Medical Information

Ensidipine is the first targeted drug for IDH2 mutant AML, with clear efficacy, but high vigilance is needed for differentiation syndrome, elevated bilirubin, and QT interval prolongation. During medication, close monitoring and multidisciplinary management should be carried out.

1、 Usage and dosage

1.1 Recommended Dosage

Initial dose: 100mg, once daily, orally administered.

Course of treatment: Continue medication until disease progression or intolerable toxicity occurs.

Usage: Can be taken with food or on an empty stomach. Swallow the whole tablet and do not crush or chew.

1.2 Dose adjustment

Differentiation syndrome: If suspected, medication should be suspended and corticosteroids should be given. The original dose can be restored after the symptoms are relieved.

Elevated bilirubin (>3 × ULN): Suspend medication and restart at 100mg after recovery to ≤ 2 × ULN; If it rises again, reduce it to 50mg.

Other toxicity levels ≥ 3: Pause until ≤ 1 and restart at 100mg. If relapse occurs, reduce to 50mg.

2、 Therapeutic effect

2.1 Objective response rate (ORR)

In a single arm clinical study, the ORR of patients with IDH2 mutation positive relapsed/refractory AML treated with amlodipine was approximately 40.3%, with a complete response (CR) rate of approximately 19.3%.

2.2 Duration of Relief

The median duration of remission is about 5.8 months, and some patients may experience relief for over 1 year.

2.3 Target of action

Selective inhibition of IDH2 mutase, reduction of carcinogenic metabolite 2-HG levels, and induction of normal differentiation of myeloid cells.

3、 Precautions

3.1 Differentiation Syndrome (DS)

Symptoms: Fever, dyspnea, hypotension, lung infiltration, peripheral edema, rapid weight gain.

Treatment: Once suspected, administer dexamethasone 10mg q12h for at least 3 days, and suspend medication if necessary.

3.2 Hyperbilirubinemia

Common but mostly reversible, should be distinguished from liver injury; Regular monitoring of bilirubin and liver function is required.

3.3 QT interval prolongation

Attention should be paid to the combined medication and electrolyte levels, and regular follow-up electrocardiograms should be conducted before and during treatment.

3.4 Embryo fetal toxicity

Animal experiments have shown embryotoxicity, and patients of childbearing age should take effective contraceptive measures during treatment and for at least 2 months after discontinuation of medication.

3.5 Drug Interactions

Avoid co administration with potent CYP3A4 inhibitors (such as ketoconazole and clarithromycin). If co administration is necessary, dosage adjustment should be considered.

Avoid combining with potent CYP3A4 inducers (such as rifampicin and phenytoin sodium) to avoid reducing efficacy.