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 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 and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Exercise Extreme Caution in:

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

GU: proteinuria, renal failure

Hemat: BLEEDING

Metab: ↓appetite

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. If QTcF interval >500 msec, stop vandetanib until QTcF interval <450 msec; then restart vandetanib at a ↓ dose.
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) may include systemic corticosteroids and discontinuation of treatment until improved; then restart vandetanib at a ↓ dose.
Assess for signs and symptoms of ILD (hypoxia, pleural effusion, cough, dyspnea). For acute or worsening pulmonary symptoms, interrupt therapy and discontinue vandetanib if ILD confirmed.
Monitor for signs and symptoms of ischemic cerebrovascular event; discontinue vandetanib if symptoms occur.
Assess for signs and symptoms of HF (intake and output, daily weight, peripheral edema, rales, dyspnea) periodically during therapy.
Assess for signs of easy bruising and bleeding. If severe hemorrhage occurs, discontinue vandetanib.
Monitor BP and control hypertension during therapy.
Monitor for diarrhea, electrolyte imbalances, and dehydration. If severe diarrhea occurs, hold therapy until resolved; then resume vandetanib at a ↓ dose.
Monitor for signs and symptoms of RPLS (seizures, headache, visual disturbances, confusion, altered mental status); discontinue vandetanib if symptoms occur.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Correct hypocalcemia, hypokalemia, and hypomagnesemia prior to 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 ↓ serum glucose, WBC, hemoglobin, neutrophils, and platelets.
- May ↑ serum ALT, creatinine, bilirubin, and glucose.

Implementation ⬆ ⬇

REMS: 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 requirements and to enroll in the CAPRELSA REMS Program, call 1-800-817-2722 or visit www.caprelsarems.com.
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 ounces of noncarbonated 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 noncarbonated 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.
Emphasize the importance of regular follow-up exams, ECGs, and blood counts to determine progress and monitor for side effects.
Advise patients to notify health care professional if rash or signs and symptoms of ILD or RPLS occur. If diarrhea occurs, instruct patient to treat with antidiarrheal medications, maintain hydration, 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 ≥1 mo before elective dental surgery, invasive dental procedures, or elective surgeries and then held for ≥2 wk after major surgery until adequate wound healing.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during and for 4 mo after therapy and to avoid breastfeeding during therapy and for 4 mo after final dose. May impair female and male fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇