Vandetanib Dosage

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Usual Adult Dose for:

Additional dosage information:

Usual Adult Dose for Thyroid Cancer

Initial dose: 300 mg orally once daily. Treatment should continue until the patient no longer benefits from therapy or unacceptable toxicity occurs.

Renal Dose Adjustments

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

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): Data not available
Moderate to severe liver dysfunction (Child-Pugh B or C): Not recommended

Dose Adjustments

No dosage adjustment is recommended based on gender, ethnicity, or geriatric status.

For a corrected QT interval, Fridericia (QTcF) greater than 500 ms, dosing of vandetanib should be interrupted until QTcF returns to less than 450 ms, then vandetanib may be resumed at a reduced dose.

For CTCAE (Common Terminology Criteria for Adverse Events) grade 3 or greater toxicity, dosing of vandetanib should be interrupted until the toxicity resolves or improves to CTCAE grade 1, then vandetanib may be resumed at a reduced dose.

For CTCAE grade 3 or greater toxicities, the 300 mg daily dose can be reduced to 200 mg daily and then to 100 mg daily as necessary.

Precautions

Vandetanib can prolong the QT interval in a concentration-dependent manner and has been associated with Torsades de pointes, ventricular tachycardia, and sudden death. Vandetanib should not be administered to patients with a QTcF interval greater than 450 ms, a history of Torsades de pointes, hypocalcemia, hypokalemia, hypomagnesemia, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure. Use of vandetanib should be avoided in patients receiving other drugs known to prolong the QT interval. Use of vandetanib in patients with ventricular arrhythmias or recent myocardial infarction has not been evaluated. Electrolyte abnormalities (i.e., hypocalcemia, hypokalemia, hypomagnesemia) should be corrected prior to initiating treatment with vandetanib. Serum electrolytes (i.e., potassium, calcium, magnesium), thyroid stimulating hormone (TSH) levels, and ECGs to monitor the QT interval are recommended at baseline, at 2 to 4 weeks, and 8 to 12 weeks after starting treatment with vandetanib and every 3 months thereafter. The recommended ECG monitoring for QT assessment should be repeated after any dose reduction for QT prolongation or any dose interruptions greater than 2 weeks. If vandetanib is administered concomitantly with another drug known to prolong the QT interval, more frequent ECG monitoring is recommended. In addition, more frequent monitoring of electrolytes and ECG may be necessary in patients with diarrhea. In patients who develop a QTcF greater than 500 ms, treatment with vandetanib should be interrupted until the QTcF returns to less than 450 ms and dosing of vandetanib can be resumed at a reduced dose.

Use of vandetanib in combination with strong inducers of CYP450 3A4 (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) should be avoided. Concomitant use of St. John's Wort should also be avoided.

If CTCAE grade 3 or greater skin reaction occurs, treatment with vandetanib should be interrupted until the reaction has improved. After the skin reaction has improved, a dose reduction or permanent discontinuation of vandetanib should be considered. In order to avoid photosensitivity reactions during periods of sun exposure, patients should be advised to wear sunscreen and protective clothing during the treatment period and for 4 months after discontinuation of vandetanib.

Interstitial lung disease (ILD) or pneumonitis with fatalities have been reported in patients treated with vandetanib. ILD should be considered in patients experiencing nonspecific respiratory symptoms such as hypoxia, pleural effusion, cough or dyspnea, and in whom infectious, neoplastic, and other causes have been excluded. Patients should contact their healthcare provider if any new or worsening respiratory symptoms develop. Treatment with vandetanib may continue with close monitoring in patients who develop radiological changes suggestive of ILD, but have few or no symptoms. In patients experiencing moderate respiratory symptoms, interruption of treatment with vandetanib should be considered until symptoms improve. If symptoms of ILD are severe, vandetanib should be discontinued until symptoms resolve. Permanent discontinuation of vandetanib should be considered in patients who experience severe symptoms of ILD. Use of corticosteroids and antibiotics may be considered in patients with moderate to severe symptoms of ILD.

Following an ischemic cerebrovascular event, the safety of continued treatment with vandetanib is unknown. In patients who experience a severe ischemic cerebrovascular event, treatment with vandetanib should be discontinued.

Vandetanib should not be used in patients with a recent history of hemoptysis of greater than or equal to half teaspoon of red blood and vandetanib should be discontinued in patients with severe hemorrhage.

Patients should be monitored for signs and symptoms of heart failure during treatment. Discontinuation of vandetanib may be required in patient with heart failure.

Diarrhea frequently occurs in patients treated with vandetanib; therefore, routine use of antidiarrheals are recommended. Since diarrhea may cause electrolyte disturbances, serum electrolytes and ECG should be closely monitored in patients with diarrhea. In patients with severe diarrhea, treatment with vandetanib should be temporarily interrupted until diarrhea improves. After improvement, treatment with vandetanib may be resumed at a reduced dose.

Blood pressure should be monitored during treatment with vandetanib. A dose reduction or interruption of vandetanib treatment may be required in patients who develop hypertension. Treatment with vandetanib should not be restarted if hypertension cannot be controlled.

Discontinuation of vandetanib should be considered in patients who develop reversible posterior leukoencephalopathy syndrome.

Adverse events may not resolve quickly because of vandetanib's long half-life (19 days); therefore, appropriate monitoring is recommended.

Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Dialysis

Data not available

Other Comments

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for vandetanib. It includes a Medication Guide, communication plan, elements to assure safe use, and an implementation system. Additional information is available at www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm.

Vandetanib may be administered with or without food.

If a dose is missed, the missed dose should be skipped if it is less than 12 hours before the next scheduled dose.

Vandetanib tablets should not be crushed and direct contact (skin or mucous membranes) with crushed tablets should be avoided. If contact with crushed tablets occurs, thorough washing is recommended. However, in patients who have difficulty swallowing solids, vandetanib tablets can be dispersed in a glass containing 2 ounces of noncarbonated water and stirred for about 10 minutes until the tablet is dispersed (it will not completely dissolve). No other liquids should be used. The dispersion should be swallowed immediately and any residue in the glass should be mixed with an additional 4 ounces of noncarbonated water and swallowed. The dispersion may also be administered through nasogastric or gastrostomy tubes.

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