sunitinib (Rx)

Brand and Other Names:Sutent
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 12.5mg
  • 25mg
  • 50mg

Gastrointestinal Stromal Tumor

Indicated for treatment of gastrointestinal stromal tumor (GIST) after disease progression on or intolerance to imatinib mesylate

50 mg PO qDay for 4 weeks, THEN 2 weeks drug-free, repeat cycle

Continue until disease progression or unacceptable toxicity

Renal Cell Carcinoma

Indicated for treatment of advanced renal cell carcinoma (RCC)

50 mg PO qDay for 4 weeks, THEN 2 weeks drug-free, repeat cycle

Continue until disease progression or unacceptable toxicity

Adjuvant treatment of RCC

  • Indicated for the adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy
  • 50 mg PO qDay for 4 weeks, THEN 2 weeks drug-free, repeat cycle for a total of nine 6-week cycles

Pancreatic Neuroendocrine Tumors

Indicated for progressive, well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable locally advanced or metastatic disease

37.5 mg PO qDay continuously without a scheduled off-treatment period

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage modifications for adverse reactions

  • Dose interruption and/or dose modification in 12.5-mg increments or decrements is recommended based on individual safety and tolerability
  • Maximum dose administered in the pNET study was 50 mg daily
  • In the adjuvant RCC study, the minimum dose administered was 37.5 mg

Coadministration with CYP3A4 inhibitors or inducers

  • Strong CYP3A4 inhibitors
    • Use an alternative with no or minimal enzyme inhibition potential is recommended
    • If coadministration is unavoidable, consider reducing sunitinib dose to a minimum of 37.5 mg (GIST and RCC) or 25 mg (pNET) PO qDay
  • Strong CYP3A4 inducers
    • Use an alternative with no or minimal enzyme inhibition potential is recommended
    • Consider increasing sunitinib dose to a maximum of 87.5 mg (GIST and RCC) or 62.5 mg (pNET) daily if coadministered with a CYP3A4 inducer cannot be avoided
    • If dose is increased, monitor carefully for toxicity

Renal impairment

  • No dose adjustment necessary with any degree of renal impairment in patients not on dialysis
  • ESRD on hemodialysis: No adjustment to the starting dose is required; however, compared to patients with normal renal function, the sunitinib exposure is 47% lower in patients with ESRD on hemodialysis; may require gradual dose increase (up to 2-fold) based on safety and tolerability

Hepatic impairment

  • Mild to moderate (Child-Pugh Class A or B): Dose adjustment not necessary for initial dose; monitor subsequent doses
  • Severe (Child-Pugh Class C): Not studied

Dosing Considerations

Monitor CBC count, blood chemistries

Safety and efficacy not established

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Interactions

Interaction Checker

and sunitinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Dyspepsia (MRCC 46%)

            Altered taste (MRCC 43%; GIST 21%)

            Fatigue (GIST 42%; MRCC 74%)

            Diarrhea (GIST 40%; MRCC 55%)

            Rash (MRCC 38%; GIST 14%)

            Vomiting (MRCC 37%; GIST 24%)

            Constipation (MRCC 34%; GIST 20%)

            Skin discoloration (MRCC 33%; GIST 30%)

            Abdominal pain (GIST 33%; MRCC 20%)

            Nausea (GIST 31%; MRCC 54%)

            Anorexia (MRCC 31%; GIST 33%)

            Mucositis/stomatitis (GIST 29%; MRCC 53%)

            Dyspnea (MRCC 28%; GIST 10%)

            HTN (MRCC 28%; GIST 15%)

            Arthralgia (MRCC 28%; GIST 12%)

            Bleeding (MRCC 26%; GIST 18%)

            Headache (MRCC 25%; GIST 13%)

            Asthenia (GIST 22%)

            Lymphopenia (MRCC 21%)

            Fever (GIST 18%; MRCC 15%),

            Limb pain (MRCC 18%)

            Back pain (MRCC 17%; GIST 11%)

            Myalgia (MRCC 17%; GIST 14%)

            Cough (MRCC 17%; GIST 8%)

            Dry skin (17%)

            Hair color changes (17%)

            Neutropenia (MRCC 13%; GIST 11%)

            Alopecia (MRCC 12%)

            Hand-foot syndrome (MRCC 12%; GIST 14%)

            Dehydration (MRCC 11%)

            1-10%

            Venous thrombotic events

            Hemorrhoids

            Pancreatitis

            Flu-like syndrome

            <1%

            Hepatotoxicity

            Acute renal failure

            Adrenal dysfunction

            Postmarketing Reports

            Blood and lymphatic system disorders: Thrombotic microangiopathy; hemorrhage associated with thrombocytopenia (hold dose, following resolution, treatment may be resumed at the discretion of the treating physician)

            Immune system disorders: Hypersensitivity reactions, including angioedema Infections and infestations: Serious infection (with or without neutropenia); necrotizing fasciitis, including of the perineum; most commonly observed infections include respiratory, urinary tract, skin infections, and sepsis

            Metabolism and nutrition disorders: Tumor lysis syndrome

            Musculoskeletal and connective tissue disorders: Fistula formation, sometimes associated with tumor necrosis and/or regression; osteonecrosis of the jaw, and myopathy and/or rhabdomyolysis with or without acute renal failure

            Renal and urinary disorders: Renal impairment and/or failure; proteinuria; rare cases of nephrotic syndrome (discontinue treatment)

            Respiratory disorders: Pulmonary embolism; pulmonary hemorrhage, pleural effusion

            Skin and subcutaneous tissue disorders: Pyoderma gangrenosum, including positive dechallenges

            Vascular disorders: Arterial thromboembolic events, most frequent events included CVA, TIA, cerebral infarction, arterial (including aortic) aneurysms, dissections, and rupture

            Reversible posterior leukoencephalopathy syndrome

            Impaired wound healing

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            Warnings

            Black Box Warnings

            Hepatotoxicity

            • Hepatotoxicity may be severe, and in some cases fatal
            • Monitor liver function tests (ALT, AST, bilirubin) before treatment initiation, during each treatment cycle, and as clinically indicated
            • Interrupted for Grade 3 or 4 drug-related hepatic related adverse events and discontinued if there is no resolution
            • Do not restart if subsequently experience severe changes in liver function tests or other signs and symptoms of liver failure emerge
            • Safety in patients with ALT or AST >2.5x ULN or, if due to liver metastases, >5x ULN has not been established

            Contraindications

            None

            Cautions

            Fatal liver failure has been observed (see Black Box Warnings)

            Hemorrhagic events including tumor-related hemorrhage reported; perform serial complete blood counts and physical examinations

            Adrenal hemorrhage observed in animal studies; monitor adrenal function in case of stress such as surgery, trauma or severe infection

            Monitor urine protein; interrupt treatment for 24-hr urine protein ≥3 g; discontinue for repeat episodes of protein ≥3 g despite dose reductions or nephrotic syndrome

            Hyperthyroidism, some followed by hypothyroidism, have been reported; monitor thyroid function at baseline, periodically during treatment and as clinically indicated; initiate and/or adjust therapies for thyroid dysfunction as appropriate

            Impaired wound healing reported; withhold therapy for at least 3 weeks prior to elective surgery; do not administer for at least 2 weeks following major surgery and until adequate wound healing; safety of resumption of therapy after resolution of wound healing complications has not been established

            Severe cutaneous reactions have been reported, including cases of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, some of which were fatal; necrotizing fasciitis, including fatal cases, also reported

            Advise women of childbearing potential of potential hazard to fetus

            Prolonged QT intervals and Torsade de Pointes may occur in a dose-dependent manner; use caution in patients at higher risk for developing QT interval prolongation; consider monitoring with on-treatment ECG and electrolytes

            Cases of tumor lysis syndrome (TLS) reported in patients with RCC and GIST with high tumor burden; monitor closely and treat as necessary

            Thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, sometimes leading to renal failure or fatal outcome reported in clinical trials and postmarketing experience; not approved for use in combination with bevacizumab

            Hypoglycemia may occur; monitor blood glucose levels regularly during and after discontinuation treatment; assess if antidiabetic drugs dosage modifications are necessary

            Monitor for hypertension and treat as needed with standard antihypertensive therapy; in cases of severe hypertension, temporary suspend treatment until hypertension is controlled

            Osteonecrosis

            • Osteonecrosis of the jaw reported; concomitant exposure to other risk factors, such as bisphosphonates or dental disease/invasive dental procedures, may increase risk of ONJ
            • Perform oral examination prior to initiation of therapy and periodically during therapy; advise patients regarding good oral hygiene practices
            • Withhold treatment for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures, if possible; withhold treatment for development of ONJ until complete resolution

            Reversible posterior leukoencephalopathy syndrome (RPLS)

            • RPLS some of which were fatal reported
            • Patients can present with hypertension, headache, decreased alertness, altered mental functioning, and visual loss, including cortical blindness
            • Magnetic resonance imaging is necessary to confirm diagnosis; withhold therapy until resolution;
            • Safety of reinitiating therapy in patients with RPLS unknown

            Cardiovascular risks

            • Cardiovascular events (eg, heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction), some of which were fatal, have been reported
            • Increased risk for heart failure and high grade heart failure; discontinue treatment if patient presents with signs or symptoms of congestive heart failure (CHF); interrupt and/or reduce dose in patients without clinical evidence of CHF who either have an ejection fraction (EF) of >20% but <50% below baseline or below the lower limit of normal if baseline EF is not obtained
            • Cardiac dysfunction occurs 28 to 180 days after sunitinib initiation and most commonly after the third cycle
            • Heart failure risk is associated with preexisting hypertension and coronary artery disease
            • Monitor for signs and symptoms of congestive heart failure

            Drug interaction overview

            • Coadministration with strong CYP3A4 inhibitors
              • Use an alternative with no or minimal CYP3A4 activity
              • Strong CYP3A4 inhibitors may increase sunitinib concentrations
            • Coadministration with strong CYP3A4 inducers
              • Use an alternative with no or minimal CYP3A4 activity
              • Coadministration with CYP3A4 inducers may decrease sunitinib concentrations
            • Coadministration with QT-prolonging drugs
              • Treatment is associated with QTc interval prolongation; monitor QT interval with ECGs more frequently in patients who require treatment with concomitant medications known to prolong the QT interval
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            Pregnancy & Lactation

            Pregnancy

            Based on animal reproduction studies and its mechanism of action, fetal harm may occur when administered to pregnant females

            No data available in pregnant women to inform a drug-associated risk

            Verify pregnancy status of females of reproductive potential before initiating treatment

            Animal data

            • Oral administration of sunitinib to pregnant rats and rabbits throughout organogenesis resulted in teratogenicity (embryolethality, craniofacial and skeletal malformations) at 5.5 and 0.3 times the combined AUC (the combined systemic exposure of sunitinib plus its active metabolite) in patients administered the recommended daily doses of 50 mg, respectively
            • Advise females of reproductive potential of the potential risk to a fetus

            Contraception

            • Females of reproductive potential: Use effective contraceptive during treatment and for at least 4 weeks after final dose
            • Males with female partners of reproductive potential: Use effective contraceptive during treatment and for 7 weeks after final dose

            Infertility

            • Based on findings in animals, male and female fertility may be impaired

            Lactation

            There is no information regarding the presence of sunitinib and its metabolites in human milk

            Sunitinib and its metabolites were excreted in rat milk at concentrations up to 12-fold higher than in plasma

            Advise females not to breastfeed during treatment and for at least 4 weeks after final dose

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Multikinase inhibitor (including VEGF and PDGF receptor tyrosine kinases) some of which are implicated in tumor growth, angiogenesis, and metastasis

            Absorption

            Steady-state concentrations of sunitinib and its primary active metabolite are achieved within 10-14

            Peak plasma time: 6-12 hr

            Distribution

            Vd: 2,230 L

            Protein bound

            • Sunitinib: 95%
            • Active metabolite: 90%

            Metabolism

            Primarily metabolized by CYP3A4 to its primary active metabolite, which is further metabolized by CYP3A4

            Elimination

            Clearance: 34-62 L/hr

            Half-life

            • Single-oral dose: ~40-60 hr
            • Active metabolite: 80-110 hr

            Excretion

            • Feces: ~ 61%
            • Urine: ~16%
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            Administration

            Oral administration

            Take with or without food

            Do not drink grapefruit juice or eat grapefruit during your treatment

            Missed dose

            • Missed dose <12 hr: Take the missed dose right away
            • Missed dose >12 hr: Take next dose at regular time
            • Do not make up missed dose

            Storage

            Tablets: Store at room temperature at 68-77°F (20-25°C)

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            Formulary

            FormularyPatient Discounts

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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.