lvosidenib Tablets indar

I. Drug Name

Generic Name: Ivosidenib Tablets

English Name: Ivosidenib Tablets

Brand Name: Tuoshuwo, TIBSOVO

Dosage Form: Film-coated tablets

Specification: 0.25 g per tablet; 60 tablets per box

Manufacturer: INDAR Pharmaceuticals Pvt Ltd

II. Indications and Usage

This product is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of:

1.  Acute Myeloid Leukemia (AML):

In combination with azacitidine, for the treatment of newly diagnosed adult AML patients aged 75 years or older, or those ineligible for intensive induction chemotherapy, who harbor a susceptible IDH1 mutation.

As a single agent, for the treatment of adult AML patients with relapsed or refractory IDH1 mutations.

2.  Cholangiocarcinoma: For the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma who harbor an IDH1 mutation.

Key Prerequisite: The presence of an IDH1 mutation must be confirmed by an FDA-approved or National Medical Products Administration (NMPA)-approved test method prior to use.

III. Dosage and Administration

Recommended Dosage:

Monotherapy: 500 mg orally once daily, taken until disease progression or unacceptable toxicity occurs.

Combination Therapy (with Azacitidine): Ivosidenib 500 mg orally once daily, taken on Days 1 through 28 of each 28-day cycle; Azacitidine is administered via subcutaneous injection or intravenous infusion on Days 1 through 7 of each cycle.

Administration: May be taken with or without food. Tablets should be swallowed whole; do not crush, chew, or break the tablets. If gastrointestinal discomfort occurs, it is recommended to take the medication with food.

Dosage Adjustment: Detailed dosage adjustment guidelines are provided for adverse reactions such as differentiation syndrome, QTc interval prolongation, and hepatotoxicity (involving temporary interruption followed by resumption at the original dose or dose reduction to 250 mg).

IV. Contraindications

Patients with severe hypersensitivity to ivosidenib or to any of the excipients.

V. Warnings and Precautions

1.  Differentiation Syndrome: Occurs in approximately 25% of patients; severe cases may be fatal. Typical symptoms include fever, cough, dyspnea, pleural or pericardial effusion, pulmonary edema, hypotension, etc. If suspected, corticosteroid treatment—such as dexamethasone (10 mg twice daily)—should be initiated immediately and continued until symptoms resolve. Depending on the severity, treatment should be temporarily interrupted or permanently discontinued.

2.  QTc Interval Prolongation: Monitor ECGs and serum electrolytes (potassium, magnesium, calcium) prior to treatment, at least weekly for the first 3 weeks after initiating treatment, and periodically thereafter. Avoid concomitant use with drugs known to prolong the QTc interval. Adjust the dosage based on the degree of QTc prolongation.

3.  Guillain-Barré Syndrome: Monitor for new or worsening symptoms of neuropathy (e.g., weakness, paresthesia, difficulty walking). Permanently discontinue the drug if Guillain-Barré syndrome is suspected or confirmed.

4.  Acute Respiratory Distress Syndrome (ARDS): Cases have been reported. Monitor patients for new or worsening respiratory symptoms.

5.  Fetal Toxicity: May cause fetal harm. Patients of reproductive potential must use effective contraception.

VI. Adverse Reactions

Based on clinical trial data, common adverse reactions (incidence ≥ 20%) include:

Monotherapy: Fatigue, arthralgia, diarrhea, dyspnea, edema, nausea, rash, fever, cough, constipation, mucositis, vomiting, and ECG QTc interval prolongation.

Combination Therapy: Nausea, fatigue, arthralgia, constipation, dyspnea, fever, diarrhea, rash, cough, mucositis, vomiting, edema, anemia, thrombocytopenia, and neutropenia.

Laboratory Abnormalities: Leukocytosis (due to differentiation syndrome), decreased hemoglobin, thrombocytopenia, hyperglycemia, hypomagnesemia, hypokalemia, hypocalcemia, and increased alkaline phosphatase.

VII. Drug Interactions

Strong CYP3A4 Inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's wort): These agents significantly decrease plasma concentrations of ivosidenib, potentially compromising efficacy; therefore, concomitant use should be avoided. Known QTc-prolonging medications: These increase the risk of arrhythmias; concomitant use should be avoided whenever possible. If co-administration is necessary, enhanced ECG monitoring is required.

QTc Monitoring: When used concomitantly with other medications metabolized via CYP3A4, exposure to Ivosidenib may be altered; close monitoring for adverse reactions is required.

VIII. Use in Specific Populations

Hepatic Impairment: No dose adjustment is required for mild hepatic impairment. For patients with moderate hepatic impairment, the recommended dose is 250 mg once daily. Use is not recommended in patients with severe hepatic impairment.

Renal Impairment: No dose adjustment is required for mild to moderate renal impairment. Data are limited for patients with severe renal impairment or end-stage renal disease (ESRD); use with caution.

Pediatric Use: Safety and efficacy have not been established.

Geriatric Use: Elderly patients (≥65 years of age) may be at higher risk for certain adverse reactions (e.g., dyspnea, fatigue, decreased appetite, edema).

IX. Pharmacology

Pharmacologic Class: Targeted small-molecule inhibitor.

Mechanism of Action: Ivosidenib selectively inhibits the mutated IDH1 enzyme, thereby reducing the production of the oncogenic metabolite 2-hydroxyglutarate (2-HG). This induces the differentiation of leukemia cells rather than directly killing them, thereby helping to restore normal cellular differentiation processes.

X. Storage

Store at room temperature between 20°C and 25°C; excursions between 15°C and 30°C are permitted during short-term transport.

Keep the medication in its original packaging; protect from light and moisture.

Keep out of reach of children.

Important Note:

This package insert is not a substitute for professional medical advice. Before using Ivosidenib, patients must undergo a comprehensive evaluation by a specialist physician and strictly adhere to the detailed dosing instructions provided by their physician and pharmacist. Testing for IDH1 gene mutations is mandatory prior to initiating treatment. Regular monitoring and follow-up are required throughout the course of treatment. Product Specifications

Product Name: Ivosidenib Tablets 0.25g × 60 Tablets/Box

Common Name: Ivosidenib Tablets

Active Ingredient: Ivosidenib

Dosage Form: Film-coated tablets

Specification: 0.25g per tablet; 60 tablets per box

Manufacturer: INDAR Pharmaceuticals Pvt Ltd

Indications: This product is an isocitrate dehydrogenase-1 (IDH1) inhibitor indicated for the treatment of:

1. Acute Myeloid Leukemia (AML):

*   In combination with azacitidine, for the treatment of newly diagnosed adult patients aged 75 years or older, or those ineligible for intensive induction chemotherapy, who have AML with a susceptible IDH1 mutation.

*   As a single agent, for the treatment of adult patients with relapsed or refractory AML with an IDH1 mutation.

2. Cholangiocarcinoma: For the treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation.

Key Prerequisite: The presence of an IDH1 mutation must be confirmed using a diagnostic test approved by the FDA or the National Medical Products Administration (NMPA) prior to use.

Dosage and Administration:

Recommended Dosage:

*   Monotherapy: 500 mg orally once daily, continued until disease progression or the occurrence of unacceptable toxicity.

*   Combination Therapy (with Azacitidine): Ivosidenib 500 mg orally once daily, taken on Days 1 through 28 of each 28-day cycle; Azacitidine is administered via subcutaneous injection or intravenous infusion on Days 1 through 7 of each cycle.

Administration Method: May be taken with or without food. Tablets should be swallowed whole; do not crush, chew, or split the tablets. If gastrointestinal upset occurs, it is recommended to take the medication with food.

Dosage Adjustment: Detailed dosage adjustment guidelines are provided for adverse reactions such as differentiation syndrome, QTc interval prolongation, and hepatotoxicity (involving temporary suspension followed by resumption at the original dose or dose reduction to 250 mg).