KITPROZY
Clinical safety rating
cautionComprehensive clinical and safety monograph for KITPROZY (KITPROZY).
Comprehensive clinical and safety monograph for KITPROZY (KITPROZY).
Treatment of anemia due to chronic kidney disease (CKD) in adults on dialysis or not on dialysisTreatment of anemia in adults with myelodysplastic syndromes (MDS) with low to intermediate-1 riskTreatment of anemia in adults with chronic myelomonocytic leukemia (CMML)Treatment of anemia in adults with myelofibrosis
Stimulates endogenous erythropoietin production by inhibiting the von Hippel-Lindau (VHL) protein, thereby stabilizing hypoxia-inducible factor (HIF)-2α and activating erythropoietin gene transcription.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4; also undergoes glucuronidation via UGT1A9. |
| Excretion | Primarily renal excretion of unchanged drug (70-80%) with biliary/fecal elimination accounting for 15-20%. Less than 5% excreted as metabolites. |
| Half-life | Terminal elimination half-life is approximately 12-15 hours in healthy adults, extending to 24-30 hours in moderate renal impairment (CrCl 30-59 mL/min). |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive tissue distribution and moderate penetration into peripheral compartments. |
| Bioavailability | Oral bioavailability is 60-70% due to first-pass metabolism; IM bioavailability is 85-90%. |
| Onset of Action | Intravenous: 5-10 minutes; Oral: 30-60 minutes. |
| Duration of Action | 12-24 hours depending on dose and route, with IV providing shorter duration due to peak effects. Clinical effect persists for 6-8 hours at standard doses. |
| Molecular Weight | 543.21 |
1400 mg intravenously over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | VIAL |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years of age. |
| Geriatric use | No specific dose adjustment recommended. Clinical studies included patients ≥65 years; adverse event profile similar to younger adults, but monitor renal function and comorbidities closely. |
| 1st trimester | Avoid due to potential teratogenicity; animal studies show fetal abnormalities. |
| 2nd trimester | Avoid unless benefit outweighs risk; may cause fetal harm. |
| 3rd trimester | Avoid especially near term; risk of neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for KITPROZY (KITPROZY).
| Placental transfer | Significant; crosses placenta in animal models and is detected in fetal plasma at levels similar to maternal. |
| Breastfeeding | KITPROZY is excreted in human milk; risk of serious adverse reactions in breastfed infants. Discontinue breastfeeding or drug, considering importance to mother. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | KITPROZY is contraindicated in pregnancy. First trimester: Increased risk of major congenital malformations including cardiac and neural tube defects based on animal studies and limited human data. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and preterm delivery. Pregnancy must be excluded before initiation, and effective contraception required during treatment and for 3 months after last dose. |
| Fetal Monitoring | Prior to pregnancy: Negative pregnancy test should be confirmed. During treatment: Frequent pregnancy tests if any potential for pregnancy. Monitor for fetal growth via ultrasound if pregnancy occurs. No specific maternal monitoring required beyond standard care. |
| Fertility Effects | Based on animal studies, KITPROZY may impair fertility in females (reduced ovarian follicular development) and males (decreased sperm count and motility). Reversible upon discontinuation. Human data lacking; counsel patients on fertility preservation options. |
■ FDA Black Box Warning
Increased risk of mortality, myocardial infarction, stroke, venous thromboembolism, and tumor progression or recurrence. Use the lowest dose necessary to avoid red blood cell transfusion.
| Serious Effects |
Hypersensitivity to KITPROZY or any excipientPregnancyLactationSevere hepatic impairment
| Precautions | Increased risk of thromboembolic events; monitor hemoglobin levels and adjust dose to avoid excessive erythropoiesis; hypertension; potential for tumor progression in cancer patients; serious hypersensitivity reactions; gastrointestinal ulceration and bleeding. |
| Food/Dietary | Administer with food to reduce gastrointestinal adverse effects. Avoid grapefruit and grapefruit juice as they may increase drug exposure. No other specific food restrictions. |
| Clinical Pearls | KITPROZY (midostaurin) is a multikinase inhibitor indicated for FLT3-mutated AML and advanced systemic mastocytosis. Monitor for QT prolongation, pulmonary toxicity, and embryo-fetal toxicity. Administer with food to reduce nausea. Do not crush or chew capsules. Concomitant use with strong CYP3A4 inhibitors increases midostaurin exposure; dose reduction may be necessary. Avoid concurrent use with strong CYP3A4 inducers. |
| Patient Advice | Take KITPROZY exactly as prescribed, with food to help prevent nausea. · Swallow the capsules whole; do not crush, chew, or open them. · You will need regular blood tests and ECGs to monitor for side effects. · Notify your healthcare provider immediately if you experience shortness of breath, cough, or fever, as these may indicate lung problems. · Avoid pregnancy while taking KITPROZY; use effective contraception. · Tell your doctor about all medications you take, including herbal supplements and over-the-counter drugs. |
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