sunitinib

Contraindicated in:

Hypersensitivity;
New York Heart Association class II-IV HF;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Renal impairment;
Hepatic impairment;
Concurrent use of bisphosphonates or a history of dental disease (may ↑ risk of osteonecrosis of the jaw [ONJ]);
History of myocardial ischemia or MI;
Left ventricular ejection fraction <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: hypertension, DEEP VEIN THROMBOSIS, HF, MI, peripheral edema, QT interval prolongation, TORSADES DE POINTES

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

EENT: epistaxis

Endo: hypoglycemia, hypothyroidism, adrenal insufficiency, hyperthyroidism

F and E: dehydration, hypophosphatemia

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

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

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

Metab: hyperuricemia

MS: arthralgia, back pain, limb pain, myalgia, osteonecrosis (primarily ONJ)

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

Resp: PULMONARY EMBOLISM

Misc: fever, TUMOR LYSIS SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, includingketoconazole, may ↑ levels and the risk of toxicity; avoid concurrent use, if possible. If concurrent use necessary, ↓ sunitinib dose.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use, if possible. If concurrent use necessary, ↑ sunitinib dose.
Concurrent use with alendronate, ibandronate, pamidronate, risedronate, 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.

Availability ⬆ ⬇

(Generic available)

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

Route/Dosage ⬆ ⬇

Gastrointestinal Stromal Tumor and Renal Cell Carcinoma

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 inhibitors: 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 inducers: 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 Renal Cell Carcinoma

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 inhibitors: 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 inducers: 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.

Pancreatic Neuroendocrine Tumor

PO (Adults ): 37.5 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inhibitors: 25 mg once daily until disease progression or unacceptable toxicity. Concurrent use of strong CYP3A4 inducers: 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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits multiple receptor tyrosine kinases, which are enzymes implicated in tumor growth, abnormal vascular growth, and tumor metastases.

Therapeutic effects:

Decreased tumor spread.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Protein Binding: Sunitinib: 95%; primary active metabolite: 90%.

Metabolism/Excretion: Metabolized by the liver via the CYP3A4 isoenzyme to its primary active metabolite. This metabolite is further metabolized by CYP3A4. Excretion is primarily fecal.

Half-Life: Sunitinib: 40–60 hr; primary active metabolite: 80–110 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

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 breastfeeding during and for 4 wk after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for 7 wk after last dose. May impair male and female fertility.

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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆