Tibsovo

Acute myeloid leukemia (AML) — with a susceptible IDH1 mutation: newly diagnosed in patients ≥75 years or with comorbidities precluding induction chemo (monotherapy or with azacitidine); relapsed or refractory AML; Cholangiocarcinoma — locally advanced or metastatic, previously treated, with an IDH1 mutation as detected by an FDA-approved test

AML/Cholangiocarcinoma: 500 mg orally once daily until disease progression or unacceptable toxicity
Take with or without food
Strong CYP3A4 inhibitors: Reduce to 250 mg once daily
Continue for a minimum of 6 months in AML to allow time for clinical response

Tablets: 250 mg

None listed.

• Differentiation Syndrome: In 25% of AML patients (including fatal cases). Symptoms include dyspnea, pulmonary infiltrates, pleural/pericardial effusions, rapid weight gain, edema, fever, hypotension. Treat with corticosteroids and hemodynamic monitoring. Withhold if not improved in 48 hours.
• QTc Prolongation: 10.2% QTc >480 ms. Monitor ECG weekly for first 3 weeks, then monthly for 2 months. Correct electrolytes.
• Guillain-Barré Syndrome: Reported. Monitor for weakness, numbness, paresthesia.
• Leukocytosis: In 30% of AML patients. Monitor and manage with hydroxyurea if needed.
• Embryo-Fetal Toxicity

Fatigue (37%), leukocytosis (30%), arthralgia (25%), diarrhea (24%), dyspnea (23%), edema (22%), nausea (21%), mucositis (18%), ECG QT prolonged (10%), rash (14%), decreased appetite (14%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Ivosidenib is a small-molecule inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Susceptible IDH1 mutations (R132H, R132C, R132L, R132G, R132S) produce the oncometabolite 2-hydroxyglutarate (2-HG), which causes epigenetic alterations and blocks cellular differentiation. Ivosidenib inhibits the mutant IDH1 enzyme, reducing 2-HG levels and restoring cellular differentiation.

Tmax: 3 hours. Half-life: approximately 93 hours at steady state. Protein binding: 92-96%. Metabolized primarily by CYP3A4 (also induces its own metabolism). Fecal excretion (77%), urinary excretion (17%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• ClarIDHy — Ivosidenib vs. placebo in IDH1-mutated advanced cholangiocarcinoma. Phase III, n=185.
  🔬 NCT02989857 ↗ 📄 Primary Publication ↗

Tibsovo has FDA-approved indications across the following cancer types covered on PipelineEvidence: