Pharmacology Update
Efavirenz/Emtricitabine/Tenofovir Tablets (Atripla™)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has approved the first, one tablet, once-daily, three-drug combination for the treatment of HIV-1 infections. This fixed-dose combination contains efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg (EET). It was approved in less than 3 months under the FDA's fast track program. EET was developed as a joint venture between Bristol-Myers Squibb and Gilead Sciences and will be marketed as Atripla™.
Indications
EET is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.1
Dosage
The recommended dose is one tablet daily on an empty stomach and at bedtime to reduce adverse events.1
Potential Advantages
EET is the first one-tablet once-daily complete regimen for treatment of HIV-1. The combination significantly reduces pill burden and may improve medication adherence. This three-drug regimen appears to have synergistic antiviral activity.1
Potential Disadvantages
The most common adverse events include headache, dizziness, abdominal pain, nausea, vomiting and rash.
Comments
The approval of EET was based on a 48-week randomized open-label, active control, trial. The active control was efavirenz, zidovudine and lamivudine (EZL).1 The study participants were 511 antiretroviral naïve patients with a mean baseline CD4 count of 245 cells/mm3 and a median baseline plasma HIV-1 RNA of 5.01 log10 copies/mL. Percentage of patients achieving HIV-1 RNA < 400 copies/mL through week 48 were 84% for EET and 73% for EZL. HIV-1 RNA < 50 copies/mL were 80% for EET and 70% for EZL. The mean increase in CD4 was 190 cells/mm3 and 158 cell/mm3 and discontinuation rate for adverse events was 4% and to 9% respectively. Combining three drugs in one does not affect their pharmacokinetics as one EET tablet is bioequivalent to each component administered individually.1 According to the manufacturers, Atripla will cost $1,150.88 for a 30-day supply.
Clinical Implications
The approval of EET reduces pill burden to the minimum of one tablet once a day. This should increase convenience and improve adherence. Currently efavirenz + (zidovudine or tenofovir) + lamivudine or emtricitabine are the preferred NNRTI-based regimens for initial treatment of treatment-naïve patients.2 Findings from a recently published randomized controlled trial in treatment-naïve patients concluded that there was no significant difference in efficacy or safety with a 3-drug regimen (zidovudine, lamivudine, and efavirenz) compared to a 4-drug regimen (zidovudine, lamivudine, efavirenz, and abacavir).3
References
1. Atripla Product Information. Bristol-Myers Squibb and Gilead. July 2006.
2. Guideline for use of antiretroviral agents in HIV-1 infected adults and adolescents. www.aidsinfo.nih.gov/ContentFiles/AboutHIVTreatmentGuidelines_FS_en.pdf. Accessed September 13, 2006.
3. Gulick RM, et al. Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA. 2006;296:769-778.
The FDA has approved the first, one tablet, once-daily, three-drug combination for the treatment of HIV-1 infections.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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