TIBSOVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIBSOVO (TIBSOVO).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIBSOVO (TIBSOVO).
| Breastfeeding | No data on presence in human milk, effects on breastfed infants, or milk production. Due to potential for serious adverse reactions, breastfeedin is not recommended during treatment and for at least 1 month after the last dose. M/P ratio not available. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
None known
| Precautions | ["Differentiation syndrome (can be fatal, treat with corticosteroids and hemodynamic support)","QT prolongation (monitor ECG and electrolytes)","Embryo-fetal toxicity"] |
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| 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. |