October 21, 2003
/fda/The Food and Drug Administration (FDA) approved, on October 20, 2003, Lexiva (Fosamprenavir calcium), manufactured by GlaxoSmithKline of Research Triangle Park, NC and Vertex Pharmaceuticals, Incorporated of Cambridge, MA.
Lexiva is a prodrug of amprenavir, a protease inhibitor used to treat infection with the human immunodeficiency virus (HIV-1). Lexiva is rapidly converted to amprenavir by cellular or serum phosphatases in the body.
Lexiva is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. The approval of Lexiva was based on two studies in antiretroviral naive patients and one study in protease inhibitor experienced patients.
In study APV30001, Lexiva (1,400 mg twice daily) was compared to nelfinavir (1,250 mg twice daily) in 249 antiretroviral naive patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The proportions of patients who achieved and maintained confirmed HIV RNA <400 copies/mL (<50 copies/mL) through week 48 was 66% (57%) for the Lexiva group and 52% (42%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 201 cells/mm3 in the group receiving Lexiva and 216 cells/mm3 in the nelfinavir group.
In study APV30002, Lexiva (1,400 mg once daily) plus ritonavir (200 mg once daily) was compared to nelfinavir (1,250 mg twice daily) in 649 treatment-naive patients. Both treatment groups also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The proportions of patients who achieved and maintained confirmed HIV RNA <400 copies/mL (<50 copies/mL) through week 48 was 69% (58%) for the Lexiva group and 68% (55%) for the nelfinavir group, respectively. Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 203 cells/mm3 in the group receiving Lexiva and 207 cells/mm3 in the nelfinavir group.
In study APV30003, two different regimens of Lexiva plus ritonavir (Lexiva 700 mg twice daily plus ritonavir 100 mg twice daily or Lexiva 1,400 mg once daily plus ritonavir 200 mg once daily) was compared to lopinavir/ritonavir (400 mg/100 mg twice daily) in 315 patients who had experienced virologic failure to 1 or 2 prior protease inhibitor-containing regimens.
The time-averaged changes in plasma HIV-1 RNA from baseline (AAUCMB) at 48 weeks (the endpoint on which the study was powered) were Ð1.4 log10 copies/mL for twice-daily Lexiva/ritonavir and Ð1.67 log10 copies/mL for the lopinavir/ritonavir group.
The proportions of patients who achieved and maintained confirmed HIV-1 RNA <400 copies/mL were 58% with twice-daily Lexiva/ritonavir and 61% with lopinavir/ritonavir (95% CI for the difference -16.6, 10.1).
The proportions of patients with HIV-1 RNA <50 copies/mL with twice-daily Lexiva/ritonavir and with lopinavir/ritonavir were 46% and 50%, respectively (95% CI for the difference -18.3, 8.9). Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 81 cells/mm3 with twice-daily Lexiva/ritonavir and 91 cells/mm3 with lopinavir/ritonavir.
The following points should be considered when initiating therapy with Lexiva/ritonavir in protease inhibitor-experienced patients.
The most common treatment-emergent adverse events in clinical studies of Lexiva were diarrhea, nausea, vomiting, headache, and rash and were generally mild to moderate in severity. Treatment discontinuation due to adverse events occurred in 6.4% of patients receiving Lexiva and in 5.9% of patients receiving comparator treatments.
Lexiva tablets are available for oral administration in a strength of 700 mg of fosamprenavir as fosamprenavir calcium (equivalent to approximately 600 mg of amprenavir).
Lexiva tablets may be taken with or without food.
The recommended oral dose of Lexiva, alone or in combination with ritonavir, is as follows:
The twice-daily plus ritonavir dose is supported by pharmacokinetic and safety data.
Protease Inhibitor-Experienced Patients:
Once-daily administration of Lexiva plus ritonavir is not recommended in protease inhibitor-experienced patients.
Ritonavir is used to increase the plasma concentration of Lexiva.
Please see the attached label for additional details about product details, clinical trial data, and indications. (PDF format)