SUNItinib


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SUNItinib

(su-ni-ti-nib) ,

Sutent

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Gastrointestinal stromal tumor (GIST) that has progressed or intolerance to imatinib.Advanced renal cell carcinoma (RCC).Advanced pancreatic neuroendocrine tumors (pNET).

Action

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

Therapeutic effects

Decreased tumor spread.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: Sunitinib—95%; primary active metabolite—90%.
Metabolism and Excretion: Metabolized by the CYP3A4 enzyme system 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 (blood levels)

ROUTEONSETPEAKDURATION
POunknown6–12 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy, lactation;Concurrent use of ketoconazole or St. John's wort.
Use Cautiously in: Hepatic/renal impairment;Concurrent use of bisphosphonates or a history of dental disease (may ↑ risk of jaw osteonecrosis) Obstetric: Childbearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • Reversible Posterior Leukoencephalopathy Syndrome (life-threatening)
  • fatigue (most frequent)
  • dizziness
  • headache

Cardiovascular

  • chf (life-threatening)
  • hypertension (most frequent)
  • peripheral edema
  • QT interval prolongation
  • thromboembolic events

Ear, Eye, Nose, Throat

  • epistaxis (most frequent)

Gastrointestinal

  • hepatotoxicity
  • diarrhea (most frequent)
  • dyspepsia (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • altered taste
  • anorexia
  • cholecystitis
  • constipation
  • esophagitis
  • ↑ lipase/amylase
  • ↑ liver enzymes
  • oral pain

Dermatologic

  • erythema multiforme (life-threatening)
  • alopecia
  • hand-foot syndrome
  • hair color change
  • impaired wound healing
  • rash
  • skin discoloration

Endocrinologic

  • hypothyroidism (most frequent)
  • adrenal insufficiency
  • hyperthyroidism

Fluid and Electrolyte

  • dehydration
  • hypophosphatemia

Hematologic

  • hemorrhage
  • anemia (most frequent)
  • lymphopenia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • hyperuricemia (most frequent)

Musculoskeletal

  • arthralgia
  • back pain
  • limb pain
  • myalgia
  • osteonecrosis (primarily of jaw)

Miscellaneous

  • tumor lysis syndrome (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Ketoconazole and other inhibitors of the CYP3A4 enzyme system may ↑ levels and the risk of toxicity; ↓ dose to 37.5 mg daily (for GIST and RCC) or 25 mg daily (for pNET); avoid these strong inhibitors, if possible.Rifampin and other inducers of the CYP3A4 enzyme system may ↓ levels and effectiveness; ↑ dose to 87.5 mg daily (for GIST and RCC) or 62.5 mg daily (for pNET); avoid these strong inducers, if possible.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).St. John's wort may ↓ levels and effectiveness; avoid concurrent use.Blood levels and effects are ↑ by grapefruit juice; concurrent use should be avoided.

Route/Dosage

GIST and RCC

Oral (Adults) 50 mg once daily for 4 wk, followed by 2-wk rest; alteration of dose is based on safety/tolerability and is made in 12.5-mg increments/decrements.

pNET

Oral (Adults) 37.5 mg once daily.

Availability

Capsules: 12.5 mg, 25 mg, 37.5 mg, 50 mg

Nursing implications

Nursing 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. Discontinue sunitinib if signs of HF occur.
  • Monitor for hypertension and treat with standard antihypertensive therapy. If severe hypertension occurs, may discontinue sunitinib until controlled.
  • Monitor ECG and electrolytes periodically during therapy; may cause QT prolongation and torsades de pointes.
  • 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 ↑ creatinine, hypokalemia, hyperuricemia, and ↑ uric acid.
    • Monitor ALT, AST, and bilirubin before starting therapy, during each cycle of treatment, and as clinically indicated. Stop therapy if Grade 3 or 4 drug-related hepatic adverse events occur and discontinue if there is no resolution. Do not restart sunitinib if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure. 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.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)
Nausea (Adverse Reactions)

Implementation

  • Do not confuse sunitinib with sorafenib.
  • Oral: Administer once daily with or without food.

Patient/Family Teaching

  • Instruct patient to take sunitinib as directed. Take missed doses as soon as remembered, but not just before next dose. 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 of liver failure (itching, yellow eyes or skin, dark urine, pain or discomfort in the right upper stomach area) 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.
  • Advise patient to notify health care professional if bleeding or swelling occur.
  • Advise women of childbearing potential to avoid becoming pregnant while receiving sunitinib.

Evaluation/Desired Outcomes

  • Decrease in tumor spread.
References in periodicals archive ?
It is based on findings from the pivotal Phase 3 Keynote-426 trial, which demonstrated that Keytruda in combination with axitinib reduced the risk of death by 47% compared with sunitinib in patients with advanced RCC.
This study's objective was to evaluate the therapeutic impact of combining ilixadencel with Sutent (sunitinib).
Based on a 2-to-1 randomization, patients received either two intratumoral doses of ilixadencel before nephrectomy (surgical removal of the tumor-affected kidney) and subsequent treatment with sunitinib or sunitinib therapy alone post-nephrectomy.
Deciphera expects to submit an NDA to the FDA in the first quarter of 2020 for the treatment of patients with advanced gastrointestinal stromal tumors who have receive prior treatment with Imatinib, Sunitinib and Regorafenib.
Prior information notice without call for competition: Supply of exclusive medicines: sunitinib
Summary: The demand of sunitinib malate is increasing, and global advancement of technology and increasing prevalence of pancreatic cancer are the prime growth drivers of the global sunitinib malate market.
This randomized controlled trial enrolled 450 patients, with intermediate and poor-risk MSKCC criteria, over 10 years across multiple centers in Europe and randomly assigned patients to receive either sunitinib alone (n=224) or to undergo CN followed by sunitinib (n=226).
Muna's MSc research thesis, titled 'The Role of p90 Ribosomal S6 Kinase and Autophagy in Sunitinib and Ponatinib-Induced Cardiotoxicity', investigated the cardiotoxic effects associated with ponatinib and sunitinib, small molecules tyrosine kinase inhibitors, used for various types of cancer.
The study found that patients who received the immunotherapy drug avelumab plus axitinib, a targeted agent, had a significant advantage in progression-free survival compared with those who received sunitinib (Sutent), a targeted drug that has been a standard treatment for advanced clear cell renal cell carcinoma - the most common form of kidney cancer.
New York, NY, November 22, 2018 --(PR.com)-- The research on "Sunitinib Stimulates Expression of VEGFC by Tumor Cells and Promotes Lymphangiogenesis In Clear Cell Renal Cell Carcinomas" was conducted by Maeva Dufies, Sandy Giuliano, Gilles Pages and team.
MONDAY, June 4, 2018 (HealthDay News) -- For patients with metastatic renal cell carcinoma classified as having intermediate or poor prognostic risk, sunitinib alone is noninferior to nephrectomy and sunitinib, according to a study published online June 3 in the New England Journal of Medicine.
In patients with imatinib-resistant or imatinib-intolerant GIST, sunitinib has shown promising benefit in phase I-III clinical trials and is now widely recognized as second-line therapy worldwide.