Vandetanib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- CAPRELSA
Boxed Warning
CAPRELSA can prolong the QT interval. Torsades de pointes and sudden death have occurred in patients receiving CAPRELSA. Do not use CAPRELSA in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome. Correct hypocalcemia, hypokalemia and/or hypomagnesemia prior to CAPRELSA administration. Monitor electrolytes periodically. Avoid drugs known to prolong the QT interval [see Warnings and Precautions (5.1)].
Indications and Usage
CAPRELSA is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease. Use CAPRELSA in patients with indolent, asymptomatic or slowly progressing disease only after careful consideration of the treatment related risks of CAPRELSA.
Dosage and Administration
The recommended dose of CAPRELSA is 300 mg taken orally once daily until disease progression or unacceptable toxicity occurs. CAPRELSA may be taken with or without food. Do not take a missed dose within 12 hours of the next dose. Do not crush CAPRELSA tablets. The tablets can be dispersed in 2 ounces of water by stirring for approximately 10 minutes (will not completely dissolve). Do not use other liquids for dispersion. Swallow immediately after dispersion. Mix any remaining residue with 4 additional ounces of water and swallow. The dispersion can also be administered through nasogastric or gastrostomy tubes.
Contraindications
Do not use in patients with congenital long QT syndrome [see Boxed Warning].
Adverse Reactions
The following serious adverse reactions are discussed elsewhere in the label: QT Prolongation and Torsades de Pointes [see Boxed Warning, Warnings and Precautions (5.1)] Severe Skin Reactions [see Warnings and Precautions (5.2)] Interstitial Lung Disease [see Warnings and Precautions (5.3)] Ischemic Cerebrovascular Events [see Warnings and Precautions (5.4)] Hemorrhage [see Warnings and Precautions (5.5)] Heart Failure [see Warnings and Precautions (5.6)] Diarrhea [see Warnings and Precautions (5.7)] Hypothyroidism [see Warnings and Precautions (5.8)] Hypertension [see Warnings and Precautions (5.9)] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.10)] Renal Failure [see Warnings and Precautions (5.12)] Embryo-Fetal Toxicity [see Warnings and Precautions (5.15)] Osteonecrosis [see Warnings and Precautions (5.16)]
Mechanism of Action
In vitro studies have shown that vandetanib inhibits the tyrosine kinase activity of the EGFR and VEGFR families, RET, BRK, TIE2, and members of the EPH receptor and Src kinase families. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment. In addition, the N-desmethyl metabolite of the drug, representing 7 to 17.1% of vandetanib exposure, has similar inhibitory activity to the parent compound for VEGF receptors (KDR and Flt-1) and EGFR. In vitro, vandetanib inhibited epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells. In vivo, vandetanib administration reduced tumor cell-induced angiogenesis, tumor vessel permeability, and inhibited tumor growth and metastasis in mouse models of cancer.
Overdosage
In the event of an overdose, monitor patients closely for QTc prolongation. Adverse events including QT interval prolongation should be monitored closely as they may not resolve fully until approximately three plasma half-lives of the drug.