SUNItinib (Monograph)

Brand name: Sutent
Drug class: Antineoplastic Agents
- Kinase Inhibitors
- Receptor Tyrosine Kinase Inhibitors
- Tyrosine Kinase Inhibitors
VA class: AN900
Chemical name: N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
Molecular formula: C₂₂H₂₇FN₄O₂
CAS number: 557795-19-4

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Antineoplastic agent; an inhibitor of multiple receptor tyrosine kinases.

Uses for SUNItinib

Gastrointestinal Stromal Tumor (GIST)

Treatment of GIST in adults who are intolerant of or whose disease has progressed during imatinib therapy.

Some experts recommend imatinib as standard therapy for the treatment of locally advanced, inoperable or metastatic GIST (including patients who did not relapse during therapy with adjuvant imatinib) in patients with imatinib-sensitive mutations. Following disease progression or intolerance to imatinib, sunitinib is standard second-line therapy in patients with metastatic or recurrent GIST.

Renal Cell Carcinoma

Treatment of advanced renal cell carcinoma.

Adjuvant treatment of renal cell carcinoma in patients at high risk of recurrence following nephrectomy.

Combination regimens (e.g., immune checkpoint inhibitor in combination with a tyrosine kinase inhibitor) have generally become a standard for the treatment of advanced RCC.

Some experts also state that subsequent monotherapy with a tyrosine kinase inhibitor (e.g., sunitinib, pazopanib) may be offered to patients who experience a treatment-limiting immune-mediated adverse effect following combination therapy with an immune checkpoint inhibitor or as a second-line option following disease progression during immune checkpoint inhibitor-based therapy.

Neuroendocrine Tumors (NET) of Pancreatic Origin

Treatment of progressive, well-differentiated NET of pancreatic origin in patients with unresectable, locally advanced, or metastatic disease.

Systemic therapy (e.g., lutetium Lu 177 dotatate, somatostatin analog, targeted therapy, cytotoxic chemotherapy) is generally used for disease control and symptom palliation in patients with metastatic disease. Long-acting somatostatin analogs are generally considered first-line therapy for metastatic NET, while sunitinib and everolimus are generally used in the second-line setting.

Other Uses

Has been studied in nongastrointestinal stromal tumor sarcomas^{† [off-label]} and thyroid cancer^{† [off-label]}.

SUNItinib Dosage and Administration

General

Pretreatment Screening

• Monitor liver function tests (ALT, AST, and bilirubin concentrations) prior to initiation of sunitinib.

• Consider monitoring left ventricular ejection fraction (LVEF) at baseline.

• Blood pressure at baseline.

• Perform urinalysis at baseline.

• Perform thyroid function tests at baseline.

• Assess blood glucose levels at baseline.

• Perform an oral examination prior to initiating therapy.

• Verify pregnancy status in females of reproductive potential.

Patient Monitoring

• Monitor liver function tests (ALT, AST, and bilirubin concentrations) during each cycle, and as clinically indicated.

• Consider monitoring LVEF periodically as indicated.

• Carefully monitor for clinical signs or symptoms of CHF.

• Monitor for development of or worsening of proteinuria. Perform urinalysis periodically during therapy; assess urine protein levels over a 24-hour period as clinically indicated.

• Monitor patients at high risk of developing QT interval prolongation (i.e., concomitant antiarrhythmic therapy, preexisting cardiac disease, bradycardia, or electrolyte disturbances). Consider periodic monitoring of ECGs and electrolytes (i.e., magnesium, potassium) during therapy.

• Monitor QT interval more frequently in patients receiving sunitinib concomitantly with a potent cytochrome P-450 (CYP) 3A4 inhibitor or drug known to prolong the QT interval.

• Monitor blood pressure as clinically indicated.

• Monitor for hemorrhagic events (e.g., serial CBCs, physical examinations).

• Monitor for tumor lysis syndrome.

• Monitor for signs or symptoms of thyroid dysfunction. Periodically monitor thyroid function during therapy and as clinically indicated.

• Monitor blood glucose levels regularly during therapy and as clinically indicated; continue monitoring following discontinuance of the drug.

• Perform oral examinations periodically during therapy.

Administration

Oral Administration

Administer orally without regard to meals.

Dosage

Available as sunitinib malate; dosage expressed in terms of sunitinib.

Adults

GIST

Oral

50 mg once daily for 4 consecutive weeks followed by a 2-week period without the drug. May continue therapy (i.e., 6-week cycles) for as long as the patient derives clinical benefit or until unacceptable toxicity occurs; in principal efficacy study, therapy was continued for a median of 5–6 cycles.

Renal Cell Carcinoma

Advanced Renal Cell Carcinoma

Oral

50 mg once daily for 4 consecutive weeks followed by a 2-week period without the drug. May continue therapy (i.e., 6-week cycles) for as long as the patient derives clinical benefit or until unacceptable toxicity occurs; in principal efficacy study, therapy was continued for a median of 11.1 months.

Adjuvant Treatment of Renal Cell Carcinoma

Oral

50 mg once daily for 4 consecutive weeks followed by a 2-week period without the drug. Continue therapy for 9 cycles.

NET of Pancreatic Origin

Oral

37.5 mg once daily continuously (i.e., without an off-treatment period). May continue therapy for as long as the patient derives clinical benefit or until unacceptable toxicity occurs; in principal efficacy study, therapy was continued for a median of 4.6 months.

Dosage Modification

Oral

Dosage of sunitinib should be adjusted in increments or decrements of 12.5 mg daily (i.e., 1 dose level), depending on individual patient safety and tolerability.

If dosage modification is required, the dosage of sunitinib should be reduced as described in Table 1 in patients with GIST, renal cell carcinoma, or NET of pancreatic origin.

Hepatotoxicity

If grade 3 hepatotoxicity occurs, withhold therapy; when toxicity resolves or improves to grade 0 or 1, may resume therapy at a reduced dosage. If grade 3 hepatotoxicity recurs, permanently discontinue sunitinib.

Permanently discontinue sunitinib in patients who experience grade 4 hepatotoxicity.

Cardiovascular Toxicities

If manifestations of CHF develop, discontinue sunitinib. In patients without clinical evidence of CHF but in whom left ventricular ejection fraction (LVEF) is >20% but <50% below baseline or below the lower limit of normal if LVEF was not assessed at baseline, sunitinib therapy should be withheld; when toxicity resolves or improves to grade 0 or 1, may resume therapy at a reduced dosage.

For grade 3 hypertension, withhold sunitinib; when hypertension resolves or improves to grade 0 or 1, may resume therapy at a reduced dosage. For grade 4 hypertension, permanently discontinue sunitinib.

Hemorrhagic Events

If grade 3 or 4 hemorrhagic events occur, withhold sunitinib therapy; when toxicity resolves or improves to grade 0 or 1, may resume therapy at a reduced dosage or discontinue therapy depending on the severity and persistence of the hemorrhagic event. If grade 3 or 4 hemorrhagic events do not resolve, discontinue sunitinib therapy.

Proteinuria

Interrupt therapy or reduce dosage if proteinuria ≥3 g per 24 hours (in the absence of nephrotic syndrome) occurs. When proteinuria resolves or improves to grade 0 or 1, may resume at a reduced dosage. If nephrotic syndrome occurs or if proteinuria recurs despite dosage reduction, permanently discontinue therapy.

Other Toxicities

Permanently discontinue sunitinib in patients who experience any grade thrombotic microangiopathy, dermatologic toxicities (i.e., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, necrotizing fasciitis) or reversible posterior leukoencephalopathy syndrome.

If osteonecrosis of the jaw or impaired wound healing occurs, sunitinib therapy may be resumed at a reduced dosage or discontinued depending on the severity and persistence of the adverse effects; however, safety of resuming sunitinib therapy in patients who experience osteonecrosis of the jaw or impaired wound healing has not been established.

Concomitant Use with Drugs and Foods Affecting Hepatic Microsomal Enzymes

Concomitant use with potent inhibitors or inducers of CYP3A4 may alter the combined plasma concentrations of sunitinib and its primary active metabolite.

If concomitant use with a potent CYP3A4 inhibitor cannot be avoided, consider reducing sunitinib dosage to no less than 37.5 mg daily (in patients receiving sunitinib for GIST or advanced renal cell carcinoma) or no less than 25 mg daily (in patients receiving sunitinib for progressive, well-differentiated NET of pancreatic origin).

If concomitant use with a CYP3A4 inducer cannot be avoided, consider increasing sunitinib dosage up to maximum of 87.5 mg daily (in patients receiving sunitinib for GIST or advanced renal cell carcinoma) or 62.5 mg daily (in patients receiving sunitinib for progressive, well-differentiated NET of pancreatic origin); monitor patient carefully for toxicity.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): No initial dosage adjustment required.

Severe hepatic impairment (Child-Pugh class C): Not studied.

Renal Impairment

Mild, moderate, or severe renal impairment: No initial dosage adjustment required; adjust subsequent dosages based on safety and tolerability.

End-stage renal disease undergoing hemodialysis: No initial dosage adjustment required; subsequent dosages may be increased gradually up to twofold based on safety and tolerability.

Geriatric Patients

No specific dosage recommendations.

Cautions for SUNItinib

Contraindications

• Manufacturer states none known.

Warnings/Precautions

Warnings

Hepatotoxicity

Severe hepatotoxicity, sometimes fatal, reported. Hepatic failure reported; manifestations include jaundice, elevated aminotransferase concentrations and/or hyperbilirubinemia in conjunction with encephalopathy, coagulopathy, and/or renal failure.

Monitor liver function tests (ALT, AST, and bilirubin concentrations) prior to initiation of sunitinib, during each cycle, and as clinically indicated. If grade 3 hepatotoxicity occurs, interrupt sunitinib therapy until the toxicity resolves or improves to grade 1 or less, then resume sunitinib at a reduced dosage. If grade 4 hepatotoxicity occurs or grade 3 hepatotoxicity persists, discontinue sunitinib therapy. Do not restart sunitinib therapy in patients who subsequently experience severe changes in liver function tests or exhibit other manifestations of hepatic failure.

Safety not established in patients with AST and/or ALT concentrations >2.5 times the ULN or, if caused by liver metastases, >5 times the ULN.

Other Warnings and Precautions

Cardiovascular Effects

Cardiovascular events (including heart failure, myocardial ischemia, myocardial infarction, and cardiomyopathy), sometimes fatal, reported.

Decreases in LVEF to below the lower limit of normal reported; grade 3 reductions in left ventricular systolic function (i.e., LVEF <40%) reported rarely. Fatal heart failure and fatal cardiac arrest reported rarely. In a pooled safety population, heart failure resolved in the majority of patients.

Unknown whether patients with recent (i.e., within 12 months) history of cardiovascular disease (e.g., MI, severe or unstable angina, coronary or peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or TIA, pulmonary embolism) or prior anthracycline use or cardiac radiation may be at a higher risk of developing drug-related left ventricular dysfunction since such patients were excluded from clinical studies.

Consider monitoring LVEF prior to initiating therapy and periodically as clinically indicated. Monitor patients for signs and symptoms of congestive heart failure; if manifestations of congestive heart failure develop, discontinue sunitinib. In patients without clinical evidence of congestive heart failure but in whom LVEF is >20% but <50% below baseline or below the lower limit of normal if LVEF was not assessed at baseline, interrupt therapy and/or reduce the dosage.

Prolongation of QT Interval and Torsades de Pointes

Dose-dependent prolongation of the QT interval reported; may result in increased risk of ventricular arrhythmias, including torsades de pointes. Torsades de pointes reported rarely.

Monitor patients at high risk of developing QT interval prolongation, including patients receiving antiarrhythmic agents or potent CYP3A4 inhibitors, and patients with relevant preexisting cardiac disease, bradycardia, or electrolyte disturbances.

Consider more frequent QT interval monitoring and reduction of sunitinib dosage in patients receiving concomitant potent CYP3A4 inhibitors or drugs known to prolong the QT interval.

Hypertension

Hypertension reported.

Monitor blood pressure at baseline and as clinically indicated; treat hypertension as needed with standard antihypertensive therapy. If grade 3 hypertension occurs, interrupt sunitinib until hypertension resolves or improves to grade 1 or less; may then resume therapy at a lower dosage. If grade 4 hypertension occurs, discontinue sunitinib therapy.

Hemorrhage

Hemorrhagic events (including epistaxis and GI, respiratory, tumor, urinary tract, and brain hemorrhage), sometimes fatal, reported. Most events were grade 1–2; grade 3 or higher events also reported. The most common hemorrhagic event was epistaxis, and the most common grade 3 or higher event was GI hemorrhage.

Tumor-related hemorrhage reported. May occur suddenly and, in the case of pulmonary tumors, may present as severe and life-threatening hemoptysis or pulmonary hemorrhage. Pulmonary hemorrhage, sometimes fatal, reported in patients receiving sunitinib for GIST, advanced renal cell carcinoma, or metastatic lung cancer^{† [off-label]}.

Serious, sometimes fatal GI complications, including GI perforation, reported rarely in patients with intra-abdominal malignancies.

Clinically monitor for hemorrhagic events (i.e., serial CBCs, physical examinations). If grade 3 or 4 hemorrhagic events occur, withhold sunitinib therapy; when the hemorrhagic event resolves or improves to grade 0 or 1, may then resume therapy at a reduced dosage or discontinue therapy depending on the severity and persistence of the hemorrhagic event.

Tumor Lysis Syndrome

Tumor lysis syndrome, sometimes fatal, reported primarily in patients with GIST or advanced renal cell carcinoma. Increased risk in patients with a large tumor burden; closely monitor such patients and treat as clinically indicated.

Thrombotic Microangiopathy

Thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome reported; sometimes results in renal failure or death. These events occurred in clinical trials and postmarketing experience when sunitinib was administered alone or in combination with bevacizumab.

If thrombotic microangiopathy occurs, discontinue sunitinib therapy. Reversal of the effects of thrombotic microangiopathy have been observed following discontinuance of sunitinib therapy.

Proteinuria

Proteinuria and nephrotic syndrome, sometimes resulting in renal failure or death, reported.

Monitor for development or worsening of proteinuria. Perform urinalysis prior to initiation of sunitinib and periodically during therapy; further assess with a 24-hour urine collection as clinically indicated. Interrupt sunitinib therapy and reduce dosage if proteinuria ≥3 g per 24 hours (in the absence of nephrotic syndrome) occurs. If nephrotic syndrome occurs or if proteinuria recurs despite dosage reduction, permanently discontinue therapy.

Safety of continued sunitinib therapy in patients with moderate to severe proteinuria not systematically evaluated.

Dermatologic Effects

Severe and sometimes fatal cutaneous reactions, including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, reported. Cases of necrotizing fasciitis, including fatalities, also reported.

Permanently discontinue sunitinib if erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, or necrotizing fasciitis occur.

If necrotizing fasciitis occurs, discontinue sunitinib therapy.

Reversible Posterior Leukoencephalopathy Syndrome

Reversible posterior leukoencephalopathy syndrome (RPLS), sometimes fatal, has been reported in less than 1% of patients receiving sunitinib. If manifestations of RPLS (e.g., hypertension, headache, decreased alertness, altered mental functioning, visual loss, cortical blindness) occur, discontinue sunitinib therapy. Use magnetic resonance imaging (MRI) to confirm diagnosis of RPLS.

Thyroid Dysfunction

Hyperthyroidism, sometimes followed by hypothyroidism, reported.

Obtain thyroid function tests at baseline and periodically during treatment, and treat hypothyroidism or hyperthyroidism before initiating sunitinib therapy.

During sunitinib therapy, observe all patients closely for manifestations of thyroid dysfunction, including hypothyroidism, hyperthyroidism, and thyroiditis; if signs and/or symptoms of thyroid dysfunction develop, obtain thyroid function tests and provide treatment per standard medical practice.

Hypoglycemia

Symptomatic hypoglycemia, including cases associated with loss of consciousness or hospitalization, reported. Some patients did not have preexisting abnormalities in glucose homeostasis at baseline. Reductions in blood glucose levels may be worse in patients with diabetes.

In patients with diabetes, assess if antidiabetic therapies need to be adjusted to minimize the risk of hypoglycemia.

Monitor blood glucose at baseline, regularly during therapy, as clinically indicated, and after discontinuance of sunitinib therapy.

Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) reported. Risk of ONJ is increased in patients with dental disease or in those receiving concomitant bisphosphonate therapy.

Prior to initiating sunitinib and periodically during therapy, routine oral examinations and appropriate preventive dentistry should be performed. If possible, withhold sunitinib at least 3 weeks before scheduled dental surgery or invasive dental treatments. If ONJ occurs, sunitinib therapy may be resumed at a reduced dosage or discontinued depending on the severity and persistence of the adverse effect; however, safety of resuming sunitinib therapy in patients who develop ONJ has not been established.

Wound-healing Complications

Impaired wound healing reported.

Withhold sunitinib at least 3 weeks before elective surgery and for at least 2 weeks after major surgery and until adequate wound healing occurs. If impaired wound healing occurs, resume sunitinib therapy at a reduced dosage or discontinue depending on severity and persistence of the adverse effect. Safety of resuming sunitinib therapy in patients who experience impaired wound healing has not been established.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm based on its mechanism of action and animal findings. Teratogenicity, embryotoxicity, and fetotoxicity have been demonstrated in animals.

Avoid pregnancy during therapy. Advise females of reproductive potential to use effective methods of contraception during sunitinib therapy and for 4 weeks after the last dose. Males who are partners with females of reproductive potential should use effective contraception during treatment and for at least 7 weeks after the last dose. If sunitinib is used during pregnancy or if the patient becomes pregnant while receiving the drug, apprise patient of potential fetal hazard.

Specific Populations

Pregnancy

May cause fetal harm.

If sunitinib is used during pregnancy or if the patient becomes pregnant while receiving the drug, apprise patient of potential fetal hazard.

Lactation

Distributed into milk in rats; drug concentration up to 12-fold higher in milk than in plasma. Not known whether sunitinib or its primary active metabolite is distributed into human milk. Discontinue nursing or the drug because of potential risk in nursing infants. Females should not breast-feed for at least 4 weeks after discontinuing sunitinib therapy.

Females and Males of Reproductive Potential

Verify pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective methods of contraception during sunitinib therapy and for 4 weeks after the last dose. Males who are partners with females of reproductive potential should use effective contraception during treatment and for at least 7 weeks after the last dose.

May impair male and female fertility based on animal studies.

Pediatric Use

Safety and efficacy not established.

Maximum tolerated dose, apparent clearance, and volume of distribution adjusted for body surface area for sunitinib and its major active metabolite are lower in pediatric patients compared to adults. In an open-label study evaluating sunitinib in pediatric patients 2 years to <17 years of age with refractory solid tumors, sunitinib was poorly tolerated and the study was amended to exclude patients with previous exposure to anthracyclines or cardiac radiation due to the occurrence of dose-limiting cardiotoxicity. Effect of sunitinib on open tibial growth plates in pediatric patients has not been established.

Geriatric Use

Among 7527 patients receiving sunitinib for GIST, renal cell carcinoma, or NET of pancreatic origin in clinical studies, incidence of grade 3 or 4 adverse effects was higher in patients ≥65 years of age compared to younger adults.

In the clinical studies evaluating sunitinib in patients with GIST or metastatic renal cell carcinoma, no overall differences in safety and efficacy observed relative to younger adults.

Insufficient data in patients with NET of pancreatic origin to determine if patients ≥65 years of age respond differently relative to younger patients.

Hepatic Impairment

Systemic exposure not affected by mild or moderate (Child-Pugh class A or B) hepatic impairment. Safety and efficacy not established in patients with severe (Child-Pugh class C) hepatic impairment.

Clinical studies excluded patients with AST or ALT concentrations >2.5 times the ULN or, if due to liver metastases, >5 times the ULN.

Renal Impairment

Systemic exposure not affected by severe (Cl_Cr <30 mL/minute) renal impairment.

Systemic exposure was decreased in patients with end-stage renal disease undergoing hemodialysis.

Common Adverse Effects

Adverse effects occurring in ≥25% of patients: Fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia.

Drug Interactions

Sunitinib and its primary active metabolite are metabolized principally by CYP3A4.

Sunitinib does not inhibit or induce major CYP isoenzymes.

Drugs and Foods Affecting Hepatic Microsomal Enzymes

Potent inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased combined plasma concentrations of sunitinib and its primary active metabolite).

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased combined plasma concentrations of sunitinib and its primary active metabolite).

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11: Pharmacokinetic interaction unlikely.

Specific Drugs and Foods

SUNItinib Pharmacokinetics

Absorption

Bioavailability

Following oral administration, peak plasma concentrations are attained within 6–12 hours.

Food

Food has no effect on bioavailability of sunitinib.

Special Populations

In individuals with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, systemic exposure after a single dose was similar to that observed in individuals with normal hepatic function.

In individuals with severe renal impairment (Cl_Cr <30 mL/minute), systemic exposure after a single dose was similar to that observed in individuals with normal renal function.

In individuals with end-stage renal disease undergoing hemodialysis, systemic exposure was decreased by 47% compared to those with normal renal function.

Pharmacokinetics assessed in 2 open-label studies in 56 pediatric patients 2 years to <17 years of age with refractory solid tumors, high-grade glioma, or ependymoma. Maximum tolerated dose, apparent clearance, and volume of distribution adjusted for body surface area for sunitinib and its major active metabolite were lower in pediatric patients compared to adults.

Pharmacokinetics of sunitinib and its primary active metabolite are not substantially affected by age (18–84 years of age), body weight (34–168 kg), race (white, Black, or Asian), sex, or ECOG performance status.

Distribution

Extent

Sunitinib and metabolites are distributed into milk in animals; not known whether the drug or its primary active metabolite is distributed into human milk.

Plasma Protein Binding

Approximately 95% (for sunitinib) and 90% (for primary active metabolite).

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A4 to several metabolites.

Primary active metabolite appears to be equipotent to sunitinib; this metabolite accounts for approximately 23–37% of total plasma concentrations of the drug and also is metabolized by CYP3A4.

Elimination Route

Excreted in feces (61%) and urine (16%), mainly as sunitinib and primary active metabolite. Minor metabolites recovered in feces and urine but generally not found in plasma.

Half-life

Approximately 40–60 hours (for sunitinib) or 80–110 hours (for primary active metabolite).

Special Populations

Results of one pharmacokinetic study indicated a slightly longer sunitinib half-life in individuals with mild (Child-Pugh score of 5–6) or moderate (Child-Pugh score of 7–9) hepatic impairment; however, clearance of sunitinib not significantly different from that in individuals with normal hepatic function.

Stability

Storage

Oral

Capsules

20–25°C (excursions permitted between 15–30°C).

Actions

• Inhibits multiple receptor tyrosine kinases (RTKs), which are involved in the initiation of various cascades of intracellular signaling events that lead to cell proliferation and/or influence processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis), based on the respective kinase.

• May inhibit signal transduction pathways involving multiple receptor (i.e., cell surface) tyrosine kinases, including platelet-derived growth factor receptors (i.e., PDGFR-α, PDGFR-β), vascular endothelial growth factor receptors (i.e., VEGFR-1, VEGFR-2, VEGFR-3), stem cell factor receptor (i.e., c-Kit), fms-like tyrosine kinase 3 (Flt-3), colony stimulating factor receptor type 1 (CSF-1R), and the glial cell line-derived neurotrophic factor receptor (RET).

• Shown to inhibit growth of tumor cells expressing dysregulated target RTKs (i.e., PDGFR, RET, c-Kit) in vitro; also shown to inhibit PDGFR-β- and VEGFR-2-dependent tumor angiogenesis in vivo.

Advice to Patients

• Importance of reading the manufacturer’s patient information prior to beginning sunitinib therapy and rereading it each time the prescription is refilled.

• If a dose is missed by less than 12 hours, importance of administering the missed dose right away. If a dose is missed by more than 12 hours, the dose should be skipped and the next dose should be taken at the regularly scheduled time.

• Risk of hepatotoxicity. Importance of contacting clinician promptly if manifestations of hepatotoxicity (e.g., abdominal pain [particularly in the right upper quadrant], dark urine, generalized pruritus, jaundice) occur.

• Risk of cardiovascular events. Importance of promptly informing clinician if symptoms of heart failure develop.

• Risk of QT prolongation and torsades de pointes.

• Risk of hypertension and importance of monitoring blood pressure regularly. Importance of informing clinician if signs or symptoms of hypertension occur.

• Risk of adverse GI effects (e.g., diarrhea, nausea, vomiting, dyspepsia, and constipation). Advise patients to seek medical attention if they experience persistent or severe abdominal pain because there is a risk of GI perforation.

• Risk of adverse dermatologic effects (e.g., skin discoloration due to the drug color [yellow]; hair or skin depigmentation; skin dryness, thickness, or cracking; blisters or rash on the hands and soles of the feet), including severe cutaneous reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and necrotizing fasciitis). Importance of informing clinician immediately if severe dermatologic reactions occur.

• Increased risk of bleeding. Importance of promptly informing clinician of any manifestations or episodes of bleeding (e.g., abdominal pain or swelling; hematemesis; black, sticky stools; hematuria; headache; change in mental status).

• Risk of reversible posterior leukoencephalopathy syndrome. Importance of informing clinician if signs or symptoms of reversible posterior leukoencephalopathy syndrome occur.

• Risk of osteonecrosis of the jaw. Importance of advising patient that their clinician should examine their mouth before sunitinib therapy. Importance of informing dentist about sunitinib treatment prior to dental procedures. Importance of informing clinician of any signs or symptoms of osteonecrosis of the jaw.

• Risk of thyroid dysfunction. Importance of informing clinician if symptoms of abnormal thyroid function (e.g., persistent or worsening fatigue, hair loss, weight gain or loss, irregular menstrual cycles, feeling hot or cold) occur.

• Risk of hypoglycemia. Importance of informing clinician if signs or symptoms of hypoglycemia occur.

• Risk of impaired wound healing. Advise patients that sunitinib may impair wound healing. Importance of informing clinician of any planned surgical procedures.

• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of advising females not to breast-feed during and for at least 4 weeks after discontinuance of therapy.

• Risk of impaired fertility in females and males.

• Risk of fetal harm. Necessity of advising females to avoid pregnancy while receiving therapy. Necessity of advising females of reproductive potential to use effective contraception during sunitinib therapy and for at least 4 weeks after the last dose of the drug. Necessity of advising males who are partners of such females that they should use effective contraception during sunitinib therapy and for at least 7 weeks after the last dose of the drug.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John’s wort), as well as any concomitant illnesses.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Sunitinib can only be obtained through designated specialty pharmacies. Contact the manufacturer or consult the Pfizer website for specific availability information.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Reload page with references included

Frequently asked questions

• Does Sutent shrink tumors?
• Is Sutent considered a chemotherapy drug?

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