Ivosidenib is an isocitrate dehydrogenase-1 (IDH1) inhibitor, indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) who harbor an IDH1 mutation.
How to Use Ivosidenib
1. Administration Regimen
(1) Dosage: The recommended dosage is 500mg taken orally once daily, either with meals or on an empty stomach. However, high-fat meals should be avoided (as they may increase the drug's blood concentration).
(2) Treatment Course: Continue administration until disease progression or the occurrence of intolerable toxicity. It is recommended to receive treatment for at least 6 months to evaluate the clinical response.
2. Precautions
(1) Swallow the tablet whole; do not split, crush, or chew it.
(2) If vomiting occurs after administration or a dose is missed, do not take an additional dose. Do not administer a repeat dose within 12 hours.
3. Dosage Adjustment
(1) Differentiation Syndrome (incidence rate: 19%): Initiate glucocorticoid therapy immediately and suspend ivosidenib administration. Resume administration after symptoms resolve.
(2) When QTc interval > 480 msec: Suspend administration; resume at 500mg/day after QTc interval returns to normal.
(3) When QTc interval > 500 msec: Reduce the dosage to 250mg/day.
(4) For other grade ≥3 toxicities: Suspend administration until toxicity resolves to grade ≤2, then resume at a reduced dosage.
5. Monitoring Requirements
(1) Before administration, confirm the IDH1 mutation status (using the FDA-approved Abbott detection method).
(2) During treatment, regularly monitor electrocardiogram (ECG), complete blood count, electrolytes, and liver function.
Drug Interactions of Ivosidenib
1. CYP3A4 Inhibitors
(1) Strong Inhibitors (e.g., itraconazole): Reduce the dosage of ivosidenib to 250mg/day and monitor the QTc interval.
(2) Moderate Inhibitors (e.g., fluconazole): May increase the exposure of ivosidenib; use in combination with caution.
2. CYP3A4 Inducers
Strong Inducers (e.g., rifampicin): Concomitant use is prohibited, as they may reduce the efficacy of ivosidenib.
3. Other Interactions
(1) QTc-Prolonging Drugs (e.g., fluoroquinolones): Avoid concomitant use; if co-administration is necessary, enhance ECG monitoring.
(2) Hormonal Contraceptives: Ivosidenib may reduce their efficacy; it is recommended to switch to non-hormonal contraceptive methods.
Medication Recommendations for Special Populations of Ivosidenib
1. Pregnancy and Lactation
(1) Pregnant Women: Animal studies have shown embryotoxicity. Effective contraception is required during treatment (females: 2 months after discontinuing the drug; males: 5 months after discontinuing the drug).
(2) Lactation: Breastfeeding is prohibited; breastfeeding can be resumed only after at least 1 month of discontinuing the drug.
2. Hepatic Impairment
No dosage adjustment is required for patients with mild to moderate hepatic impairment. Data on severe hepatic impairment (total bilirubin > 3×ULN) is lacking, and individualized evaluation is needed.
3. Elderly and Pediatric Patients
(1) Elderly Patients (patients aged ≥65 years account for 63%): No dosage adjustment is required, but close monitoring of cardiovascular events is necessary.
(2) Pediatric Patients: The efficacy has not been established.
4. Other Precautions
(1) Impact on Fertility: May impair reproductive function; evaluate fertility needs before initiating medication.
(2) Tumor Lysis Syndrome: Patients with hyperleukocytosis require prophylactic hydration and electrolyte monitoring.
