XOSPATA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XOSPATA (XOSPATA).
Gilteritinib is a tyrosine kinase inhibitor that inhibits FLT3 (FMS-like tyrosine kinase 3) receptor signaling, including FLT3-ITD and FLT3-TKD mutations, leading to apoptosis in leukemic cells.
| Metabolism | Primarily metabolized by CYP3A4; also involves CYP2C8, UGT1A9, and other minor pathways. |
| Excretion | Fecal (64%) and renal (16%) as metabolites; <1% unchanged in urine. |
| Half-life | Terminal half-life 9.1 hours (range 4.4–16.1 hours); supports once-daily dosing. |
| Protein binding | 99.8% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 1410 L (approximately 20 L/kg based on 70 kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability 30–40% under fasting conditions; absorption reduced with high-fat meal. |
| Onset of Action | Clinical response (e.g., complete remission) typically within 1–2 treatment cycles (28-day cycles). |
| Duration of Action | Duration of response varies; continuous daily dosing until disease progression or unacceptable toxicity. |
120 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; for GFR <30 mL/min, not recommended due to insufficient data. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce to 80 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustments are required based on age alone; monitor for adverse effects due to potential age-related decreased organ function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XOSPATA (XOSPATA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Gilteritinib is likely excreted in animal milk. M/P ratio unknown. Breastfeeding is not recommended during treatment and for at least 2 months after last dose. |
| Teratogenic Risk | XOSPATA (gilteritinib) is embryotoxic and fetotoxic in animal studies. There are no adequate human data. Based on mechanism of action (FLT3 inhibition), there is potential for teratogenicity. Use is contraindicated in pregnancy unless no alternative. First trimester: high risk of structural abnormalities. Second and third trimesters: potential for fetal growth restriction and impaired hematopoiesis. |
■ FDA Black Box Warning
None.
| Serious Effects |
["None."]
| Precautions | ["Differentiation syndrome: Can be fatal; treat with corticosteroids and hemodynamic monitoring.","Posterior reversible encephalopathy syndrome (PRES): Monitor for neurological symptoms; discontinue if occurs.","QT prolongation: Monitor electrolytes and ECG; avoid use in patients with QTc > 450 ms.","Pancreatitis: Monitor lipase and amylase.","Hepatotoxicity: Monitor liver function tests.","Embryo-fetal toxicity: Can cause fetal harm; advise effective contraception."] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential, liver function tests (AST, ALT, bilirubin), serum amylase and lipase, electrolytes, and ECG for QTc prolongation. In pregnancy, fetal monitoring includes ultrasound for growth and anatomy, and assessment for oligohydramnios. |
| Fertility Effects | Animal studies show impaired fertility in females (decreased implantation, increased pre- and post-implantation loss). Reversible upon discontinuation. Effects on male fertility not studied, but may impair spermatogenesis due to antiproliferative effects. |