VANFLYTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VANFLYTA (VANFLYTA).
VANFLYTA (quizartinib) is a kinase inhibitor that targets FMS-like tyrosine kinase 3 (FLT3), including FLT3 internal tandem duplication (FLT3-ITD) and wild-type FLT3. It also inhibits KIT, PDGFRA, PDGFRB, CSF1R, and RET. By inhibiting FLT3, it blocks downstream signaling pathways involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4 to an active metabolite (AC886); also involves CYP2C8, CYP2C9, and CYP2D6 to a minor extent. |
| Excretion | Primarily hepatic metabolism with <10% excreted unchanged in urine and <1% in feces. |
| Half-life | 26.5 hours (range 15–46 hours) for quizartinib; metabolite AC886 has half-life of 37.8 hours. Supports once-daily dosing. |
| Protein binding | 99.4% bound to plasma proteins (primarily albumin and α1-acid glycoprotein). |
| Volume of Distribution | Vd/F = 543 L (approximately 7.3 L/kg for a 74 kg adult), indicating extensive extravascular distribution. |
| Bioavailability | Not applicable; administered orally with no specific bioavailability data, but absolute bioavailability is not determined. |
| Onset of Action | Not applicable; clinical effect (composite complete remission) is typically assessed after 1–2 cycles (each cycle 28 days). |
| Duration of Action | Continuous daily dosing until disease progression or unacceptable toxicity; median duration of exposure in trials was 3.5 months. |
40 mg orally twice daily on days 1-14 and 15-28 of each 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >= 30 mL/min. For GFR < 30 mL/min, use with caution, no specific dose recommendation available. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 30 mg twice daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment. Clinical studies included patients aged ≥65 years; monitor for increased toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VANFLYTA (VANFLYTA).
| Breastfeeding | No data on the presence of quizartinib in human milk, effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in breastfed infants (e.g., myelosuppression, cardiac toxicity), advise women not to breastfeed during treatment with VANFLYTA and for at least 1 month after the last dose. M/P ratio: Unknown. |
| Teratogenic Risk | FDA Pregnancy Category D. Based on its mechanism of action (FLT3 inhibitor) and animal studies, VANFLYTA (quizartinib) can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration to pregnant rats and rabbits during organogenesis resulted in embryo-fetal mortality and structural abnormalities at maternal exposures below the human AUC at the recommended dose. There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk to a fetus. First trimester: Highest risk for major malformations, particularly cardiovascular and skeletal defects. Second and third trimesters: Risk of impaired growth, oligohydramnios, and fetal death. Avoid use during pregnancy unless maternal benefit outweighs fetal risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to quizartinib or any of its excipients."]
| Precautions | ["QT interval prolongation, torsade de pointes, and cardiac arrest: Monitor electrocardiograms (ECGs) and correct electrolyte abnormalities.","Differentiation syndrome: If suspected, discontinue VANFLYTA and administer corticosteroids.","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential to use effective contraception."] |
Loading safety data…
| Fetal Monitoring | Monitor complete blood count (CBC) with differential at baseline, weekly for the first 2 cycles, every 2 weeks for the next 2 cycles, and monthly thereafter. Monitor ECG for QTc interval prolongation at baseline and periodically during treatment, especially in patients with risk factors. Monitor electrolytes (potassium, magnesium, calcium) and correct abnormalities before and during treatment. Monitor for signs of pancreatitis (amylase, lipase) monthly. Perform pregnancy testing in females of reproductive potential prior to initiation and periodically during treatment. |
| Fertility Effects | Based on findings from animal studies, VANFLYTA may impair fertility in females and males of reproductive potential. In female rats, ovulation and fertility were impaired at doses resulting in exposures less than the human exposure at the recommended dose. The effects were reversible after a 4-week drug-free period. In male rats, testicular toxicity (degeneration of seminiferous tubules and reduced sperm count) was observed at exposures below human exposure, and effects on fertility were not fully reversible. Human data are lacking; advise patients of potential risk to fertility. |