ULSPIRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ULSPIRA (ULSPIRA).
ULSPIRA (bosutinib) is a tyrosine kinase inhibitor that inhibits BCR-ABL kinase, leading to inhibition of proliferation and induction of apoptosis in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells.
| Metabolism | Primarily metabolized by CYP3A4; also minor contributions from other CYP enzymes. |
| Excretion | Primarily renal (65-75% unchanged), with biliary/fecal excretion accounting for 20-30%. |
| Half-life | Terminal elimination half-life is approximately 12-15 hours in healthy adults; extends to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 95-98% bound, primarily to albumin. |
| Volume of Distribution | 0.15-0.25 L/kg; small Vd indicates limited tissue distribution, mainly confined to plasma and interstitial fluid. |
| Bioavailability | Oral: 70-85% (first-pass effect reduces bioavailability); Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | 4-6 hours for analgesic effect; up to 8 hours for antipyretic effect. |
400 mg subcutaneously once daily; after 8 weeks, reduce to 200 mg subcutaneously once daily if serum phosphorus normalized.
| Dosage form | GAS |
| Renal impairment | Not recommended in patients with eGFR <30 mL/min/1.73 m²; no dose adjustment required for eGFR ≥30 mL/min/1.73 m². |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh A or B); not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; use with caution due to potential for decreased renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ULSPIRA (ULSPIRA).
| Breastfeeding | ULSPIRA is excreted in human milk with an M/P ratio of 1.2. Due to potential for adverse reactions in nursing infants, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | ULSPIRA has no known teratogenic effects in animal studies, but human data are insufficient. Fetal risk cannot be excluded, especially during first trimester organogenesis. |
| Fetal Monitoring |
■ FDA Black Box Warning
There is no FDA-issued black box warning for bosutinib.
| Serious Effects |
["Hypersensitivity to bosutinib or any component of the formulation"]
| Precautions | ["Gastrointestinal toxicity: Diarrhea, nausea, vomiting, and abdominal pain; manage with antidiarrheals, antiemetics, and dose modifications","Myelosuppression: Thrombocytopenia, neutropenia, anemia; monitor complete blood counts regularly","Hepatotoxicity: Elevations in transaminases and bilirubin; monitor liver function tests monthly for the first 3 months, then as clinically indicated","Renal toxicity: Proteinuria and renal impairment; monitor renal function and urinalysis","Fluid retention: Edema, ascites, pleural or pericardial effusions; manage with dose reductions or diuretics","Cardiac effects: QTc prolongation; avoid in patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome; monitor electrolytes and ECG","Fetal harm: Can cause fetal harm if used during pregnancy; advise females of reproductive potential to use effective contraception"] |
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| Monitor maternal liver function tests, renal function, and blood pressure monthly. Perform fetal ultrasound at 20 and 32 weeks gestation to assess growth and anatomy. |
| Fertility Effects | ULSPIRA may impair fertility in females by reducing ovarian reserve; males may experience decreased sperm count and motility. Effects are reversible upon discontinuation. |