TIBSOVO
Clinical safety rating
cautionComprehensive clinical and safety monograph for TIBSOVO (TIBSOVO).
Comprehensive clinical and safety monograph for TIBSOVO (TIBSOVO).
Acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation, relapsed or refractoryAcute myeloid leukemia (AML) with an IDH2 mutation, newly diagnosed in patients ≥75 years or with comorbidities ineligible for intensive induction chemotherapy
Isocitrate dehydrogenase-2 (IDH2) inhibitor; targets mutant IDH2 isoforms to reduce 2-hydroxyglutarate (2-HG) levels, promoting myeloid differentiation.
| Metabolism | Primarily metabolized by CYP3A4; also a minor substrate of CYP2C19, CYP2D6, and UGT1A1. |
| Excretion | Primarily hepatic metabolism (CYP3A4) and fecal excretion (77% unchanged and metabolites); renal elimination accounts for <1% of absorbed dose. |
| Half-life | Terminal elimination half-life: 50-60 hours, supporting once-daily dosing with steady-state reached in approximately 2 weeks. |
| Protein binding | >99.9% bound, primarily to serum albumin. |
| Volume of Distribution | Volume of distribution (Vd/F): approximately 2.2 L/kg (range 1.7-2.8), indicating extensive extravascular distribution. |
| Bioavailability | Estimated absolute bioavailability is approximately 60-70% after oral administration. |
| Onset of Action | Clinical effect (reduction in IDH1 mutant allele burden) typically observed within 1-2 months of continuous oral administration. |
| Duration of Action | Duration of therapeutic effect is sustained with continuous dosing; drug levels decline gradually after discontinuation, with clinical effects persisting for several weeks. |
| Molecular Weight | 535.02 |
500 mg orally once daily taken with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or dialysis. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh class A). Moderate or severe hepatic impairment (Child-Pugh class B or C) has not been studied; use with caution and monitor for adverse effects. |
| Pediatric use | Safety and effectiveness have not been established in pediatric patients; no dosing recommendations available. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients aged 65 years and older, but no overall differences in safety or efficacy were observed compared to younger patients. |
| 1st trimester | Limited human data; animal studies show developmental toxicity including skeletal abnormalities and reduced fetal weight. Avoid use unless benefit outweighs risk. |
| 2nd trimester | No adequate human studies; potential for fetal toxicity based on animal data. Use only if clearly needed. |
| 3rd trimester | Risk of fetal toxicity; avoid use near term due to potential for adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for TIBSOVO (TIBSOVO).
| Placental transfer | Ivosidenib likely crosses the placenta based on molecular weight (about 535 Da) and animal studies showing fetal exposure. |
| Breastfeeding | It is unknown if ivosidenib is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 1 month after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on animal studies and its mechanism of action (IDH1 inhibition), TIBSOVO (ivosidenib) may cause fetal harm. No adequate human data exist. It is teratogenic in rats at exposures below the clinical dose. Avoid use in pregnancy unless benefit outweighs risk. Confirm negative pregnancy test before initiation. First trimester: risk of major malformations unknown but potential. Second/third trimester: potential for fetal growth restriction and oligohydramnios due to effects on cellular metabolism. Use effective contraception during treatment and for at least 1 month after the last dose. |
| Fetal Monitoring | Monitor complete blood counts, hepatic function, and ECG for QTc prolongation. In pregnancy, perform serial fetal ultrasound to monitor for growth restriction and amniotic fluid volume. Assess for signs of fetal distress. Women of reproductive potential should have pregnancy testing prior to and periodically during therapy. Monitor for differentiation syndrome (fever, dyspnea, pulmonary infiltrates, pleural effusions), which may require hospitalization. |
| Fertility Effects | Based on animal studies, TIBSOVO may impair fertility in males and females of reproductive potential. In rats, testicular degeneration and decreased spermatogenesis were observed. In female rats, prolonged estrous cycles and reduced corpora lutea occurred. Reversibility unknown. |
■ FDA Black Box Warning
None
| Serious Effects |
History of serious hypersensitivity reaction to ivosidenib or any excipients
| Precautions | Differentiation syndrome (can be fatal, treat with corticosteroids and hemodynamic support), QT prolongation (monitor ECG and electrolytes), Embryo-fetal toxicity |
| Food/Dietary | Take on an empty stomach (no food for at least 1 hour before or 2 hours after). Avoid grapefruit and grapefruit juice (CYP3A4 inhibition). High-fat meals significantly increase absorption; avoid concomitant intake. |
| Clinical Pearls | TIBSOVO (ivosidenib) is an IDH1 inhibitor indicated for IDH1-mutant acute myeloid leukemia (AML) and cholangiocarcinoma. Monitor for differentiation syndrome, which can be fatal; treat with corticosteroids and hemodynamic support. ECG monitoring for QTc prolongation is required; avoid concomitant use with strong CYP3A4 inhibitors or inducers. Assess liver function before and during therapy. Administer on an empty stomach at least 1 hour before or 2 hours after a meal. |
| Patient Advice | Take TIBSOVO on an empty stomach, at least 1 hour before or 2 hours after eating. · Do not crush or chew the tablets; swallow them whole. · Tell your doctor immediately if you experience fever, cough, difficulty breathing, or swelling (signs of differentiation syndrome). · Report any symptoms of heart rhythm changes (dizziness, fainting, chest pain) or liver problems (yellowing skin, dark urine, abdominal pain). · Avoid grapefruit and grapefruit juice during treatment. · Inform all healthcare providers that you are taking TIBSOVO. |
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