Aliivosidenib Lvosidenib

[Basic Drug Information]

Brand Name: Tibsovo, Aliivosidenib

Generic Name: Ivosidenib

Dosage Form & Strength: 250 mg/tablet; 60 tablets per box

Pharmacological Class: Isocitrate Dehydrogenase-1 (IDH1) Inhibitor

Manufacturer: Lao United Pharmaceutical Group Co., Ltd.

Lao National Drug Administration Approval No.: 07 L 1130/24

Storage Conditions: 20°C–25°C (excursions permitted between 15°C–30°C)

Ivosidenib is an innovative medication used to treat specific types of Acute Myeloid Leukemia (AML). The emergence of this drug offers new hope to AML patients, particularly those for whom traditional chemotherapy has proven ineffective. In this article, we will explore in detail the usage and dosage of Ivosidenib, as well as how it helps patients combat this serious disease.

[Mechanism of Action]

Ivosidenib is an oral medication that exerts its therapeutic effect by targeting IDH1 mutations. IDH1 is an enzyme involved in normal cellular metabolic processes; however, in certain cancer cells, IDH1 undergoes mutations that drive the growth and survival of these cells. Ivosidenib works by inhibiting the activity of this mutated enzyme, thereby disrupting the metabolic abnormalities within cancer cells and suppressing their proliferation.

[Indications]

Ivosidenib is primarily indicated for the treatment of adult patients with Acute Myeloid Leukemia (AML) harboring an IDH1 mutation. This includes newly diagnosed adult patients, as well as those who have undergone at least two prior therapies but whose disease has relapsed or remains refractory to treatment.

[Dosage and Administration]

Patient Selection

Prior to initiating treatment with Ivosidenib for adult patients with relapsed or refractory Acute Myeloid Leukemia (AML), it is mandatory to confirm the presence of an Isocitrate Dehydrogenase-1 (IDH1) mutation in the patient's bone marrow or peripheral blood. The patient's IDH1 mutation status must be determined using a validated diagnostic assay. Patients determined to harbor an IDH1 mutation—based on results from a hospital or laboratory IDH1 mutation test—are eligible to receive Ivosidenib treatment.

Recommended Dosage

The recommended dosage is 500 mg, taken orally once daily, either on an empty stomach or with food, until disease progression or unacceptable toxicity occurs. For patients who do not experience disease progression or unacceptable toxicity, treatment should be continued for at least 6 months to allow for adequate assessment of clinical response.

Ivosidenib may be taken with or without food. Avoid taking it with high-fat meals. Swallow the tablets whole; do not break, crush, or chew the tablets.

Take the medication at the same time each day. If vomiting occurs after taking the dose, do not take a replacement dose. Resume the regular dosing schedule at the usual time the following day.

If a dose is missed or not taken at the scheduled time, take the missed dose as soon as possible (provided it is at least 12 hours before the next scheduled dose); however, if it is less than 12 hours before the next scheduled dose, do not take the missed dose, but instead resume the regular dosing schedule the following day. Do not take two doses within a 12-hour period.

Lactation: Women are advised not to breastfeed.

Monitoring for Toxicity

Monitor blood cell counts and blood chemistry prior to the first dose; at least once weekly during the first month of treatment; once every two weeks during the second month of treatment; and once monthly thereafter throughout the treatment period. During the first month of treatment, monitor blood creatine phosphokinase (CPK) levels once weekly. Perform an electrocardiogram (ECG) at least once weekly during the first three weeks of treatment, and at least once monthly thereafter throughout the treatment period. Any abnormal findings should be addressed promptly.

Dosage Adjustment for Concomitant Use with Strong CYP3A4 Inhibitors

If concomitant administration with a strong CYP3A4 inhibitor is necessary, reduce the dosage of this product to 250 mg, taken once daily. At least 5 half-lives after discontinuing the strong CYP3A4 inhibitor, the dosage of this product may be restored to the recommended dose of 500 mg, taken once daily. [Use in Pregnant and Lactating Women]

Contraception

Female patients of reproductive potential, and male patients with female partners of reproductive potential, should use effective methods of contraception during treatment and for at least 1 month after the last dose. Co-administration with this product may reduce the concentrations of hormonal contraceptives; therefore, patients receiving treatment with this product should use alternative methods of contraception during treatment and for at least 1 month after the last dose. Females of reproductive potential should undergo a pregnancy test prior to initiating treatment with this product.

Pregnancy

Treatment with this product during pregnancy may cause harm to the fetus. If this product is used during pregnancy, or if the patient becomes pregnant while taking this product, the patient should be apprised of the potential risk to the fetus.

Lactation

There are currently no data regarding the presence of this product or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants, it is recommended that women discontinue breastfeeding during treatment with this product and for at least 1 month after the last dose.

Fertility

No animal or human fertility toxicity studies have been conducted with this product.

[Adverse Reactions]

1. The most common adverse reactions (≥20%) are fatigue, leukocytosis, arthralgia, diarrhea, dyspnea, edema, nausea, mucositis, ECG QT interval prolongation, rash, pyrexia, cough, and constipation.

2. The most common laboratory abnormalities (≥20%) are decreased hemoglobin, decreased calcium, decreased sodium, decreased magnesium, increased uric acid, decreased potassium, increased alkaline phosphatase, increased aspartate aminotransferase (AST), decreased phosphate, and increased creatinine.

[Special Populations]

Hepatic Impairment

No initial dose adjustment is required for patients with mild or moderate (Child-Pugh A or B) hepatic impairment.

The pharmacokinetics and safety of Ivosidenib tablets in patients with severe hepatic impairment (Child-Pugh C) have not been established. For patients with pre-existing severe hepatic impairment, the risks and potential benefits should be considered prior to initiating treatment with Ivosidenib tablets. Renal Impairment

For patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m², MDRD), no adjustment to the starting dose is required.

The pharmacokinetics and safety of Ivosidenib in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m², MDRD) or renal impairment requiring dialysis have not been established. For patients with pre-existing severe renal impairment or those requiring dialysis, the risks and potential benefits should be considered prior to initiating treatment with Ivosidenib tablets.

Geriatric Patients

No dose adjustment is required for geriatric patients.

Pediatric Patients

No clinical study data are available regarding the use of this product in patients under 18 years of age.