vandetanib

ROUTE	ONSET	PEAK	DURATION
PO	unknown	4–10 hr	24 hr

Contraindicated in:

Congenital long QT syndrome or QTcF interval >450 msec;
Hypocalcemia (serum calcium should be within normal range), hypokalemia (serum potassium should be >4.0 mEq/L and within normal range), or hypomagnesemia (serum magnesium should be within normal range);
Severe renal impairment (CCr <30 mL/min);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Diarrhea (↑ risk of electrolyte abnormalities and risk of arrhythmias);
Renal impairment (dose ↓ recommended for CCr 30–<50 mL/min with close monitoring of QT interval);
Moderate or severe hepatic impairment;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Concurrent use of other drugs know to prolong QT interval (avoid if possible; if medically necessary, monitoring is required).

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, HF, QT interval prolongation, TORSADES DE POINTES

Derm: acne, photosensitivity reaction, rash, impaired wound healing, pruritus, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

Endo: hypothyroidism

F and E: hypocalcemia

GI: ↓appetite, abdominal pain, diarrhea, nausea, dyspepsia, GI PERFORATION, vomiting

GU: proteinuria, renal failure

Hemat: BLEEDING

Neuro: fatigue, headache, depression, insomnia, REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY SYNDROME (RPLS), STROKE

Resp: INTERSTITIAL LUNG DISEASE (ILD), upper respiratory tract infection

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, and phenobarbital, may ↓ levels and effectiveness; avoid concurrent use.
Concurrent use with QT interval prolonging drugs, including some antiarrhythmics (amiodarone, disopyramide, procainamide, sotalol, dofetilide), chloroquine, clarithromycin, granisetron, haloperidol, methadone, moxifloxacin, and pimozide may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
May ↑ levels and the risk of toxicity of metformin and digoxin.

Drug-Natural Products:

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

Route/Dosage ⬆ ⬇

PO (Adults ): 300 mg once daily.

Renal Impairment

PO (Adults ): CCr 30–<50 mL/min: 200 mg once daily. CCr <30 mL/min: Not recommended.

Availability ⬆ ⬇

Tablets: 100 mg; 300 mg

Assessment ⬆ ⬇

May prolong the QT interval. Obtain ECG at baseline, at 2–4 wk, at 8–12 wk after starting therapy and every 3 mo thereafter. Use these parameters to assess QT interval following dose reduction for QT interval prolongation or dose interruption >2 wk. 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 ILD (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 HF (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 RPLS (seizures, headache, visual disturbances, confusion, altered mental status); discontinue therapy if symptoms occur.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- 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 wk, at 8–12 wk, 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, serum creatinine, serum bilirubin, and serum glucose.

Implementation ⬆ ⬇

Due to the cardiac risks, only prescribers and pharmacies certified with the Caprelsa REMS program are able to prescribe and dispense vandetanib. To learn about the specific REMS requirements and to enroll in the CAPRELSA REMS Program, call 1-800-817-2722 or visit www.caprelsarems.com.
Correct hypocalcemia, hypokalemia, and hypomagnesemia prior to therapy.
PO: May be administered daily without regard to food. DNC: Swallow tablets whole; do not crush, break, or chew. If unable to swallow tablet, tablet may be dispersed in a glass containing 2 oz 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 oz 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 hr 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.
May impair wound healing. Advise patient to notify health care professionals of therapy. Therapy must be stopped for at least 1 month before elective dental surgery, invasive dental procedures, or elective surgeries and then held for at least 2 wk after major surgery until adequate wound healing.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 4 mo after therapy and to avoid breastfeeding during therapy and for 4 month after final dose. May impair female and male fertility.
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.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

0310- AstraZeneca Pharmaceuticals LP
- 0310-7820- CAPRELSA
  - 0310-7820-30- 30 TABLET in 1 BOTTLE, PLASTIC (0310-7820-30)

0310- AstraZeneca Pharmaceuticals LP
- 0310-7840- CAPRELSA
  - 0310-7840-30- 30 TABLET in 1 BOTTLE, PLASTIC (0310-7840-30)

58468- Genzyme Corporation
- 58468-7820- CAPRELSA
  - 58468-7820-3- 1 BOTTLE, PLASTIC in 1 CARTON (58468-7820-3) > 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

58468- Genzyme Corporation
- 58468-7840- CAPRELSA
  - 58468-7840-3- 1 BOTTLE, PLASTIC in 1 CARTON (58468-7840-3) > 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇