Tibsovo Ivosidenib Tablets

1. Indications and Usage
Relapsed or Refractory Acute Myeloid Leukemia (AML):
Indicated for adult patients with relapsed or refractory AML with a susceptible IDH1 mutation, as detected by an FDA-approved test.
Newly Diagnosed Acute Myeloid Leukemia (AML):
Indicated for adult patients with newly diagnosed AML with a susceptible IDH1 mutation who are ≥75 years old or who have comorbidities that preclude intensive induction chemotherapy.
Cholangiocarcinoma:
Indicated for adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1mutation, as detected by an FDA-approved test, who have previously received systemic chemotherapy.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Dose: 500 mg (two 250 mg tablets) once daily.
Treatment Duration: Continue until disease progression or unacceptable toxicity. For AML/MDS, continue for at least 6 months to assess response.
Administration Instructions:
Swallow tablets whole with water; do not crush, chew, or split.
Administer with or without food, but avoid high-fat meals.
Missed Dose: If a dose is missed, take it as soon as possible on the same day. Do not take the missed dose if it is the day of the next scheduled dose. Do not double the dose.
Vomiting: If the patient vomits after taking a dose, do not administer a replacement dose; wait until the next scheduled dose.
3. Mechanism of Action
IDH1 Inhibition:
Ivosidenib is a potent, orally bioavailable, small-molecule inhibitor of mutant IDH1.
Reduction of 2-HG:
Mutant IDH1 proteins gain a neomorphic function that produces the oncometabolite D-2-hydroxyglutarate (2-HG). Ivosidenib binds to mutant IDH1, inhibiting the production of 2-HG.
Induction of Differentiation:
Reduction of 2-HG levels leads to the reversal of epigenetic dysregulation, promoting the differentiation of leukemic blasts into mature myeloid cells, thereby inducing apoptosis and reducing tumor burden.
4. Safety and Warnings
Differentiation Syndrome:
A potentially life-threatening complication caused by the rapid differentiation of leukemic cells. Symptoms include fever, dyspnea, weight gain, pulmonary infiltrates, and hypotension. Monitor closely and administer corticosteroids promptly if suspected.
QTc Interval Prolongation:
Can cause QTc interval prolongation, which may lead to Torsades de Pointes. Obtain electrocardiograms (ECGs) and monitor electrolytes prior to initiation and regularly during treatment.
Embryo-Fetal Toxicity:
Can cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for at least 3 months after the final dose.
5. Adverse Reactions
AML (Most Common):
Differentiation syndrome, fatigue, arthralgia, diarrhea, edema, nausea, dyspnea, prolonged QT interval, pyrexia, and rash.
Cholangiocarcinoma (Most Common):
Fatigue, nausea, diarrhea, abdominal pain, decreased appetite, cough, dyspnea, and rash.
6. Drug Interactions
CYP3A4 Inducers:
Ivosidenib is a CYP3A4 inducer. Concomitant use with sensitive CYP3A4 substrates (e.g., certain anticoagulants) may decrease their exposure and efficacy.
Strong CYP3A4 Inhibitors:
Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) may significantly increase ivosidenib exposure. Dose reduction of ivosidenib may be required.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Ivosidenib.
Available Strength: 250 mg tablets.
Appearance: White to off-white, oval-shaped, film-coated tablets.
Storage: Store at room temperature (20°C–25°C / 68°F–77°F). Protect from moisture.