FDA announced approval today, August 2, 2004, of two fixed-dose combination
(FDC) antiretroviral drug products for use with other antiretroviral agents
for the treatment of HIV-1 infection. The FDCs are GlaxoSmithKline's
EPZICOM( (abacavir/lamivudine) and Gilead Sciences, Inc.'s TRUVADA
(tenofovir disoproxil/emtricitabine). These FDC approvals are important because 
they provide simplified dosing regimens - one pill, once daily, for the component 
of multi-drug therapy represented by these FDCs. 

TRUVADA (tenofovir disoproxil/emtricitabine) - Gilead Sciences, Inc.

*       TRUVADA is a fixed-dose combination (FDC) of the antiretroviral
drugs tenofovir disoproxil fumarate 300 mg (TDF) and emtricitabine 200 mg
(FTC), both of which are approved individually under the brand names of
VIREAD (tenofovir disoproxil fumarate) and EMTRIVA(tm) (emtricitabine). 

*       The approval of TRUVADA is based on bioequivalence studies
demonstrating similar pharmacokinetic parameters of the combination product
and the individual products, safety and efficacy data that exist for both
components individually, and efficacy results from studies using the
combination of TDF and lamivudine (3TC), [lamivudine is an approved product
with many similarities to FTC] are being extrapolated to support the use of
the TDF/FTC combination.

*       TRUVADA should be considered as an alternative to TDF and 3TC for
treatment naïve patients who might benefit from a once-a-day regimen. 

EPZICOM (abacavir/lamivudine) - GlaxoSmithKline

*       EPZICOM is a fixed dose combination (FDC) of the antiretroviral
drugs abacavir sulfate 600 mg and lamivudine 300 mg, both of which are
approved individually under the brand names of ZIAGEN(abacavir sulfate)
and EPIVIR(lamivudine).

*       EPZICOM is being approved based on a large well-controlled clinical
study which showed that abacavir dosed once daily had similar antiviral
effect as abacavir dosed twice daily both in conjunction with lamivudine and
efaviranz. 

The important safety issue regarding abacavir-containing products, including
EPZICOM, is abacavir hypersensitivity reaction (a serious allergic
reaction). Previous clinical trials showed that there is a possibility of
this hypersensitivity reaction occurring in approximately 8% of the
patients. EPZICOM should be discontinued a soon as a hypersensitivity
reaction is suspected. EPZICOM or other abacavir-containing products must
not be restarted following a hypersensitivity reaction because more severe
symptoms can occur within hours and may include life-threatening hypotension
and death. Information on this serious allergic reaction has been updated in
the EPZICOM package insert as well as the patient Medguide/Warning Card.

Richard Klein                                                   
Office of Special Health Issues                          
Food and Drug Administration                           
 
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration