Safety profile and tolerability of amprenavir in the treatment of adult and pediatric patients with HIV infection

Background: Amprenavir (APV) is a new HIV-1 protease inhibitor used in comb ination with other antiretroviral agents for the treatment of HIV-1 infecti on. Objective: The aim of this study was to assess the safety profile and toler ability of APV. Methods: A review of data from 358 adults enrolled in 2 phase III, randomiz ed, 48-week, controlled studies and from 268 children enrolled in 1 phase I I and 1 phase III study was conducted. The adult data were collected betwee n February 25, 1997, and April 1, 1999. Data were collected in children fro m September 10, 1997, to January 15, 1999; these data were collected before completion of either study. Adults and children who had and had not been t reated previously with antiretroviral agents were enrolled. In these studie s, APV was used in combination with 2 nucleoside reverse transcriptase inhi bitors. Results: The most common drug-related adverse events in patients receiving APV were gastrointestinal events and oral/perioral paresthesia. The majorit y of adverse events were mild or moderate in intensity, early in onset, and transient. Nausea (27/358 patients, 8%), vomiting (15/358, 4%), rash (11/3 58, 3%), and diarrhea/loose stools (9/358, 3%) were the most common adverse events associated with treatment discontinuation. Severe laboratory abnorm alities possibly related to APV were rare. In children, the nature and freq uency of adverse events were similar to these in adults. Metabolic complica tions were infrequent in APV studies to date; symptoms related to fat redis tribution were reported in <3% of patients treated with APV. Lipid or gluco se laboratory abnormalities were reported with similar frequency in the APV and control groups in both studies in adults. Conclusions: In the clinical trials reviewed, APV was generally well tolera ted when administered with other antiretroviral agents in adult and pediatr ic patients with HIV infection.