艾伏尼布(ivosidenib)的用法用量:用药指南,剂量调整,

The following content only reflects the usage and dosage standards of ivosidenib in the countries where it is registered overseas. It does not represent the approved scope of use in mainland China. Please do not make any treatment decisions based on this.

Ivosidenib is suitable for the population

1. Leukemia

It is suitable for use in combination with azacitidine or as a monotherapy, and is suitable for use in patients approved by the US FDA The detection method detects the presence of susceptible isocitrate dehydrogenase-1 (IDH1) mutations in newly diagnosed acute myeloid leukemia (AML) patients who are 75 years and older or who are unable to use intensive induction chemotherapy due to comorbidities.

Used to treat relapsed or refractory AML patients with susceptibility IDH1 mutations using detection methods approved by the US FDA.

2. Cholangiocarcinoma

It is used to treat patients with previously treated locally advanced or metastatic cholangiocarcinoma who have IDH1 mutations detected by testing methods approved by the US FDA.

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Usage and dosage of ivosidenib

1. Conventional adult dose for acute myeloid leukemia

(1), dosage

Take orally, once a day, 500 mg each time.

(2), Treatment duration

Until disease progression or unacceptable toxicity occurs.

For patients without disease progression or unacceptable toxicity, treatment should be continued for at least 6 months to allow sufficient time for clinical response.

(3) Combination treatment regimen

This product should be used in combination with azacitidine and should be administered starting from day 1 of cycle 1; the manufacturer's product information of azacitidine should be consulted.

2. Conventional adult dosage for biliary tract cancer (cholangiocarcinoma)

(1) Dosage

Take orally, 500 mg once a day.

(2), Treatment duration

Until disease progression or unacceptable toxicity occurs.

ivosidenib dose adjustment

1. Renal function adjustment

(1), mild or moderate renal insufficiency (estimated glomerular filtration rate [eGFR] ≥ 30mL/min/1.73m², using the Modification of Diet in Renal Disease [MDRD] formula): starting dose, no adjustment is recommended.

(2) Severe renal insufficiency (estimated glomerular filtration rate [eGFR] <30mL/min/1.73m², MDRD): Before starting to use ivosidenib, the risks and benefits should be weighed.

2. Liver function adjustment

(1) Mild or moderate hepatic insufficiency (Child-Pugh class A or B): starting dose, no adjustment is recommended.

(2) Severe hepatic insufficiency (Child-Pugh C grade): Before starting to use ivosidenib, the risks and benefits should be weighed.

3. Dose adjustment for toxicity

(1), differentiation syndrome

If differentiation syndrome is suspected, systemic corticosteroid therapy should be initiated and hemodynamic monitoring should be performed until symptoms are relieved and last for at least 3 days.

If severe signs/symptoms persist more than 48 hours after starting systemic corticosteroid therapy, treatment with this product should be discontinued.

Avosidenib therapy should be resumed when signs/symptoms improve to grade 2 or less.

(2) Non-infectious leukocytosis

White blood cell count (WBC) is greater than 25x10⁹/L, or the absolute increase in total white blood cells from baseline is greater than 15x10⁹/L:

Treatment with hydroxyurea should be initiated according to standard institutional practice, and leukapheresis should be performed as clinically indicated.

The dosage of hydroxyurea should be gradually reduced only after the leukocytosis improves or resolves.

If the leukocytosis does not improve after using hydroxyurea, ivonib treatment should be interrupted; after the leukocytosis is relieved, the administration should be resumed at a dose of 500 mg once daily.

(3), QTc interval is greater than 480 to 500 milliseconds

Electrolyte levels should be monitored and supplemented according to clinical indications.

Concomitant medications known to have QTc interval prolonging effects should be reviewed and adjusted.

Avosidenib treatment should be discontinued.

When the QTc interval returns to 480 milliseconds or less, ivonib therapy should be restarted at a dose of 500 mg once daily.

Electrocardiogram (ECG) monitoring should be performed at least weekly for two weeks after resolution of QTc prolongation.

(4), QTc interval is greater than 500 milliseconds

Electrolyte levels should be monitored and supplemented according to clinical indications.

Concomitant medications known to have QTc interval prolonging effects should be reviewed and adjusted.

Treatment with this product should be discontinued.

When the QTc interval returns to within 30 milliseconds of prolongation from baseline, or 480 milliseconds or less, administration should be resumed at the reduced dose of 250 mg once daily.

Electrocardiogram (ECG) monitoring should be performed at least weekly for two weeks after resolution of QTc prolongation.

If other causes of QTc prolongation can be identified, the dose of ivonib should be considered to be re-escalated to 500 mg once daily.

QTc prolongation associated with signs/symptoms of life-threatening arrhythmias: Ivonib should be permanently discontinued.

(5), Guillain-Barré syndrome

Avosidenib should be permanently discontinued.

(6) Other grade 3 adverse reactions

AML monotherapy:

Treatment with this product should be interrupted until the toxic reaction is relieved to grade 2 or below.

Dosing should be resumed at a dose of 250 mg once daily; if toxicity resolves to grade 1 or less, the dose may be increased to 500 mg once daily.

If grade 3 or higher toxic reactions occur again, this product should be discontinued.

AML plus azacitidine regimen, cholangiocarcinoma:

Ivonib treatment should be interrupted until the toxicity resolves to grade 1 or less, or returns to baseline, and then resumed at a dose of 500 mg once daily (for grade 3 toxicity), or 250 mg once daily (for grade 4 toxicity).

If grade 3 toxicity recurs for a second time, the dose of ivonib should be reduced to 250 mg once daily until toxicity resolves, then returned to 500 mg once daily.

If grade 3 toxicity recurs for a third time, or grade 4 toxicity recurs, ivosidenib should be discontinued.

(7) Dose adjustment when combined with strong CYP4503A4 inhibitors

If strong CYP4503A4 inhibitors must be used together: the dose of this product should be reduced to 250 mg once daily.

If a strong CYP4503A4 inhibitor is discontinued: After at least 5 half-lives of discontinuation of the strong CYP4503A4 inhibitor, the dose of this product should be increased to 500 mg once daily.