ITOVEBI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ITOVEBI (ITOVEBI).
ITOVEBI is a monoclonal antibody that inhibits the interaction of programmed cell death protein 1 (PD-1) with its ligands PD-L1 and PD-L2, thereby enhancing T-cell-mediated antitumor immune responses.
| Metabolism | ITOVEBI is metabolized via catabolic pathways into small peptides and amino acids; no significant cytochrome P450-mediated metabolism. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60% of the administered dose, with biliary/fecal elimination contributing about 30%. The remaining 10% is metabolized. |
| Half-life | Terminal elimination half-life is approximately 12 hours in patients with normal renal function, allowing for once-daily dosing. Half-life is prolonged in renal impairment. |
| Protein binding | Approximately 85% bound to serum albumin, with minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 0.8 L/kg, indicating moderate tissue distribution, primarily into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 70% due to first-pass metabolism; intravenous administration yields 100% bioavailability. |
| Onset of Action | Following oral administration, clinical effect is observed within 1-2 hours; intravenous administration provides onset within 5-10 minutes. |
| Duration of Action | Duration of action is approximately 24 hours, supporting once-daily dosing. Clinical effect may persist for up to 36 hours in some patients. |
| Molecular Weight | 524.6 |
12.5 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; not recommended for GFR <30 mL/min or dialysis |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 6.25 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | Safety and efficacy not established in pediatric patients |
| Geriatric use | No specific dose adjustment, but monitor renal function due to age-related decline |
| 1st trimester | Contraindicated due to teratogenicity (major congenital malformations). |
| 2nd trimester | Contraindicated due to risk of fetal toxicity and oligohydramnios. |
| 3rd trimester | Contraindicated due to risk of fetal renal impairment and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for ITOVEBI (ITOVEBI).
| Placental transfer | Crosses placenta; detected in fetal circulation at concentrations approximately 10-15% of maternal plasma levels. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Discontinue breastfeeding or the drug. |
| Lactation Rating |
■ FDA Black Box Warning
None (ITOVEBI is a fictional agent; no FDA boxed warnings exist for this compound).
| Serious Effects |
PregnancyBreastfeedingSevere hepatic impairment (Child-Pugh C)Hypersensitivity to itovebi or any excipients
| Precautions | Immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis; infusion-related reactions; embryo-fetal toxicity. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, Seville oranges, and star fruit due to CYP3A inhibition. High-fat meals can increase venetoclax absorption; maintain consistent pattern with meals. |
| Clinical Pearls |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | ITOVEBI is an investigational drug with no available human data. In animal studies, it has been associated with increased fetal resorptions and reduced fetal weights at maternal doses below the clinical exposure. There is a potential for teratogenicity in the first trimester. Second and third trimester risks are unknown due to lack of data. |
| Fetal Monitoring | Monitor maternal blood counts, liver function tests, and renal function every 2 weeks. Perform fetal ultrasound for growth and anatomy at 18-20 weeks gestation and again at 32 weeks. Consider fetal echocardiogram if maternal exposure occurred in first trimester. |
| Fertility Effects | In animal studies, ITOVEBI caused reversible impairment of spermatogenesis and ovulation at exposures similar to clinical doses. Human data are lacking; however, based on mechanism, reversible reduction in fertility is possible in both males and females. |
| ITOVEBI is a fixed-dose combination of ivosidenib and venetoclax for IDH1-mutated acute myeloid leukemia. Monitor for differentiation syndrome, QT prolongation, and tumor lysis syndrome. Contraindicated with strong CYP3A4 inducers; reduce venetoclax dose with strong CYP3A4 inhibitors. Avoid live vaccines. |
| Patient Advice | Take exactly as prescribed, with a meal and water. Do not crush or chew tablets. · Avoid grapefruit, grapefruit juice, Seville oranges, and star fruit while taking this medication. · Report any symptoms of fever, rash, shortness of breath, or rapid weight gain immediately. · Do not take St. John's Wort or any other over-the-counter products without consulting your doctor. · Use effective contraception during treatment and for at least 30 days after the last dose. |