vandetanib


vandetanib

(van-det-a-nib) vandetanib,

Caprelsa

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Treatment of symptomatic/progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease.

Action

Inhibits tyrosine kinase; results in inhibited action of epidermal growth factor (EGFR), vascular endothelial cell growth factor (VEGF) and other kinase based actions. Inhibits endothelial cell migration/proliferation/survival and new blood vessel formation. Also inhibits EGFR-dependent cell survival.

Therapeutic effects

Decreased spread of thyroid cancer.

Pharmacokinetics

Absorption: Well absorbed following oral administration.Distribution: Unknown.Metabolism and Excretion: Mostly metabolized by the liver; 44% excreted in feces, 25% in urine.Half-life: 19 days.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown4–10 hr24 hr

Contraindications/Precautions

Contraindicated in: Congenital long QT syndrome or QTcF interval >450 msec;Hypocalcemia (serum calcium should be within normal range), hypokalemia (serum potassium should >4.0 mEq/L and within normal range), or hypomagnesemia (serum magnesium should be within normal range);Concurrent use of strong inducers of the CYP3A4 enzyme system; Obstetric: Can cause fetal harm; Lactation: Avoid breast feeding.Use Cautiously in: Diarrhea (↑ risk of electrolyte abnormalities and risk of arrhythmias);Renal impairment (dose ↓ recommended for CCr <50 mL/min with close monitoring of QT interval);Moderate to severe hepatic impairment (Child-Pugh Class B or C; safety and effectiveness not established); Obstetric: Women with childbearing potential; Pediatric: Safety and effectiveness not established.Exercise Extreme Caution in: Concurrent use of other drugs know to prolong QT interval (avoid if possible; if medically necessary, monitoring is required).

Adverse Reactions/Side Effects

Central nervous system

  • reversible posterior leukoencephalopathy syndrome (life-threatening)
  • fatigue (most frequent)
  • headache (most frequent)
  • depression
  • insomnia
  • reversible posterior leukoencephalopathy

Respiratory

  • interstitial lung disease (life-threatening)

Cardiovascular

  • heart failure (life-threatening)
  • ischemic cerebrovascular events (life-threatening)
  • torsade de pointes (life-threatening)
  • hypertension (most frequent)
  • QT interval prolongation

Gastrointestinal

  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • dyspepsia
  • intestinal perforation
  • vomiting

Genitourinary

  • proteinuria

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • acne (most frequent)
  • photosensitivity reaction (most frequent)
  • rash (most frequent)
  • skin reactions (most frequent)
  • pruritus

Endocrinologic

  • hypothyroidism

Fluid and Electrolyte

  • hypocalcemia

Hematologic

  • bleeding (life-threatening)

Interactions

Drug-Drug interaction

Concurrent use of strong inducers of the CYP3A4 enzyme system including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, and phenobartital ; may ↓ levels and effectiveness and should be avoided.Concurrent use with other drugs that prolong the QT interval should avoided including some antiarrhythmics (amiodarione, disopyramide, procainamide, sotalol, dofetilide ), chloroquine, clarithromycin, dolasetreon, granisetron, haloperidol, methadone, moxifloxacin, and pimozide.St. John's Wort may ↓ levels and effectiveness and should be avoided.

Route/Dosage

Oral (Adults) 300 mg once daily.

Renal Impairment

Oral (Adults) CCr <50 mL/min—200 mg once daily.

Availability

Tablets: 100 mg, 300 mg

Nursing implications

Nursing assessment

  • May prolong QT intervals. Obtain ECG at baseline, at 2–4 wks, at 8–12 wks after starting therapy and every 3 mo there after. Use these parameters to assess QT interval following dose reduction for QT prolongation or dose interruption >2 wks. May require more frequent monitoring if diarrhea occurs.
  • Assess patient for rash periodically during therapy. Mild to moderate skin reactions may include rash, acne, dry skin, dermatitis, and pruritus and may be treated with topical or systemic corticosteroids, oral antihistamines, and topical and systemic antibiotics. Treatment of severe rash (Grade 3 or greater) may include systemic corticosteroids and discontinuation of treatment until improved. Upon improvement, may be restarted at a reduced dose.
  • Assess for signs and symptoms of interstitial lung disease (hypoxia, pleural effusion, cough, dyspnea). If radiological changes occur with few or no symptoms, therapy may continue. If symptoms are moderate, consider interrupting therapy until symptoms improve. If symptoms are severe, discontinue therapy; permanent discontinuation should be considered. Treat with antibiotics and corticosteroids.
  • Assess for signs and symptoms of heart failure (intake and output rations, daily weight, peripheral edema, rales and crackles upon lung auscultation, dyspnea) periodically during therapy.
  • Monitor BP during therapy. Control hypertension during therapy.
  • Monitor for diarrhea. If severe diarrhea develops, hold therapy until resolved.
  • Monitor for signs and symptoms of reversible posterior leukoencephalopathy syndrome (seizures, headache, visual disturbances, confusion, altered mental status); may require discontinuation of therapy.
  • Lab Test Considerations: Monitor serum calcium, potassium, and magnesium periodically during therapy. Maintain serum potassium at ≥4 mEq/L. Maintain serum calcium and magnesium within normal limits. May require more frequent monitoring if diarrhea occurs.
    • Monitor TSH at baseline, at 2–4 wks, at 8–12 wks, and every 3 mo thereafter in patients with thyroidectomy. If symptoms of hypothyroidism occur, check TSH levels and adjust thyroid replacement.
    • May cause ↓ serum glucose, WBC, hemoglobin, neutrophils, and platelets.
    • May cause ↑ serum ALT, creatinine, bilirubin, and glucose.

Potential Nursing Diagnoses

Activity intolerance

Implementation

  • Only prescribers and pharmacies certified with the Caprelsa REMS program are able to prescribe and dispense vandetanib.
  • Correct hypocalcemia, hypokalemia, and hypomagnesemia prior to therapy.
  • Oral: May be administered daily without regard to food. Swallow tablets whole, do not crush, break or chew. If unable to swallow tablet, tablet may be dispersed in a class containing 2 ounces of non-carbonated water and stirred for approximately 10 min until tablet is dispersed (will not completely dissolve). No other liquids should be used. Swallow dispersion immediately, then mix any residue with 4 ounces of non-carbonated water and swallow. Dispersion may also be administered through nasogastric or gastrostomy tubes. Avoid direct contact with crushed tablets with skin or mucous membranes. Wash thoroughly to avoid exposure.

Patient/Family Teaching

  • Instruct patient to take vandetanib as directed. Take missed doses as soon as remembered unless within 12 hrs of next dose. Instruct patient to read Medication Guide prior to starting therapy and with each Rx refill in case of changes.
  • Advise patients to notify health care professional if rash or signs and symptoms of interstitial lung disease or reversible posterior leukoencephalopathy syndrome. If diarrhea occurs, instruct patient to treat with antidiarrheal medications and notify health care professional if diarrhea becomes severe or persistent.
  • May cause tiredness, weakness, or blurred vision. Caution patients to avoid driving or other activities requiring alertness until response to medication is known.
  • Caution patient to wear sunscreen and protective clothing during and for 4 mo after therapy is discontinued to prevent photosensitivity reactions.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
  • Advise female patients to use effective contraception during and for 4 mo after therapy and to avoid breast feeding.
  • Emphasize the importance of regular follow-up exams, ECGs, and blood counts to determine progress and monitor for side effects.

Evaluation/Desired Outcomes

  • Decreased spread of thyroid cancer.