Foscarnet

Identification

Summary

Foscarnet is an antiviral used to treat CMV, HIV, and HSV infections.

Brand Names
Foscavir
Generic Name
Foscarnet
DrugBank Accession Number
DB00529
Background

An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpes viruses and HIV.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 126.0053
Monoisotopic: 125.971809718
Chemical Formula
CH3O5P
Synonyms
  • Carboxyphosphonic acid
  • Foscarmet
  • Phosphonoformate
  • Phosphonoformic acid
  • Phosphonomethanoic acid

Pharmacology

Indication

For the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) and for treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Foscarnet is an organic analogue of inorganic pyrophosphate that inhibits replication of herpes viruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet does not require activation (phosphorylation) by thymidine kinase or other kinases and therefore is active in vitro against HSV TK deficient mutants and CMV UL97 mutants. Thus, HSV strains resistant to acyclovir or CMV strains resistant to ganciclovir may be sensitive to foscarnet. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet and may not respond to therapy with foscarnet. The combination of foscarnet and ganciclovir has been shown to have enhanced activity in vitro.

Mechanism of action

Foscarnet exerts its antiviral activity by a selective inhibition at the pyrophosphate binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-5
ADNA polymerase catalytic subunit
inhibitor
HHV-1
Absorption

Poorly absorbed after oral administration (bioavailability from 12 to 22%).

Volume of distribution

Not Available

Protein binding

14-17%

Metabolism

Not metabolized.

Route of elimination

Not Available

Half-life

3.3-6.8 hours

Clearance
  • 2.13 +/- 0.71 mL/min/kg [patients had normal renal function (CrCl > 80 mL/min]
  • 68 +/- 8 mL/min/kg [CrCl was 50-80 mL/min]
  • 34 +/- 9 mL/min/kg [CrCl was 25-49 mL/min]
  • 20 +/- 4 mL/min/kg [CrCl was 10 - 24 mL/min]
Adverse Effects
Adverseeffects
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Toxicity

Oral, rat LD50: >2,000 mg/kg. Signs of overdose include renal impairment.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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
AbacavirFoscarnet may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Foscarnet.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Foscarnet.
AcetaminophenFoscarnet may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acidThe risk or severity of nephrotoxicity can be increased when Acetylsalicylic acid is combined with Foscarnet.
AclidiniumFoscarnet may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineThe risk or severity of QTc prolongation can be increased when Foscarnet is combined with Acrivastine.
AcyclovirThe risk or severity of nephrotoxicity can be increased when Acyclovir is combined with Foscarnet.
Adefovir dipivoxilThe risk or severity of nephrotoxicity can be increased when Adefovir dipivoxil is combined with Foscarnet.
AdenosineThe risk or severity of QTc prolongation can be increased when Foscarnet is combined with Adenosine.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Foscarnet sodium8C5OQ81LWT63585-09-1DFHAXXVZCFXGOQ-UHFFFAOYSA-K
International/Other Brands
Triapten
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FoscavirInjection, solution24 mg/1mLIntravenousClinigen Group PLC2012-07-09Not applicableUS flag
FoscavirInjection24 mg/1mLIntravenousAstra Zeneca Lp2007-10-31Not applicableUS flag
Foscavir UKInjection, solution24 mg/1mLIntravenousClinigen Healthcare Ltd.2010-09-222015-01-01US flag
VocarviSolution24 mg / mLIntravenousSterimax Inc2021-03-30Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FoscarnetInjection, solution24 mg/1mLIntravenousFresenius Kabi USA, LLC2021-01-29Not applicableUS flag
Foscarnet SodiumInjection, solution24 mg/1mLIntravenousGland Pharma Limited2021-04-21Not applicableUS flag
Foscarnet SodiumInjection, solution24 mg/1mLIntravenousSagent Pharmaceuticals2021-05-15Not applicableUS flag
Foscarnet SodiumInjection, solution24 mg/1mLIntravenousHospira, Inc.2006-01-262012-02-01US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Foscavir UKFoscarnet sodium (24 mg/1mL)Injection, solutionIntravenousClinigen Healthcare Ltd.2010-09-222015-01-01US flag

Categories

ATC Codes
J05AD01 — Foscarnet
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as organic phosphonic acids. These are organic compounds containing phosphonic acid.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Organic phosphonic acids
Direct Parent
Organic phosphonic acids
Alternative Parents
Organic carbonic acids and derivatives / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Aliphatic acyclic compound / Carbonic acid derivative / Hydrocarbon derivative / Organic oxide / Organic oxygen compound / Organooxygen compound / Organophosphonic acid / Organophosphorus compound / Organopnictogen compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
one-carbon compound, phosphonic acids, carboxylic acid (CHEBI:127780)
Affected organisms
  • Human Herpes Virus

Chemical Identifiers

UNII
364P9RVW4X
CAS number
4428-95-9
InChI Key
ZJAOAACCNHFJAH-UHFFFAOYSA-N
InChI
InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6)
IUPAC Name
phosphonoformic acid
SMILES
OC(=O)P(O)(O)=O

References

Synthesis Reference

Charles E. McKenna, "Preparation and use of thiophosphonates and thio-analogues of phosphonoformic acid." U.S. Patent US5072032, issued February, 1953.

US5072032
General References
Not Available
Human Metabolome Database
HMDB0014670
KEGG Drug
D00579
KEGG Compound
C06456
PubChem Compound
3415
PubChem Substance
46507873
ChemSpider
3297
BindingDB
50011181
RxNav
33562
ChEBI
127780
ChEMBL
CHEMBL666
ZINC
ZINC000008101109
Therapeutic Targets Database
DAP001383
PharmGKB
PA449706
PDBe Ligand
PPF
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Foscarnet
PDB Entries
1ei6 / 1nki / 2it4 / 2rk8 / 3kd5 / 3t01 / 4mv7 / 5hp1
FDA label
Download (101 KB)
MSDS
Download (50.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentCytomegalovirus (CMV) Infection / Human Immunodeficiency Virus (HIV) Infections / Hypocalcemia1
4CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHerpes Zoster1
4CompletedTreatmentViral sepsis1
4RecruitingTreatmentCytomegalovirus (CMV) Infection / Hematological Diseases1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Cytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentCytomegalovirus (CMV)1
3CompletedTreatmentCytomegalovirus Retinitis / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentGastrointestinal Diseases / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHerpes Simplex / Human Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
  • Hospira inc
  • Clinigen healthcare ltd
Packagers
  • AstraZeneca Inc.
  • Hospira Inc.
  • Spectrum Pharmaceuticals
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous
Injection, solutionIntravenous24 mg/1mL
InjectionIntravenous24 mg/1mL
InjectionIntravenous500 ML
Injection, solutionIntravenous24 MG/ML
InjectionIntravenous24 mg/ml
SolutionIntravenous24 mg / mL
Prices
Unit descriptionCostUnit
Sodium phosphonoformate powder286.3USD g
Foscavir 24 mg/ml infus bottle0.43USD ml
Foscarnet 24 mg/ml infus bttl0.37USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)88.06 °CNot Available
water solubilityCompleteNot Available
logP-2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility16.8 mg/mLALOGPS
logP-1.6ALOGPS
logP-0.83ChemAxon
logS-0.88ALOGPS
pKa (Strongest Acidic)-0.096ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area94.83 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity19.07 m3·mol-1ChemAxon
Polarizability7.89 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9396
Blood Brain Barrier+0.9382
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.8162
P-glycoprotein inhibitor INon-inhibitor0.9783
P-glycoprotein inhibitor IINon-inhibitor0.9962
Renal organic cation transporterNon-inhibitor0.9731
CYP450 2C9 substrateNon-substrate0.8114
CYP450 2D6 substrateNon-substrate0.861
CYP450 3A4 substrateNon-substrate0.7282
CYP450 1A2 substrateNon-inhibitor0.8825
CYP450 2C9 inhibitorNon-inhibitor0.9124
CYP450 2D6 inhibitorNon-inhibitor0.9086
CYP450 2C19 inhibitorNon-inhibitor0.9202
CYP450 3A4 inhibitorNon-inhibitor0.9608
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.996
Ames testNon AMES toxic0.9139
CarcinogenicityNon-carcinogens0.5461
BiodegradationNot ready biodegradable0.5449
Rat acute toxicity1.7117 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9831
hERG inhibition (predictor II)Non-inhibitor0.96
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
HHV-5
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nucleotide binding
Specific Function
Replicates viral genomic DNA in the late phase of lytic infection, producing long concatemeric DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity facto...
Gene Name
UL54
Uniprot ID
P08546
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
137100.705 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. [Article]
  4. Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. [Article]
  5. Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. [Article]
Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
136419.66 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Ducancelle A, Alain S, Petit F, Sanson Le Pors MJ, Mazeron MC: Development and validation of a non-radioactive DNA polymerase assay for studying cytomegalovirus resistance to foscarnet. J Virol Methods. 2007 May;141(2):212-5. Epub 2007 Jan 2. [Article]
  4. Bonnafous P, Naesens L, Petrella S, Gautheret-Dejean A, Boutolleau D, Sougakoff W, Agut H: Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet. Antivir Ther. 2007;12(6):877-88. [Article]
  5. Tchesnokov EP, Gilbert C, Boivin G, Gotte M: Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet. J Virol. 2006 Feb;80(3):1440-50. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Wada S, Tsuda M, Sekine T, Cha SH, Kimura M, Kanai Y, Endou H: Rat multispecific organic anion transporter 1 (rOAT1) transports zidovudine, acyclovir, and other antiviral nucleoside analogs. J Pharmacol Exp Ther. 2000 Sep;294(3):844-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Symporter activity
Specific Function
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucin...
Gene Name
SLC16A1
Uniprot ID
P53985
Uniprot Name
Monocarboxylate transporter 1
Molecular Weight
53943.685 Da
References
  1. Tamai I, Sai Y, Ono A, Kido Y, Yabuuchi H, Takanaga H, Satoh E, Ogihara T, Amano O, Izeki S, Tsuji A: Immunohistochemical and functional characterization of pH-dependent intestinal absorption of weak organic acids by the monocarboxylic acid transporter MCT1. J Pharm Pharmacol. 1999 Oct;51(10):1113-21. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 22, 2021 23:18