Additionally, the product labeling was updated to provide dosing recommendations for pediatric patients ages 3 to less than 6 years of age and for adult and pediatric patients greater than 6 years of age who can not swallow Prezista tablets.
Section 2: Dosage and Administration was updated to provide the dosing instructions for the oral suspension in pediatric patients and for adult patients who have difficulty swallowing Prezista tablets. Treatment-naïve adults and treatment experienced adults with no darunavir resistance associated substitutions can take Prezista 8 ml once daily with 1.25 ml of ritonavir once daily with food. The 8 mL dose should be taken as two 4 mL administrations with the included oral dosing syringe.
For treatment-experienced adults with at least one darunavir resistance associated substitution the dose for oral suspension is 6 mL twice daily with 1.25 mL ritonavir twice daily with food.
For pediatric patients, dosing with oral suspension or tablets is based on weight. Please refer to full prescribing information for details. Do not use Prezista/ritonavir in pediatric patients below 3 years of age.
Section 6 Adverse Reactions (ADRs) was update to reflect clinical trial experience in pediatric patients from Study TMC1140C228 as follows:
ADRs to PREZISTA/ritonavir (all grades, greater than or equal to 3%), excluding laboratory abnormalities, were diarrhea (19%), vomiting (14%) and rash (10%).
There were no Grade 3 or 4 laboratory abnormalities considered as ADRs in this study.
Section 12.3 Pharmacokinetics was updated to provide population pharmacokinetic estimates of darunavir exposure in pediatric patients.
Section 14: Clinical Studies was updated to reflect the results from the pediatric trial as follows:
Study TMC114-C228Treatment-experienced pediatric subjects between the ages of 3 and less than 6 years and weighing greater than or equal to 10 kg to less than 20 kg received PREZISTA oral suspension with ritonavir oral solution plus background therapy consisting of at least two active non-protease inhibitor antiretroviral drugs. Twenty-one subjects received at least one dose of PREZISTA/ritonavir.
The 21 subjects had a median age of 4.4 years (range 3 to less than 6 years), and were 48% male, 57% Black, 29%, Caucasian and 14% other. The mean baseline plasma HIV-1 was 4.34 log10 copies/mL, the median baseline CD4+ cell count was 927 x 106 cells/l (range: 209 to 2,429 x 106 cells/l) and the median baseline CD4+ percentage was 27.7% (range: 15.6% to 51.1%). Overall, 24% of subjects had a baseline plasma HIV-1 RNA greater than or equal to 100,000 copies/mL. All subjects had used greater than or equal to 2 nucleoside reverse transcriptase inhibitors (NRTIs), 62% of subjects had used greater than or equal to 1 non-nucleoside reverse transcriptase inhibitors (NNRTI) and 76% had previously used at least one HIV protease inhibitor (PI).
Twenty subjects (95%) completed the 24 week period. One subject prematurely discontinued treatment due to vomiting assessed as related to ritonavir.
The proportion of subjects with HIV-1 RNA less than 50 copies/mL and less than 400 copies/mL was -57% and 81%, respectively. The mean change in CD4+ percentage from baseline was 4%. The mean change in CD4+ cell count from baseline was 109 x 106 cells/L.
Dose recommendations from the two studies were based on the following:
Similar darunavir plasma exposures in children compared to adults, and
Similar virologic response rates and safety profile in children compared to adults
The complete label will be posted soon at Drugs@FDA
Prezista, a protease inhibitor, is a product of Tibotec Therapeutics.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
No hay comentarios:
Publicar un comentario