Adding to its earlier approvals for use in adults with acute myeloid leukemia (AML), on August 25, 2021, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo®) for adults with previously treated, locally advanced or metastatic cholangiocarcinoma. Cholangiocarcinoma, or cancer of the bile ducts, is a rare cancer, and ivosidenib is the only currently approved agent for patients with an IDH1 variant.
Oral targeted therapy, small molecule inhibitor
Mechanism of Action
Ivosidenib targets a variant in the IDH1 enzyme, decreasing 2-hydroxyglutarate levels, reducing blast counts, and increasing the percentage of mature myeloid cells.
Treatment of patients with an IDH1 variant, as detected by an FDA-approved test, who have:
- Relapsed or refractory AML
- Newly diagnosed AML (only in patients aged 75 or older with comorbidities that prohibit the use of intensive induction chemotherapy)
- Previously treated, locally advanced or metastatic cholangiocarcinoma
Two tablets, orally, once a day, with or without food
The most common adverse events in AML (≥ 20%) are fatigue, arthralgia, leukocytosis, diarrhea, edema, nausea, dyspnea, mucositis, prolonged QT interval, rash, cough, decreased appetite, myalgia, constipation, pyrexia; decreased hemoglobin, calcium, sodium, magnesium, potassium, and phosphate; and increased uric acid, alkaline phosphatase, aspartate aminotransferase, and creatinine. The most common adverse events in cholangiocarcinoma (≥ 15%) are fatigue, nausea, abdominal pain, diarrhea, cough, decreased appetite, ascites, vomiting, anemia, and rash. Less common events in cholangiocarcinoma (≥ 10%) are decreased hemoglobin; increased aspartate aminotransferase and bilirubin. The package insert contains warnings for QTc interval prolongation, Guillain-Barré syndrome, and differentiation syndrome for all indications.
Patients with AML could experience differentiation syndrome while taking ivosidenib occurring as early as day 1 following the start of therapy and during the first three months. Symptoms include fever; dyspnea; hypoxia; rapid weight gain; peripheral edema; hypotension; hepatic, renal, or multiorgan dysfunction; or the presence of pulmonary infiltrates and pleural or pericardial effusions. Stop ivosidenib for suspected differentiation syndrome and treat promptly with corticosteroids and hemodynamic monitoring until symptoms resolve. Obtain a baseline echocardiogram prior to initiating therapy and at least once weekly for the first three weeks and then at least once monthly for the duration. Refer to the package insert for a full listing of dose modifications.
Drug-Drug and Drug-Food Interactions
Avoid high-fat meals at the time of the dose. Ivosidenib also interacts with strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, QTc prolonging drugs, and hormonal contraceptives. Refer to the package insert for full description of interactions and recommended management.
Take tablets whole; do not split or crush. If you vomit after taking a dose, do not take another two tablets; rather, wait until your next scheduled dose. Do not take two doses within a 12-hour period. Do not breastfeed while taking ivosidenib and for at least one month after the last dose. If you are using a hormonal birth control, you may need alternative methods of contraception. Store the tablets at room temperature.
No differences in effectiveness or safety were noted in clinical trials in patients 65 years and older compared to younger patients.
Ivosidenib may cause embryo-fetal toxicity.
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