SUTENT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SUTENT (SUTENT).
Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor that inhibits platelet-derived growth factor receptors (PDGFR-α and PDGFR-β), vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2, VEGFR-3), stem cell factor receptor (c-KIT), FMS-like tyrosine kinase-3 (FLT3), colony-stimulating factor 1 receptor (CSF-1R), and the glial cell line-derived neurotrophic factor receptor (RET). It inhibits angiogenesis and tumor cell proliferation.
| Metabolism | Primarily metabolized by CYP3A4; the major metabolite (N-desethyl sunitinib) is also active and is further metabolized by CYP3A4. |
| Excretion | Renal: 16% of total radioactivity; Fecal: ~70% of total radioactivity (primarily as unchanged parent and metabolites). |
| Half-life | Terminal elimination half-life of sunitinib is 40-60 hours; for its primary active metabolite (SU12662) it is 80-110 hours. Steady-state achieved by day 14. |
| Protein binding | 95% bound to human plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 2230 L (enterprise, not weight-adjusted). The Vd is large, indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 40% (range 30-50%). |
| Onset of Action | Oral: Clinical response (e.g., tumor shrinkage) typically observed within 1-4 weeks of continuous daily dosing (50 mg once daily, 4 weeks on/2 weeks off schedule). |
| Duration of Action | Duration of therapeutic effect persists for the treatment cycle (e.g., 4 weeks on) and declines during the 2-week off period. Continuous daily dosing at lower doses (37.5 mg) may maintain effect. |
| Molecular Weight | 398.47 |
| Action Class | Tyrosine kinase inhibitors |
| Brand Substitutes | Sunixar 25 Capsule, Sutib 25 Capsule, Adsunib 25 Capsule, Nitnib 25 Capsule, Sunicine 25mg Capsule, Sutib 50 Capsule, Sunicine 50mg Capsule, Nitnib 50 Capsule, Adsunib 50 Capsule, Svitinib 50 Capsule |
50 mg orally once daily for 4 weeks, followed by 2 weeks off (schedule 4/2).
| Dosage form | CAPSULE |
| Renal impairment | No adjustment for mild-to-moderate renal impairment (CrCl ≥30 mL/min); avoid use in severe impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh Class A: 50 mg daily; Class B: reduce to 37.5 mg daily; Class C: not recommended. |
| Pediatric use | Not approved for pediatric use; no established weight-based dosing. |
| Geriatric use | No specific dose adjustment; monitor renal function and blood pressure more frequently due to increased sensitivity to adverse effects. |
| 1st trimester | Contraindicated due to teratogenicity in animal studies and potential for fetal harm. |
| 2nd trimester | Avoid use; may cause fetal harm based on mechanism of action and animal data. |
| 3rd trimester | Avoid use; may cause fetal harm and oligohydramnios. |
Clinical note
Comprehensive clinical and safety monograph for SUTENT (SUTENT).
| Placental transfer | Placental transfer is expected based on molecular weight (398.47 Da) and animal studies showing fetal abnormalities. |
| Breastfeeding | No human data; based on molecular weight and plasma protein binding, excretion into milk is possible. Discontinue drug or discontinue breastfeeding due to potential for serious adverse reactions in nursing infants. |
| Lactation Rating |
■ FDA Black Box Warning
Hepatotoxicity: Severe, sometimes fatal hepatotoxicity has been observed. Monitor liver function tests before and during treatment. Interrupt or discontinue SUTENT and manage as appropriate.
| Serious Effects |
Hypersensitivity to sunitinib or any component of the formulation
| Precautions | Hepatotoxicity: Monitor liver function tests before and during therapy; interrupt or discontinue for severe hepatotoxicity., Cardiovascular events: Hypertension, QT prolongation, left ventricular dysfunction, including heart failure; monitor blood pressure and cardiac function., Hemorrhage: Severe, sometimes fatal hemorrhagic events; monitor for signs and symptoms., Thyroid dysfunction: Monitor thyroid function; manage with thyroid hormone replacement as needed., Adrenal insufficiency: Reported; monitor for symptoms., Proteinuria: Monitor urine protein; discontinue for nephrotic syndrome., Wound healing complications: Withhold therapy for at least 24 days prior to elective surgery., Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue if signs/symptoms occur., Thrombotic microangiopathy (TMA): Reported; discontinue if TMA occurs. |
| Food/Dietary |
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| L5 |
| Teratogenic Risk | Pregnancy category D. First trimester: high risk of embryofetal toxicity including skeletal and cardiovascular malformations. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and preterm delivery due to antiangiogenic effects. Avoid use in pregnancy. |
| Fetal Monitoring | Monitor maternal blood pressure, thyroid function (TSH), cardiac function (LVEF), and renal function (serum creatinine, urine protein). Perform fetal ultrasound for growth and amniotic fluid volume. Monitor for signs of hemorrhage, thromboembolism, and hepatotoxicity. |
| Fertility Effects | Sunitinib may impair male and female fertility. In animal studies, it caused reduced fertility, embryo-fetal toxicity, and testicular degeneration. Monitor for menstrual irregularities or azoospermia; consider fertility preservation before initiation. |
| Avoid grapefruit and grapefruit juice during treatment. St. John's wort may reduce efficacy. No other significant interactions. |
| Clinical Pearls | Monitor for hypertension and proteinuria; manage with antihypertensives. Check thyroid function before and during therapy due to risk of hypothyroidism. Monitor liver enzymes and cardiac function, especially in patients with pre-existing conditions. Dose adjustments needed for hepatic impairment (Child-Pugh Class C). |
| Patient Advice | Take with or without food, but avoid grapefruit juice. · Report any signs of bleeding, unusual bruising, or fatigue. · Monitor blood pressure regularly and report high readings. · Watch for changes in skin color (yellowing or darkening) or nail changes. · Use effective contraception during treatment and for at least 4 weeks after stopping. · Avoid sun exposure; use sunscreen and protective clothing. |