SUNITINIB

SUNITINIB (sun-i-ti'nib) Sutent Classifications: antineoplastic agent; growth factor receptor inhibitor; tyrosine kinase inhibitor; Therapeutic:antineoplastic; growth factor receptor inhibitor; tyrosine kinase inhibitor Prototype: Gefitinib Pregnancy Category: D

Availability

12.5 mg, 25 mg, 50 mg capsules

Action

An antineoplastic agent that is a selective inhibitor of receptor tyrosine kinases (RTKs) in solid tumors. Carcinogenic activity within these tumors is a result of tumor angiogenesis and proliferation.

Therapeutic Effect

Sunitinib causes tumor regression and decreased tumor growth.

Uses

Treatment of advanced renal cell cancer; treatment of gastrointestinal stromal tumors (GIST) after disease progression on or intolerance to imatinib.

Contraindications

Hypersensitivity to sunitinib; uncontrolled hypertension, acute MI; fever, abnormal bleeding, sore throat; children, pregnancy (category D), lactation.

Cautious Use

Cardiac disease, CHF, history of hypertension, history of MI; CVA; females of childbearing age.

Route & Dosage

Advanced Renal Cell Cancer Adult: PO 50 mg/d for 4 wk, followed by 2 wk off treatment; repeat 6-wk cycle as needed. Dosage Adjustments with Concurrent Hepatic CYP3A4 Modifiers CYP3A4 Inducers: increase to maximum of 87.5 mg/d CYP3A4 Inhibitors: decrease to minimum of 37.5 mg/d

Administration

Oral

• Note that this drug is given on a 6-wk cycle: 4 wk on therapy and 2 wk off.
• Incremental dosage changes of 12.5 mg are recommended.
• Store at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

Body as a Whole: Alopecia, asthenia, dizziness, fatigue, fever, hair color change, headache, peripheral edema. CV: Hypertension, myocardial ischemia. GI: Abdominal pain, altered taste, anorexia, constipation, diarrhea, dyspepsia, flatulence, glossodynia, nausea, mucositis, stomatitis, vomiting. Hematologic: Anemia, bleeding, neutropenia, lymphopenia, thrombocytopenia. Metabolic: Dehydration, elevated hepatic enzymes (AST/ALT, alkaline phosphatase, pancreatic enzymes, amylasemia, lipasemia), hypothyroidism, hyperbilirubinemia. Musculoskeletal: Arthralgia, back pain, myalgia/limb pain. Respiratory: Cough, dyspnea. Skin: Dry skin, hand-foot syndrome, rash, skin discoloration.

Interactions

Drug: Coadministration of CYP3A4 inducers (e.g., carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) may decrease plasma levels of sunitinib. Coadministration of CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase plasma levels of sunitinib. Food: Grapefruit and grapefruit juice may increase the plasma levels of sunitinib. Herbal: St. John's wort may decrease the plasma levels of sunitinib.

Pharmacokinetics

Peak: 6–12 h. Distribution: 95–98% protein bound. Metabolism: Extensive hepatic metabolism. Elimination: Primarily fecal elimination (61%) with minor renal elimination. Half-Life: 40–60 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for and report S&S of bleeding (e.g., GI, GU, gingival, etc.).
• Monitor BP regularly and assess regularly for S&S of congestive heart failure. Withhold drug and notify physician if severe hypertension or signs of heart failure develop.
• Lab tests: At the beginning of each treatment cycle, CBC with differential and platelet count; periodic serum electrolytes; thyroid function tests with symptoms suggestive of hypothyroidism.

Patient & Family Education

• Follow directions for taking the drug (see Administration).
• Do not use any prescription or nonprescription drugs without consulting a physician.
• Skin discoloration (yellow color) and/or loss of skin and hair pigmentation may occur with this drug.
• Report any of the following to a health care provider: painful redness of palms and soles of feet; severe abdominal pain, vomiting, and diarrhea; signs of bleeding; chest pain or discomfort; shortness of breath; swelling of feet, legs, or hands; rapid weight gain.
• Women of childbearing age are advised not be become pregnant while taking sunitinib.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug