Ivosidenib is a targeted therapeutic drug for relapsed or refractory acute myeloid leukemia (AML) with IDH1 mutations. Although it has good efficacy, various side effects may occur during medication.
Side Effects of Ivosidenib
1. Differentiation Syndrome
(1) Incidence Rate: Occurs in 19% of patients and may be life-threatening.
(2) Symptoms: Fever (23%), dyspnea (33%), peripheral edema (32%), hypotension (12%), etc. Symptoms may appear as early as 1 day after starting medication.
(3) High-Risk Period: The first 3 months after the start of treatment.
2. Cardiotoxicity
(1) QT Interval Prolongation: 9% of patients have a QTc interval > 500 milliseconds, and 14% of patients have a QTc interval increase of > 60 milliseconds compared with the baseline, which may trigger ventricular fibrillation.
(2) Precipitating Factors: Concomitant use of CYP3A4 inhibitors or QT-prolonging drugs (such as antiarrhythmic drugs, fluoroquinolones).
3. Other Common Reactions
(1) Hematological System: Anemia (60%), leukocytosis (38%), thrombocytopenia (18%).
(2) Digestive System: Diarrhea (34%), nausea (31%), mucositis (28%).
(3) Systemic Symptoms: Fatigue (39%), arthralgia (36%), rash (26%).
Measures to Alleviate Ivosidenib Side Effects
1. Management of Differentiation Syndrome
(1) Emergency Treatment: Immediately administer dexamethasone intravenously (10mg every 12 hours) and monitor hemodynamics.
(2) Medication Adjustment: If symptoms persist for more than 48 hours, ivosidenib should be suspended, and medication can be resumed after symptoms resolve.
2. Response to QT Interval Prolongation
(1) Monitoring Requirements: Electrocardiogram (ECG) should be performed weekly in the first 3 weeks of treatment, and then once a month thereafter.
(2) QTc > 480 milliseconds: Suspend medication; resume at 500mg/day after QTc interval returns to normal.
(3) QTc > 500 milliseconds: Reduce the dosage to 250mg/day.
(4) With arrhythmia symptoms: Discontinue medication permanently.
3. Management of Other Symptoms
(1) Gastrointestinal Reactions: A 5-HT3 receptor antagonist (such as ondansetron) combined with dexamethasone is recommended to prevent vomiting.
(2) Leukocytosis: Hydroxyurea or leukapheresis should be used; if ineffective, ivosidenib should be suspended.
Daily Precautions for Ivosidenib Use
1. Medication Standards
(1) Dosage and Administration: Take 500mg orally at a fixed time every day; avoid high-fat diets (which can increase blood drug concentration by 98%).
(2) Management of Missed Doses: If a dose is missed, take it as soon as possible within 12 hours; if vomiting occurs after medication, no additional dose is needed.
2. Monitoring and Follow-Up
(1) 1st Month of Treatment: Complete blood count, electrolytes, and CPK (creatine phosphokinase) should be checked weekly.
(2) From the 2nd Month Onward: Check once every 2 weeks, and then once a month thereafter.
(3) Special Populations: Patients with hepatic or renal impairment should use the drug with caution; there is no clear data for patients with moderate to severe hepatic impairment.
3. Lifestyle
(1) Avoid grapefruit and its products (which affect CYP3A4 metabolism).
(2) Patients of childbearing age should use contraception until 2 months (for females) or 5 months (for males) after discontinuing the drug.
