On December 17, 2015, the Indications and Usage section of the STRIBILD (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir 300mg) label was updated to include patients who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure in order to replace their current regimen. Patients should have no known substitutions associated with resistance to the individual components of STRIBILD.
The major changes to the label include the following:
Section 1: Indications and Usage update as follows:
STRIBILD® is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of STRIBILD
Section 5: Warnings and Precautions subsections 5.4 and 5.5 were updated as follows:
- 5.4 Avoid Use with Other Antiretroviral Products
STRIBILD is not recommended for coadministration with the following:
- cobicistat (TYBOST);
- elvitegravir (VITEKTA);
- products containing emtricitabine or tenofovir DF (ATRIPLA, COMPLERA, EMTRIVA, TRUVADA, VIREAD);
- products containing lamivudine (COMBIVIR, EPIVIR, EPIVIR-HBV, EPZICOM, TRIUMEQ, TRIZIVIR)
- adefovir dipivoxil (HEPSERA);
- products containing ritonavir (NORVIR, KALETRA)
- Addition of section 5.5 Risk of Adverse Reactions of Loss of Virologic Response Due to Drug Interactions
The concomitant use of STRIBILD and other drugs may result in known or potentially significant drug interactions, some of which may lead to:
- Loss of therapeutic effect of STRIBILD and possible development of resistance.
- Possible clinically significant adverse reactions from greater exposures of concomitant drugs.
See Table 6 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations [see Drug Interactions (7.5)]. Consider the potential for drug interactions prior to and during STRIBILD therapy; review concomitant medications during STRIBILD therapy; and monitor for the adverse reactions associated with the concomitant drugs.
Section 6.1- Adding the adverse reactions for those who are virologically suppressed
The following subheading was added to this section:
In Virologically-Suppressed HIV-1-Infected Subjects
No new adverse reactions to STRIBILD through Week 48 were identified in 584 virologically stably suppressed subjects switching to STRIBILD from a regimen containing a RTV-boosted protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). In a combined analysis of Studies 115 and 121, the frequency of adverse reactions (all grades) was 24% in subjects switching to STRIBILD compared to 6% of subjects in either group who stayed on their baseline antiretroviral regimen, RTV-boosted PI + TRUVADA or NNRTI + TRUVADA. Common adverse reactions that occurred in greater than or equal to 2% of subjects switching to STRIBILD were nausea (4%), flatulence (2%), and headache (2%). The proportion of subjects who discontinued treatment with STRIBILD, the RTV-boosted PI, or the NNRTI due to adverse events, was 2%, 3% and 1%, respectively.
Section 12.4 Microbiology was updated to include information on elvitegravir, emtricitabine/tenofovir DF and elvitegravir, cobicistat, emtricitabine, and tenofovir DF
Section 14 Clinical Studies was updated to include trial result information from Study 115 and Study 121
In Virologically-Suppressed HIV-1-Infected Subjects with No History of Virologic Failure
In Study 115, subjects had to be on either their first or second antiretroviral regimen with no history of virologic failure, with no current or past history of resistance to the antiretroviral components of STRIBILD and must have been suppressed (HIV-1 RNA <50 copies/mL) on a ritonavir-boosted PI in combination with TRUVADA for at least 6 months prior to screening. Subjects were randomized in a 2:1 ratio to either switch to STRIBILD (STRIBILD arm, N=293; randomized and dosed) or stay on their baseline antiretroviral regimen for 48 weeks (PI + RTV + TRUVADA arm, N=140; randomized and dosed). Subjects had a mean age of 41 years (range 21-76), 86% were male, 80% were White, and 15% were Black. The mean baseline CD4+ cell count was 610 cells per mm3 (range 74-1919). At screening subjects were receiving atazanavir (40%), darunavir (40%), lopinavir (17%), fosamprenavir (3%), or saquinavir (<1%) as the PI in their regimen.
In Study 121, subjects had to be on either their first or second antiretroviral regimen with no history of virologic failure, with no current or past history of resistance to the antiretroviral components of STRIBILD and must have been suppressed (HIV-1 RNA <50 copies/mL) on a NNRTI in combination with TRUVADA for at least 6 months prior to screening. Subjects were randomized in a 2:1 ratio to either switch to STRIBILD (STRIBILD arm, N = 291; randomized and dosed), or stay on their baseline antiretroviral regimen for 48 weeks (NNRTI +TRUVADA arm, N = 143; randomized and dosed). Subjects had a mean age of 41 years (range 20-72), 93% were male, 78% were White, and 17% were Black. The mean baseline CD4+ cell count was 588 cells per mm3 (range 100-1614). Randomization was stratified by use of efavirenz in the baseline regimen. At screening subjects were receiving efavirenz (78%) (predominantly as ATRIPLA [74%]), nevirapine (17%), rilpivirine (4%) (as COMPLERA [4%]), or etravirine (1%) as the NNRTI in their regimen.
Virologic outcomes of Study 115 and Study 121 are presented in Table 11. Five treated subjects were excluded from the efficacy analysis: in Study 115, three STRIBILD subjects had protocol-prohibited documented resistance and one PI + RTV + TRUVADA subject was not on a protease inhibitor-based regimen at screening; in Study 121, one STRIBILD subject had protocol-prohibited documented resistance.
Table 11 Virologic Outcomes of Randomized Treatment in Study 115 and Study 121 at Week 48
|
|
Study GS-US-236-0115a |
Study GS-US-236-0121a |
||
|---|---|---|---|---|
|
STRIBILD (N=290) |
PI+RTV+TRUVADA (N=139) |
STRIBILD (N=290) |
NNRTI+TRUVADA (N=143) |
|
|
Virologic Success HIV-1 RNA<50 copies/mL |
94% |
87% |
93% |
88% |
|
Virologic Failureb |
1% |
1% |
1% |
1% |
|
No Virologic Data in Week 48 Window |
6% |
12% |
6% |
11% |
|
Discontinued Study Drug Due to AE or Deathc |
2% |
1% |
2% |
1% |
|
Discontinued Study Drug Due to Other Reasons and Last Available HIV-1 RNA <50 copies/mLd |
4% |
10% |
4% |
9% |
|
Missing Data During Window but on Study Drug |
0% |
0% |
0% |
1% |
a. Week 48 window is between Day 295 and 378 (inclusive).
b. Includes subjects who had ≥50 copies/mL in the Week 48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a viral value of ≥50 copies/mL.
c. Includes subjects who discontinued due to adverse event or death at any time point from Day 1 through the time window if this resulted in no virologic data on treatment during the specified window.
d. Includes subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy, eg., withdrew consent, loss to follow-up, etc.
Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration
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