The recommended daily dose is 300 mg of vandetanib taken orally. Vandetanib treatment should be continued until patients are no longer benefiting from treatment or an unacceptable toxicity occurs.
Vandetanib may be taken with or without food.
If a patient misses a dose, the missed dose should not be taken if it is less than 12 hours before the next dose.
For Patients who have Difficulty Swallowing Solids
Vandetanib tablets should not be crushed. If vandetanib tablets cannot be taken whole, the tablets can be dispersed in a glass containing 2 ounces of non-carbonated water and stirred for approximately 10 minutes until the tablet is dispersed (will not completely dissolve). No other liquids should be used. The dispersion should be swallowed immediately. To ensure the full dose is received, any residues in the glass should be mixed again with an additional 4 ounces of non-carbonated water and swallowed.
The dispersion can also be administered through nasogastric or gastrostomy tubes.
Direct contact of crushed tablets with the skin or mucous membranes should be avoided. If such contact occurs, wash thoroughly. Avoid exposure to crushed tablets.
2.1 Dosage AdjustmentIn the event of corrected QT interval, Fridericia (QTcF) greater than 500 ms, interrupt dosing until QTcF returns to less than 450 ms, then resume at a reduced dose.
For CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or greater toxicity, interrupt dosing until toxicity resolves or improves to CTCAE grade 1, and then resume at a reduced dose.
Because of the 19-day half-life, adverse reactions including a prolonged QT interval may not resolve quickly. Monitor appropriately [see Warnings and Precautions (5.1-5.7, 5.9)].
The 300-mg daily dose can be reduced to 200 mg (two 100-mg tablets) and then to 100 mg for CTCAE grade 3 or greater toxicities.
2.2 Elderly
No adjustment in starting dose is required for patients over 65 years of age. There are limited data for patients over the age of 75. [see Dosage and Administration (2.4)]
2.3 Concomitant Strong CYP3A4 Inducers
Avoid the concomitant use of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital). Patients should also avoid taking St. John’s Wort. [see Warnings and Precautions (5.11)and Drug Interactions (7.1)]
2.4 Patients With Renal Impairment
The starting dose should be reduced to 200 mg in patients with moderate (creatinine clearance ≥30 to <50 mL/min) and severe (creatinine clearance <30 mL/min) renal impairment. [see Warnings and Precautions (5.12)and Use in Specific Populations (8.6)]
2.5 Patients with Hepatic Impairment
Single dose pharmacokinetic data from volunteers with hepatic impairment receiving 800 mg suggest that there were no differences in pharmacokinetics compared to patients with normal hepatic function. There are limited data in patients with liver impairment (serum bilirubin greater than 1.5 times the upper limit of normal). Vandetanib is not recommended for use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, as safety and efficacy have not been established.
