NAV

Fosamprenavir

Identification

Summary

Fosamprenavir is an antiretroviral agent used for the treatment and postexposure prophylaxis of human immunodeficiency virus (HIV-1) infection.

Brand Names
Lexiva, Telzir
Generic Name
Fosamprenavir
DrugBank Accession Number
DB01319
Background

Fosamprenavir is a prodrug of amprenavir, an inhibitor of human immunodeficiency virus (HIV) protease.

Type
Small Molecule
Groups
Approved
Structure
3D
Similar Structures
Weight
Average: 585.607
Monoisotopic: 585.190986967
Chemical Formula
C25H36N3O9PS
Synonyms
  • FOS-APV
  • Fosamprenavir
External IDs
  • GW-433908
  • GW433908
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Pharmacology

Indication

Indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus (HIV-1) infection, as well as postexposure prophylaxis of HIV infection in individuals who have had occupational or nonoccupational exposure to potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission. The use of fosamprenavir is pending revision due to a potential association between the drug and myocardial infarction and dyslipidemia in HIV infected adults.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHiv-1 infection••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Fosamprenavir is hydrolyzed by cellular phosphatases to the antiretroviral protease inhibitor amprenavir. This hydrolysis allows for the slow release of amprenavir, reducing the number of pills a patient must take.

Mechanism of action

Fosamprenavir is a prodrug that is rapidly hydrolyzed to amprenavir by cellular phosphatases in the gut epithelium as it is absorbed. Amprenavir is an inhibitor of HIV-1 protease. During HIV replication, HIV protease cleaves viral polypeptide products of the Gag and Gag-Pol genes to form structural proteins of the virion core and essential viral enzymes. Amprenavir interferes with this process by binding to the active site of HIV-1 protease, thereby preventing the processing of viral Gag and Gag-Pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles.

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

The absolute oral bioavailability of amprenavir after administration of fosamprenavir in humans has not been established. After administration of a single 1,400 mg dose in the fasted state, fosamprenavir oral suspension (50 mg/mL) and fosamprenavir tablets (700 mg) provided similar amprenavir exposures (AUC), however, the Cmax of amprenavir after administration of the suspension formulation was 14.5 % higher compared with the tablet.

Volume of distribution

Not Available

Protein binding

Very high (approximately 90%); primarily bound to alpha 1 -acid glycoprotein. Higher amounts of unbound amprenavir present as amprenavir serum concentrations increase.

Metabolism

In the gut epithelium during absorption, fosamprenavir is rapidly and almost completely hydrolyzed to amprenavir and inorganic phosphate prior to reaching the systemic circulation. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system.

Route of elimination

Excretion of unchanged amprenavir in urine and feces is minimal. The renal elimination of unchanged amprenavir represents approximately 1% of the administered dose; therefore, renal impairment is not expected to significantly impact the elimination of amprenavir. Amprenavir, the active metabolite of fosamprenavir, is metabolized in the liver by the cytochrome P450 enzyme system.

Half-life

The plasma elimination half-life of amprenavir (the active metabolite) is approximately 7.7 hours.

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbametapirThe serum concentration of Fosamprenavir can be increased when it is combined with Abametapir.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Fosamprenavir.
AcalabrutinibThe serum concentration of Acalabrutinib can be increased when it is combined with Fosamprenavir.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Fosamprenavir.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Fosamprenavir.
Food Interactions
  • Avoid alcohol. Drug impairs alcohol metabolism.
  • Avoid fatty foods.
  • Take with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Fosamprenavir calciumID1GU2627N226700-81-8PMDQGYMGQKTCSX-HQROKSDRSA-L
Fosamprenavir sodiumXSG28FSA0W226700-80-7FZMGUXZZROZJIT-KMIZVRHLSA-L
Active Moieties
NameKindUNIICASInChI Key
Amprenavirprodrug5S0W860XNR161814-49-9YMARZQAQMVYCKC-OEMFJLHTSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
LexivaTablet, film coated700 mg/1OralAvera McKennan Hospital2015-03-302017-05-24US flag
LexivaTablet, film coated700 mg/1OralState of Florida DOH Central Pharmacy2014-11-01Not applicableUS flag
LexivaTablet, film coated700 mg/1OralGlaxosmithkline Inc2003-11-062012-11-19US flag
LexivaSuspension50 mg/1mLOralViiV Healthcare Company2010-10-04Not applicableUS flag
LexivaTablet, film coated700 mg/1OralPhysicians Total Care, Inc.2003-11-062011-09-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Fosamprenavir CalciumTablet, coated700 mg/1OralSun Pharmaceutical Industries, Inc.2019-11-28Not applicableUS flag
Fosamprenavir CalciumTablet, film coated700 mg/1OralMylan Pharmaceuticals Inc.2017-09-18Not applicableUS flag

Categories

ATC Codes
J05AE07 — Fosamprenavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Aminobenzenesulfonamides
Alternative Parents
Phenylbutylamines / Amphetamines and derivatives / Benzenesulfonyl compounds / Phosphoethanolamines / Aniline and substituted anilines / Monoalkyl phosphates / Organosulfonamides / Tetrahydrofurans / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds
show 7 more
Substituents
Alkyl phosphate / Amine / Aminobenzenesulfonamide / Aminosulfonyl compound / Amphetamine or derivatives / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Benzenesulfonyl group / Carboximidic acid derivative / Dialkyl ether
show 24 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
sulfonamide (CHEBI:82941)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
WOU1621EEG
CAS number
226700-79-4
InChI Key
MLBVMOWEQCZNCC-OEMFJLHTSA-N
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
IUPAC Name
{[(2R,3S)-1-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid
SMILES
CC(C)CN(C[C@@H](OP(O)(O)=O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1

References

Synthesis Reference
US6559815
General References
  1. Smith KY, Weinberg WG, Dejesus E, Fischl MA, Liao Q, Ross LL, Pakes GE, Pappa KA, Lancaster CT: Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT. AIDS Res Ther. 2008 Mar 28;5:5. doi: 10.1186/1742-6405-5-5. [Article]
  2. Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS: Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women. HIV Clin Trials. 2007 Nov-Dec;8(6):371-80. [Article]
  3. Chapman TM, Plosker GL, Perry CM: Fosamprenavir: a review of its use in the management of antiretroviral therapy-naive patients with HIV infection. Drugs. 2004;64(18):2101-24. [Article]
  4. Furfine ES, Baker CT, Hale MR, Reynolds DJ, Salisbury JA, Searle AD, Studenberg SD, Todd D, Tung RD, Spaltenstein A: Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob Agents Chemother. 2004 Mar;48(3):791-8. [Article]
  5. Sension M: Initial therapy for human immunodeficiency virus: broadening the options. HIV Clin Trials. 2004 Mar-Apr;5(2):99-111. [Article]
  6. Wood R, Arasteh K, Stellbrink HJ, Teofilo E, Raffi F, Pollard RB, Eron J, Yeo J, Millard J, Wire MB, Naderer OJ: Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2004 Jan;48(1):116-23. [Article]
  7. Falcoz C, Jenkins JM, Bye C, Hardman TC, Kenney KB, Studenberg S, Fuder H, Prince WT: Pharmacokinetics of GW433908, a prodrug of amprenavir, in healthy male volunteers. J Clin Pharmacol. 2002 Aug;42(8):887-98. [Article]
  8. Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
Human Metabolome Database
HMDB0015416
KEGG Drug
D02497
PubChem Compound
131536
PubChem Substance
46504901
ChemSpider
116245
RxNav
358262
ChEBI
82941
ChEMBL
CHEMBL1664
ZINC
ZINC000003941829
Therapeutic Targets Database
DAP000707
PharmGKB
PA10084
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fosamprenavir
FDA label
Download (374 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Proteinuria1
4CompletedTreatmentChronic Infection With HIV / HCV Coinfection1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Hypertriglyceridemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Dept Health Central Pharmacy
  • GlaxoSmithKline Inc.
  • Physicians Total Care Inc.
  • Remedy Repack
  • ViiV Healthcare ULC
Dosage Forms
FormRouteStrength
Tablet, coatedOral700 mg/1
SuspensionOral50 mg/1mL
Tablet, film coatedOral700 mg/1
SuspensionOral50 MG/ML
SuspensionOral50 mg / mL
TabletOral700 mg
Tablet, film coatedOral700 MG
Prices
Unit descriptionCostUnit
Lexiva 700 mg tablet14.78USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2224738No2002-08-272016-06-28Canada flag
CA2231700No2005-08-092018-03-10Canada flag
US6436989Yes2002-08-202018-06-24US flag
US6514953Yes2003-02-042020-01-15US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.685 mg/mLALOGPS
logP0.84ALOGPS
logP1.92Chemaxon
logS-2.9ALOGPS
pKa (Strongest Acidic)1.22Chemaxon
pKa (Strongest Basic)2.45Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area177.72 Å2Chemaxon
Rotatable Bond Count13Chemaxon
Refractivity144.95 m3·mol-1Chemaxon
Polarizability57.53 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6363
Blood Brain Barrier+0.5379
Caco-2 permeable+0.6992
P-glycoprotein substrateSubstrate0.6482
P-glycoprotein inhibitor IInhibitor0.7374
P-glycoprotein inhibitor IINon-inhibitor0.7819
Renal organic cation transporterNon-inhibitor0.8671
CYP450 2C9 substrateSubstrate0.5877
CYP450 2D6 substrateSubstrate0.6061
CYP450 3A4 substrateSubstrate0.5805
CYP450 1A2 substrateNon-inhibitor0.7454
CYP450 2C9 inhibitorNon-inhibitor0.6627
CYP450 2D6 inhibitorNon-inhibitor0.8835
CYP450 2C19 inhibitorNon-inhibitor0.6591
CYP450 3A4 inhibitorNon-inhibitor0.6317
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6969
Ames testNon AMES toxic0.598
CarcinogenicityNon-carcinogens0.78
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5018 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9846
hERG inhibition (predictor II)Non-inhibitor0.8356
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0006-9105310000-2bf3c66449e76886fd4c
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-06s9-0003690000-3516ea6d3cbd3ce991bf
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00c0-9100860000-050f40e53c622954f23b
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4j-9400580000-52c2f90ab3236946001d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1906430000-a18437e00d01a54f0479
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-08i0-8900220000-80914c09a5acd11566c2
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9501000000-54d8d97677d12651ef22
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-240.1437914
predicted
DarkChem Lite v0.1.0
[M-H]-219.83711
predicted
DeepCCS 1.0 (2019)
[M+H]+239.9463914
predicted
DarkChem Lite v0.1.0
[M+H]+221.66199
predicted
DeepCCS 1.0 (2019)
[M+Na]+240.2766914
predicted
DarkChem Lite v0.1.0
[M+Na]+227.2678
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Details1. Human immunodeficiency virus type 1 protease
Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS: Evaluation of sex differences of fosamprenavir (with and without ritonavir) in HIV-infected men and women. HIV Clin Trials. 2007 Nov-Dec;8(6):371-80. [Article]
  2. Furfine ES, Baker CT, Hale MR, Reynolds DJ, Salisbury JA, Searle AD, Studenberg SD, Todd D, Tung RD, Spaltenstein A: Preclinical pharmacology and pharmacokinetics of GW433908, a water-soluble prodrug of the human immunodeficiency virus protease inhibitor amprenavir. Antimicrob Agents Chemother. 2004 Mar;48(3):791-8. [Article]
  3. Sension M: Initial therapy for human immunodeficiency virus: broadening the options. HIV Clin Trials. 2004 Mar-Apr;5(2):99-111. [Article]
  4. Wood R, Arasteh K, Stellbrink HJ, Teofilo E, Raffi F, Pollard RB, Eron J, Yeo J, Millard J, Wire MB, Naderer OJ: Six-week randomized controlled trial to compare the tolerabilities, pharmacokinetics, and antiviral activities of GW433908 and amprenavir in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother. 2004 Jan;48(1):116-23. [Article]
  5. Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]
  2. Hester EK, Chandler HV, Sims KM: Fosamprenavir: drug development for adherence. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1301-10. doi: 10.1345/aph.1G034. Epub 2006 Jun 6. [Article]
  3. FDA Approved Drug Products: Colcrys (colchicine) tablets for oral use (May 2020) [Link]
  4. Amprenavir FDA label [Link]

Drug created at June 30, 2007 17:17 / Updated at February 20, 2024 23:54