The main changes include revisions to the Dosage and Administration section as follows:
The recommended total daily dose to be administered once daily to pediatric patients weighing at least 20 kg who can swallow capsules is based on body weight (kg), consistent with the recommended adult dosing guidelines (see Table 1). Please consult the complete prescribing information for Videx Pediatric Powder for Oral Solution for dosage and administration of pediatric patients weighing less than 20 kg or who can not swallow capsules.

Table 1: Recommended Dosage (Adult and Pediatric Patients)
Body Weight                                             Dose   
20 kg to less than 25 kg                            200 mg once daily      
25 kg to less than 60 kg                            250 once daily 
At least 60 kg                                           400 mg once daily      
 

Section 8.4 Pediatric Use was updated to state the following:

Use of didanosine in pediatric patients from 2 weeks of age through adolescence is supported by evidence from adequate and well-controlled studies of didanosine in adult and pediatric patients [see Dosage and Administration (2), Adverse Reactions (6.1), Clinical Pharmacology (12.3) and Clinical Studies (14). Additional pharmacokinetic studies in pediatric patients support use of the Videx EC in pediatric patients who weigh at least 20 kg. 

Section 12.3 was added to describe the population pharmacokinetic analysis for children:
A population pharmacokinetic analysis was conducted on pooled didanosine plasma concentration data from 9 clinical trials in 106 pediatric (neonate to 18 years of age) and 45 adult patients (greater than 18 years of age). Results showed that body weight is the primary factor associated with oral clearance. Based on the data analyzed, dosing schedule (once versus twice daily) and formulation (powder for oral solution, tablet and delayed-release capsule) did not have an effect on oral clearance. Didanosine exposure similar to that at recommended adult doses can be achieved in pediatric patients with a weight-based dosing scheme.

The results and conclusion from the hepatic impairment study were included in Section 12.3.
Hepatic Impairment:  The pharmacokinetics of didanosine have been studied in 12 non-HIV infected subjects with moderate (n=8) to severe (n=4) hepatic impairment (Child-Pugh Class B or C). Mean AUC and Cmax values following a single 400 mg dose of didanosine were approximately 13% and 19% higher, respectively, in patients with hepatic impairment compared to matched healthy subjects. No dose adjustment is needed, because a similar range and distribution of AUC and Cmax values was observed for subjects with hepatic impairment and matched controls.

The following new language for disposal of unused medicines was incorporated in Section 17.

Dispose of unused medicines through community take-back disposal programs when available or place Videx EC in an unrecognizable closed container in the household trash.

Additionally, the label was converted to Physician Labeling Rule (PLR) format to make product labeling more informative and accessible.

The revised label will be available soon at Drugs@FDA
 

Videx EC  is a product of Bristol-Myers Squibb

Richard Klein
Office of Special Health Issues
Food and Drug Administration

Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration