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 Vandetanib, 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.
. Pediatric Use
Safety and efficacy of Vandetanib in pediatric patients have not been established.
. Geriatric Use
In total, 18% of medullary thyroid cancer patients treated with Vandetanib 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.
Renal Impairment
The pharmacokinetics of Vandetanib 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 Vandetanib 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 Warning and Precautions (5.12)].
Hepatic Impairment
The pharmacokinetics of Vandetanib 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). Vandetanib is not recommended for use in patients with moderate and severe hepatic impairment, as safety and efficacy have not been established. [see Dosage and Administration (2.5)and Warnings and Precautions (5.13)].
10. OVERDOSAGE
There is no specific treatment in the event of overdose with Vandetanib and possible symptoms of overdose have not been established. Because of the 19-day half-life, adverse reactions may not resolve quickly. In phase 1 clinical trials, a limited number of patients were treated with daily doses of up to 600 mg and healthy volunteers with daily doses up to 1200 mg. An increase in the frequency and severity of some adverse reactions, like rash, diarrhea and hypertension, was observed at multiple doses at and above 300 mg in healthy volunteer studies and in patients. In addition the possibility of QTc prolongation and Torsades de pointes should be considered.
Adverse reactions associated with overdose are to be treated symptomatically; in particular, severe diarrhea must be managed appropriately. In the event of an overdose, further doses of Vandetanib must be interrupted, and appropriate measures taken to assure that an adverse event has not occurred, i.e., ECG within 24 hours to determine QTc prolongation [see Dosage and Administration (2.1)].
11. DESCRIPTION
Vandetanib tablets for daily oral ad |
