AGENERASE ORAL SOLUTION SIDE EFFECTS

SIDE EFFECTS

In clinical studies, adverse events leading to amprenavir discontinuation occurred primarily during the first 12 weeks of therapy, and were mostly due to gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain/discomfort), which were mild to moderate in severity.

Skin rash occurred in 22% of patients treated with amprenavir in studies PROAB3001 and PROAB3006. Rashes were usually maculopapular and of mild or moderate intensity, some with pruritus. Rashes had a median onset of 11 days after amprenavir initiation and a median duration of 10 days. Skin rashes led to amprenavir discontinuation in approximately 3% of patients. In some patients with mild or moderate rash, amprenavir dosing was often continued without interruption; if interrupted, reintroduction of amprenavir generally did not result in rash recurrence.

Severe or life-threatening rash (Grade 3 or 4), including cases of Stevens -Johnson syndrome, occurred in approximately 1% of recipients of AGENERASE (see WARNINGS). Amprenavir therapy should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms.

Table 1. Selected Clinical Adverse Events of All Grades Reported in > 5% of Adult Patients

Among amprenavir-treated patients in Phase 3 studies, 2 patients developed de novo diabetes mellitus, 1 patient developed a dorsocervical fat enlargement (buffalo hump), and 9 patients developed fat redistribution.

In studies PROAB3001 and PROAB3006, no increased frequency of Grade 3 or 4 AST, ALT, amylase, or bilirubin elevations was seen compared to controls.

Pediatric Patients: An adverse event profile similar to that seen in adults was seen in pediatric patients.

Concomitant Therapy With Ritonavir: Tables 2 and 3 present adverse clinical events and laboratory abnormalities observed in subjects who received AGENERASE plus ritonavir. Since the trials were small, open- label, of varying duration, and often included different patient populations, direct comparisons to the frequency of events with AGENERASE Capsules alone (see Table 1) cannot be made.

Table 2. Selected Clinical Adverse Events of All Grades Reported in Adult Patients in Open-Label Clinical Trials of AGENERASE Capsules in Combination With Ritonavir Capsules

Table 3. Grade 3/4 Laboratory Abnormalities Reported in ≥ 2% of Adult Patients in Open-Label Clinical Trials of AGENERASE Capsules in Combination With Ritonavir