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Tibsovo Generic Name & Formulations
Legal Class
Rx
General Description
Ivosidenib 250mg; tabs.
Pharmacological Class
Isocitrate dehydrogenase-1 (IDH1) inhibitor.
How Supplied
Tabs—60
Manufacturer
Generic Availability
NO
Mechanism of Action
Ivosidenib targets the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro. The inhibition of the mutant IDH1 enzyme by ivosidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH1-mutated AML. Ivosidenib also reduced 2-HG levels in a patient-derived xenograft intra-hepatic cholangiocarcinoma mouse model with IDH1 R132C.
Tibsovo Indications
Indications
Previously treated, locally advanced or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.
Tibsovo Dosage and Administration
Adult
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
Not established.
Tibsovo Contraindications
Not Applicable
Tibsovo Boxed Warnings
Boxed Warning
Differentiation syndrome in AML.
Tibsovo Warnings/Precautions
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 Pharmacokinetics
Elimination
Fecal (77%), renal (17%). Mean terminal half-life: 58 hours (in AML); 129 hours (in cholangiocarcinoma).
Tibsovo Interactions
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.
Tibsovo Adverse Reactions
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.
Tibsovo Clinical Trials
See Literature
Tibsovo Note
Not Applicable
Tibsovo Patient Counseling
See Literature
Tibsovo Generic Name & Formulations
Legal Class
Rx
General Description
Ivosidenib 250mg; tabs.
Pharmacological Class
Isocitrate dehydrogenase-1 (IDH1) inhibitor.
How Supplied
Tabs—60
Manufacturer
Generic Availability
NO
Mechanism of Action
Ivosidenib targets the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro. The inhibition of the mutant IDH1 enzyme by ivosidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH1-mutated AML. Ivosidenib also reduced 2-HG levels in a patient-derived xenograft intra-hepatic cholangiocarcinoma mouse model with IDH1 R132C.
Tibsovo Indications
Indications
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.
Tibsovo Dosage and Administration
Adult
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
Not established.
Tibsovo Contraindications
Not Applicable
Tibsovo Boxed Warnings
Boxed Warning
Differentiation syndrome in AML.
Tibsovo Warnings/Precautions
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 Pharmacokinetics
Elimination
Fecal (77%), renal (17%). Mean terminal half-life: 58 hours (in AML); 129 hours (in cholangiocarcinoma).
Tibsovo Interactions
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.
Tibsovo Adverse Reactions
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.
Tibsovo Clinical Trials
See Literature
Tibsovo Note
Not Applicable
Tibsovo Patient Counseling
See Literature
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