ased
18 (9%)
0
3 (3%)
0
Alanine aminotransferase elevations occurred in 51% of patients on Vandetanib in the randomized medullary thyroid cancer (MTC) study. Grade 3-4 ALT elevations were seen in 2% of patients and no patients had a concomitant increase in bilirubin. Elevations in ALT have resulted in temporary discontinuation of Vandetanib. However, 16 of 22 patients with a grade 2 elevation in ALT continued 300 mg Vandetanib. Seven patients who continued Vandetanib had a normal ALT within 6 months. In the protocol, ALT was monitored every 3 months and more frequently as indicated.
7. DRUG INTERACTIONS
CYP3A4 Inducers
Drugs that are CYP3A4 inducers can alter Vandetanib plasma concentrations. The concomitant use of known strong CYP3A4 inducers should be avoided while receiving Vandetanib therapy. St. John’s Wort may decrease Vandetanib exposure unpredictably and should be avoided [see Dosage and Administration (2.3)and Warnings and Precautions (5.11)].
CYP3A4 Inhibitors
In healthy subjects, no clinically significant interaction was shown between Vandetanib and the potent CYP3A4 inhibitor, itraconazole.
Drugs that Prolong the QT Interval
The administration of Vandetanib with agents that may prolong the QT interval should be avoided [see Warnings and Precautions (5.11)].
8. USE IN SPECIFIC POPULATIONS
. Pregnancy
Pregnancy Category D[see Warnings and Precautions (5.14)].
Vandetanib can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Vandetanib in pregnant women. Vandetanib is embryotoxic, fetotoxic, and teratogenic to rats, at exposures equivalent to or lower than those expected at the recommended human dose of 300 mg/day. When Vandetanib was administered to female rats prior to mating and through the first week of pregnancy, there were increases in pre-implantation loss and post-implantation loss resulting in a significant reduction in the number of live embryos. This dose administered to rats during organogenesis, caused an increase in post-implantation loss including embryofetal death. Vandetanib caused total litter loss when administered at a dose of 25 mg/kg/day during organogenesis until expected parturition. When administered during organogenesis, Vandetanib doses of 1, 10 and 25 mg/kg/day (approximately 0.03, 0.4, and 1.0 times respectively, the Cmax in patients with cancer at the recommended human dose) caused malformations of the heart vessels and delayed ossification of the skull, vertebrae and sternum, indicating delayed fetal development. A no effect level for these malformations was not identified in this study. In a rat pre- and post-natal development study, at doses producing maternal toxicity (1 and 10 mg/kg/day) during gestation and/or lactation, Vandetanib, decreased pup survival, and/or reduced post-natal pup growth. Reduced post-natal pup growth was associated with a delay in physical development.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid pregnancy while taking Vandetanib and for at least four months following the last dose of Vandetanib.
. Nursing Mothers
In nonclinical studies, Vandetanib was excreted in rat milk and found in plasma of pups following dosing to lactating rats. Vandetanib transfer in |
