Fosamprenavir (Lexiva, Telzir)

Published October 30, 2003; Updated May 17, 2012
Susa Coffey, MD
Selected References
5. Corbett AH, Davidson L, Park JJ, Patterson K, Eron JJ, Ngo L, Lim ML, Shelton M, Wire MB, and Kashuba ADM. Dose Separation Strategies to Overcome the Pharmacokinetic Interaction of a Triple Protease Inhibitor Regimen Containing Fosamprenavir, Lopinavir, and Ritonavir. 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, Feburary 8-11, 2004. Abstract 611.
6. Kashuba  AD, Tierney  C, Downey  GF, Acosta  EP, Vergis  EN, Klingman  K, Mellors  JW, Eshleman  SH, Scott  TR, Collier  AC.
Combining fosamprenavir with lopinavir/ritonavir substantially reduces amprenavir and lopinavir exposure: ACTG protocol A5143 results. AIDS. 2005 Jan;19(2):145-52
[PubMed ID: 15668539]
OBJECTIVE: To evaluate fosamprenavir/lopinavir (LPV)/ritonavir (RTV), fosamprenavir/RTV, or LPV/RTV in antiretroviral treatment-experienced patients. Lack of drug interaction data prompted a pharmacokinetic substudy to minimize subject risk. DESIGN: Multi-center, open-label, selectively randomized, steady-state pharmacokinetic study in HIV-infected subjects. METHODS: A planned independent interim review occurred after at least eight subjects were randomized to each arm. Subjects received twice daily LPV/RTV 400/100 mg (arm A; n = 8); fosamprenavir/RTV 700/100 mg (arm B; n = 8) or LPV/RTV/fosamprenavir 400/100/700 mg (arm C; n = 17). Plasma samples were collected over 12 h between study weeks 2 and 4. Pharmacokinetic parameters were compared based on a one-sided t-test on log-transformed data with a Peto stopping boundary (P < 0.001). RESULTS: Amprenavir mean area under the curve over 12 h (AUC0-12 h) and concentration at 12 h (C12 h) (microg/ml) were, respectively, 42.7 microg x h/ml (range, 33.1-55.1) and 2.4 microg/ml (range, 1.4-3.2) in arm B and 17.4 microg x h/ml (range, 4.6-41.3) and 0.9 microg/ml (range, 0.2-2.7) in arm C: geometric mean ratio (GMR) arm C:B was 0.36 [99.9% upper confidence boundary (UCB), 0.64] and 0.31 (99.9% h UCB, 0.61), respectively (P < or = 0.0001). Lopinavir AUC0-12 h and C12 h were, respectively, 95.3 microg x h/ml (range, 60.3-119.3) and 6.3 microg/ml (range, 2.2-9.2) in arm A and 54.4 microg x h/ml (range, 23.5-112.2) and 3.0 microg/ml (range, 0.4-7.9) in arm C: GMR arm C:A of 0.52 (99.9% UCB, 0.89) and 0.39 (99.9% UCB, 0.98), respectively (P < or = 0.0008). Ritonavir exposure was not significantly different between arms. CONCLUSION: APV and LPV exposures are significantly reduced using LPV/RTV/fosamprenavir, possibly increasing the risk of virologic failure. Consequently, A5143 was closed to enrollment.