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. |
| Molecular Weight | 456.32 |
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 | Contraindicated due to risk of fetal malformations based on animal studies; use only if maternal benefit outweighs potential fetal risk. |
| 2nd trimester | Contraindicated due to risk of fetal harm; limited data but potential for adverse effects on fetal development. |
| 3rd trimester | Avoid use as may cause fetal harm; consider alternative therapy. |
Clinical note
Comprehensive clinical and safety monograph for ULSPIRA (ULSPIRA).
| Placental transfer | Readily crosses placenta in animal studies; human data limited but expected significant transfer due to molecular size and lipophilicity. |
| Breastfeeding | Not recommended due to potential for serious adverse reactions in breastfed infants; if used, monitor infant for toxicity and consider alternative feeding methods. |
■ FDA Black Box Warning
There is no FDA-issued black box warning for bosutinib.
| Serious Effects |
Hypersensitivity to active substance or excipientsSevere hepatic impairment (Child-Pugh class C)Concurrent use with MAOIs or within 14 days of MAOI therapyPregnancy
| 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 |
| Food/Dietary |
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| Lactation Rating |
| L5 (Avoid) |
| 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 | 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. |
| No specific food restrictions. Can be taken with or without food. Avoid excessive alcohol intake as it may increase risk of lactic acidosis. |
| Clinical Pearls | ULSPIRA (empagliflozin) is an SGLT2 inhibitor. Monitor renal function before initiation and periodically; euglycemic DKA can occur with normal glucose levels. Hold for 3 days before scheduled surgery. Not for use in type 1 diabetes. |
| Patient Advice | Take once daily with or without food. · Drink plenty of water to prevent dehydration. · Report symptoms of urinary tract infection or genital yeast infections promptly. · Seek immediate medical attention for signs of ketoacidosis (nausea, vomiting, abdominal pain, confusion, unusual fatigue) even if blood sugar is normal. · Do not stop this medication without consulting your doctor. |