sunitinib

Contraindicated in:

Hypersensitivity
NYHA class II-IV HF
OB: Pregnancy (may cause fetal harm)
Lactation: Lactation.

Use Cautiously in:

Hepatic/renal impairment
Concurrent use of bisphosphonates or a history of dental disease (may ↑ risk of jaw osteonecrosis)
History of myocardial ischemia or MI
LVEF <50% and >20% below baseline with no signs/symptoms of HF (need to interrupt therapy or ↓ dose)
Diabetes (↑ risk of hypoglycemia)
History of QT interval prolongation, use of antiarrhythmics, cardiac disease, bradycardia, or electrolyte disturbances
Rep: Women of reproductive potential and men with female partners of reproductive potential
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: HF, MI, TORSADES DE POINTES, hypertension, peripheral edema, QT interval prolongation, thromboembolic events.

Derm: ERYTHEMA MULTIFORME, NECROTIZING FASCIITIS, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, alopecia, hand-foot syndrome, hair color change, impaired wound healing, rash, skin discoloration.

EENT: epistaxis.

Endo: hypoglycemia, hypothyroidism, adrenal insufficiency, hyperthyroidism.

F and E: dehydration, hypophosphatemia.

GI: hepatotoxicity, GI PERFORATION, diarrhea, dyspepsia, nausea, stomatitis, vomiting, altered taste, anorexia, cholecystitis, constipation, esophagitis, ↑ lipase/amylase, ↑ liver enzymes, oral pain.

GU: hemolytic uremic syndrome, ↓ fertility, nephrotic syndrome, proteinuria, renal failure.

Hemat: hemorrhage, thrombotic thrombocytopenic purpura, anemia, lymphopenia, neutropenia, thrombocytopenia.

Metab: hyperuricemia.

MS: arthralgia, back pain, limb pain, myalgia, osteonecrosis (primarily of jaw).

Neuro: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), fatigue, dizziness, headache.

Misc: TUMOR LYSIS SYNDROME, fever.

Interactions ⬆ ⬇

Drug-Drug:

Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and the risk of toxicity; avoid concurrent use, if possible. If strong inhibitor must be used, ↓ sunitinib dose.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use, if possible. If strong inducer must be used, ↑ sunitinib dose.
Concurrent use with alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, or zoledronic acid may ↑ risk of jaw osteonecrosis
↑risk of microangiopathic hemolytic anemia when used with bevacizumab; concurrent use not recommended.
Concurrent use of other QT-interval prolonging medications may ↑ risk of torsades de pointes.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and the risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

GIST and RCC

PO (Adults): 50 mg once daily for 4 wk, followed by 2 wk off; continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 37.5 mg once daily for 4 wk, followed by 2 wk off; continue until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inducer — 87.5 mg once daily for 4 wk, followed by 2 wk off; continue until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults): End-stage renal disease (on hemodialysis) — No initial adjustment required; subsequent dosage ↑ (up to 2-fold) may be required due to reduced exposure.

Adjuvant Treatment of RCC

PO (Adults): 50 mg once daily for 4 wk, followed by 2 wk off for a total of nine 6-wk cycles. Concurrent use of strong CYP3A4 inhibitor — 37.5 mg once daily for 4 wk, followed by 2 wk off for a total of nine 6-wk cycles. Concurrent use of strong CYP3A4 inducer — 87.5 mg once daily for 4 wk, followed by 2 wk off for a total of nine 6-wk cycles.

Renal Impairment

PO (Adults): End-stage renal disease (on hemodialysis) — No initial adjustment required; subsequent dosage ↑ (up to 2-fold) may be required due to reduced exposure.

pNET

PO (Adults): 37.5 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitor — 25 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inducer — 62.5 mg once daily until disease progression or unacceptable toxicity.

Renal Impairment

PO (Adults): End-stage renal disease (on hemodialysis) — No initial adjustment required; subsequent dosage ↑ (up to 2-fold) may be required due to reduced exposure.

Implementation ⬆ ⬇

Do not confuse sunitinib with sorafenib.
Recommended Dose Modifications: For patients with GIST and Advanced RCC:First dose reduction,37.5 once daily. Second dose reduction, 25 mg once daily. For patients with Adjuvant RCC:First dose reduction, 37.5 mg once daily. For patients with pNET:First dose reduction, 25 mg once daily.
PO: Administer once daily with or without food.

US Brand Names ⬆ ⬇

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Availability ⬆ ⬇

(Generic available)

Capsules: 12.5 mg; 25 mg; 37.5 mg; 50 mg;

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	6–12 hr	24 hr

Assessment ⬆ ⬇

Monitor for signs of HF (dyspnea, edema, jugular venous distention) during therapy. Assess left ventricular ejection fraction (LVEF) at baseline and periodically during therapy in patients with cardiac events in the previous 12 mo and a baseline ejection fraction in patients without cardiovascular risk factors. If asymptomatic cardiomyopathy (LVEF >20% but <50% below baseline or below lower limit of normal if baseline was not obtained) occurs, hold sunitinib until resolution to Grade 0 or 1 or baseline. Resume at a reduced dose. If clinically manifested HF occurs, discontinue sunitinib permanently.
Monitor for hypertension and treat with standard antihypertensive therapy. If Grade 3 hypertension occurs, hold sunitinib until resolution to Grade 0 or 1 or baseline. Resume at a reduced dose. If Grade 4 hypertension occurs, permanently discontinue therapy.
Monitor for signs and symptoms of bleeding (epistaxis, GI bleeding) during therapy. If Grade 3 or 4 hemorrhage occurs, hold sunitinib until resolution to Grade 0 to 1 or baseline. Either resume at reduced dose or discontinue depending on the severity and persistence of adverse reaction.
Perform an oral examination before starting and periodically during therapy. Monitor for signs and symptoms of osteonecrosis of the jaw (tooth or jaw pain, swelling of the jaw) during therapy. Patients taking bisphosphonates, who have dental disease, or undergo invasive dental procedures, are at increased risk. Hold sunitinib for at least 3 wks before scheduled dental surgery or invasive dental procedures, if possible. Hold therapy for development of ONJ until complete resolution occurs.
Monitor ECG and electrolytes periodically during therapy; may cause QT prolongation and torsades de pointes.
Monitor for rash. If progressive skin rash with blisters or mucosal lesions or necrotizing fasciitis occurs, discontinue and do not restart sunitinib.
Monitor for signs and symptoms of PRES (hypertension, headache, decreased alertness, altered mental functioning, visual loss, including cortical blindness) during therapy. Magnetic resonance imaging is necessary to confirm diagnosis. Discontinue sunitinib in patients developing PRES.

Lab Test Considerations:

Monitor CBC with platelet count and serum chemistries including phosphate at the beginning of each treatment cycle. May cause neutropenia, lymphopenia, anemia, and thrombocytopenia. May cause ↑ serum creatinine, hypokalemia, and hyperuricemia.
- Monitor ALT, AST, and bilirubin before starting therapy, during each cycle of treatment, and as clinically indicated. If Grade 3 hepatotoxicity occurs, hold sunitinib until resolution to Grade 0 or 1 or baseline. Resume therapy at reduced dose. If Grade 3 hepatotoxocity recurs or Grade 4 hepatotoxicity occurs, permanently discontinue sunitinib. May cause ↑ AST, ALT, alkaline phosphatase, total and indirect bilirubin, amylase, and lipase.
- Monitor thyroid function at baseline and in patients with symptoms of hypothyroidism or hyperthyroidism. May be treated with standard medical practice.
- Monitor urinalysis for urine protein at baseline and periodically during therapy. Follow up with 24-hr urine protein as clinically indicated. If 3 grams proteinuria in 24 hrs in the absence of nephrotic syndrome occurs, hold sunitinib until resolution to Grade 0 or 1 or baseline. Resume therapy at reduced dose. If nephrotic syndrome or recurrent proteinuria of 3 grams per 24 hrs despite dose reductions occurs, permanently discontinue sunitinib.
- Monitor blood glucose levels periodically during and after therapy. Assess if antidiabetic drug dose needs to be adjusted to minimize the risk of hypoglycemia.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take sunitinib as directed. Take missed doses as soon as remembered if within 12 hr of missed dose. If >12 hr since missed dose, omit dose and take next dose at regular time. Do not take more than 1 dose at a time. Tell your health care professional about the missed dose.
Advise patient to avoid grapefruit juice and grapefruit products during therapy.
Instruct patient to notify health care professional promptly if signs and symptoms of liver failure (itching, yellow eyes or skin, dark urine, pain or discomfort in the right upper stomach area), rash, bleeding (painful, swollen abdomen, black, sticky stools, bloody urine, vomiting blood, headache, coughing up blood, change in your mental status), ONJ (tooth or jaw pain, jaw swelling) or tumor lysis syndrome (nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness) occur.
Advise patient that GI disorders (diarrhea, nausea, stomatitis, dyspepsia, vomiting) are common and may require antiemetic and antidiarrheal medications.
Inform patient that sunitinib may cause discoloration (yellow) of skin and depigmentation of hair or skin.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Advise patient to notify health care professionals of therapy. Therapy must be stopped for at least 3 wk before scheduled dental surgery, invasive dental procedures, or elective surgeries and then held for at least 2 wk after major surgery until adequate wound healing.
Advise patient to notify health care professional if bleeding or swelling occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and after therapy and to avoid breast feeding during and for 4 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 7 wks after last dose. May impair male and female fertility.

section name header

Pronunciation ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Implementation ⬆ ⬇

US Brand Names ⬆ ⬇

Classifications ⬆ ⬇

Availability ⬆ ⬇

Time/Action Profile ⬆ ⬇

Assessment ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

Code ⬆