Viramune
XR package insert includes the same Contraindications, Warnings
and Precautions and Drug Interactions as immediate release
Viramune.
ADVERSE REACTIONS:
Clinical
Trial Experience
Trial 1100.1486 (VERxVE)
In Trial
1100.1486 (VERxVE) treatment-naive subjects received a
lead-in dose of immediate-release Viramune 200 mg once daily
for 14 days (n=1068) and then were randomized to receive either
immediate-release Viramune 200 mg twice daily (n=506) or Viramune
XR 400 mg once daily (n=505). All subjects received tenofovir
+ emtricitabine as background therapy. Subjects were enrolled
with CD4+ counts less than 250 cells/mm3 for women and less
than 400 cells/mm3 for men. Data on potential symptoms of
hepatic events were prospectively collected in this trial.
The safety data include all subject visits up to the time
of the last subject's completion of the 48 week primary endpoint
in the trial (mean observation period 61 weeks).
After the lead-in period, the incidence of any hepatic event
was 9% in the immediate-release Viramune group and 6% in the
Viramune XR group; the incidence of symptomatic hepatic events
(anorexia, jaundice, vomiting) was 3% and 2%, respectively.
The incidence of Grade 3 or 4 ALT/AST elevation was 7% in
the immediate-release Viramune group and 6% in the Viramune
XR group. Overall, there was a comparable incidence of symptomatic
hepatic events among men and women enrolled in VERxVE.
Severe or life-threatening rash considered to be related to
nevirapine treatment occurred in 1% of subjects during the
lead-in phase with immediate-release Viramune, and in 1% of
subjects in either treatment group during the randomization
phase. In addition, five cases of Stevens-Johnson syndrome
were reported in the trial, all of which occurred within the
first 30 days of nevirapine treatment.
No Grade 2 or above adverse reactions judged to be related
to treatment by the investigator occurred in more than 2%
of subjects during the 14-day lead-in with immediate-release
Viramune (200 mg once daily), with the exception of rash which
occurred in 4% of subjects.
Adverse reactions of at least moderate intensity (Grades 2
or above) and considered to be related to treatment by the
investigator in at least 2% of treatment-naive subjects receiving
either immediate-release Viramune or Viramune XR after randomization
in Trial 1100.1486 are rash - 3% for each for Viramune immediate
release and Viramune XR and clinical hepatitis 3% for Viramune
immediate release vs 2% Viramune XR.
CLINICAL TRIAL RESULTS:
The
clinical efficacy of Viramune XR is based on 48-week data
from an ongoing, randomized, double-blind, double-dummy Phase
3 trial (Trial 1100.1486, VERxVE) in treatment-naive subjects
and on 24-week data in an ongoing, randomized, open-label
trial in subjects who switched from immediate-release Viramune
tablets administered twice daily to Viramune XR tablets administered
once daily (Trial 1100.1526, TRANxITION).
Treatment-naive Subjects
Trial
1100.1486 (VERxVE) is a Phase 3 trial in which treatment-naïve
subjects received immediate-release Viramune 200 mg once daily
for 14 days and then were randomized to receive either immediate-release
Viramune 200 mg twice daily or Viramune XR 400 mg once daily.
All subjects received tenofovir + emtricitabine as background
therapy. Randomization was stratified by screening HIV-1 RNA
level (less than or equal to 100,000 copies/mL and greater
than 100,000 copies/mL). Subject demographic and baseline
disease characteristics were balanced between the two treatment
groups. With respect to demographics: 85% of the subjects
were male, 75% were white, 20% were black, and approximately
29% were from North America. With respect to baseline disease
characteristics: mean viral load was 4.7 log10 copies/mL,
mean CD4 cell count was 228 cells/mm3 and 73% of subjects
had clade B HIV-1 subtype. Approximately two-thirds of the
subjects had a baseline HIV-RNA level of less than or equal
to 100,000 copies/mL.
The Week 48 outcomes in the Trial 1100.1486 (VERxVE) were
as follows: Virologic success (HIV RNA < 50 copies/mL):
75% Viramune Immediate Release vs 80% Viramune XR, Virologic
failure 13% Viramune Immediate Release vs 11% Viramune XR,
Virologic failure. These outcomes include all subjects who
were randomized after the 14 day lead-in with immediate-release
Viramune and received at least one dose of blinded study medication.
At 48 weeks, mean change from baseline in CD4+ cell count
adjusting for baseline HIV-1 viral load stratum was 191 cells/mm3
and 206 cells/mm3 for the groups receiving immediate-release
Viramune and Viramune XR, respectively.
Subjects Switching from Immediate-release Viramune to Viramune
XR
Trial
1100.1526 (TRANxITION) is a Phase 3 trial to evaluate safety
and antiviral activity of switching from immediate-release
Viramune to Viramune XR. In this open-label trial, 443 subjects
already on an antiviral regimen containing immediate-release
Viramune 200 mg twice daily with HIV-1 RNA less than 50 copies/mL
were randomized in a 2:1 ratio to Viramune XR 400 mg once
daily or immediate-release Viramune 200 mg twice daily. Approximately
half of the subjects had tenofovir+emtricitabine as their
background therapy, with the remaining subjects receiving
abacavir sulfate+lamivudine or zidovudine+lamivudine. Approximately
half of the subjects had at least 3 years of exposure to immediate-release
Viramune prior to entering the trial.
At 24 weeks after randomization in Trial 1100.1526, 94% of
subjects receiving immediate-release Viramune 200 mg twice
daily and 95% of subjects receiving Viramune XR 400 mg once
daily continued to have HIV-1 RNA less than 50 copies/mL.
The complete product label will be posted shortly on the Drugs@FDA
web site.
Viramune, an nonnucleoside reverse transcriptase inhibitor
(NNRTI) is a product of Boehringer Ingelheim Pharmaceuticals,
Inc., Ridgefield, CT.
4/1/11
Source
R
Klein and K Struble, FDA. Approval of VIRAMUNE XR (nevirapine)
400 mg extended release tablet. HIV/AIDS Update. March 18,
2011.
