vandetanib

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.

Availability ⬆ ⬇

Tablets: 100 mg; 300 mg

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.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Inhibits tyrosine kinase; results in inhibited action of epidermal growth factor (EGFR), vascular endothelial cell growth factor, 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.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Mostly metabolized by the liver; 44% excreted in feces, 25% in urine.

Half-Life: 19 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

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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Indications ⬇

Contraind./Precautions ⬆ ⬇