Usual Adult Dose for Thyroid Cancer

Initial dose: 300 mg orally once daily.
Duration of therapy: Continue drug until disease progression or unacceptable toxicity occurs.

Use: For the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Renal Dose Adjustments

Mild renal impairment (CrCl 50 mL/min or greater): No dose adjustment recommended.
Moderate to severe renal impairment (CrCl less than 50 mL/min): Initial dose: 200 mg orally once daily.

Liver Dose Adjustments

Mild hepatic impairment: No dose adjustment recommended.
Moderate and severe hepatic impairment: Use not recommended.

Dose Adjustments

QT Interval Prolongation:

• For corrected QT interval Fridericia (QTcF) greater than 500 milliseconds (msec): Interrupt therapy; may resume at a reduced dose when QTcF returns to less than 450 msec.

• For common terminology criteria for adverse event (CTCAE) Grade 3 or greater: Interrupt therapy; may resume at reduced dose of 200 mg orally once daily when toxicity resolves or improves to CTCAE grade 1.

• For recurrent toxicities: Interrupt therapy; may resume at reduced dose of 100 mg orally once daily when toxicity resolves or improves to CTCAE grade 1; assess if continued treatment is warranted.

Precautions

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. It includes a medication guide, communication plan, elements to assure safe use, and implementation system. For additional information: www.fda.gov/REMS.

US BOXED WARNINGS:

• Vandetanib can prolong the QT interval.
• Torsades de pointes and sudden death have occurred in patients receiving vandetanib.

• Do not use in patients with long QT syndrome.
• Do not use in patients with hypocalcemia, hypokalemia, hypomagnesemia; correct electrolyte levels prior to administration and monitor electrolytes periodically.
• Avoid use with drugs known to prolong the QT interval.
• Only prescribers and pharmacies certified with the restricted distribution program may prescribe and dispense vandetanib.

Dialysis

Data not available

Other Comments

Administration advice:

• May be taken with or without food.
• Do not crush or chew tablets; swallow whole with water.
• For patients who have difficulty swallowing tablets, a dispersion of the tablet in water may be used: Drop tablet in 2 ounces of non-carbonated water, stir for about 10 minutes (tablet will not completely dissolve); swallow the dispersion immediately; to ensure complete dosing, mix any remaining residue with 4 ounces of non-carbonated water and swallow. The dispersion may also be administered through nasogastric or gastrostomy tubes.
• If contact occurs with crushed tablet, wash affected area well with water.
• Missed dose: If a dose is missed, the missed dose should be skipped if it is less than 12 hours before the next scheduled dose. Patients should not take a double dose to make up for a missed dose.

• For patients with indolent, asymptomatic, or slowly progressing disease, carefully consider treatment-related risks.
• Treatment should be initiated and supervised by a clinician experienced with the management of medullary thyroid cancer, use of anticancer medicinal products, and experienced in the assessment of ECGs.

• Obtain an ECG, serum potassium, calcium, magnesium, and TSH, at baseline, at 2 to 4 weeks, at 8 to 12 weeks, and every 3 months thereafter; maintain potassium at 4 mEq/L or higher (within normal range).
• Monitor electrolytes and ECG more frequently as clinically indicated.
• Perform ophthalmologic examination, including slit lamp examination, in patients who experience visual changes.

• Advise patient to contact healthcare provider if they experience cardiac symptoms, skin reactions, respiratory symptoms, diarrhea, or CNS symptoms such as seizures, visual disturbances, or difficulty thinking.
• Advise patient to use effective contraception during therapy and for 4 months following the last dose; if pregnancy is suspected, patients should seek medical advice and counseling.
• Advise patient to use appropriate sun protection during therapy and for 4 months following the last dose.