Fosamprenavir adverse reactions

# Adverse Reactions
- Severe or life-threatening skin reactions have been reported with the use of LEXIVA.
- The most common moderate to severe adverse reactions in clinical trials of LEXIVA were diarrhea, rash, nausea, vomiting, and headache.
- Treatment discontinuation due to adverse events occurred in 6.4% of subjects receiving LEXIVA and in 5.9% of subjects receiving comparator treatments. The most common adverse reactions leading to discontinuation of LEXIVA (incidence less than or equal to 1% of subjects) included diarrhea, nausea, vomiting, AST increased, ALT increased, and rash.

## Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The data for the 3 active-controlled clinical trials described below reflect exposure of 700 HIV-1infected subjects to LEXIVA Tablets, including 599 subjects exposed to LEXIVA for greater than 24 weeks, and 409 subjects exposed for greater than 48 weeks. The population age ranged from 17 to 72 years. Of these subjects, 26% were female, 51% Caucasian, 31% black, 16% American Hispanic, and 70% were antiretroviral-naive. Sixty-one percent received LEXIVA 1,400 mg once daily plus ritonavir 200 mg once daily; 24% received LEXIVA 1,400 mg twice daily; and 15% received LEXIVA 700 mg twice daily plus ritonavir 100 mg twice daily.
Selected adverse reactions reported during the clinical efficacy trials of LEXIVA are shown in Tables 3 and 4. Each table presents adverse reactions of moderate or severe intensity in subjects treated with combination therapy for up to 48 weeks.
Skin rash (without regard to causality) occurred in approximately 19% of subjects treated with LEXIVA in the pivotal efficacy trials. Rashes were usually maculopapular and of mild or moderate intensity, some with pruritus. Rash had a median onset of 11 days after initiation of LEXIVA and had a median duration of 13 days. Skin rash led to discontinuation of LEXIVA in less than 1% of subjects. In some subjects with mild or moderate rash, dosing with LEXIVA was often continued without interruption; if interrupted, reintroduction of LEXIVA generally did not result in rash recurrence.
The percentages of subjects with Grade 3 or 4 laboratory abnormalities in the clinical efficacy trials of LEXIVA are presented in Tables 5 and 6.
LEXIVA with and without ritonavir was studied in 237 HIV-1infected pediatric subjects aged at least 4 weeks to 18 years in 3 openlabel trials, APV20002, APV20003, and APV29005 . Vomiting and neutropenia occurred more frequently in pediatric subjects compared to adults. Other adverse events occurred with similar frequency in pediatric subjects compared with adults.
The frequency of vomiting among pediatric subjects receiving LEXIVA twice daily with ritonavir was 20% in subjects aged at least 4 weeks to less than 2 years and 36% in subjects aged 2 to 18 years compared with 10% in adults. The frequency of vomiting among pediatric subjects receiving LEXIVA twice daily without ritonavir was 60% in subjects aged 2 to 5 years compared with 16% in adults.
The median duration of drugrelated vomiting episodes in APV29005 was 1 day (range: 1 to 3 days), in APV20003 was 16 days (range: 1 to 38 days), and in APV20002 was 9 days (range: 4 to 13 days). Vomiting was treatment limiting in 4 pediatric subjects across all 3 trials.
The incidence of Grade 3 or 4 neutropenia (neutrophils less than 750 cells per mm3) seen in pediatric subjects treated with LEXIVA with and without ritonavir was higher (15%) than the incidence seen in adult subjects (3%). Grade 3/4 neutropenia occurred in 10% (5/51) of subjects aged at least 4 weeks to less than 2 years and 16% (28/170) of subjects aged 2 to 18 years.