Expanded Indication for Viread, to Include the Treatment of Patients 12 to Less Than 18 Years of Age
March 24, 2010
On March 24, 2010, the FDA approved revised labeling for Viread (tenofovir disproxil fumarate) to expand the indication to include the treatment of HIV HIV infection in combination with other antiretroviral agents in patients 12 to less than 18 years of age based on 48-week clinical data from Study GS-US-104-0321.
Following are the major changes to the label.
2.2 Recommended Dose in Adolescents (>12 Years of Age and >35 kg)
2.3 Dose Adjustment for Renal Impairment
No data are available to make dose recommendations in adolescent patients with renal impairment.
WARNINGS AND PRECAUTIONS
In a clinical study of HIV-1 infected adolescent subjects (Study 321), bone effects were similar to adult subjects. Under normal circumstances BMD increases rapidly in adolescents. In this study, the mean rate of bone gain was less in the VIREAD-treated group compared to the placebo group. Six VIREAD treated adolescents and one placebo treated adolescent had significant (>4%) lumbar spine BMD loss in 48 weeks. Among 28 subjects receiving 96 weeks of VIREAD, Z-scores declined by -0.341 for lumbar spine and -0.458 for total body. Skeletal growth (height) appeared to be unaffected. Markers of bone turnover in VIREAD-treated adolescents suggest increased bone turnover, consistent with the effects observed in adults.
6 ADVERSE REACTIONS
Bone effects observed in adolescent subjects were consistent with those observed in adult clinical trials [See Warnings and Precautions(5.6)].
8 USE IN SPECIFIC POPULATIONS
In Study 321, 87 treatment-experienced subjects 12 to <18 years of age were treated with VIREAD (N=45) or placebo (N=42) in combination with an optimized background regimen (OBR) for 48 weeks. The mean baseline CD4 cell count was 374 cells/mm3 and the mean baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. At baseline, 90% of subjects harbored NRTI resistance-associated substitutions in their HIV-1 isolates. Overall, the trial failed to show a difference in virologic response between the VIREAD and placebo treatment groups. Subgroup analyses suggest the lack of difference in virologic response may be attributable to imbalances between treatment arms in baseline viral susceptibility to VIREAD and OBR.
Although changes in HIV-1 RNA in these highly treatment-experienced adolescent subjects were less than anticipated, the comparability of the pharmacokinetic and safety data to that observed in adults supports the use of VIREAD in patients >12 years of age who weigh >35 kg and whose HIV-1 isolate is expected to be sensitive to VIREAD. [See Warnings and Precautions (5.6), Adverse Reactions (6.1), and Clinical Pharmacology (12.3)].
Safety and effectiveness in patients less than12 years of age have not been established.
12 CLINICAL PHARMACOLOGY
Pharmacokinetic studies have not been performed in pediatric subjects <12 years of age.
The complete revised label will be posted shortly to the FDA web site at Drugs@FDA.
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