WARNINGS: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT EXACERBATION OF HEPATITIS B
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See Warnings and Precautions].
ATRIPLA is not approved for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of ATRIPLA have not been established in patients coinfected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued EMTRIVA or VIREAD, which are components of ATRIPLA. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue ATRIPLA. If appropriate, initiation of anti-hepatitis B therapy may be warranted [See Warnings and Precautions].
|
| |
ATRIPLA SUMMARY
ATRIPLA™ is a fixed dose combination tablet containing efavirenz, emtricitabine, and tenofovir disoproxil fumarate (tenofovir DF). SUSTIVA® is the brand name for efavirenz, a non-nucleoside reverse transcriptase inhibitor. EMTRIVA is the brand name for emtricitabine, a synthetic nucleoside analog of cytidine. VIREAD is the brand name for tenofovir DF, which is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. VIREAD and EMTRIVA are the components of TRUVADA®. ATRIPLA Tablets are for oral administration. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine, and 300 mg of tenofovir DF (which is equivalent to 245 mg of tenofovir disoproxil) as active ingredients.
ATRIPLA 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.
Description of Clinical Studies
Clinical Study 934 supports the use of ATRIPLA Tablets in antiretroviral treatment naïve HIV-1 infected patients. Additional data in support of the use of ATRIPLA in treatment naïve patients can be found in the prescribing information for VIREAD.
In antiretroviral treatment-experienced patients, the use of ATRIPLA Tablets may be considered for patients with HIV strains that are expected to be susceptible to the components of ATRIPLA as assessed by treatment history or by genotypic or phenotypic testing (see MICROBIOLOGY, Drug Resistance and Cross Resistance).
Study 934: Emtricitabine + Tenofovir Disoproxil Fumarate + Efavirenz Compared with Zidovudine/Lamivudine + Efavirenz
Data through 48 weeks are reported for Study 934, a randomized, open-label, active-controlled multicenter study comparing emtricitabine + tenofovir DF administered in combination with efavirenz versus zidovudine/lamivudine fixed-dose combination administered in combination with efavirenz in 511 antiretroviral-naïve patients. Patients had a mean age of 38 years (range 18–80), 86% were male, 59% were Caucasian and 23% were Black. The mean baseline CD4 cell count was 245 cells/mm3 (range 2–1191) and median baseline plasma HIV-1 RNA was 5.01 log10 copies/mL (range 3.56–6.54). Patients were stratified by baseline CD4 count (< or ≥ 200 cells/mm3) and 41% had CD4 cell counts <200 cells/mm3. Fifty-one percent (51%) of patients had baseline viral loads >100,000 copies/mL. Treatment outcomes through 48 weeks for those patients who did not have efavirenz resistance at baseline (n=487) are presented in Table 6.
Table 6 Outcomes of Randomized Treatment at Week 48 (Study 934) | Outcome at Week 48 | FTC + TDF + EFV
(N=244) | AZT/3TC+ EFV
(N=243) |
|---|
| % | % |
|---|
| ResponderPatients achieved and maintained confirmed HIV-1 RNA <400 copies/mL through Week 48. | 84% | 73% |
| Virologic failureIncludes confirmed viral rebound and failure to achieve confirmed <400 copies/mL through Week 48. | 2% | 4% |
| Rebound | 1% | 3% |
| Never suppressed through week 48 | 0% | 0% |
| Change in antiretroviral regimen | 1% | 1% |
| Death | <1% | 1% |
| Discontinued due to adverse event | 4% | 9% |
| Discontinued for other reasonsIncludes lost to follow-up, patient withdrawal, noncompliance, protocol violation and other reasons. | 10% | 14% |
The difference in the proportion of patients who achieved and maintained HIV-1 RNA <400 copies/mL through 48 weeks largely results from the higher number of discontinuations due to adverse events and other reasons in the zidovudine/lamivudine group in this open-label study. In addition, 80% and 70% of patients in the emtricitabine + tenofovir DF and the zidovudine/lamivudine group, respectively, achieved and maintained HIV-1 RNA <50 copies/mL. The mean increase from baseline in CD4 cell count was 190 cells/mm3 in the emtricitabine + tenofovir DF group, and 158 cells/mm3 for the zidovudine/lamivudine group.
Through 48 weeks, 7 patients in the emtricitabine + tenofovir DF group and 5 patients in the zidovudine/lamivudine group experienced a new CDC Class C event.
|
NEWS HIGHLIGHTS
Published Studies Related to Atripla (Efavirenz / Emtricitabine / Tenofovir)
Simplification of antiretroviral therapy to a single-tablet regimen consisting of efavirenz, emtricitabine, and tenofovir disoproxil fumarate versus unmodified antiretroviral therapy in virologically suppressed HIV-1-infected patients. [2009.06.01]
OBJECTIVE: To evaluate a simplification strategy for HIV-1-infected patients virologically suppressed on antiretroviral therapy (ART) by switching to a single-tablet regimen consisting of efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). DESIGN:: Prospective, randomized, controlled, open-label, multicenter study... CONCLUSION: Simplification to EFV/FTC/TDF maintained high and comparable rates of virologic suppression vs. SBR through 48 weeks.
Bioequivalence of efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen. [2007.10.01]
OBJECTIVE: Efavirenz (EFV; 600 mg), emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) are preferred agents for treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics (PK) and bioequivalence of an investigational coformulation of EFV/FTC/TDF (test) single-tablet regimen compared with the commercially available individual dosage forms (EFV+FTC+TDF; reference treatment) in healthy subjects... CONCLUSIONS: The coformulation of EFV/FTC/TDF is bioequivalent to administration of its individual components.
Bioequivalence of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate Single-Tablet Regimen. [2007.07.19]
OBJECTIVE:: Efavirenz (EFV; 600 mg), emtricitabine (FTC; 200 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) are preferred agents for treatment of HIV-1 infection in adults. This study evaluated the pharmacokinetics (PK) and bioequivalence of an investigational coformulation of EFV/FTC/TDF (test) single-tablet regimen compared with the commercially available individual dosage forms (EFV+FTC+TDF; reference treatment) in healthy subjects... CONCLUSIONS:: The coformulation of EFV/FTC/TDF is bioequivalent to administration of its individual components.
Efavirenz/emtricitabine/tenofovir disoproxil fumarate fixed-dose combination: first-line therapy for all? [2007.02]
ATRIPLA (Bristol-Myers Squibb and Gilead Sciences) is a complete regimen in a single, fixed-dose combination tablet that contains: efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg.This article reviews relevant efficacy and safety data of efavirenz, emtricitabine and tenofovir disoproxil fumarate, compared with other once-daily agents or certain common alternate drugs presently used as initial therapy in treatment-naive patients.
Efavirenz/emtricitabine/tenofovir disoproxil fumarate: triple combination tablet. [2006]
A new formulation combining fixed doses of the nucleoside reverse transcriptase inhibitors emtricitabine (200mg) and tenofovir disoproxil fumarate (tenofovir DF; 300 mg) with the non-nucleoside reverse transcriptase inhibitor efavirenz (600 mg) represents the first once-daily, one-tablet antiretroviral regimen...
Clinical Trials Related to Atripla (Efavirenz / Emtricitabine / Tenofovir)
The Bioequivalence of Atripla in an Oral Liquid Formulation Compared With the Tablet Formulation in Healthy Volunteers [Recruiting]
The primary objective of this study is to determine the average bioequivalence of tenofovir,
emtricitabine and efavirenz in an extemporaneously prepared oral liquid formulation (test
formulation) compared with the commercially available tablet formulation (reference
formulation). The study is designed as an open-label, randomized, 2-period, 2-treatment,
2-sequence, single-dose intensive pharmacokinetic study conducted in healthy volunteers.
Subjects will be randomized to receive the Atripla tablet (reference formulation) or the
Atripla tablet crushed and mixed in OraSweet solution (test formulation) on Study Day 1.
Subjects will undergo a 12-hour intensive pharmacokinetic evaluation after ingesting a
single dose of either the test or reference formulation. On days 2 and 3, subjects will
provide an additional pharmacokinetic sample 24 and 48 hours post dose, respectively.
Subjects will complete a washout period from day 2 to day 14 during which no study drugs
will be ingested. On day 14, subjects will ingest either the reference or test formulation
(opposite of the formulation received on Study Day 1). All subjects will undergo another
12-hour intensive pharmacokinetic evaluation. On days 16 and 17 subjects will provide an
additional pharmacokinetic sample 24 and 48 hours post dose, respectively. Adverse events
and concomitant medications will be documented throughout the study.
The sample size is 16 and is based upon a 10% drop-out rate (i. e. due to lost to follow-up,
treatment discontinuation, etc.). Since the investigators are expecting two subjects not to
complete the study, the investigators expect 14 evaluable subjects. If the discontinuation
rate is greater than 10%, the investigators will continue to enroll until the investigators
get 14 evaluable subjects. The primary endpoint is to determine average bioequivalence for
test and reference formulations of tenofovir, emtricitabine and efavirenz according to the
FDA guidance on bioequivalence testing. The ratio of the test to reference formulation mean
Cmax and AUC24 for each drug and the 90% confidence interval around each mean ratio will be
determined. Average bioequivalence will be met if 90% confidence intervals around the Cmax,
and AUC24 mean ratios for each drug falls within the FDA's predefined limits of 0. 80 to
1. 25.
ONCE - Only Nocturnal Combination Evaluation of Antiretroviral-Experienced HIV 1 Infected Subjects Switching to Atripla [Recruiting]
A single tablet regimen (STR) of efavirenz, emtricitabine and tenofovir disoproxil fumarate
(tenofovir DF) is the first complete HAART that is offered as one tablet once a day. The
individual components of this HAART regimen have demonstrated efficacy and safety in HIV
treatment-naive patients and offer simplification that in turn may increase adherence and
improve clinical outcomes. This study aims to evaluate the effectiveness (efficacy, safety
and tolerability) of a STR simplification strategy in patients on HAART who have achieved
viral suppression in a real world clinical setting.
Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women [Not yet recruiting]
Raltegravir not only has a unique mechanism of action, but may also have other unique
effects on suppression of viral replication, viral reservoir, and immune reconstitution in
blood and other important compartments. This may in part be due to the pharmacokinetics of
Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug
in this study, with both drugs being used as part of a three-drug regimen with tenofovir and
emtricitabine.
The primary objectives are to determine differences in the effects of 2 anti-retroviral
regimens, Raltegravir + Truvada versus Atripla, with respect to:
1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ
hybridization).
2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine
profiles.
The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut
tissue; relative tissue/compartment penetration compared to Efavirenz.
Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients [Recruiting]
CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and
tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve
subjects. Subjects will be ineligible if they have any evidence of drug resistant virus in
the past or at the time of screening (if never previously tested). Those who are found to be
eligible will be randomized 1: 1 to initiate either LPV/r (400/100 mg) plus RAL (400mg), both
given twice-daily, or fixed dose combination of EFV (600 mg), TDF (300 mg) and FTC (200 mg)
given as once-daily Atripla® for 48 weeks.
Hypotheses
1. The novel nucleoside-sparing combination of LPV/r + RAL will have a faster phase 1
viral decay rate compared to standard-of-care therapy with EFV/TDF/FTC in
antiretroviral-naïve patients.
1. Faster phase 1 viral decay dynamics will be associated with improved longer-term
(week 48) viral suppression.
2. Faster phase 1 viral decay dynamics will be associated with accelerated early (Day
0-14) clearance of cell-associated HIV DNA.
3. Faster phase 1 viral decay dynamics will be associated with greater early
(baseline to week 12) CD4+ T-cell recovery.
2. The LPV/r + RAL arm will have greater decreases in early (baseline to week 4) CD4/CD8
T-cell immune activation and apoptosis which will be associated with greater late
(week 12 to week 48) CD4+ T-cell recovery.
3. Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol
and triglycerides from baseline than those receiving EFV/TDF/FTC.
ROCKET I - Randomized Open Label Switch for Cholesterol Elevation on Kivexa Evaluation Trial [Recruiting]
This study aims to investigate whether patients switching their backbone from Kivexa to
Truvada, who already have raised total cholesterol prior to switching, have an improvement
in their total cholesterol after 12 weeks of treatment. If an improvement is demonstrated
the study aims to show whether this has a beneficial effect on the patient's overall
cardiovascular risk and long term prognosis.
|
PATIENT REVIEWS / RATINGS / COMMENTSBased on a total of 1 ratings/reviews, Atripla has an overall score of 10. The effectiveness score is 10 and the side effect score is 6. The scores are on ten point scale: 10 - best, 1 - worst.
| | Atripla review by 37 year old male patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Highly Effective |
| Side effects: | | Moderate Side Effects | | |
Treatment Info |
| Condition / reason: | | HIV |
| Dosage & duration: | | 600mg taken every night at 9pm for the period of been on it for one year |
| Other conditions: | | none |
| Other drugs taken: | | none | | |
Reported Results |
| Benefits: | | increased CD4 count,and lower viral load. |
| Side effects: | | flushed face, sleepiness, equilibrium out of balance |
| Comments: | | one pill everynight at 9pm for as long as the treatment works, can be very long term. |
|
|
|
Page last updated: 2009-10-20
|
