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Dosage of Ivosidenib

This product should be administered under the supervision of a physician experienced in the use of antineoplastic agents. The recommended dose is 500 mg orally once daily.

Dosage in Adults

1. Acute Myeloid Leukemia (AML)

Newly Diagnosed AML (Monotherapy)

Administer 500 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity occurs. Most patients achieve the best clinical response within 6 months of initiating ivosidenib therapy; therefore, treatment should be continued for at least 6 months to fully evaluate the therapeutic effect.

Newly Diagnosed AML (Combination Therapy)

Administer 500 mg orally once daily in combination with azacitidine. Continue treatment until disease progression or unacceptable toxicity occurs. Most patients achieve the best clinical response within 6 months of initiating ivosidenib therapy; therefore, the combination therapy with azacitidine should be continued for at least 6 months to fully evaluate the therapeutic effect.

Ivosidenib should be initiated on Day 1 of Cycle 1, in conjunction with azacitidine administered at a dose of 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. Refer to the package insert of azacitidine for additional dosage information.

2. Relapsed or Refractory AML

Administer 500 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity occurs. Most patients achieve the best clinical response within 6 months of initiating ivosidenib therapy; therefore, treatment should be continued for at least 6 months to fully evaluate the therapeutic effect.

3. Relapsed or Refractory Myelodysplastic Syndromes (MDS)

Administer 500 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity occurs. For patients without disease progression or unacceptable toxicity, ivosidenib treatment should be continued for at least 6 months to fully evaluate the clinical efficacy.

4. Locally Advanced or Metastatic Cholangiocarcinoma

Administer 500 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity occurs.

5. Glioma

Administer 500 mg orally once daily for the treatment of IDH-mutant glioma† (off-label use).

Dosage Adjustment for Toxicity

1. Differentiation Syndrome

If severe signs or symptoms of differentiation syndrome (e.g., fever, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusion, hypotension, peripheral edema, rapid weight gain, hepatic or renal impairment, or multi-organ dysfunction) persist for more than 48 hours despite systemic glucocorticoid therapy, withhold ivosidenib until toxicity resolves to Grade 2 or lower.

2. Non-infectious Leukocytosis

Withhold ivosidenib if non-infectious leukocytosis (white blood cell count >25,000/mm³ or absolute increase in total white blood cells >15,000/mm³) persists after initiation of hydroxyurea therapy. Resume ivosidenib at a dose of 500 mg once daily when leukocytosis resolves.

3. QT Interval Prolongation

If QTc interval is 480–500 milliseconds, withhold ivosidenib treatment; resume the original dose (500 mg once daily) when QTc interval improves to ≤480 milliseconds. Monitor electrocardiogram (ECG) at least once weekly for 2 weeks after resolution of QT prolongation.

If QTc interval is >500 milliseconds, withhold ivosidenib treatment; resume at a reduced dose of 250 mg once daily when QTc interval improves to ≤480 milliseconds or ≤30 milliseconds above baseline. If QT interval prolongation is confirmed to be caused by other etiologies, the dose may be re-escalated to 500 mg once daily.

Permanently discontinue ivosidenib in patients who develop symptomatic QTc interval prolongation (e.g., life-threatening ventricular arrhythmias).

4. Guillain-Barré Syndrome

Permanently discontinue ivosidenib if Guillain-Barré syndrome occurs.

5. Other Toxicities in Patients Receiving AML Monotherapy or MDS Treatment

Withhold ivosidenib in patients who experience Grade 3 or higher adverse reactions during AML monotherapy or MDS treatment. Resume at a reduced dose of 250 mg once daily when toxicity resolves to Grade 2 or lower; if toxicity further improves to Grade 1 or lower, the dose may be re-escalated to 500 mg once daily.

Permanently discontinue ivosidenib if Grade 3 or higher adverse reactions recur.

6. Other Toxicities in Patients Receiving AML Combination Therapy with Azacitidine or Cholangiocarcinoma Treatment

Withhold ivosidenib in patients who experience Grade 3 or higher adverse reactions during AML combination therapy with azacitidine or cholangiocarcinoma treatment.

When toxicity improves to Grade 1 or baseline:

a. For Grade 3 toxicity: Resume at 500 mg once daily.

b. For Grade 4 toxicity: Resume at a reduced dose of 250 mg once daily.

c. If Grade 3 or higher adverse reactions recur for the second time: Reduce the dose to 250 mg once daily until toxicity resolves, then resume at 500 mg once daily.

d. Permanently discontinue ivosidenib if Grade 3 toxicity recurs for the third time or Grade 4 toxicity recurs.

Dosage in Special Populations

1. Patients with Hepatic Impairment

a. Mild or moderate hepatic impairment (Child-Pugh Class A or B): No initial dose adjustment is required.

b. Severe hepatic impairment (Child-Pugh Class C): Not studied. The potential risks and benefits of treatment should be carefully weighed before initiating therapy.

2. Patients with Renal Impairment

Mild or moderate renal impairment (eGFR 30 to <90 mL/min/1.73 m²): No initial dose adjustment is required.

Severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis-dependent patients: Not studied. The potential risks and benefits of treatment should be carefully weighed before initiating therapy.

3. Geriatric Patients

No special dosage recommendations are provided by the manufacturer.

from FDA，2023.10