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Elvitegravir / Vitekta FDA Approval
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On September 24, 2014, FDA approved Vitekta (elvitegravir) 85 mg and 150 mg tablets. Vitekta is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor indicated in combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults.
Dosing and Administration
Vitekta must be administered once daily with food in combination with a protease inhibitor coadministered with ritonavir and another antiretroviral drug. The protease inhibitor and ritonavir dosing regimens presented in the Table 1 below are the recommended regimens for use with Vitekta. For additional dosing instructions for these protease inhibitors and other concomitant antiretroviral drugs, refer to their respective prescribing information.
Table 1 Recommended Regimens*
No dose adjustment of Vitekta is required for patients with renal impairment.
No dose adjustment of Vitekta is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment. Vitekta has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Therefore, Vitekta is not recommended for use in patients with severe hepatic impairment
Data to support approval
The data to support the approval of Vitekta was from a phase 3 trial, (Study 145) in treatment-experienced adult patients with HIV-1 infection in which 712 HIV-1 infected, antiretroviral treatment-experienced adults received Vitekta (N=354) or raltegravir (N=358), each administered with a background regimen consisting of a fully active protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for at least 96 weeks. [see clinical studies section below for details]
Adverse Reactions:
The proportion of subjects who discontinued study treatment due to adverse events, regardless of severity, was 3% in the Vitekta group and 4% in the raltegravir group. The most common adverse reaction (all Grades, incidence greater than or equal to 5%) in subjects receiving Vitekta in Study 145 was diarrhea. The most commonly reported adverse reactions (all grade) for Vitekta and raltegravir containing regimens, respectively were diarrhea (7% vs 5%), nausea (4% vs 3%) and headache (3% each)
The following limitations of use were included in section 1: Indications and Usage:
· There are no comparative pharmacokinetic or clinical data evaluating Vitekta with cobicistat as single entities compared to STRIBILD®.
· Vitekta coadministered with protease inhibitors and cobicistat is not recommended
· Coadministration of Vitekta with dosage regimens or HIV-1 protease
inhibitors other than those presented in Table 1 is not recommended.
Contraindications:
There are no contraindications to Vitekta.
Due to the need to use Vitekta with a protease inhibitor coadministered with ritonavir, consult prescribing information of coadministered protease inhibitor and ritonavir for their contraindications.
Warnings and Precautions:
A highlight of the warnings and precautions are as follows:
· Do not use with protease inhibitors coadministered with cobicistat. (5.2)
· Do not use with other elvitegravir-containing drugs, including STRIBILD.
Drug Interactions:
Elvitegravir is metabolized by CYP3A. Drugs that induce CYP3A activity are expected to increase the clearance of elvitegravir, as well as ritonavir. This may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance. The table below provides dosing recommendations as a result of potentially clinically significant drug interactions with Vitekta.a
Based on drug interaction studies conducted with elvitegravir, no clinically significant drug interactions have been either observed or expected when elvitegravir is combined with the following drugs: abacavir, darunavir, emtricitabine, etravirine, fosamprenavir, maraviroc, stavudine, tipranavir, tenofovir disoproxil fumarate, zidovudine; H2-receptor antagonists such as famotidine; proton-pump inhibitors such as omeprazole; and the HMG-CoA reductase inhibitors atorvastatin, pravastatin, and rosuvastatin.
Clinical Studies
The efficacy of Vitekta in treatment-experienced adult patients with HIV-1 infection is based on the analyses through 96 weeks from one randomized, double-blind, active-controlled trial, Study 145, in treatment-experienced, HIV-1 infected subjects (N=702). In Study 145, subjects were randomized in a 1:1 ratio to receive either Vitekta (150 mg or 85 mg) once daily or raltegravir 400 mg twice daily, each administered with a background regimen (BR) containing a fully active protease inhibitor coadministered with ritonavir and a second antiretroviral drug. The BR was selected by the investigator based on genotypic/phenotypic resistance testing and prior antiretroviral treatment history.
Virologic outcomes were similar across the treatment arms through 96 weeks as presented in the table below. The mean increase from baseline in CD4+ cell count at Week 96 was 205 cells/mm3 in Vitekta-treated subjects and 198 cells/mm3 in raltegravir-treated subjects.
Virologic Outcomes of Randomized Treatment of Study 145 in HIV-1 Infected Treatment-Experienced Adults (Week 96a Analysis)
a. The Week 96 analysis window is between Day 645 and 700 (inclusive).
b. Difference (95% CI) of response rate is Ð0.5% (Ð7.9%, 6.8%) at Week 96.
c. Includes subjects who had ³50 copies/mL in the Week 96 window; subjects who discontinued early due to lack or loss of efficacy; subjects who had a viral load ³50 copies/mL at the time of change in background regimen; 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 ³50 copies/mL.
d. 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.
e. 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.
Labeling for Vitekta will be posted soon at Drugs@FDA.
Vitekta is a product of Gilead Sciences, Foster City, CA.
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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