Extrait

In Europe beginning in 2008, COMBIVIR (CBV) scored tablet formulation was approved for use in the pediatric population weighing more than 14 kg or for patients requiring dosage adjustment, such as those with renal or hepatic impairment, or patients experiencing dose-limiting adverse reactions. The overall aim of this proposal is to carry out a study on usage and long term safety of COMBIVIR scored tablet in children with HIV infection in a “real world” setting. This retrospective analysis will evaluate 4 years of post scored tablet launch data to provide detailed information on the adverse event (AE) profile (particularly anemia, neutropenia and bone marrow depression) of COMBIVIR in children and adolescents ≤ 18 years. The study will include all HIV-infected children and adolescents ≤ 18 years, within the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC), who received the licensed dosing regimen of COMBIVIR scored tablet between 2008 and 2012 inclusive. The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) was established in 2008, and conducts epidemiological research on the prognosis and outcome of HIV-infected pregnant women and children, and children exposed to HIV in utero, across Europe. It is part of the Paediatric European Network for the Treatment of AIDS (PENTA). As the number of children infected with HIV in Europe is relatively small, one network running paediatric trials and cohorts is essential to efficiently answer research questions in this population. The MAH anticipates that approximately 300 HIV infected children and adolescents ≤18 years treated with COMBIVIR will be included in each comparison period for this study. COMBIVIR (CBV) is a fixed dose combination of the nucleoside analogue reverse transcriptase inhibitors zidovudine (ZDV) and lamivudine (3TC) which have potent activity against HIV-1 and HIV-2. COMBIVIR, which contains 150 mg lamivudine and 300 mg zidovudine was first approved in the USA in September 1997, and in the EU, via the centralised procedure, in March 1998. In 2008, scored tablet formulation of COMBIVIR was approved and should not be prescribed for pediatric patients weighing less than 14 kg or patients requiring dosage adjustment, such as those with renal or hepatic impairment, or patients experiencing dose-limiting adverse reactions. Oral solutions of ZDV and 3TC are available for pediatric use with body weight based dosing. The MAH is providing support in the form of antiviral drug supply, including scored solid forms of COMBIVIR. Upon CHMP request, the MAH committed to submit a proactive pharmacovigilance survey and to submit a safety review focusing on COMBIVIR paediatric scored tablets every 6 months. There are four main objectives for this study. First, we will describe the characteristics of children ≤18 years, who received COMBIVIR (scored tablets) between January 2008 and December 2012 inclusive. Second, the rate of adverse events for anemia, neutropenia, bone marrow depression, hepatobilliary disorders as measured by ALT, AST and serum bilirubin, and lactic acidosis when reported as a serious adverse event among HIV-infected will be estimated. Reasons for stopping COMBIVIR will be described. And lastly, the characteristics of children with adverse events will be compared to those with no adverse events to assess potential selection bias; those with missing data will also be compared to those with complete data to see if there is a difference. This is a retrospective, observational analysis evaluating 4 years of post scored tablet launch data to provide detailed information on the AE profile of COMBIVIR in children and adolescents aged ≤ 18 years. Frequency of AE events will be tabulated and a descriptive analysis summarizing COMBIVIR safety among the paediatric population will comprise study results. As the extent of AE reporting is variable within cohorts, with most cohorts only collecting data on serious adverse events, data on AEs for this study will also include data on reasons for antiretroviral drug discontinuations. For each laboratory adverse event, the overall rate and corresponding 95% confidence intervals in the study population will be estimated. Rates will also be estimated separately by duration of time on COMBIVIR (<12 months, 12-24 months, 25+ months) and for the following sample size allowing a) age group, b) weight bands and c) dose.

Critère d'inclusion

• HIV-Associated Lipodystrophy Syndrome

Liens

• gsk