IQIRVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IQIRVO (IQIRVO).
Selective inhibitor of the mutant isocitrate dehydrogenase 1 (IDH1) enzyme, reducing the production of the oncometabolite 2-hydroxyglutarate (2-HG) and promoting myeloid differentiation.
| Metabolism | Primarily metabolized by cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2C9, CYP2C19, and CYP2D6. |
| Excretion | Primarily biliary/fecal excretion with minimal renal elimination (<5%). |
| Half-life | Terminal half-life is approximately 24 hours, supporting once-daily dosing. |
| Protein binding | High protein binding (≥99%), primarily to serum albumin. |
| Volume of Distribution | Approximately 0.2 L/kg (mean Vd/F = 15 L), indicating limited extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 30%. |
| Onset of Action | Orally: within 2 hours. |
| Duration of Action | Approximately 24 hours, consistent with once-daily dosing. |
For NBNC (non-B, non-C) hepatocellular carcinoma with no prior systemic therapy: 110 mg orally once daily with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or ESRD. |
| Liver impairment | Child-Pugh A: No dose adjustment. Child-Pugh B: Reduce dose to 80 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients below 18 years of age. |
| Geriatric use | No specific dose adjustment recommended. Patients aged ≥65 years should be monitored for increased toxicity, particularly fatigue and elevated transaminases. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IQIRVO (IQIRVO).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not determined. Consider developmental benefits of breastfeeding vs. potential adverse effects. |
| Teratogenic Risk | No human data; animal studies show no teratogenic effects at clinically relevant doses. Risk cannot be excluded; use only if benefit outweighs potential risk. |
| Fetal Monitoring | Monitor liver function tests (ALT, AST, bilirubin) monthly; monitor for signs of hepatotoxicity, gastrointestinal disturbances, and metabolic acidosis. |
■ FDA Black Box Warning
Differentiation syndrome, which can be fatal if not treated, has been reported with ivosidenib. Symptoms include fever, dyspnea, pulmonary infiltrates, pleural effusions, pericardial effusions, rapid weight gain, peripheral edema, hepatic, renal, or multi-organ dysfunction. Corticosteroids and hemodynamic monitoring are recommended.
| Serious Effects |
["None known."]
| Precautions | ["Differentiation syndrome: monitor for symptoms; treat with corticosteroids and hemodynamic support; interrupt ivosidenib if severe.","QT interval prolongation: assess electrolytes and ECG before and during treatment; avoid concomitant QT-prolonging drugs.","Elevated liver enzymes: monitor LFTs at least weekly for first 3 months; reduce dose or hold for persistent elevations.","Embryo-fetal toxicity: can cause fetal harm; advise effective contraception."] |
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| Fertility Effects | No data on human fertility; animal studies show no impairment at therapeutic doses. |