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Foscarnet

PubChem CID
3415
Structure
Foscarnet_small.png
Foscarnet_3D_Structure.png
Molecular Formula
Synonyms
  • foscarnet
  • Phosphonoformic acid
  • Phosphonoformate
  • Carboxyphosphonic acid
  • 4428-95-9
Molecular Weight
126.01 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-18
Description
Phosphonoformic acid is phosphoric acid in which one of the hydroxy groups is replaced by a carboxylic acid group. It is used as the trisodium salt as an antiviral agent in the treatment of cytomegalovirus retinitis (CMV retinitis, an inflamation of the retina that can lead to blindness) and as an alternative to ganciclovir for AIDS patients who require concurrent antiretroviral therapy but are unable to tolerate ganciclovir due to haematological toxicity. It has a role as an antiviral drug, a sodium-dependent Pi-transporter inhibitor, a HIV-1 reverse transcriptase inhibitor and a geroprotector. It is a one-carbon compound, a member of phosphonic acids and a carboxylic acid. It is functionally related to a phosphonic acid and a formic acid. It is a conjugate acid of a phosphonatoformate and a phosphonoformate(2-).

Foscarnet sodium is an antiviral prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of cytomegalovirus (CMV) retinitis in individuals with AIDS. Foscarnet sodium is also FDA-approved for the treatment of a certain type of herpes simplex virus (HSV)infection, called acyclovir-resistant mucocutaneous HSV infection, in people with weakened immune systems.

CMV diseases—such as those affecting the eye (retinitis)—and HSV diseases can be opportunistic infections (OIs) of HIV.

An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpes viruses and HIV.
See also: Foscarnet Sodium (has salt form).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Foscarnet.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

phosphonoformic acid
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

ZJAOAACCNHFJAH-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C(=O)(O)P(=O)(O)O
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

CH3O5P
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

63585-09-1

2.3.3 European Community (EC) Number

112-287-0

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 PharmGKB ID

2.3.15 RXCUI

2.3.16 Wikidata

2.3.17 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Foscarnet
  • Foscarnet Barium (2:3) Salt
  • Foscarnet Calcium (2:3) Salt
  • Foscarnet Disodium Salt
  • Foscarnet Magnesium (2:3) Salt
  • Foscarnet Manganese (2+) (2:3) Salt
  • Foscarnet Sodium
  • Foscarnet Sodium Hexahydrate
  • Foscarnet Trilithium Salt
  • Foscarnet Tripotassium Salt
  • Foscarnet Trisodium Salt
  • Foscavir
  • Phosphonoformate
  • Phosphonoformic Acid
  • Trisodium Phosphonoformate

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
126.01 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3
Property Value
-2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
125.97181019 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
125.97181019 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
94.8 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
7
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
120
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Melting Point

88.06 °C
88.06 °C

3.2.3 Solubility

Complete
1.68e+01 g/L

3.2.4 LogP

-2.1
-2.1

3.2.5 Collision Cross Section

128.92 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

3.2.6 Other Experimental Properties

Hexahydrate, mp >250 °C/Foscarnet sodium/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 729

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals
S10 | SWISSPHARMA | Pharmaceutical List with Consumption Data | DOI:10.5281/zenodo.2623484
3.3.1.1 Human Drugs
Human drug -> Prescription

4 Spectral Information

4.1 1D NMR Spectra

4.1.1 13C NMR Spectra

Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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Thumbnail

4.1.2 31P NMR Spectra

Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
Thumbnail
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug 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.

7.2 LiverTox Summary

Foscarnet a simple pyrophosphate molecule which has antiviral activity against many viruses and is used intravenously in therapy of serious cytomegalovirus infections, largely in immunocompromised patients. Foscarnet has been associated with mild-to-moderate serum aminotransferase elevations during intravenous therapy, but not with episodes of clinically apparent liver injury.

7.3 Drug Classes

Antiviral Agents

7.4 HIV / AIDS and Opportunistic Infection Drugs

What is Foscarnet Sodium

Foscarnet sodium is an antiviral prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of cytomegalovirus (CMV) retinitis in individuals with AIDS. Foscarnet sodium is also FDA-approved for the treatment of a certain type of herpes simplex virus (HSV)infection, called acyclovir-resistant mucocutaneous HSV infection, in people with weakened immune systems.

CMV diseases—such as those affecting the eye (retinitis)—and HSV diseases can be opportunistic infections (OIs) of HIV.

Drug Class
Antiviral (Pyrophosphate Analog DNA Polymerase Inhibitor)

7.5 Clinical Trials

7.5.1 ClinicalTrials.gov

7.5.2 EU Clinical Trials Register

7.5.3 NIPH Clinical Trials Search of Japan

7.6 Therapeutic Uses

Antiviral Agents; Reverse Transcriptase Inhibitors
National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)
Foscarnet sodium injection is indicated for the treatment of acyclovir-resistant mucocutaneous HSV infections in immunocompromised patients. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
Foscarnet sodium injection is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). Combination therapy with foscarnet sodium and ganciclovir is indicated for patients who have relapsed after monotherapy with either drug. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

7.7 Drug Warnings

/BOXED WARNING/ Renal impairment is the major toxicity of foscarnet sodium injection. Frequent monitoring of serum creatinine, with dose adjustment for changes in renal function, and adequate hydration with administration of foscarnet sodium injection, is imperative.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/BOXED WARNING/ Seizures, related to alterations in plasma minerals and electrolytes, have been associated with foscarnet sodium injection treatment. Therefore, patients must be carefully monitored for such changes and their potential sequelae. Mineral and electrolyte supplementation may be required.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/BOXED WARNING/ Foscarnet sodium injection is indicated for use only in immunocompromised patients with CMV retinitis and mucocutaneous acyclovir-resistant HSV infections.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
Foscarnet sodium injection is contraindicated in patients with clinically significant hypersensitivity to foscarnet sodium.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
For more Drug Warnings (Complete) data for Foscarnet (31 total), please visit the HSDB record page.

7.8 Drug Tolerance

Strains of both HSV and CMV that are resistant to foscarnet sodium can be readily selected in vitro by passage of wild type virus in the presence of increasing concentrations of the drug. All foscarnet sodium resistant mutants are known to be generated through mutation in the viral DNA polymerase gene. CMV strains with double mutations conferring resistance to both foscarnet sodium and ganciclovir have been isolated from patients with AIDS. The possibility of viral resistance should be considered in patients who show poor clinical response or experience persistent viral excretion during therapy.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

8 Pharmacology and Biochemistry

8.1 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.

8.2 MeSH Pharmacological Classification

Reverse Transcriptase Inhibitors
Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. (See all compounds classified as Reverse Transcriptase Inhibitors.)
Antiviral Agents
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)

8.3 FDA Pharmacological Classification

FDA UNII
364P9RVW4X
Active Moiety
FOSCARNET
Pharmacological Classes
Mechanisms of Action [MoA] - DNA Polymerase Inhibitors
Pharmacological Classes
Pyrophosphate Analog [EXT]
Pharmacological Classes
Established Pharmacologic Class [EPC] - Pyrophosphate Analog DNA Polymerase Inhibitor
Pharmacological Classes
Mechanisms of Action [MoA] - Chelating Activity
FDA Pharmacology Summary
Foscarnet is a Pyrophosphate Analog DNA Polymerase Inhibitor. The mechanism of action of foscarnet is as a DNA Polymerase Inhibitor, and Chelating Activity.

8.4 ATC Code

S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

J - Antiinfectives for systemic use

J05 - Antivirals for systemic use

J05A - Direct acting antivirals

J05AD - Phosphonic acid derivatives

J05AD01 - Foscarnet

8.5 Absorption, Distribution and Excretion

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

The pharmacokinetics, absolute bioavailability, /and/ accumulation over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function. Peak plasma drug concentrations were (mean +/- standard deviation) 46.4 +/- 10.8 uM (90 mg/kg QD), 45.7 +/- 6.9 uM (90 mg/ kg BID), and 64.9 +/- 31.7 uM (180 mg/kg QD) on day 1 and rose to 86.2 +/- 35.8, 78.7 +/- 35.2, and 86.4 +/- 25.0 uM, respectively, on day 8. The mean peak concentration in plasma following the intravenous administration of foscarnet (90 mg/kg) was 887.3 +/- 102.7 uM (n = 13). The terminal half-life in plasma remained unchanged, averaging 5.5 +/- 2.2 hr on day 1 (n = 15) and 6.6 +/- 1.9 hr on day 8 (n = 13), whereas it was 5.7 +/- 0.7 hr following intravenous dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7% (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively. The overall 24-hr urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day 1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous dosing. The glomerular filtration rate and creatinine clearance remained constant, and the mean 24-hr renal clearances of foscarnet for the entire study group were 96 +/- 18 mL/min (day 1), 88 +/- 13 mL/min (day 8), and 103 +/- 16 mL/min after intravenous dosing.
Noormohamed FH et al; Antimicrob Agents Chemother. 42 (2): 293-7 (1998)
Six patients with human immunodeficiency virus were given foscarnet in oral solution, 4000 mg every 6 hours for 3 days, followed by a washout period for 2 days and continuous intravenous infusion of 16,000 mg/24 hr over 72 hours. After oral foscarnet, plasma concentrations were less than 33 mumol/L in four patients; two had occasional concentrations of 35 to 50 mumol/L. The extent of absorption varied between 12% and 22%. During intravenous infusion, plasma concentrations ranged between 75 and 265 mumol/L. The disposition of foscarnet was triphasic, with mean half-lives of 0.45, 3.3, and 18 hours. Excretion data suggested elimination was by tubular secretion and glomerular filtration. Renal clearance was 176 mL/min 1.73 sq m. The apparent nonrenal clearance, 40 mL/min 1.73 sq m, probably reflects sequestration of foscarnet into bone. Ten percent to 28% of the cumulative dose may have been deposited in bone 2 days after infusion. A slight increase in serum calcium levels and changes in serum phosphate values may reflect the uptake of foscarnet in bone. Five patients had diarrhea (oral) and two had thrombophlebitis (intravenous).
Sjovall J et al; Clin Pharmacol Ther 44 (1): 65-73 (1988)
It is not known whether foscarnet sodium is excreted in human milk...
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

8.6 Metabolism / Metabolites

Not metabolized.

8.7 Biological Half-Life

3.3-6.8 hours
...The foscarnet half-lives during continuous cyclic peritoneal dialysis (CCPD) and continuous ambulatory peritoneal dialysis (CAPD).were 41.4 and 45.8 hours, respectively. These values are significantly greater than the half-life of 4.5 hours observed in patients with normal renal function and about half that reported in anuric patients undergoing hemodialysis during the interdialytic period. The CCPD and CAPD clearances of foscarnet were 5.8 and 4.5 mL/min, respectively; the CAPD clearances of creatinine and urea nitrogen were 4.1 and 6.0 mL/min, respectively. The patient's estimated total body clearance values of foscarnet during CCPD and CAPD were 9.8 and 8.8 mL/min, respectively. Thus, CCPD and CAPD augmented the patient's residual clearance of foscarnet by 145% and 105%, respectively. ...
Alexander AC et al; Ann Pharmacother 30 (10): 1106-9 (1996)
The pharmacokinetics, absolute bioavailability, /and/ accumulation over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function ... The terminal half-life in plasma remained unchanged, averaging 5.5 +/- 2.2 hr on day 1 (n = 15) and 6.6 +/- 1.9 hr on day 8 (n = 13), whereas it was 5.7 +/- 0.7 hr following intravenous dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7% (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively. The overall 24-hr urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day 1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous dosing.
Noormohamed FH et al; Antimicrob Agents Chemother. 42 (2): 293-7 (1998)

8.8 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.
Foscarnet sodium is an organic analogue of inorganic pyrophosphate that inhibits replication of herpesviruses in vitro including cytomegalovirus (CMV) and herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Foscarnet sodium 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. Foscarnet sodium 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 sodium. However, acyclovir or ganciclovir resistant mutants with alterations in the viral DNA polymerase may be resistant to foscarnet sodium and may not respond to therapy with foscarnet sodium. The combination of foscarnet sodium and ganciclovir has been shown to have enhanced activity in vitro.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
The pyrophosphate (PP(i)) analog foscarnet inhibits viral DNA-polymerases and is used to treat cytomegalovirus and human immunodeficiency vius infections. Nucleotide cyclases and DNA-polymerases catalyze analogous reactions, i.e. a phosphodiester bond formation, and have similar topologies in their active sites. Inhibition by foscarnet of adenylyl cyclase isoforms was therefore tested with (i) purified catalytic domains C1 and C2 of types I and VII (IC1 and VIIC1) and of type II (IIC2) and (ii) membrane-bound holoenzymes (from mammalian tissues and types I, II, and V heterologously expressed in Sf9 cell membranes). Foscarnet was more potent than PP(i) in suppressing forskolin-stimulated catalysis by both, IC1/IIC2 and VIIC1/IIC2. Stimulation of VIIC1/IIC2 by Galpha(s) relieved the inhibition by foscarnet but not that by PP(i). The IC(50) of foscarnet on membrane-bound adenylyl cyclases also depended on their mode of regulation. These findings predict that receptor-dependent cAMP formation is sensitive to inhibition by foscarnet in some, but not all, cells. This was verified with two cell lines; foscarnet blocked cAMP accumulation after A(2A)-adenosine receptor stimulation in PC12 but not in HEK-A(2A) cells. Foscarnet also inhibited soluble and, to a lesser extent, particulate guanylyl cylase. Thus, foscarnet interferes with the generation of cyclic nucleotides, an effect which may give rise to clinical side effects. The extent of inhibition varies with the enzyme isoform and with the regulatory input.
Kudlacek O et al; J Biol Chem. 276 (5): 3010-6 (2001)

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Cytoplasm
  • Membrane

9 Use and Manufacturing

9.1 Uses

MEDICATION

9.2 Methods of Manufacturing

Phosphonoformate is prepared by saponification of the triethyl ester of phosphonoformate with NaOH. Trisodium phosphonoformate hexahydrate is recrystallized from H2O.
Actor P et al; Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2012). NY, NY: John Wiley & Sons; Chemotherapeutics. Online Posting Date: June 15, 2000

9.3 Formulations / Preparations

Each milliliter of foscarnet sodium injection contains 24 mg of foscarnet sodium hexahydrate in Water for Injection, USP. Hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH of the solution to 7.4. Foscarnet sodium injection contains no preservatives. /Available in/ 500 or 250 mL bottles.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
Foscavir

10 Safety and Hazards

10.1 Hazards Identification

10.1.1 GHS Classification

Pictogram(s)
Health Hazard
Signal
Warning
GHS Hazard Statements

H341 (100%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H373 (100%): May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

Precautionary Statement Codes

P203, P260, P280, P318, P319, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

10.1.2 Hazard Classes and Categories

Muta. 2 (100%)

STOT RE 2 (100%)

10.1.3 Skin, Eye, and Respiratory Irritations

Accidental skin and eye contact with foscarnet sodium solution may cause local irritation and burning sensation.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

10.2 Accidental Release Measures

10.2.1 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

10.2.2 Preventive Measures

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

10.3 Handling and Storage

10.3.1 Storage Conditions

Store at 20 to 25 °C (68 to 77 °F). Protect from excessive heat (above 40 °C) and from freezing.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

10.4 Stability and Reactivity

10.4.1 Hazardous Reactivities and Incompatibilities

Other drugs and supplements can be administered to a patient receiving foscarnet sodium. However, care must be taken to ensure that foscarnet sodium is only administered with 0.9% sodium chloride injection or 5% dextrose solution and that no other drug or supplement is administered concurrently via the same catheter.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
Foscarnet has been reported to be chemically incompatible with 30% dextrose, amphotericin B, and solutions containing calcium such as Ringer's lactate and TPN.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
Physical incompatibility with other IV drugs has also been reported including acyclovir sodium, ganciclovir, trimetrexate glucuronate, pentamidine isethionate, vancomycin, trimethoprim/sulfamethoxazole, diazepam, midazolam, digoxin, phenytoin, leucovorin, and prochlorperazine. Because of foscarnet's chelating properties, a precipitate can potentially occur when divalent cations are administered concurrently in the same catheter.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

10.5 Regulatory Information

10.5.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including foscarnet sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Foscarnet sodium/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 18, 2013: https://www.fda.gov/cder/ob/

11 Toxicity

11.1 Toxicological Information

11.1.1 Hepatotoxicity

Intravenous foscarnet therapy is associated with mild-to-moderate serum ALT elevations in a proportion of patients, but the drug is usually given to patients with multiorgan disease and conditions that may be associated with some degree of hepatic injury. The ALT elevations are usually asymptomatic and resolve even with continuation of foscarnet. Single case reports of clinically apparent liver injury that were possibly attributable to foscarnet have been reported. The pattern of injury was cholestatic arising within weeks of starting foscarnet but the clinical features of the liver injury have not been described in any detail.

Likelihood score: D (possible cause of clinically apparent liver injjry).

11.1.2 Drug Induced Liver Injury

Compound
foscarnet
DILI Annotation
Ambiguous DILI-concern
Severity Grade
3
Label Section
Adverse reactions
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

11.1.3 Interactions

Concomitant administration of foscarnet and parenteral pentamidine has been associated with hypocalcemia, including severe hypocalcemia resulting in death. Toxicity associated with concomitant administration of foscarnet and orally inhaled pentamidine has not been reported to date.
American Society of Health-System Pharmacists 2012; Drug Information 2012. Bethesda, MD. 2012
Abnormal renal function has occurred in patients receiving foscarnet in combination with ritonavir and/or saquinavir.
American Society of Health-System Pharmacists 2012; Drug Information 2012. Bethesda, MD. 2012
To report a possible interaction between foscarnet and ciprofloxacin in two patients with AIDS, cytomegalovirus (CMV) retinitis, and disseminated Mycobacterium avium complex (MAC) infection and to review the available literature related to foscarnet-associated seizures. Case report information was obtained from Medical Service Daily Rounds during the patients' hospitalization and from the patients' medical records. Computerized (MEDLINE) and manual (Index Medicus) search methods were used to obtain English-language literature published between 1980 and 1993.Foscarnet is a synthetic antiviral agent with activity against herpesviruses and HIV. The incidence of seizures with foscarnet infusion is high, ranging from 13 to 15 percent. Predisposing factors such as renal impairment, electrolyte and metabolic abnormalities, and underlying neurologic disorders have been associated with seizures during foscarnet therapy. We describe two patients with AIDS who developed generalized tonic-clonic seizures while receiving foscarnet and ciprofloxacin for the treatment of CMV retinitis and disseminated MAC infection, respectively. Neither of the patients had any of the aforementioned risk factors for foscarnet-associated seizures. Concurrent administration of ciprofloxacin, a known epileptogenic agent, and foscarnet may predispose patients to the development of seizures.
Fan-Harvard P et al; Ann Pharmacother 28 (7-8): 869-72 (1994)

11.1.4 Antidote and Emergency Treatment

There is no specific antidote for foscarnet sodium overdose. Hemodialysis and hydration may be of benefit in reducing drug plasma levels in patients who receive an overdosage of foscarnet sodium, but the effectiveness of these interventions has not been evaluated. The patient should be observed for signs and symptoms of renal impairment and electrolyte imbalance. Medical treatment should be instituted if clinically warranted.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1
For more Antidote and Emergency Treatment (Complete) data for Foscarnet (7 total), please visit the HSDB record page.

11.1.5 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ The literature has been reviewed for contact dermatitis from topical antiviral drugs. 15 agents have been identified including acyclovir, imiquimod, podophyllin, podofilox, cidofovir, penciclovir, vidarabine, idoxuridine, trifluridine, tromantadine, lamivudine, interferon intralesional injections and ophthalmic solution, fomivirsen and foscarnet intravitreal injections and ganciclovir intraocular implants. Patch testing has been documented in certain individuals and cross-sensitization has been observed to contribute significantly to some allergic reactions.
Holdiness MR; Contact Dermatitis. 44 (5): 265-9 (2001)
/SIGNS AND SYMPTOMS/ In controlled clinical trials performed in the United States, overdosage with foscarnet sodium injection was reported in 10 out of 189 patients. All 10 patients experienced adverse events and all except one made a complete recovery. One patient died after receiving a total daily dose of 12.5 g for three days instead of the intended 10.9 g. The patient suffered a grand mal seizure and became comatose. Three days later the patient expired with the cause of death listed as respiratory/cardiac arrest. The other nine patients received doses ranging from 1.14 times to 8 times their recommended doses with an average of 4 times their recommended doses. Overall, three patients had seizures, three patients had renal function impairment, four patients had paresthesias either in limbs or periorally, and five patients had documented electrolyte disturbances primarily involving calcium and phosphate.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/CASE REPORTS/ Foscarnet (FC) is a new antiviral agent which has been recently proposed for the treatment of severe cytomegalovirus (CMV) infections in immunocompromised patients. When used intravenously (i.v.), main adverse effects of FC are a fall in hemoglobin, and an increase in liver enzymes and serum calcium. Although increased serum creatinine has been noted in several patients, deterioration of renal function is often accounted for by the concomitant use of other nephrotoxic drugs, the severity of underlying disease or the presence of graft rejection. Consequently FC is often considered as a non or poorly nephrotoxic drug. We report 4 cases of acute renal failure (ARF) which can be exclusively attributed to FC. FC was used for CMV chorioretinitis in 3 AIDS patients and in one non-immunocompromised patient. ARF was diagnosed between the 6th and 15th day of treatment, with oligoanuria in two patients (one of whom required two hemodialysis periods). ARF was most likely secondary to acute toxic tubulopathy. Three patients did not receive any other nephrotoxic drug. The fourth patient received concomitantly sulfadiazine but renal function returned to baseline value after FC completion although sulfadiazine was continued. In conclusion, our 4 observations suggest that FC may be responsible for acute tubulopathy.
Cacoub Pet al; Clin Nephrol 29 (6): 315-8 (1988)
/CASE REPORTS/ A case of fixed drug eruption (FDE) secondary to foscarnet is reported. This drug has recently become available on a compassionate use basis for treatment of cytomegalovirus (CMV) infection which may cause significant disease in immunosuppressed patients. Foscarnet provides a useful alternative to the only licensed anti-CMV drug currently available, namely ganciclovir (DHPG), as it has a different toxicity profile. In particular, it does not appear to cause bone marrow suppression which is of importance in AIDS patients as many of them are taking concurrent zidovudine.
Connolly GM et al; Genitourin Med 66 (2): 97-8 (1990)
For more Human Toxicity Excerpts (Complete) data for Foscarnet (11 total), please visit the HSDB record page.

11.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Carcinogenicity studies were conducted in rats and mice at oral doses of 500 mg/kg/day and 250 mg/kg/day. Oral bioavailabilty in unfasted rodents is < 20%. No evidence of oncogenicity was reported at plasma drug levels equal to 1/3 and 1/5, respectively, of those in humans (at the maximum recommended human daily dose) as measured by the area-under-the-time/concentration curve (AUC).
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Daily subcutaneous doses up to 75 mg/kg administered to female rats prior to and during mating, during gestation, and 21 days post-partum caused a slight increase (< 5%) in the number of skeletal anomalies compared with the control group. Daily subcutaneous doses up to 75 mg/kg administered to rabbits and 150 mg/kg administered to rats during gestation caused an increase in the frequency of skeletal anomalies/variations. On the basis of estimated drug exposure (as measured by AUC), the 150 mg/kg dose in rats and 75 mg/kg dose in rabbits were approximately one-eighth (rat) and one-third (rabbit) the estimated maximal daily human exposure. These studies are inadequate to define the potential teratogenicity at levels to which women will be exposed.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/GENOTOXICITY/ Foscarnet sodium showed genotoxic effects in the BALB/3T3 in vitro transformation assay at concentrations greater than 0.5 ug/mL and an increased frequency of chromosome aberrations in the sister chromatid exchange assay at 1000 ug/mL. A high dose of foscarnet (350 mg/kg) caused an increase in micronucleated polychromatic erythrocytes in vivo in mice at doses that produced exposures (area under curve) comparable to that anticipated clinically.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c
/ALTERNATIVE and IN VITRO TESTS/ This research evaluated the ability of phosphonoformic acid to inhibit bovine herpesvirus 1 (BHV-1) in cumulus cells commonly used in co-culture with bovine in vitro-produced embryos. At 200 and 400 ug/mL, phosphonoformic acid inhibited 4 logs of BHV-1. Subsequently, phosphonoformic acid (200 and 400 ug/mL) added to both in vitro fertilization and culture medium resulted in a decrease in the proportion of developed blastocysts, and the number of cells per blastocyst was lower in the treated embryos. Therefore, while phosphonoformic acid can effectively inhibit replication of BHV-1 in co-culture cells, it also inhibits development of in vitro-produced bovine embryos.
Marley MSet al; Vet Ther 7 (2): 156-66 (2006)

11.1.7 Protein Binding

14-17%

11.2 Ecological Information

11.2.1 Environmental Fate / Exposure Summary

Foscarnet's production and administration as an antiviral may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C indicates foscarnet will exist in both the vapor and particulate phases in the atmosphere. Vapor-phase foscarnet will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 13 days. Particulate-phase foscarnet will be removed from the atmosphere by wet and dry deposition. Foscarnet does not contains chromophores that absorb at wavelengths >290 nm and, therefore, is not expected to be susceptible to direct photolysis by sunlight. If released to soil, foscarnet is expected to have moderate mobility based upon an estimated Koc of 330. The estimated pKa of 3.13 indicates that this compound will exist almost entirely in the anion form in the environment. Anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as a anion and anions do not volatilize. Foscarnet is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data in soil or water were not available. If released into water, foscarnet is expected to adsorb to suspended solids and sediment based upon the estimated Koc. The estimated pKa indicates foscarnet will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to foscarnet may occur through inhalation and dermal contact with this compound at workplaces where foscarnet is produced or used. Exposure to foscarnet among the general population may be limited to those administered the drug. (SRC)

11.2.2 Artificial Pollution Sources

Foscarnet's production and administration as an antiviral(1) may result in its release to the environment through various waste streams(SRC).
(1) US Natl Inst Health; DailyMed. Current Medical Information. Available from, as of Mar 6, 2013: https://dailymed.nlm.nih.gov/dailymed/about.cfm

11.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that foscaranet is expected to have moderate mobility in soil(SRC). The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form in the environment. Anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a anion and anions do not volatilize. Foscarnet is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) SPARC; pKa/property server. Ver 4.5., Sept, 2009. Available from, as of Mar 7, 2013: https://archemcalc.com/sparc/
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 330(SRC), determined from a structure estimation method(2), indicates that foscarnet is expected to adsorb to suspended solids and sediment(SRC). The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of -1.93(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).
(1) Swann RL et al; Res Rev 85: 17-28 (1983)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) SPARC; pKa/property server. Ver 4.5., Sept, 2009. Available from, as of Mar 7, 2013: https://archemcalc.com/sparc/
(4) Franke C et al; Chemosphere 29: 1501-14 (1994)
(5) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), foscarnet, which has an estimated vapor pressure of 1.6X10-6 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase foscarnet is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 13 days(SRC), calculated from its rate constant of 8.0X10-13 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase foscarnet may be removed from the air by wet and dry deposition(SRC). Foscarnet does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

11.2.4 Environmental Biodegradation

Biodegradation data in soil or water were not available. (SRC, 2013)

11.2.5 Environmental Abiotic Degradation

The rate constant for the vapor-phase reaction of foscarnet with photochemically-produced hydroxyl radicals has been estimated as 8.0X10-13 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 13 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Foscarnet is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Foscarnet does not contain chromophores that absorb at wavelengths >290 nm(2) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).
(1) Meylan WM, Howard PH; Chemosphere 26: 2293-99 (1993)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

11.2.6 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for foscarnet(SRC), using an estimated log Kow of -1.93(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).
(1) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)

11.2.7 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of foscarnet can be estimated to be 330(SRC). According to a classification scheme(2), this estimated Koc value suggests that foscarnet is expected to have moderate mobility in soil. The estimated pKa of foscarnet is 3.13(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)
(3) SPARC; pKa/property server. Ver 4.5., Sept, 2009. Available from, as of Mar 7, 2013: https://archemcalc.com/sparc/
(4) Doucette WJ; pp. 141-188 in Handbook of Property Estimation Methods for Chemicals. Boethling RS, Mackay D, eds. Boca Raton, FL: Lewis Publ (2000)

11.2.8 Volatilization from Water / Soil

The estimated pKa of 3.13(1) indicates foscarnet will exist almost entirely in the anion form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(SRC). Foscarnet is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-6 mm Hg(SRC), determined from a fragment constant method(2).
(1) SPARC; pKa/property server. Ver 4.5., Sept, 2009. Available from, as of Mar 7, 2013: https://archemcalc.com/sparc/
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2010. Available from, as of Mar 7, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

11.2.9 Effluent Concentrations

Antiviral drugs have been recently recognized as one of the emerging contaminants in the environment. These are discharged after therapeutic use through human excretion. Effluent containing high concentration of antiviral drugs discharged from production facilities is also a cause of concern to nearby aquatic bodies. There is an increased interest in their removal because they are highly bioactive. Some antiviral drugs are resistant to conventional methods of degradation, and there is a risk of development of antiviral resistance in humans and animals if exposed repeatedly for long periods. To date, the potential human, animal, and ecological risks associated with the discharge of these antiviral compounds to the environment are not well documented. This study presents a brief summary on occurrence, ecotoxicological risks, and physicochemical properties of antiviral drugs in the environment. The needs regarding removal, disposal, and treatment of antiviral drugs are also addressed(1). /Antiviral drugs/
(1) Jain S et al; Water Air Soil Pollution 224: 1410 (2013)

11.2.10 Milk Concentrations

It is not known whether foscarnet sodium is excreted in human milk; however, in lactating rats administered 75 mg/kg, foscarnet sodium was excreted in maternal milk at concentrations three times higher than peak maternal blood concentrations.
US Natl Inst Health; DailyMed. Current Medication Information for FOSCARNET SODIUM injection, solution (September 2009). Available from, as of March 14, 2013: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=eec8727b-c98c-41a4-90b8-d49a8e01e63c

11.2.11 Probable Routes of Human Exposure

Occupational exposure to foscarnet may occur through inhalation and dermal contact with this compound at workplaces where foscarnet is produced or used. Exposure to foscarnet among the general population may be limited to those administered the drug. (SRC)

12 Associated Disorders and Diseases

13 Literature

13.1 Consolidated References

13.2 NLM Curated PubMed Citations

13.3 Springer Nature References

13.4 Thieme References

13.5 Nature Journal References

13.6 Chemical Co-Occurrences in Literature

13.7 Chemical-Gene Co-Occurrences in Literature

13.8 Chemical-Disease Co-Occurrences in Literature

14 Patents

14.1 Depositor-Supplied Patent Identifiers

14.2 WIPO PATENTSCOPE

14.3 Chemical Co-Occurrences in Patents

14.4 Chemical-Disease Co-Occurrences in Patents

14.5 Chemical-Gene Co-Occurrences in Patents

15 Interactions and Pathways

15.1 Protein Bound 3D Structures

15.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

15.2 Chemical-Target Interactions

15.3 Drug-Drug Interactions

16 Biological Test Results

16.1 BioAssay Results

17 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Drug Groups

18.6 WHO ATC Classification System

18.7 FDA Pharm Classes

18.8 ChemIDplus

18.9 ChEMBL Target Tree

18.10 UN GHS Classification

18.11 NORMAN Suspect List Exchange Classification

18.12 CCSBase Classification

18.13 EPA DSSTox Classification

18.14 LOTUS Tree

18.15 MolGenie Organic Chemistry Ontology

19 Information Sources

  1. CAS Common Chemistry
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    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    Phosphonocarboxylic acid
    https://echa.europa.eu
  6. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  7. Hazardous Substances Data Bank (HSDB)
  8. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  9. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  10. ChEBI
  11. Drug Database, Clinicalinfo.hiv.gov
    LICENSE
    Unless otherwise noted, material presented on the HIV.gov website is considered Federal government information and is in the public domain. That means this information may be freely copied and distributed. We request that you use appropriate attribution to HIV.gov.
    https://www.hiv.gov/about-us/mission-and-team
  12. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  13. LiverTox
  14. LOTUS - the natural products occurrence database
    LICENSE
    The code for LOTUS is released under the GNU General Public License v3.0.
    https://lotus.nprod.net/
  15. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  16. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  17. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  18. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  19. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  20. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  21. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  23. EU Clinical Trials Register
  24. Japan Chemical Substance Dictionary (Nikkaji)
  25. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
  26. KNApSAcK Species-Metabolite Database
  27. Metabolomics Workbench
  28. Nature Chemical Biology
  29. NIPH Clinical Trials Search of Japan
  30. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  31. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    FOSCARNET SODIUM
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  32. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  33. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  34. Protein Data Bank in Europe (PDBe)
  35. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
    Data files contained in the PDB archive (ftp://ftp.wwpdb.org) are free of all copyright restrictions and made fully and freely available for both non-commercial and commercial use. Users of the data should attribute the original authors of that structural data.
    https://www.rcsb.org/pages/policies
  36. SpectraBase
  37. Springer Nature
  38. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  39. Wikidata
  40. Wikipedia
  41. Medical Subject Headings (MeSH)
    LICENSE
    Works produced by the U.S. government are not subject to copyright protection in the United States. Any such works found on National Library of Medicine (NLM) Web sites may be freely used or reproduced without permission in the U.S.
    https://www.nlm.nih.gov/copyright.html
    Reverse Transcriptase Inhibitors
    https://www.ncbi.nlm.nih.gov/mesh/68018894
  42. PubChem
  43. GHS Classification (UNECE)
  44. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  45. PATENTSCOPE (WIPO)
  46. NCBI
CONTENTS