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  • CLASSES

    Small Molecule Antineoplastic Multikinase Inhibitors

    BOXED WARNING

    Hepatic disease, hepatotoxicity

    Use sunitinib with caution in patients with pre-existing hepatic disease; the safety of sunitinib in patients with ALT or AST greater than 2.5 times the upper limit of normal (ULN), or greater than 5 times ULN if due to liver metastases, has not been established. Hepatotoxicity has occurred with sunitinib use in clinical trials which may result in liver failure or death. Monitor liver function tests (ALT, AST, bilirubin) at baseline, during each treatment cycle, and as clinically indicated. An interruption of therapy and dose reduction is necessary for grade 3 hepatotoxicity. Discontinue sunitinib for grade 3 hepatotoxicity that does not resolve, recurrent grade 3 hepatotoxicity, grade 4 hepatotoxicity, and in patients who subsequently experience severe changes in liver function tests or other signs and symptoms of liver failure.[31970]

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, multi-targeted tyrosine kinase inhibitor with anti-angiogenic and anti-tumor activities
    Used for gastrointestinal stromal tumor (GIST), renal cell carcinoma, and pancreatic neuroendocrine tumors (pNET)
    Black-box warning for hepatotoxicity; monitor hepatic function and adjust therapy accordingly

    COMMON BRAND NAMES

    Sutent

    HOW SUPPLIED

    Sunitinib/Sunitinib Malate/Sutent Oral Cap: 12.5mg, 25mg, 37.5mg, 50mg

    DOSAGE & INDICATIONS

    For the treatment of renal cell cancer (RCC).
    For the adjuvant treatment of renal cell cancer (RCC) in patients at high risk of recurrence following nephrectomy.
    Oral dosage
    Adults

    50 mg PO once daily for 4 weeks on-treatment, followed by 2 weeks off-treatment, for a total of nine 6-week cycles. Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, double-blind clinical trial in patients with a high risk of recurrent RCC following nephrectomy, adjuvant treatment with sunitinib significantly improved median disease-free survival (DFS) compared with placebo (6.8 months vs. 5.6 months); in this trial, patients were required to have clear cell histology. At the time of the DFS analysis, overall survival data were not yet mature.

    For the treatment of advanced renal cell cancer (RCC).
    Oral dosage
    Adults

    50 mg PO once daily for 4 weeks on-treatment, followed by 2 weeks off-treatment until disease progression or unacceptable toxicity. Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized clinical trial of patients with metastatic RCC, treatment with sunitinib significantly improved the median progression-free survival (PFS) compared with interferon alpha (47.3 months vs. 22 months); the objective response rate (ORR) was also significantly improved (27.5% vs. 5.3%). In 2 multicenter, single-arm clinical trials of patients with metastatic, cytokine-refractory RCC, treatment with sunitinib had an ORR of 34% to 36.5%, with a median duration of response not reached to 54 weeks.

    For the treatment of gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib.
    Oral dosage
    Adults

    50 mg PO once daily for 4 weeks on-treatment, followed by 2 weeks off-treatment, until disease progression or unacceptable toxicity. Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. A randomized double-blind placebo controlled trial compared the time-to-tumor progression (TTP) in GIST patients with disease progression during imatinib therapy or who were intolerant to imatinib with best supportive care. At a planned interim analysis, there was a statistically significant advantage for sunitinib over placebo in the primary endpoint of median TTP (27.3 weeks vs. 6.4 weeks), as well as the secondary endpoint of progression-free survival (24.1 weeks vs. 6 weeks); overall survival data were not mature.

    For the treatment of unresectable, locally advanced or metastatic, progressive, well-differentiated pancreatic malignant neuroendocrine tumor (NET).
    Oral dosage
    Adults

    37.5 mg PO once daily until disease progression or unacceptable toxicity. Dose interruption and/or dose modification in 12.5 mg increments or decrements is recommended based on individual safety and tolerability. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. At a prespecified interim analysis, the Independent Data Monitoring Committee recommended premature termination of a multicenter, randomized, double-blind clinical trial of patients with unresectable pNET, after treatment with sunitinib significantly improved progression-free survival (PFS) compared with placebo (10.2 months vs. 5.4 months); the objective response rate was 9.3% vs. 0%, respectively. The use of somatostatin analogs was allowed in the study.[31970]

    MAXIMUM DOSAGE

    Adults

    87.5 mg/day PO for gastrointestinal stromal tumors and renal cell cancer; 62.5 mg/day PO for pancreatic neuroendocrine tumor.

    Geriatric

    87.5 mg/day PO for gastrointestinal stromal tumors and renal cell cancer; 62.5 mg/day PO for pancreatic neuroendocrine tumor.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Baseline Hepatic Impairment
    Mild to moderate hepatic impairment (Child-Pugh class A or B): No dose adjustment is required.
    Severe hepatic impairment (Child-Pugh class C): Sunitinib has not been studied in these patients.[31970]
     
    Treatment-Related Hepatotoxicity
    Grade 3: Upon resolution to grade 1 or less or baseline, resume sunitinib at a reduced dose. Discontinue adjuvant sunitinib for patients with RCC and grade 3 hepatotoxicity at a reduced dose of 37.5 mg once daily. Discontinue sunitinib for patients with advanced RCC, GIST, or pNET and grade 3 hepatotoxicity at a reduced dose of 25 mg once daily. Permanently discontinue sunitinib for recurrent grade 3 hepatotoxicity despite dose reductions.
    Grade 4: Permanently discontinue sunitinib.[31970]

    Renal Impairment

    Mild, moderate, or severe renal impairment (CrCl 80 mL/min or less), not on hemodialysis: No dose adjustment is recommended.
    End-stage renal disease (ESRD) on hemodialysis: No starting dose adjustment is recommended. However, given the decreased exposure compared to patients with normal renal function, subsequent doses may be increased gradually up to 2-fold based on safety and tolerability.

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 1
    NIOSH (Draft) 2020 List: Table 2
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
    Emetic Risk
    Minimal/Low
    Administer prn antiemetics as necessary.

    Oral Administration

    Administer orally with or without food.

    STORAGE

    Sutent:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease, hepatotoxicity

    Use sunitinib with caution in patients with pre-existing hepatic disease; the safety of sunitinib in patients with ALT or AST greater than 2.5 times the upper limit of normal (ULN), or greater than 5 times ULN if due to liver metastases, has not been established. Hepatotoxicity has occurred with sunitinib use in clinical trials which may result in liver failure or death. Monitor liver function tests (ALT, AST, bilirubin) at baseline, during each treatment cycle, and as clinically indicated. An interruption of therapy and dose reduction is necessary for grade 3 hepatotoxicity. Discontinue sunitinib for grade 3 hepatotoxicity that does not resolve, recurrent grade 3 hepatotoxicity, grade 4 hepatotoxicity, and in patients who subsequently experience severe changes in liver function tests or other signs and symptoms of liver failure.[31970]

    Diabetes mellitus, hypoglycemia

    Use sunitinib with caution in patients with diabetes mellitus or who are at risk for hypoglycemia. Sunitinib has been associated with symptomatic hypoglycemia which may result in loss of consciousness or hospitalization; reductions in blood glucose may be worse in patients with diabetes. Monitor blood glucose levels at baseline, regularly during treatment, as clinically indicated, and after discontinuation of sunitinib. Adjustments in medications for diabetes may be necessary to minimize the risk of hypoglycemia. In clinical trials, pre-existing abnormalities in blood glucose were not present in all patients who experienced hypoglycemia.

    Impaired wound healing, surgery

    Impaired wound healing has occurred in patients treated with sunitinib. Discontinue sunitinib at least 3 weeks prior to elective surgery; do not administer sunitinib for at least 2 weeks following major surgery and until adequate wound healing. The safety of resuming sunitinib after resolution of wound healing complications has not been established.

    Angina, cardiac disease, cardiomyopathy, coronary artery bypass graft surgery (CABG), heart failure, myocardial infarction, radiation therapy

    Use sunitinib with caution in patients with a history of cardiac disease, as cardiovascular events including heart failure, cardiomyopathy, myocardial ischemia, and myocardial infarction, some of which were fatal, have been reported. Baseline and periodic evaluations of left ventricular ejection fraction (LVEF) should be considered for all patients during sunitinib treatment. Discontinue sunitinib in the presence of clinical manifestations of CHF. An interruption of therapy or dose reduction may be necessary for patients with a reduced ejection fraction in the absence of clinical evidence of CHF. Also, cardiac disease, heart failure, cardiomyopathy, and myocardial infarction may increase the risk of developing a prolonged QT interval when using sunitinib. Patients who had cardiac events (e.g., myocardial infarction, severe/unstable angina, peripheral or coronary artery bypass graft surgery (CABG), symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism) within the previous 12 months were excluded from sunitinib clinical trials; patients with prior anthracycline use or cardiac radiation therapy were also excluded from some studies. It is unknown whether patients with these conditions may be at higher risk of developing sunitinib-related left-ventricular dysfunction. [28457] [31970] [56592]

    Apheresis, AV block, bradycardia, celiac disease, females, fever, geriatric, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, long QT syndrome, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias including torsade de pointes (TdP). Consider periodic ECG monitoring for QT prolongation and monitoring electrolytes (i.e., magnesium, potassium); monitor the QT interval more frequently when concomitantly administered with strong CYP3A4 inhibitors or other drugs known to prolong the QT interval. Use sunitinib with caution in patients with a history of QT prolongation or those with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, cardiac disease, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, decreased thyroid function, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. [28457] [56592]  

    Hypertension

    Use sunitinib with caution in patients with pre-existing hypertension, as it has been reported in patients treated with sunitinib therapy. Monitor blood pressure at baseline and as clinically indicated during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for grade 3 or higher hypertension.

    Bleeding

    Severe bleeding events have been reported in patients treated with sunitinib, some of which resulted in fatalities. Tumor-related hemorrhage has also occurred and may be sudden in onset. Monitor patients for bleeding events; clinical assessment should include serial complete blood counts (CBCs) and physical examinations. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for grade 3 or 4 hemorrhagic events.

    Dental disease, dental work

    Dental disease, invasive dental work, and bisphosphonate use may increase the risk of osteonecrosis of the jaw (ONJ) in patients receiving sunitinib. Patients should receive a dental examination prior to starting sunitinib therapy and periodically during treatment; advise patients regarding good oral hygiene practices. If possible, hold sunitinib treatment for at least 3 weeks prior to scheduled dental surgery or invasive dental procedures. If ONJ occurs, hold sunitinib treatment until complete resolution. The safety of resuming sunitinib therapy after resolution of ONJ has not been established.

    Hyperthyroidism, hypothyroidism

    Use sunitinib with caution in patients with pre-existing hyperthyroidism or hypothyroidism; these patients should be treated per standard medical practice prior to initiation of sunitinib therapy. Cases of hyperthyroidism, some followed by hypothyroidism, have been reported in clinical trials with sunitinib treatment and through postmarketing experience. Monitor thyroid function at baseline, periodically during treatment, and as clinically indicated as well as for signs and symptoms of thyroid dysfunction. Initiate and/or adjust therapies for thyroid dysfunction as appropriate. Of note, hypothyroidism may increase the risk of developing a prolonged QT interval when using sunitinib. [28457] [31970] [56592]

    Proteinuria, renal failure

    Use sunitinib with caution in patients with pre-existing proteinuria, as proteinuria and nephrotic syndrome have been reported after treatment with sunitinib, some of which resulted in renal failure and fatal outcomes. Perform baseline and periodic urinalyses during treatment, with follow-up measurement of 24-hour urine protein as clinically indicated; monitor patients for the development or worsening of proteinuria. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary in patients with proteinuria of more than 3 grams in 24 hours; discontinue sunitinib for patients with nephrotic syndrome. The safety of continuing sunitinib in patients with moderate to severe proteinuria has not been evaluated.[31970]

    Tumor lysis syndrome (TLS)

    Tumor lysis syndrome (TLS), some cases fatal, has been reported in patients who received sunitinib in clinical studies and in postmarketing surveillance. Most patients who developed TLS had renal cell carcinoma (RCC) or gastrointestinal stromal tumor (GIST); patients generally at risk of TLS are those with a high tumor burden. Monitor these patients closely for TLS and treat as clinically indicated.

    Serious rash

    A serious rash including erythema multiform, Stevens-Johnson syndrome, and toxic epidermal necrolysis has been reported in patients treated with sunitinib in clinical trials; some cases were fatal. Permanently discontinue sunitinib therapy for these severe cutaneous adverse reactions. Necrotizing fasciitis, including fatal cases, has also been reported in patients treated with sunitinib, including of the perineum and secondary to fistula formation; discontinue sunitinib in patients who develop necrotizing fasciitis.

    Encephalopathy

    Reversible Posterior Leukoencephalopathy Syndrome (RPLS), also known as Posterior Reversible Encephalopathy Syndrome (PRES), has rarely been reported with sunitinib use. Symptoms of RPLS include hypertension, headache, decreased alertness, altered mental status, and visual loss including cortical blindness; this syndrome may be confirmed on magnetic resonance imaging. Permanently discontinue sunitinib in patients developing RPLS.

    Children

    The safety and effectiveness of sunitinib in children and adolescents have not been established. The maximum tolerated dose (MTD) normalized for body surface area was lower in pediatric patients compared to adults in 2 open-label studies in pediatric patients (age, 2 to 16 years) with refractory solid tumors, high-grade glioma, or ependymoma. Sunitinib was poorly tolerated in pediatric patients. Patients with refractory solid tumors with previous exposure to anthracyclines or cardiac radiation were excluded from one of these trials after a study amendment due to the occurrence of dose-limiting cardiotoxicity. No responses were reported in patients in either of the trials. The effect of sunitinib on open tibial growth plates in pediatric patients has not been adequately studied.[31970]

    Pregnancy

    Pregnancy should be avoided during sunitinib treatment and for at least 4 weeks after the last dose. Although there are no adequately controlled studies in pregnant women, based on its mechanism of action and animal studies, sunitinib can cause fetal harm or death when administered during pregnancy. Women who are pregnant or who become pregnant while receiving sunitinib should be apprised of the potential hazard to the fetus. In animal development and reproductive toxicology studies, oral administration of sunitinib to pregnant rats and rabbits during organogenesis resulted in teratogenicity (embryolethality, craniofacial malformations, and skeletal malformations [e.g., ribs, vertebrae]) at approximately 5.5 and 0.3 times the combined AUC (sunitinib plus its active metabolite) in patients administered sunitinib 50 mg per day, respectively. Additionally, in rats, reduced neonatal body weight was observed at birth and persisted during the preweaning period in both genders and during the postweaning period in males at doses resulting in an AUC approximately 2 times the combined AUC of a 50 mg daily dose.

    Contraception requirements, infertility, pregnancy testing, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during sunitinib treatment. Sunitinib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 4 weeks after treatment with sunitinib. Males with female partners of reproductive potential should use effective contraception during treatment with sunitinib and for at least 7 weeks after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of sunitinib. Women who become pregnant while receiving sunitinib should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of sunitinib on human fertility, male and female infertility has been observed in animal studies.

    Breast-feeding

    Due to the potential for serious adverse reactions in nursing infants from sunitinib, advise women to discontinue breast-feeding during treatment and for 4 weeks after the final dose. It is not known whether sunitinib is present in human milk, although many drugs are excreted in human milk.

    ADVERSE REACTIONS

    Severe

    palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / 4.0-16.0
    fatigue / Early / 5.0-15.0
    hyperuricemia / Delayed / 0-14.0
    hypertension / Early / 4.0-13.0
    neutropenia / Delayed / 0-13.0
    asthenia / Delayed / 5.0-11.0
    diarrhea / Early / 4.0-10.0
    hyponatremia / Delayed / 2.0-8.0
    hypophosphatemia / Delayed / 0-7.0
    dyspnea / Early / 0-6.0
    hyperglycemia / Delayed / 0-6.0
    nausea / Early / 1.0-6.0
    stomatitis / Delayed / 1.0-6.0
    abdominal pain / Early / 0-5.0
    elevated hepatic enzymes / Delayed / 2.0-5.0
    hypothyroidism / Delayed / 0-5.0
    back pain / Delayed / 0-5.0
    myalgia / Early / 0-5.0
    renal failure (unspecified) / Delayed / 0-5.0
    thrombocytopenia / Delayed / 0-5.0
    vomiting / Early / 0-5.0
    bleeding / Early / 0-4.2
    thrombosis / Delayed / 1.0-4.0
    thromboembolism / Delayed / 1.0-4.0
    hypokalemia / Delayed / 1.0-4.0
    anorexia / Delayed / 0-3.0
    weight loss / Delayed / 0-3.0
    hyperkalemia / Delayed / 1.0-3.0
    arthralgia / Delayed / 0-3.0
    heart failure / Delayed / 3.0-3.0
    leukopenia / Delayed / 0-3.0
    lymphopenia / Delayed / 0-3.0
    pulmonary embolism / Delayed / 0-2.0
    rash / Early / 1.0-2.0
    hypoglycemia / Early / 0-2.0
    chest pain (unspecified) / Early / 0-2.0
    peripheral edema / Delayed / 0-2.0
    dyspepsia / Early / 0-2.0
    epistaxis / Delayed / 0-1.0
    fever / Early / 0-1.0
    chills / Rapid / 0-1.0
    cough / Delayed / 0-1.0
    constipation / Delayed / 0-1.0
    dysgeusia / Early / 0-1.0
    hypoalbuminemia / Delayed / 0-1.0
    hepatic failure / Delayed / 0-1.0
    xerosis / Delayed / 0-1.0
    hair discoloration / Delayed / 0-1.0
    skin discoloration / Delayed / 0-1.0
    pruritus / Rapid / 0-1.0
    hypocalcemia / Delayed / 0-1.0
    hypercalcemia / Delayed / 0-1.0
    leukoencephalopathy / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    headache / Early / 0-1.0
    dizziness / Early / 0-1.0
    pancreatitis / Delayed / 0-1.0
    edema / Delayed / 0-1.0
    gastroesophageal reflux / Delayed / 0-1.0
    esophagitis / Delayed / 0-1.0
    torsade de pointes / Rapid / 0-0.1
    stroke / Early / Incidence not known
    hypertensive crisis / Early / Incidence not known
    GI bleeding / Delayed / Incidence not known
    hematemesis / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    thrombotic microangiopathy / Delayed / Incidence not known
    hemolytic-uremic syndrome / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    cholecystitis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    necrotizing fasciitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    nephrotic syndrome / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    osteonecrosis / Delayed / Incidence not known
    tumor lysis syndrome (TLS) / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    aortic dissection / Delayed / Incidence not known

    Moderate

    hypomagnesemia / Delayed / 0-19.0
    hypernatremia / Delayed / 10.0-12.0
    depression / Delayed / 0-11.0
    hemorrhoids / Delayed / 0-10.0
    erythema / Early / 0-1.0
    QT prolongation / Rapid / Incidence not known
    hematoma / Early / Incidence not known
    melena / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    hemoptysis / Delayed / Incidence not known
    psoriaform rash / Delayed / Incidence not known
    hyperthyroidism / Delayed / Incidence not known
    myopathy / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    glossitis / Early / Incidence not known

    Mild

    pharyngitis / Delayed / 0-14.0
    flatulence / Early / 0-14.0
    alopecia / Delayed / 2.0-14.0
    xerostomia / Early / 0-13.0
    influenza / Delayed / 0-5.0
    infection / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    gingivitis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Alfuzosin: (Moderate) Use caution and monitor for evidence of QT prolongation if sunitinib is administered with alfuzosin. Sunitinib can prolong the QT interval. Alfuzosin may also prolong the QT interval in a dose-dependent manner.
    Amiodarone: (Major) Avoid coadministration of amiodarone with sunitinib if possible due to the risk of QT prolongation. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP), although the frequency is less with amiodarone than with other Class III agents. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with sunitinib. Amisulpride causes dose- and concentration- dependent QT prolongation. Sunitinib can prolong the QT interval.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with sunitinib due to increased sunitinib exposure as well as the risk of QT prolongation and torsade de pointes (TdP). Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and TdP. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval, such as sunitinib. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Apalutamide: (Major) Avoid coadministration of apalutamide with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Apomorphine: (Moderate) Use apomorphine and sunitinib together with caution due to the risk of additive QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Sunitinib can prolong the QT interval.
    Aripiprazole: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with aripiprazole. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. Sunitinib can prolong the QT interval.
    Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with sunitinib if possible due to the risk of QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor ECGs for QT prolongation. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with sunitinib due to the risk of QT prolongation. If concomitant use is unavoidable, consider ECG monitoring. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Artemether; lumefantrine is also associated with prolongation of the QT interval.
    Asenapine: (Major) Avoid coadministration of asenapine with sunitinib due to the risk of QT prolongation. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Asenapine has also been associated with QT prolongation.
    Atazanavir: (Major) Avoid coadministration of atazanavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Atazanavir; Cobicistat: (Major) Avoid coadministration of atazanavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Atomoxetine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Sunitinib can prolong the QT interval.
    Azithromycin: (Major) Avoid coadministration of azithromycin with sunitinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Bedaquiline: (Major) Monitor ECGs for QT prolongation if coadministration of bedaquiline with sunitinib is necessary; discontinuation of bedaquiline therapy may be necessary for ventricular arrhythmias or QT prolongation. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Bedaquiline has also been reported to prolong the QT interval.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid coadministration of phenobarbital with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Buprenorphine: (Major) Avoid coadministration of buprenorphine with sunitinib. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Sunitinib can also prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Avoid coadministration of buprenorphine with sunitinib. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Sunitinib can also prolong the QT interval.
    Cabotegravir; Rilpivirine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Sunitinib can prolong the QT interval.
    Carbamazepine: (Major) Avoid coadministration of carbamazepine with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Ceritinib: (Major) Avoid coadministration of ceritinib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Chloramphenicol: (Major) Avoid coadministration of chloramphenicol with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Chloroquine: (Major) Avoid coadministration of chloroquine with sunitinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Sunitinib can also prolong the QT interval.
    Chlorpromazine: (Major) Monitor patients for QT prolongation if coadministration of chlorpromazine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Chlorpromazine, a phenothiazine, is also associated with an established risk of QT prolongation and TdP.
    Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
    Ciprofloxacin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with ciprofloxacin. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Sunitinib can prolong the QT interval.
    Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), the use of sunitinib with cisapride is contraindicated. Prolongation of the QT interval and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Sunitinib can cause dose-dependent QT prolongation, which may also increase the risk for ventricular arrhythmias, including TdP.
    Citalopram: (Major) Coadministration of citalopram with sunitinib is not recommended due to the risk of QT prolongation. If concomitant use is unavoidable, ECG monitoring is recommended. Both drugs can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Clarithromycin: (Major) Avoid coadministration of clarithromycin with sunitinib due to increased sunitinib exposure as well as the risk of QT prolongation and torsade de pointes (TdP). Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and TdP. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Clofazimine: (Moderate) Concomitant use of clofazimine and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Clozapine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Sunitinib can prolong the QT interval.
    Cobicistat: (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Codeine; Promethazine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Crizotinib: (Major) Avoid coadministration of crizotinib with sunitinib due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Sunitinib can also prolong the QT interval.
    Darunavir: (Major) Avoid coadministration of darunavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Darunavir; Cobicistat: (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. (Major) Avoid coadministration of darunavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. (Major) Avoid coadministration of darunavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of ritonavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Ritonavir is a strong CYP3A4 inhibitor that also causes QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Dasatinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with dasatinib. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Sunitinib can also prolong the QT interval.
    Degarelix: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with degarelix. Sunitinib can prolong the QT interval. Androgen deprivation therapy (i.e., degarelix) may also prolong the QT/QTc interval.
    Delavirdine: (Major) Avoid coadministration of delavirdine with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Desflurane: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Deutetrabenazine: (Moderate) Monitor for evidence of QT prolongation if sunitinub is administered with deutetrabenazine. Sunitinib can prolong the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Monitor patients for QT prolongation if coadministration of quinidine with sunitinib is necessary. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Disopyramide: (Major) Monitor patients for QT prolongation if coadministration of disopyramide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Disopyramide administration is also associated with QT prolongation and TdP.
    Dofetilide: (Major) Coadministration of dofetilide and sunitinib is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Sunitinib can prolong the QT interval.
    Dolasetron: (Moderate) Administer dolasetron with caution in combination with sunitinib as concurrent use may increase the risk of QT prolongation. Sunitinib can prolong the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
    Dolutegravir; Rilpivirine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Sunitinib can prolong the QT interval.
    Donepezil: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with donepezil. Sunitinib can prolong the QT interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Donepezil; Memantine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with donepezil. Sunitinib can prolong the QT interval. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy.
    Dronedarone: (Contraindicated) Because of the potential for TdP, use of sunitinib with dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as sunitinib. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Efavirenz: (Major) Consider alternatives to efavirenz when coadministering with sunitinib. QTc prolongation has been observed with the use of efavirenz. Sunitinib can also prolong the QT interval.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Consider alternatives to efavirenz when coadministering with sunitinib. QTc prolongation has been observed with the use of efavirenz. Sunitinib can also prolong the QT interval.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Consider alternatives to efavirenz when coadministering with sunitinib. QTc prolongation has been observed with the use of efavirenz. Sunitinib can also prolong the QT interval.
    Eliglustat: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with eliglustat. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Sunitinib can prolong the QT interval.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of cobicistat with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Sunitinib can prolong the QT interval.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Sunitinib can prolong the QT interval.
    Encorafenib: (Major) Avoid coadministration of encorafenib and sunitinib due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Sunitinib can also prolong the QT interval.
    Enflurane: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Entrectinib: (Major) Avoid coadministration of entrectinib with sunitinib due to the risk of QT prolongation. If coadministration is necessary, monitor for evidence of QT prolongation. Both entrectinib and sunitinib have been associated with QT prolongation.
    Enzalutamide: (Major) Avoid coadministration of enzalutamide with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Eribulin: (Major) Closely monitor ECGs for QT prolongation if coadministration of eribulin with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Eribulin has also been associated with QT prolongation.
    Erythromycin: (Major) Monitor patients for QT prolongation if coadministration of erythromycin with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Erythromycin is also associated with QT prolongation and TdP.
    Erythromycin; Sulfisoxazole: (Major) Monitor patients for QT prolongation if coadministration of erythromycin with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Erythromycin is also associated with QT prolongation and TdP.
    Escitalopram: (Moderate) Use escitalopram with caution in combination with sunitinib as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Sunitinib can prolong the QT interval.
    Ezogabine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with ezogabine as concurrent use may increase the risk of QT prolongation. Both ezogabine and sunitinib have been associated with QT prolongation.
    Fingolimod: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with fingolimod. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of torsade de pointes (TdP) in patients with bradycardia. Sunitinib can prolong the QT interval.
    Flecainide: (Major) Monitor patients for QT prolongation if coadministration of flecainide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs that have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
    Fluconazole: (Contraindicated) FDA-approved labeling for fluconazole contraindicates use with CYP3A4 substrates that prolong the QT interval such as sunitinib. If alternative therapy is not available and concurrent use cannot be avoided, closely monitor for evidence of QT prolongation. Fluconazole is a moderate CYP3A4 inhibitor that has been associated with QT prolongation. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Coadministration of sunitinib with a strong CYP3A4 inhibitor increased the combined AUC of sunitinib and active metabolite by 51% in healthy subjects. The effect of moderate CYP3A4 inhibitors like fluconazole has not been studied.
    Fluoxetine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with fluoxetine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Sunitinib can also prolong the QT interval.
    Fluphenazine: (Minor) Monitor for evidence of QT prolongation if sunitinib is administered with fluphenazine. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Sunitinib can prolong the QT interval.
    Fluvoxamine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with fluvoxamine. QT prolongation and torsade de pointes (TdP) has been reported during fluvoxamine post-marketing use. Sunitinib can prolong the QT interval.
    Fosamprenavir: (Major) Avoid coadministration of fosamprenavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and fosamprenavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Foscarnet: (Major) Avoid coadministration of foscarnet with sunitinib due to the risk of QT prolongation. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Fosphenytoin: (Major) Avoid coadministration of fosphenytoin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Gemifloxacin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with gemifloxacin. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Sunitinib can prolong the QT interval.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and sunitinib together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Sunitinib can prolong the QT interval.
    Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and sunitinib is necessary. Both drugs have been associated with QT prolongation.
    Glasdegib: (Major) Avoid coadministration of glasdegib with sunitinib due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Sunitinib can also prolong the QT interval.
    Goserelin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with goserelin. Sunitinib can prolong the QT interval. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
    Granisetron: (Moderate) Monitor patients for QT prolongation if coadministration of granisetron with sunitinib is necessary. Sunitinib can cause QT prolongation. Granisetron has also been associated with QT prolongation.
    Grapefruit juice: (Major) Advise patients to avoid taking sunitinib with grapefruit juice due to increased sunitinib exposure, which may increase the risk of QT prolongation or other side effects. Sunitinib is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Halogenated Anesthetics: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with sunitinib. Sunitinib can prolong the QT interval. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
    Halothane: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Hydroxychloroquine: (Major) Avoid coadministration of sunitinib and hydroxychloroquine due to an increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine and sunitinib can prolong the QT interval.
    Hydroxyzine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with hydroxyzine. Postmarketing data indicate that hydroxyzine causes QT prolongation and torsade de pointes (TdP). Sunitinib can prolong the QT interval.
    Ibutilide: (Major) Monitor patients for QT prolongation if coadministration of ibutilide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
    Idelalisib: (Major) Avoid coadministration of idelalisib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Iloperidone: (Major) Avoid coadministration of iloperidone with sunitinib. Since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect such as sunitinib, which cause dose-dependent QT prolongation, leading to an increased risk for ventricular arrhythmias including torsades de points (TdP).
    Indinavir: (Major) Avoid coadministration of indinavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with sunitinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and electrolytes prior to the start of treatment and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Isoflurane: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of rifampin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exposure to sunitinib and its primary active metabolite by 46%.
    Isoniazid, INH; Rifampin: (Major) Avoid coadministration of rifampin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exposure to sunitinib and its primary active metabolite by 46%.
    Itraconazole: (Major) Avoid sunitinib use during and for 2 weeks after discontinuation of itraconazole treatment due to increased sunitinib exposure, which may increase the risk of QT prolongation. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Itraconazole is a strong CYP3A4 inhibitor that has also been associated with prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Ivosidenib: (Major) Avoid coadministration of ivosidenib with sunitinib due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Sunitinib can also prolong the QT interval.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and sunitinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of sunitinib, further increasing the risk for adverse effects. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased exposure to sunitinib and its primary active metabolite by 51%.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with sunitinib due to increased sunitinib exposure as well as the risk of QT prolongation and torsade de pointes (TdP). Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and TdP. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Lapatinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with lapatinib. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Sunitinib can prolong the QT interval.
    Lefamulin: (Major) Avoid coadministration of lefamulin with sunitinib as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Sunitinib can prolong the QT interval.
    Lenvatinib: (Major) Avoid coadministration of lenvatinib with sunitinib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Sunitinib can also prolong the QT interval.
    Letermovir: (Moderate) If possible, avoid coadministration of letermovir with sunitinib in patients who are also receiving cyclosporine due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use of letermovir, cyclosporine, and sunitinib is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to 37.5 mg for patients with GIST or RCC, and to 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Levofloxacin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with levofloxacin. Sunitinib can prolong the QT interval. Levofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and sunitinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of sunitinib, further increasing the risk for adverse effects. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Coadministration with ketoconazole increased exposure to sunitinib and its primary active metabolite by 51%.
    Lithium: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with lithium. Lithium has been associated with QT prolongation. Sunitinib can prolong the QT interval.
    Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with sunitinib due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Sunitinib can prolong the QT interval.
    Lonafarnib: (Major) Avoid coadministration of lonafarnib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure of sunitinib and its primary active metabolite by 51%.
    Loperamide: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Sunitinib can prolong the QT interval.
    Loperamide; Simethicone: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with loperamide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Sunitinib can prolong the QT interval.
    Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with sunitinib due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs are associated with QT prolongation. (Major) Avoid coadministration of ritonavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Ritonavir is a strong CYP3A4 inhibitor that also causes QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as sunitinib. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Sunitinib can prolong the QT interval.
    Maprotiline: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with maprotiline. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Sunitinib can prolong the QT interval.
    Mefloquine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Sunitinib can prolong the QT interval.
    Meperidine; Promethazine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Mephobarbital: (Major) Avoid coadministration of mephobarbital with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and mephobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Methadone: (Major) Coadministration of methadone with drugs known to prolong the QT interval, such as sunitinib, should be done with extreme caution and a careful assessment of treatment risks versus benefits; monitor patients for QT prolongation. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (greater than 200 mg/day, but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Metronidazole: (Moderate) Concomitant use of metronidazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Midostaurin: (Major) Consider obtaining electrocardiograms to monitor the QT interval if midostaurin is used with other drugs that prolong the QT interval, such as sunitinib. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Prolongation of the QT interval was also reported in patients who received midostaurin in clinical trials.
    Mifepristone: (Major) Avoid use of mifepristone with sunitinib due to the risk of QT prolongation; increased sunitinib exposure may also occur. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
    Mirtazapine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with mirtazapine. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation. Sunitinib can prolong the QT interval.
    Mitotane: (Major) Avoid coadministration of mitotane with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Mobocertinib: (Major) Concomitant use of mobocertinib and sunitinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Avoid coadministration of moxifloxacin with sunitinib as concurrent use may increase the risk of QT prolongation and torsade de pointes (TdP). Quinolones have been associated with a risk of QT prolongation; although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Sunitinib can also prolong the QT interval.
    Nefazodone: (Major) Avoid coadministration of nefazodone with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Nelfinavir: (Major) Avoid coadministration of nelfinavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Nilotinib: (Major) Avoid the concomitant use of nilotinib and sunitinib; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have occurred in patients who received nilotinib therapy. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points.
    Nirmatrelvir; Ritonavir: (Major) Avoid coadministration of ritonavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Ritonavir is a strong CYP3A4 inhibitor that also causes QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Octreotide: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Sunitinib can prolong the QT interval.
    Ofloxacin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with ofloxacin. Sunitinib can prolong the QT interval. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Olanzapine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Sunitinib can prolong the QT interval.
    Olanzapine; Fluoxetine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with fluoxetine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation and TdP have been reported in patients treated with fluoxetine. Sunitinib can also prolong the QT interval. (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Sunitinib can prolong the QT interval.
    Olanzapine; Samidorphan: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with olanzapine. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Sunitinib can prolong the QT interval.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Avoid coadministration of ritonavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Ritonavir is a strong CYP3A4 inhibitor that also causes QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Ondansetron: (Major) Monitor ECG for evidence of QT prolongation if coadministration of ondansetron and sunitinib is necessary. Both drugs have been associated with a dose-related increase in the QT interval. Additionally, there have been postmarketing reports of torsade de pointes (TdP) with ondansetron treatment.
    Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with sunitinib. Sunitinib can prolong the QT interval. Osilodrostat is associated with dose-dependent QT prolongation.
    Osimertinib: (Major) Avoid coadministration of sunitinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Sunitinib can also prolong the QT interval.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sunitinib with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Prolongation of the QT interval and ventricular arrhythmias including fatal TdP have also been reported with oxaliplatin use in postmarketing experience.
    Ozanimod: (Major) In general, do not initiate ozanimod in patients taking sunitinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sunitinib can prolong the QT interval.
    Pacritinib: (Major) Concomitant use of pacritinib and sunitinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Avoid coadministration of paliperidone with sunitinib, if possible, due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor patients with known risk factors for cardiac disease or arrhythmias. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsade de pointes (TdP). Paliperidone has also been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose.
    Panobinostat: (Major) Concomitant use of panobinostat with other agents that prolong the QT interval, such as sunitinib, is not recommended. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Prolongation of the QT interval has also been reported with panobinostat.
    Pasireotide: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with pasireotide. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Sunitinib can prolong the QT interval.
    Pazopanib: (Major) Coadministration of pazopanib with other drugs that prolong the QT interval, such as sunitinib, is not advised. If concomitant use is unavoidable, closely monitor the patient for QT interval prolongation. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Pazopanib has also been reported to prolong the QT interval.
    Pentamidine: (Major) Monitor patients for QT prolongation if coadministration of pentamidine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Systemic pentamidine has also been associated with QT prolongation.
    Perphenazine: (Minor) Monitor for evidence of QT prolongation if sunitinib is administered with perphenazine. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Sunitinib can prolong the QT interval.
    Perphenazine; Amitriptyline: (Minor) Monitor for evidence of QT prolongation if sunitinib is administered with perphenazine. Perphenazine is associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Sunitinib can prolong the QT interval.
    Phenobarbital: (Major) Avoid coadministration of phenobarbital with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of phenobarbital with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Phenytoin: (Major) Avoid coadministration of phenytoin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as sunitinib. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Pimozide: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of sunitinib with pimozide is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and TdP. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Pitolisant: (Major) Avoid coadministration of pitolisant with sunitinib as concurrent use may increase the risk of QT prolongation. If concomitant use is necessary, monitor for evidence of QT prolongation. Pitolisant prolongs the QT interval. Sunitinib can also prolong the QT interval.
    Ponesimod: (Major) In general, do not initiate ponesimod in patients taking sunitinib due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If treatment initiation is considered, seek advice from a cardiologist and monitor for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Sunitinib can prolong the QT interval.
    Posaconazole: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as sunitinib, is contraindicated. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes. Sunitinib is a CYP3A4 substrate that can also prolong the QT interval.
    Primaquine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with primaquine. Primaquine has the potential for QT interval prolongation. Sunitinib can prolong the QT interval.
    Primidone: (Major) Avoid coadministration of primidone with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Procainamide: (Major) Monitor patients for QT prolongation if coadministration of procainamide with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Procainamide is associated with a well-established risk of QT prolongation and TdP.
    Prochlorperazine: (Minor) Monitor for evidence of QT prolongation if sunitinib is administered with prochlorperazine. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Sunitinib can prolong the QT interval.
    Promethazine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Promethazine; Dextromethorphan: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Promethazine; Phenylephrine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Sunitinib can prolong the QT interval.
    Propafenone: (Major) Monitor patients for QT prolongation if coadministration of propafenone with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Propafenone is a Class IC antiarrhythmic which increases the QT interval, but largely due to prolongation of the QRS interval.
    Quetiapine: (Major) According to the manufacturer, the use of quetiapine should be avoided in combination with drugs known to increase the QT interval such as sunitinib. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Quinidine: (Major) Monitor patients for QT prolongation if coadministration of quinidine with sunitinib is necessary. Quinidine administration is associated with QT prolongation and torsade de pointes (TdP). Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Quinine: (Major) Avoid concurrent use of quinine with other drugs that may cause QT prolongation and torsade de pointes (TdP). Quinine has been associated with QT prolongation and rare cases of TdP. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    Ranolazine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with ranolazine. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Sunitinib can prolong the QT interval.
    Relugolix: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with relugolix. Sunitinib can prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with relugolix. Sunitinib can prolong the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
    Ribociclib: (Major) Avoid coadministration of ribociclib with sunitinib due to the risk of QT prolongation; increased sunitinib exposure may also occur. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner; the ribociclib ECG changes typically occur within the first four weeks of treatment and are reversible with dose interruption. Sunitinib is a CYP3A4 substrate that can also prolong the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with sunitinib due to the risk of QT prolongation; increased sunitinib exposure may also occur. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner; the ribociclib ECG changes typically occur within the first four weeks of treatment and are reversible with dose interruption. Sunitinib is a CYP3A4 substrate that can also prolong the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Rifampin: (Major) Avoid coadministration of rifampin with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased exposure to sunitinib and its primary active metabolite by 46%.
    Rifapentine: (Major) Avoid coadministration of rifapentine with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Rilpivirine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Sunitinib can prolong the QT interval.
    Risperidone: (Moderate) Use risperidone and sunitinib together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Sunitinib can also prolong the QT interval.
    Ritonavir: (Major) Avoid coadministration of ritonavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Ritonavir is a strong CYP3A4 inhibitor that also causes QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with sunitinib. Sunitinib can prolong the QT interval. Romidepsin has been reported to prolong the QT interval.
    Saquinavir: (Contraindicated) The concomitant use of saquinavir with sunitinib is contraindicated due to the risk of QT prolongation. Sunitinib is a CYP3A4 substrate that can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Saquinavir is a strong CYP3A4 inhibitor that also increases the QT interval in a dose-dependent fashion. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
    Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with sunitinib is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Sunitinib can prolong the QT interval.
    Sertraline: (Moderate) Use caution and monitor patients for QT prolongation when administering sunitinib with sertraline. Sunitinib can prolong the QT interval. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
    Sevoflurane: (Major) Monitor patients for QT prolongation if coadministration of halogenated anesthetics with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP). Halogenated anesthetics can also prolong the QT interval.
    Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving sunitinib due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Sunitinib can prolong the QT interval.
    Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Solifenacin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Sunitinib can prolong the QT interval.
    Sorafenib: (Major) Avoid coadministration of sorafenib with sunitinib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Both drugs are associated with QTc prolongation.
    Sotalol: (Major) Monitor patients for QT prolongation if coadministration of sotalol with sunitinib is necessary. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.
    St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of St. Johns Wort with sunitinib if possible due to decreased exposure to sunitinib which could decrease efficacy. If concomitant use is unavoidable, consider increasing the daily dose of sunitinib to a maximum of 87.5 mg for patients with GIST or RCC, and to a maximum of 62.5 mg for patients with pNET; monitor carefully for toxicity. Sunitinib is a CYP3A4 substrate and St. Johns Wort is a strong CYP3A4 inducer. Because the amount of individual constituents in various St. Johns Wort products may alter the inducing effects, drug interactions are unpredictable. Coadministration with another strong CYP3A4 inducer decreased exposure to sunitinib and its primary active metabolite by 46%.
    Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with sunitinib. Sunitinib can prolong the QT interval. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP).
    Tamoxifen: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with tamoxifen. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Sunitinib can prolong the QT interval.
    Telavancin: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with telavancin. Telavancin has been associated with QT prolongation. Sunitinib can prolong the QT interval.
    Telithromycin: (Major) Avoid coadministration of telithromycin with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Telithromycin is a strong CYP3A4 inhibitor that is associated with QT prolongation and torsade de pointes (TdP). Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Temsirolimus: (Major) Avoid the use of temsirolimus with sunitinib if possible, due to the combination resulting in dose-limiting toxicity. In the first cohort of a phase 1 study with temsirolimus (15 mg/kg IV per week) and sunitinib (25 mg by mouth daily on days 1 through 28, followed by a 2-week rest), dose-limiting toxicities such as grade 3 or 4 erythematous maculopapular rash and gout/cellulitis requiring hospitalization were observed in 2 of 3 patients treated.
    Tetrabenazine: (Major) Avoid coadministration of tetrabenazine with other drugs known to prolong the corrected QT interval (QTc), such as sunitinib. Tetrabenazine causes a small increase in the QTc. Sunitinib can cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Thioridazine: (Contraindicated) Because of the potential for torsades de pointes (TdP), use of sunitinib with thioridazine is contraindicated. Sunitinib can prolong the QT interval. Thioridazine is associated with a well-established risk of QT prolongation and TdP. Coadministration may result in additive effects on the QT interval and further increase the risk of TdP.
    Tipranavir: (Major) Avoid coadministration of tipranavir with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Tolterodine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with tolterodine. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Sunitinib can prolong the QT interval.
    Toremifene: (Major) Avoid coadministration of sunitinib with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including torsades de points (TdP).
    Trazodone: (Major) Concomitant use of trazodone and sunitinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Triclabendazole: (Moderate) Concomitant use of triclabendazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Trifluoperazine: (Minor) Monitor patients for QT prolongation if coadministration of trifluoperazine with sunitinib is necessary. Sunitinib can cause dose-dependent QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
    Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving sunitinib as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Sunitinib can prolong the QT interval.
    Tucatinib: (Major) Avoid coadministration of tucatinib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Vandetanib: (Major) Avoid coadministration of vandetanib with sunitinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Sunitinib can also prolong the QT interval.
    Vardenafil: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with vardenafil. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval. Sunitinib can prolong the QT interval.
    Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as sunitinib. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Sunitinib can also prolong the QT interval.
    Venlafaxine: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with venlafaxine. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. Sunitinib can prolong the QT interval.
    Voclosporin: (Moderate) Concomitant use of voclosporin and sunitinib may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Sunitinib can prolong the QT interval.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with sunitinib due to increased sunitinib exposure as well as the risk of QT prolongation and torsade de pointes (TdP). Sunitinib is a CYP3A4 substrate that can cause QT prolongation. Clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and TdP. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Voriconazole: (Major) Avoid coadministration of voriconazole with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Voriconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and rare cases of torsade de pointes (TdP). Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
    Vorinostat: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Sunitinib can prolong the QT interval.
    Ziprasidone: (Major) Concomitant use of ziprasidone and sunitinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Sunitinib can also cause dose-dependent QT prolongation, which may increase the risk for ventricular arrhythmias, including TdP.

    PREGNANCY AND LACTATION

    Pregnancy

    Pregnancy should be avoided during sunitinib treatment and for at least 4 weeks after the last dose. Although there are no adequately controlled studies in pregnant women, based on its mechanism of action and animal studies, sunitinib can cause fetal harm or death when administered during pregnancy. Women who are pregnant or who become pregnant while receiving sunitinib should be apprised of the potential hazard to the fetus. In animal development and reproductive toxicology studies, oral administration of sunitinib to pregnant rats and rabbits during organogenesis resulted in teratogenicity (embryolethality, craniofacial malformations, and skeletal malformations [e.g., ribs, vertebrae]) at approximately 5.5 and 0.3 times the combined AUC (sunitinib plus its active metabolite) in patients administered sunitinib 50 mg per day, respectively. Additionally, in rats, reduced neonatal body weight was observed at birth and persisted during the preweaning period in both genders and during the postweaning period in males at doses resulting in an AUC approximately 2 times the combined AUC of a 50 mg daily dose.

    Due to the potential for serious adverse reactions in nursing infants from sunitinib, advise women to discontinue breast-feeding during treatment and for 4 weeks after the final dose. It is not known whether sunitinib is present in human milk, although many drugs are excreted in human milk.

    MECHANISM OF ACTION

    Sunitinib is an oral small molecule inhibitor of multiple receptor tyrosine kinases (RTKs) implicated in tumor growth, pathologic angiogenesis, and metastatic progression of cancer including platelet-derived growth factor receptors (PDGFR-alpha and PDGFR-beta), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). The inhibition of the activity of these RTKs by sunitinib has been demonstrated in biochemical and cellular assays, and the inhibition of function has been demonstrated in cell proliferation assays. Sunitinib inhibited the phosphorylation of PDGFR-beta, VEGFR2, and KIT in tumor xenografts expressing RTK targets in vivo. It demonstrated inhibition of tumor growth or tumor regression and/or inhibited metastases in some experimental models of cancer. Sunitinib inhibited the growth of tumor cells expressing dysregulated PDGFR, RET, and KIT in vitro, and inhibited PDGFR-beta- and VEGFR2-dependent tumor angiogenesis in vivo. The primary metabolite of sunitinib exhibits similar potency in biochemical and cellular assays.
     
    Several adverse reactions of sunitinib (i.e., hair and skin discoloration) are associated with the multiple signaling pathways inhibition including KIT, PDGRF, and VEGFR. The graying of hair seen in patients may be a potential surrogate marker to monitor sunitinib biologic effects.

    PHARMACOKINETICS

    Sunitinib is administered orally. Sunitinib and its primary active metabolite are 95% and 90% bound to human plasma protein in vitro, respectively, in a non-concentration dependent manner over the range of 100 ng/mL to 4,000 ng/mL. The apparent volume of distribution (Vd/F) for sunitinib was 2,230 L. After administration of a single oral dose to healthy volunteers, the terminal half-life of sunitinib is 40 to 60 hours; the terminal half-life of the primary active metabolite is 80 to 110 hours. With repeated daily administration, sunitinib accumulates 3- to 4-fold while the primary active metabolite accumulates 7- to 10-fold. Steady-state concentrations are achieved within 10 to 14 days; by day 14, combined plasma concentrations of sunitinib and its active metabolite ranged from 63 to 101 ng/mL. No significant changes in the pharmacokinetics of sunitinib or the active metabolite were observed with repeated daily administration or with repeated cycles. Sunitinib is primarily eliminated via the feces (61%), with 16% of an administered dose eliminated renally. In a human mass balance study of radiolabeled sunitinib, sunitinib and its active metabolite were the major compounds identified in pooled samples of plasma (92%), urine (86.4%), and feces (73.8%). Minor metabolites were identified in urine and feces but generally not found in plasma. Total oral clearance (CL/F) ranged from 34 L/hour to 62 L/hour, with an interpatient variability of 40%.[31970]
     
    The pharmacokinetics in healthy volunteers were similar to the solid tumor patient populations tested, including patients with GI stromal tumor (GIST) and renal cell carcinoma (RCC). No significant changes in the pharmacokinetics of sunitinib or the primary active metabolite were observed with repeated daily administration or repeated cycles.[31970]
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    Sunitinib is metabolized by CYP3A4 to its primary active metabolite, which is further metabolized by CYP3A4; the primary active metabolite comprises 23% to 37% of total exposure.[31970]

    Oral Route

    Over the dose range of 25 mg to 100 mg (0.5 to 2 times the approved recommended dose), the AUC and Cmax of sunitinib increase proportionally with dose. Maximum plasma concentrations of sunitinib are generally observed between 6 to 12 hours following oral administration (Tmax). Administration with a high-fat, high-calorie meal (approximately 150 protein calories and 500 to 600 fat calories) did not have a clinically significant effect on the exposure of sunitinib or its active metabolites.[31970]