Fosamprenavir

Fosamprenavir, sold under the brand names Lexiva and Telzir, is a medication used to treat HIV/AIDS.[3][4] It is a prodrug of the protease inhibitor and antiretroviral drug amprenavir.[5] It is marketed by ViiV Healthcare as the calcium salt.[3][4]

Fosamprenavir
Clinical data
Trade namesLexiva, Telzir
Other namesFosamprenavir calcium (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa604012
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityUnknown
Protein binding90%
MetabolismHydrolysed to amprenavir and phosphate in GI tract epithelium
Elimination half-life7.7 hours
ExcretionFecal (as metabolites of amprenavir)
Identifiers
IUPAC name
  • {[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H36N3O9PS
Molar mass585.61 g·mol−1
3D model (JSmol)
SMILES
  • O=C(O[C@H]1CCOC1)N[C@@H](Cc2ccccc2)[C@H](OP(=O)(O)O)CN(CC(C)C)S(=O)(=O)c3ccc(N)cc3
InChI
  • InChI=1S/C25H36N3O9PS/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32)/t21-,23-,24+/m0/s1 Y
  • Key:MLBVMOWEQCZNCC-OEMFJLHTSA-N Y

  • as salt: InChI=1S/C25H36N3O9PS.Ca/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21;/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32);/q;+2/p-2/t21-,23-,24+;/m0./s1
  • Key:PMDQGYMGQKTCSX-HQROKSDRSA-L
 NY (what is this?)  (verify)

Fosamprenavir was approved for medical use in the United States in October 2003,[6] and in the European Union in July 2004.[4] The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient.[3]

A head-to-head study with lopinavir showed the two drugs to have comparable potency, but patients on fosamprenavir tended to have a higher serum cholesterol.[7]

Medical uses

Fosamprenavir is used for the treatment of HIV-1 infections, typically but not necessarily in combination with low-dose ritonavir or other antiviral drugs.[8][9]

Adverse effects

The most common adverse effect is diarrhea. Other common side effects include headache, dizziness and exanthema, which is usually transient. Severe allergic reactions (Stevens–Johnson syndrome) are rare.[8]

Interactions

Amprenavir (the active metabolite of fosamrenavir, which is found in blood plasma, liver and other organs) is metabolized via the liver enzyme CYP3A4 and also weakly inhibits this enzyme. This means that combination with drugs that are also metabolized by CYP3A4 can increase their plasma concentrations and thus side effects; and combination with drugs that inhibit CYP3A4 can increase amprenavir concentrations.[8]

When combining fosamprenavir with low doses of the CYP3A4 inhibitor ritonavir, this interaction is intended as it allows for application of lower fosamprenavir doses.[8]

Pharmacology

Fosamprenavir is quickly activated to amprenavir, even before it reaches the circulation. Amprenavir is a HIV protease inhibitor.[8]

HIV-1 protease dimer with amprenavir (sticks) bound in the active site. PDB entry 3nu3[10]

References
  1. "Telzir Product information". Health Canada. 25 April 2012. Archived from the original on 14 June 2021. Retrieved 2 October 2022.
  2. "Telzir 700 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 22 June 2021. Archived from the original on 6 December 2021. Retrieved 2 October 2022.
  3. "Lexiva- fosamprenavir calcium tablet, film coated Lexiva- fosamprenavir calcium suspension". DailyMed. 1 October 2020. Archived from the original on 29 January 2022. Retrieved 2 October 2022.
  4. "Telzir EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 15 May 2021. Retrieved 2 October 2022.
  5. "Archived copy". Archived from the original on 2021-06-28. Retrieved 2022-10-03.{{cite web}}: CS1 maint: archived copy as title (link)
  6. "Drug Approval Package: Lexiva (Fosamprenavir Calcium) NDA #021548". U.S. Food and Drug Administration (FDA). Archived from the original on 15 April 2021. Retrieved 2 October 2022.
  7. Eron J, Yeni P, Gathe J, Estrada V, DeJesus E, Staszewski S, et al. (August 2006). "The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial". Lancet. 368 (9534): 476–82. doi:10.1016/S0140-6736(06)69155-1. PMID 16890834. S2CID 33612672.
  8. Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8009–17. ISBN 978-3-85200-181-4.
  9. Lexiva. Drugs.com (Report). Monograph.
  10. Shen CH, Wang YF, Kovalevsky AY, Harrison RW, Weber IT (September 2010). "Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters". The FEBS Journal. 277 (18): 3699–714. doi:10.1111/j.1742-4658.2010.07771.x. PMC 2975871. PMID 20695887.
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