Vandetanib

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. CAPRELSA is a kinase inhibitor indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

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.

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. 300 mg once daily. Dosage reduction may be necessary in the event of severe toxicities or QTc interval prolongation. The starting dose is 200 mg in patients with moderate renal impairment.

Do not use in patients with congenital long QT syndrome.

Boxed warning (qt prolongation, torsades de pointes, and sudden death 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. Prolonged QT interval, torsades de pointes, and sudden death: Monitor electrocardiograms and levels of serum potassium, calcium, magnesium and TSH. Reduce CAPRELSA dose as appropriate. Severe skin reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, some fatal. Discontinue CAPRELSA for severe skin reactions. Interstitial lung disease (ILD), including fatalities: investigate unexplained non-specific respiratory signs and symptoms.

The following serious adverse reactions are discussed elsewhere in the label: QT Prolongation and Torsades de Pointes Severe Skin Reactions Interstitial Lung Disease Ischemic Cerebrovascular Events Hemorrhage Heart Failure Diarrhea Hypothyroidism Hypertension Reversible Posterior Leukoencephalopathy Syndrome Renal Failure Embryo-Fetal Toxicity Osteonecrosis The most common adverse drug reactions (>20%) seen with CAPRELSA and with a between-arm difference of ≥5 % have been diarrhea/colitis, rash, acneiform dermatitis, hypertension, nausea, headache, upper respiratory tract infections, decreased appetite and abdominal pain.

Avoid the use of strong CYP3A4 inducers because they may decrease CAPRELSA exposure. Avoid the use of agents that prolong the QT interval.

CAPRELSA tablets should be stored at room temperature between 68°F and 77°F (20°C and 25°C), excursions permitted to 59°F–86°F (15°C-30°C).