Colorectal and other GI cancers:
Indications for: TIBSOVO
Previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.
Adult Dosage:
Swallow whole. Take at same time each day. Avoid a high-fat meal. 500mg once daily until disease progression or unacceptable toxicity. If concomitant strong CYP3A4 inhibitor is unavoidable: reduce to 250mg once daily; when inhibitor is discontinued, resume at 500mg once daily (after at least 5 half-lives of the inhibitor). Monitoring and dose modifications for toxicities: see full labeling.
Children Dosage:
Not established.
Boxed Warning:
Differentiation syndrome in AML.
TIBSOVO Warnings/Precautions:
Risk of differentiation syndrome in AML (may be fatal). If differentiation syndrome is suspected, initiate oral or IV corticosteroids and hemodynamic monitoring until resolution; interrupt dose if severe symptoms persist >48hrs after corticosteroid initiation. Congenital long QT syndrome, CHF, electrolyte abnormalities: monitor more frequently. Interrupt therapy if QTc >480–<500msec; interrupt and reduce dose if >500msec; permanently discontinue if QTc prolongation with life-threatening arrhythmias develop. Obtain ECGs prior to treatment, at least weekly for the first 3 weeks, and then once monthly thereafter. For AML: assess blood counts/chemistries prior to initiation, at least weekly for the first month, once every other week for the second month, and once monthly thereafter; monitor creatine phosphokinase weekly for the first month. Monitor for new motor and/or sensory neuropathy (eg, unilateral or bilateral weakness, sensory alterations, paresthesias, difficulty breathing); permanently discontinue if Guillain-Barré syndrome diagnosed. Severe renal or hepatic impairment. Hemodialysis. Pregnancy: may cause fetal harm. Nursing mothers: not recommended (during and for at least 1 month after the last dose).
TIBSOVO Classification:
Isocitrate dehydrogenase-1 (IDH1) inhibitor.
TIBSOVO Interactions:
See Adults. May increase risk of QT prolongation when concomitant drugs known to prolong QTc interval (eg, antiarrhythmics, fluoroquinolones, triazole antifungals, 5-HT3 receptor antagonists) or with CYP3A4 inhibitors; avoid or use alternatives. Antagonized by strong CYP3A4 inducers; avoid. Antagonizes sensitive CYP3A4 substrates and may antagonize sensitive CYP2C9 substrates; use alternatives or monitor for efficacy if use unavoidable. Concomitant itraconazole or ketoconazole: not recommended. May decrease concentrations of hormonal contraceptives; consider alternatives.
Adverse Reactions:
Fatigue, arthralgia, leukocytosis, diarrhea, edema, nausea, vomiting, dyspnea, mucositis, QT prolongation, rash, cough, decreased appetite, myalgia, constipation, pyrexia, abdominal pain, ascites, anemia, lab abnormalities; tumor lysis syndrome, Guillain-Barré syndrome.
Generic Drug Availability:
NO
How Supplied:
Tabs—60
Leukemias, lymphomas, and other hematologic cancers:
Indications for: TIBSOVO
In combination with azacitidine or as monotherapy for newly-diagnosed acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test in adults ≥75yrs old or have comorbidities that preclude use of intensive induction chemotherapy. Relapsed or refractory AML with a susceptible IDH1 mutation as detected by an FDA-approved test.
Adult Dosage:
Swallow whole. Take at same time each day. Avoid a high-fat meal. Monotherapy (newly diagnosed, relapsed, or refractory AML): 500mg once daily until disease progression or unacceptable toxicity. Combination regimen (newly diagnosed AML): 500mg once daily until disease progression or unacceptable toxicity; start on Cycle 1 Day 1 (with azacitidine 75mg/m2 SC or IV once daily) on Days 1–7 (or Days 1–5 and 8–9) of each 28-day cycle. For those without disease progression or unacceptable toxicity (monotherapy or combination regimen): continue treatment (with or without azacitidine) for a minimum of 6 months to allow time for response. If concomitant strong CYP3A4 inhibitor is unavoidable: reduce to 250mg once daily; when inhibitor is discontinued, resume at 500mg once daily (after at least 5 half-lives of the inhibitor). Monitoring and dose modifications for toxicities: see full labeling.
Children Dosage:
Not established.
Boxed Warning:
Differentiation syndrome in AML.
TIBSOVO Warnings/Precautions:
Risk of differentiation syndrome in AML (may be fatal). If differentiation syndrome is suspected, initiate oral or IV corticosteroids and hemodynamic monitoring until resolution; interrupt dose if severe symptoms persist >48hrs after corticosteroid initiation. Congenital long QT syndrome, CHF, electrolyte abnormalities: monitor more frequently. Interrupt therapy if QTc >480–<500msec; interrupt and reduce dose if >500msec; permanently discontinue if QTc prolongation with life-threatening arrhythmias develop. Obtain ECGs prior to treatment, at least weekly for the first 3 weeks, and then once monthly thereafter. For AML: assess blood counts/chemistries prior to initiation, at least weekly for the first month, once every other week for the second month, and once monthly thereafter; monitor creatine phosphokinase weekly for the first month. Monitor for new motor and/or sensory neuropathy (eg, unilateral or bilateral weakness, sensory alterations, paresthesias, difficulty breathing); permanently discontinue if Guillain-Barré syndrome diagnosed. Severe renal or hepatic impairment. Hemodialysis. Pregnancy: may cause fetal harm. Nursing mothers: not recommended (during and for at least 1 month after the last dose).
TIBSOVO Classification:
Isocitrate dehydrogenase-1 (IDH1) inhibitor.
TIBSOVO Interactions:
See Adults. May increase risk of QT prolongation when concomitant drugs known to prolong QTc interval (eg, antiarrhythmics, fluoroquinolones, triazole antifungals, 5-HT3 receptor antagonists) or with CYP3A4 inhibitors; avoid or use alternatives. Antagonized by strong CYP3A4 inducers; avoid. Antagonizes sensitive CYP3A4 substrates and may antagonize sensitive CYP2C9 substrates; use alternatives or monitor for efficacy if use unavoidable. Concomitant itraconazole or ketoconazole: not recommended. May decrease concentrations of hormonal contraceptives; consider alternatives.
Adverse Reactions:
Fatigue, arthralgia, leukocytosis, diarrhea, edema, nausea, vomiting, dyspnea, mucositis, QT prolongation, rash, cough, decreased appetite, myalgia, constipation, pyrexia, abdominal pain, ascites, anemia, lab abnormalities; tumor lysis syndrome, Guillain-Barré syndrome.
Generic Drug Availability:
NO
How Supplied:
Tabs—60
