Safety profile and tolerability of amprenavir in the treatment of adult and pediatric patients with HIV infection.
BACKGROUND
Amprenavir (APV) is a new HIV-I protease inhibitor used in combination with other antiretroviral agents for the treatment of HIV-1 infection.


OBJECTIVE
The aim of this study was to assess the safety profile and tolerability of APV.


METHODS
A review of data from 358 adults enrolled in 2 phase III, randomized, 48-week, controlled studies and from 268 children enrolled in 1 phase II and 1 phase III study was conducted. The adult data were collected between February 25, 1997, and April 1, 1999. Data were collected in children from 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 treated previously with antiretroviral agents were enrolled. In these studies, APV was used in combination with 2 nucleoside reverse transcriptase inhibitors.


RESULTS
The most common drug-related adverse events in patients receiving APV were gastrointestinal events and oral/perioral paresthesia. The majority of adverse events were mild or moderate in intensity, early in onset, and transient. Nausea (27/358 patients, 8%), vomiting (15/358, 4%), rash (11/358, 3%), and diarrhea/loose stools (9/358, 3%) were the most common adverse events associated with treatment discontinuation. Severe laboratory abnormalities possibly related to APV were rare. In children, the nature and frequency of adverse events were similar to those in adults. Metabolic complications were infrequent in APV studies to date; symptoms related to fat redistribution were reported in <3% of patients treated with APV. Lipid or glucose 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 tolerated when administered with other antiretroviral agents in adult and pediatric patients with HIV infection.
Pedneault
L
L
Glaxo Wellcome HIV and Opportunistic Infections Clinical Development, Research Triangle Park, North Carolina, USA.
Brothers
C
C
Pagano
G
G
Tymkewycz
P
P
Yeo
J
J
Millard
J
J
Fetter
A
A
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002219:Carbamates; D002648:Child; D002675:Child, Preschool; D004064:Digestive System / Q000187:drug effects; D004359:Drug Therapy, Combination; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010292:Paresthesia / Q000139:chemically induced; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir