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 CAPRELSA and for at least four months following the last dose of CAPRELSA.
8.3. 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 breast milk resulted in relatively constant exposure in pups due to the long half-life of the drug. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from CAPRELSA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4. Pediatric Use
Safety and efficacy of CAPRELSA in pediatric patients have not been established.
8.5. Geriatric Use
In total, 18% of medullary thyroid cancer patients treated with CAPRELSA were age 65 years or older, and 3% were 75 years and older. No overall differences in safety and efficacy were observed between elderly and younger patients. 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 years.
8.6 Renal Impairment
The pharmacokinetics of CAPRELSA were eva luated after a single dose of 800 mg in subjects with mild (n = 6), moderate (n = 8), and severe (n = 6) renal impairment and normal (n = 10) renal function. Subjects with mild renal impairment had comparable mean AUC and clearance values to those with normal renal function. In subjects with moderate and severe renal impairment, the average AUC of CAPRELSA increased by 39% and 41%, respectively, compared to patients with normal renal function.
The starting dose should be reduced to 200 mg in patients with moderate and severe renal impairment [see Dosage and Administration (2.4)and Warnings and Precautions (5.12)].
8.7 Hepatic Impairment
The pharmacokinetics of CAPRELSA were eva luated after a single dose of 800 mg in subjects with mild (n = 8), moderate (n = 7), and severe (n = 6) hepatic impairment and normal hepatic function (n = 5). Subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment had comparable mean AUC and clearance values to those 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). CAPRELSA is not recommended for u |
