidenib should be selected based on the presence of an IDH1 mutation.

Recommended Dosage

The recommended dosage of ivosidenib is 500 mg orally once daily until disease progression or unacceptable toxicity occurs.

For patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) who have not experienced disease progression or unacceptable toxicity, ivosidenib should be continued for at least 6 months to ensure sufficient time to observe clinical response.

Daily Administration Management

Ivosidenib may be taken with or without food.

Avoid concomitant intake with high-fat meals.

Do not split, crush, or chew ivosidenib tablets.

Take ivosidenib orally at approximately the same time each day.

Newly Diagnosed Acute Myeloid Leukemia (Combination Regimen)

Administer ivosidenib starting on Day 1 in combination with azacitidine (75 mg/m² subcutaneously or intravenously once daily) on Days 1–7 (or Days 1–5 and 8–9) of each 28-day treatment cycle. For additional dosage information regarding azacitidine, please refer to its prescribing information.

Management of Vomiting and Missed Doses

If vomiting occurs after taking ivosidenib, do not take a replacement dose; wait until the next scheduled dose.

If a dose of ivosidenib is missed or not taken at the usual time, take the missed dose as soon as possible, ensuring at least 12 hours before the next scheduled dose. Resume the normal schedule the following day. Do not take two doses within 12 hours.

Monitoring and Dose Modification for Toxicities

Perform an electrocardiogram (ECG) before initiating treatment. Monitor ECG at least weekly during the first 3 weeks of treatment, then at least monthly throughout the treatment period. If abnormalities are detected, manage promptly. In the event of toxicity, withhold dosing or reduce the dose.

Differentiation Syndrome

If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptom resolution and for at least 3 days thereafter. If severe signs and/or symptoms persist for more than 48 hours after initiating systemic corticosteroids, withhold ivosidenib; resume ivosidenib when signs and symptoms have improved to Grade 2 or lower.

Non-Infectious Leukocytosis (White Blood Cell Count > 25 × 10⁹/L, or Absolute Increase > 15 × 10⁹/L from Baseline)

Administer hydroxyurea according to institutional standards and perform leukapheresis if clinically indicated. Taper hydroxyurea only after leukocytosis improves or resolves. If leukocytosis does not improve with hydroxyurea, withhold ivosidenib; resume ivosidenib at 500 mg once daily after leukocytosis resolves.

QTc Interval > 480 ms – 500 ms

Monitor and correct electrolyte levels as clinically indicated, review and adjust concomitant medications known to prolong the QTc interval, and withhold ivosidenib. Resume ivosidenib at 500 mg once daily when the QTc interval has recovered to ≤ 480 ms, and monitor ECG at least weekly for 2 weeks after resolution of the QTc interval prolongation.

QTc Interval > 500 ms

Monitor and correct electrolyte levels as clinically indicated, review and adjust concomitant medications known to prolong the QTc interval, and withhold ivosidenib. Resume ivosidenib at 250 mg once daily when the QTc interval has recovered to within 30 ms of baseline or to ≤ 480 ms, and monitor ECG at least weekly for 2 weeks after resolution of the QTc interval prolongation. If an alternative cause for QTc interval prolongation can be identified, consider escalating the ivosidenib dose to 500 mg once daily.

QTc Interval Prolongation with Life-Threatening Arrhythmias Signs/Symptoms

Permanently discontinue ivosidenib.

Guillain-Barré Syndrome

Permanently discontinue ivosidenib.

Other Grade 3 Adverse Reactions

For monotherapy use in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS)

Withhold ivosidenib until toxicity resolves to Grade 2 or lower; upon resumption, initiate at 250 mg once daily, and if toxicity resolves to Grade 1 or lower, may increase to 500 mg once daily; if Grade 3 or higher toxicity recurs, discontinue ivosidenib.

For use in cholangiocarcinoma or in combination with azacitidine for acute myeloid leukemia (AML)

Withhold ivosidenib until toxicity resolves to Grade 1 or lower or baseline, then resume at 500 mg once daily for Grade 3 toxicity; for Grade 4 toxicity, resume at 250 mg once daily. If Grade 3 toxicity recurs (second occurrence), reduce the ivosidenib dose to 250 mg once daily until toxicity resolves, then resume at 500 mg once daily; if Grade 3 toxicity recurs a third time, or Grade 4 toxicity recurs, discontinue ivosidenib.