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Acyclovir

PubChem CID
135398513
Structure
Acyclovir_small.png
Acyclovir_3D_Structure.png
Acyclovir__Crystal_Structure.png
Molecular Formula
Synonyms
  • acyclovir
  • Aciclovir
  • 59277-89-3
  • Acycloguanosine
  • Zovirax
Molecular Weight
225.20 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2019-01-10
  • Modify:
    2025-01-18
Description
Acyclovir is an oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections. It has a role as an antiviral drug and an antimetabolite. It is an oxopurine and a member of 2-aminopurines. It is functionally related to a guanine.

Acyclovir is an antiviral prescription medicine approved by the U.S. Food and Drug Administration (FDA) to:

Treat and/or prevent the recurrence of certain types of herpes simplex virus (HSV) infections, including genital herpes 

Treat varicella zoster virus (VZV) infections, including chicken pox (primary varicella infection) and shingles (herpes zoster) 

Acyclovir is approved in different formulations and strengths for use in specific populations, including in people who are immunocompromised.

HSV and VZV infections can be opportunistic infections (OIs) of HIV.

Acyclovir is a deoxynucleoside analog antiviral used to treat herpes simplex, Varicella zoster, herpes zoster, herpes labialis, and acute herpetic keratitis. Acyclovir is generally used first line in the treatment of these viruses and some products are indicated for patients as young as 6 years old. Acyclovir was granted FDA approval on 29 March 1982.
See also: Valacyclovir (is active moiety of); Valacyclovir Hydrochloride (active moiety of); Acyclovir Sodium (active moiety of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Acyclovir.png

1.2 3D Conformer

1.3 Crystal Structures

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CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-amino-9-(2-hydroxyethoxymethyl)-1H-purin-6-one
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C8H11N5O3/c9-8-11-6-5(7(15)12-8)10-3-13(6)4-16-2-1-14/h3,14H,1-2,4H2,(H3,9,11,12,15)
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

MKUXAQIIEYXACX-UHFFFAOYSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

C1=NC2=C(N1COCCO)N=C(NC2=O)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C8H11N5O3
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

59277-89-3
125440-97-3

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 HMDB ID

2.3.9 KEGG ID

2.3.10 Metabolomics Workbench ID

2.3.11 NCI Thesaurus Code

2.3.12 Nikkaji Number

2.3.13 NSC Number

2.3.14 RXCUI

2.3.15 Wikidata

2.3.16 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • 9-((2-Hydroxyethoxy)methyl)guanine
  • Aci Sanorania
  • Aci-Sanorania
  • Acic
  • Aciclobeta
  • Aciclostad
  • Aciclovir
  • Aciclovir Alonga
  • Aciclovir Sanorania
  • aciclovir von ct
  • Aciclovir-Sanorania
  • Acifur
  • Acipen Solutab
  • Acivir
  • Activir
  • Acyclo V
  • Acyclo-V
  • Acycloguanosine
  • Acyclovir
  • Acyclovir Sodium
  • Alonga, Aciclovir
  • Antiherpes Creme
  • Avirax
  • Cicloferon
  • Clonorax
  • Cusiviral
  • Genvir
  • Herpetad
  • Herpofug
  • Herpotern
  • Herpoviric
  • Isavir
  • Laciken
  • Mapox
  • Maynar
  • Milavir
  • Opthavir
  • Sodium, Acyclovir
  • Solutab, Acipen
  • Supraviran
  • Viclovir
  • Vipral
  • Virax Puren
  • Virax-Puren
  • ViraxPuren
  • Virherpes
  • Virmen
  • Virolex
  • Virupos
  • Virzin
  • Wellcome 248U
  • Wellcome-248U
  • Wellcome248U
  • Zoliparin
  • Zovirax
  • Zyclir

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
225.20 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3-AA
Property Value
-1.9
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
5
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
225.08618923 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
225.08618923 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
115 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
16
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
308
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
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 Color / Form

Crystals from methanol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
Crystals from ethanol
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. V2: 76
White, crystalline powder
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 1203 (2013)

3.2.3 Boiling Point

3.2.4 Melting Point

255 °C
256.5-257 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
MP: Decomposes
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. V2: 76
256.5 - 257 °C

3.2.5 Solubility

1.41mg/mL at 25°C
Avaclyr Ophthalmic Ointment FDA label
White crystalline powder. Maximum solubility in water (25 °C): >100 mg/mL /Acyclovir sodium salt/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
In water, 1,620 mg/L at 25 °C
Kristl A et al; Pharmazie 48: 608-10 (1993)
Soluble in diluted hydrochloric acid; slightly soluble in water; insoluble in alcohol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
0.2 mg/mL in alcohol
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 2092
9.08e+00 g/L

3.2.6 LogP

-1.76
log Kow = -1.56
Kristl A et al; Pharmazie 48: 608-10 (1993)
-1.56
KRISTL,A ET AL. (1993)

3.2.7 Caco2 Permeability

-6.15
ADME Research, USCD

3.2.8 Dissociation Constants

pKa
2.52 and 9.35
Avaclyr Ophthalmic Ointment FDA label
pKa1= 2.27; pKa2 = 9.25
Physicians Desk Reference 67th ed. PDR Network, LLC, Montvale, NJ. p. 1203 (2013)

3.2.9 Collision Cross Section

155.82 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

145.91 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

155.98 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
146.5 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

3.3 Chemical Classes

Pharmaceutical

3.3.1 Drugs

Pharmaceuticals -> unsed in Switzerland 2014-2016
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043
Pharmaceuticals -> Metabolite of Valaciclovir
S113 | SWISSPHARMA24 | 2024 Swiss Pharmaceutical List with Metabolites | DOI:10.5281/zenodo.10501043
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiviral Agents
Human drug -> Prescription; Discontinued; Active ingredient (ACYCLOVIR)
Human drug -> Prescription
Human drug -> Discontinued
Human drug -> Prescription; Discontinued
Paediatric drug

Antiherpes medicines

Ophthalmological preparations > Anti-infective agents

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 13C NMR Spectra

1 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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2 of 2
Copyright
Copyright © 2016-2024 W. Robien, Inst. of Org. Chem., Univ. of Vienna. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 3
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NIST Number
248607
Library
Main library
Total Peaks
37
m/z Top Peak
151
m/z 2nd Highest
164
m/z 3rd Highest
45
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2 of 3
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Instrument Name
CEC21-110C
Source of Spectrum
RCM-6-62-1
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.2.2 MS-MS

1 of 9
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Spectra ID
Instrument Type
LC-ESI-qTof
Ionization Mode
Positive
Top 5 Peaks

232.168594 65432

230.152679 53624

380.257111 44764

133.063354 42168

148.074387 33700

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Notes
From GNPS Library
2 of 9
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Spectra ID
Instrument Type
LC-ESI-QQ
Ionization Mode
negative
Top 5 Peaks

224.2 100

141.8 0.52

141.4 0.18

150.2 0.06

162.3 0.06

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Notes
instrument=API3000, Applied Biosystems

4.2.3 LC-MS

1 of 50
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Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
10 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
4.731 min
Precursor m/z
226.0935
Precursor Adduct
[M+H]+
Top 5 Peaks

226.0935 999

227.0974 104

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License
CC BY
2 of 50
View All
Authors
Nikiforos Alygizakis, Katerina Galani, Nikolaos Thomaidis, University of Athens
Instrument
Bruker maXis Impact
Instrument Type
LC-ESI-QTOF
MS Level
MS2
Ionization Mode
POSITIVE
Ionization
ESI
Collision Energy
20 eV
Fragmentation Mode
CID
Column Name
Acclaim RSLC C18 2.2um, 2.1x100mm, Thermo
Retention Time
4.732 min
Precursor m/z
226.0935
Precursor Adduct
[M+H]+
Top 5 Peaks

226.0971 999

165.0528 914

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License
CC BY

4.3 IR Spectra

4.3.1 ATR-IR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II) ground
Source of Spectrum
Forensic Spectral Research
Source of Sample
Spectrum Chemical Manufacturing Corp.
Catalog Number
A1816
Lot Number
WR3021
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company Llc
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sigma/A4669>A4669</a>
Lot Number
117F0756
Copyright
Copyright © 2014-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.4 Raman Spectra

1 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Spectrum Chemical Manufacturing Corp.
Catalog Number
A1816
Lot Number
WR3021
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
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2 of 2
Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Sigma-Aldrich Company LLC
Catalog Number
<a href=https://www.sigmaaldrich.com/US/en/product/sigma/A4669>A4669</a>
Lot Number
117F0756
Copyright
Copyright © 2015-2024 John Wiley & Sons, Inc. All Rights Reserved.
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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

An acyclovir topical cream is indicated to treat recurrent herpes labialis in immunocompetent patients 12 years and older. Acyclovir oral tablets, capsules, and suspensions are indicated to treat herpes zoster, genital herpes, and chickenpox. An acyclovir topical ointment is indicated to treat initial genital herpes and limited non-life-threatening mucocutaneous herpes simplex in immunocompromised patients. An acyclovir cream with hydrocortisone is indicated to treat recurrent herpes labialis, and shortening lesion healing time in patients 6 years and older. An acyclovir buccal tablet is indicated for the treatment of recurrent herpes labialis. An acyclovir ophthalmic ointment is indicated to treat acute herpetic keratitis.
Treatment of herpes simplex labialis
Prevention of recurrences of herpes simplex labialis, Treatment of recurrent herpes simplex labialis

7.2 LiverTox Summary

Acyclovir is a nucleoside analogue and antiviral agent used in therapy of herpes and varicella-zoster virus infections. Acyclovir has not been associated with clinically apparent liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antiviral Agents
Antiviral Agents

7.4 WHO Essential Medicines

Drug
Drug Classes
Antiherpes medicines
Formulation
(1) Parenteral - General injections - IV: 250 mg in vial powder for injection (as sodium salt); (2) Oral - Liquid: 200 mg per 5 mL; (3) Oral - Solid: 200 mg tablet
Indication
(1) Zoster; (2) Varicella; (3) Herpes simplex infections
Drug
Drug Classes
Ophthalmological preparations &gt; Anti-infective agents
Formulation
Local - Ophthalmological - Ointment: 3% w/w
Indication
Herpes simplex keratitis

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 Drug Labels

Drug and label
Active ingredient and drug

7.9 HIV / AIDS and Opportunistic Infection Drugs

What is Acyclovir

Acyclovir is an antiviral prescription medicine approved by the U.S. Food and Drug Administration (FDA) to:

Treat and/or prevent the recurrence of certain types of herpes simplex virus (HSV) infections, including genital herpes&nbsp;

Treat varicella zoster virus (VZV) infections, including chicken pox (primary varicella infection) and shingles&nbsp;(herpes zoster)&nbsp;

Acyclovir is approved in different formulations and strengths for use in specific populations, including in people who are immunocompromised.

HSV and VZV infections can be opportunistic infections (OIs) of HIV.

Drug Class
Antiviral (Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor)

7.10 Clinical Trials

7.10.1 ClinicalTrials.gov

7.10.2 EU Clinical Trials Register

7.10.3 NIPH Clinical Trials Search of Japan

7.11 EMA Drug Information

1 of 2
Type
Paediatric investigation
Active Substance
Therapeutic Area
Infectious diseases
Drug Form
Muco-adhesive buccal tablet
Administration Route
Gingival use
Decision Type
W: decision granting a waiver in all age groups for all conditions or indications
Decision Date
2019-12-04
2 of 2
Type
Paediatric investigation
Active Substance
Therapeutic Area
Infectious diseases
Drug Form
Muco-adhesive buccal tablet
Administration Route
Gingival use
Decision Type
RW: decision refers to a refusal on a request for waiver in all age groups for the listed condition(s)
Decision Date
2011-04-06

7.12 Therapeutic Uses

Antiviral Agents
National Library of Medicine's Medical Subject Headings. Acyclovir. Online file (MeSH, 2014). Available from, as of November 19, 2013: https://www.nlm.nih.gov/mesh/2014/mesh_browser/MBrowser.html
IV acyclovir sodium is used for the treatment of initial and recurrent mucocutaneous herpes simplex virus (HSV-1 and HSV-2) infections and the treatment of varicella-zoster infections in immunocompromised adults and children; for the treatment of severe first episodes of genital herpes infections in immunocompetent individuals; and for the treatment of HSV encephalitis and neonatal HSV infections.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 766
Acyclovir is used orally for the treatment of initial and recurrent episodes of genital herpes; for the acute treatment of herpes zoster (shingles, zoster) in immunocompetent individuals; and for the treatment of varicella (chickenpox) in immunocompetent individuals.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 766
Oral acyclovir is indicated in the treatment of initial episodes of genital herpes infection in immunocompetent and immunocompromised patients. Parenteral acyclovir is indicated in the treatment of severe initial episodes of genital herpes infection in immunocompetent patients and in patients who are unable to take (or absorb) oral acyclovir. /Included in US product labeling/
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 26
For more Therapeutic Uses (Complete) data for ACYCLOVIR (15 total), please visit the HSDB record page.

7.13 Drug Warnings

Parenteral acyclovir therapy can cause signs and symptoms of encephalopathy. ... Acyclovir should be used with caution in patients with underlying neurologic abnormalities and in patients with serious renal, hepatic, or electrolyte abnormalities or substantial hypoxia. The drug also should be used with caution in patients who have manifested prior neurologic reactions to cytotoxic drugs or those receiving intrathecal methotrexate or interferon.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 767
Acyclovir should be used with caution in patients receiving other nephrotoxic drugs concurrently since the risk of acyclovir-induced renal impairment and/or reversible CNS symptoms is increased in these patients. Adequate hydration should be maintained in patients receiving IV acyclovir; however, in patients with encephalitis, the recommended hydration should be balanced by the risk of cerebral edema. Because the risk of acyclovir-induced renal impairment is increased during rapid IV administration of the drug, acyclovir should be given only by slow IV infusion (over 1 hour).
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 767
There are no adequate and controlled studies to date using acyclovir in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 767
Maternal Medication usually Compatible with Breast-Feeding: Acyclovir: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/
Report of the American Academy of Pediatrics Committee on Drugs in Pediatrics 93 (1): 140 (1994)
For more Drug Warnings (Complete) data for ACYCLOVIR (20 total), please visit the HSDB record page.

7.14 Drug Tolerance

Eleven strains of acyclovir (ACV)-resistant herpes simplex virus type 1 (HSV-1) were generated from HSV-1 clinical isolates by exposure to ACV. Genotype of the thymidine kinase (TK) and DNA polymerase (pol) genes from these mutants were further analyzed. Genotypic analysis revealed four non-synonymous mutations in TK gene associated with gene polymorphism and two to three non-synonymous mutations in DNA pol gene. Seven and six strains contained at least one resistance-associated mutation at TK and DNA pol gene, respectively. Resistance-associated mutations within the TK gene consisted of 64% of non-synonymous frameshift mutations within the homopolymer region of G's and C's, and 36% of non-synonymous nucleotide substitutions of the conserved gene region (C336Y, R51W and R222H), nucleotide that produced stop codon (L288Stop) and two amino acid substitutions outside the conserved region (E39G & L208F). There were 10 non-synonymous amino acid substitutions located outside the conserved region with the unclear significance to confer resistance observed. Resistance-associated mutations in DNA pol gene include insertion of G at the homopolymer region of G's (794-797) and amino acid substitutions inside (V621S) or outside (H1228D) the conserved region. In silico analysis of the mutated TK (C336Y, R51W and L208F), and DNA pol (V621S and H1228D) suggested structural changes that might alter the stability of these proteins. However, there were several mutations with unclear significance to confer ACV-resistance identified, especially mutations outside the conserved region.
Hussin A et al; Antiviral Res pii: S0166-3542(13)00254-4. doi: 10.1016/j.antiviral.2013.09.008. (2013 Sep 20) (Epub ahead of print)
Acyclovir (ACV)-resistant (ACV(r)) mutants were generated from plaque-purified ACV-sensitive herpes simplex virus type 1 (HSV-1) by culturing the virus in Vero cells in the presence of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl) purine (S2242). Three DNA polymerase (DNApol)-associated ACV(r) HSV-1 generated under ACV selection in a previous study were also included. The sensitivity of the mutants to other antivirals and their neurovirulence were determined. The treatment efficacy of ACV and ganciclovir (GCV) against ACV(r) HSV-1 infections was evaluated in mice. Amino acid substitutions were demonstrated in conserved regions II and III in DNApol in 5 of the 6 mutants, while the other substitution was located in non-conserved regions. DNApol-associated ACV(r) clones showed cross-resistance to foscarnet, penciclovir, and vidarabine but were sensitive or hypersensitive to GCV, brivudin, sorivudine, and spongothymidine. The ACV(r) clone with an N815S mutation in DNApol showed similar neurovirulence to that of the parent virus; however, those with other mutations showed attenuation. GCV was effective in the treatment of the ACV(r) clone with similar virulence to that of parent HSV-1, while ACV was less effective in mice. These results indicate the importance of the characterization of HSV-1 isolates for the proper treatment of HSV-1 infections exhibiting ACV-resistance.
Wang LX et al; Jpn J Infect Dis 66 (5): 404-10 (2013)

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Acyclovir is a deoxynucleoside analog that inhibits the action of viral DNA polymerase and DNA replication of different herpesvirus. Acyclovir has a wide therapeutic window as overdose is rare in otherwise healthy patients.

8.2 MeSH Pharmacological Classification

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

1 of 2
FDA UNII
X4HES1O11F
Active Moiety
ACYCLOVIR
Pharmacological Classes
Mechanisms of Action [MoA] - DNA Polymerase Inhibitors
Pharmacological Classes
Established Pharmacologic Class [EPC] - Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor
Pharmacological Classes
Established Pharmacologic Class [EPC] - Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor
Pharmacological Classes
Established Pharmacologic Class [EPC] - Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor
Pharmacological Classes
Nucleoside Analog [EXT]
FDA Pharmacology Summary
Acyclovir is a Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor, and Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor, and Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor. The mechanism of action of acyclovir is as a DNA Polymerase Inhibitor.
2 of 2
Non-Proprietary Name
ACYCLOVIR
Pharmacological Classes
DNA Polymerase Inhibitors [MoA]; Nucleoside Analog [EXT]; Herpesvirus Nucleoside Analog DNA Polymerase Inhibitor [EPC]; Herpes Zoster Virus Nucleoside Analog DNA Polymerase Inhibitor [EPC]; Herpes Simplex Virus Nucleoside Analog DNA Polymerase Inhibitor [EPC]

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

S - Sensory organs

S01 - Ophthalmologicals

S01A - Antiinfectives

S01AD - Antivirals

S01AD03 - Aciclovir

D - Dermatologicals

D06 - Antibiotics and chemotherapeutics for dermatological use

D06B - Chemotherapeutics for topical use

D06BB - Antivirals

D06BB03 - Aciclovir

J - Antiinfectives for systemic use

J05 - Antivirals for systemic use

J05A - Direct acting antivirals

J05AB - Nucleosides and nucleotides excl. reverse transcriptase inhibitors

J05AB01 - Aciclovir

S01AD03; J05AB01

8.5 Absorption, Distribution and Excretion

Absorption
The oral bioavailability of acyclovir is 10-20% but decreases with increasing doses. Acyclovir ointment is <0.02-9.4% absorbed. Acyclovir buccal tablets and ophthalmic ointment are minimally absorbed. The bioavailability of acyclovir is not affected by food. Acyclovir has a mean Tmax of 1.1±0.4 hours, mean Cmax of 593.7-656.5ng/mL, and mean AUC of 2956.6-3102.5h/*ng/mL.
Route of Elimination
The majority of acyclovir is excreted in the urine as unchanged drug. 90-92% of the drug can be excreted unchanged through glomerular filtration and tubular secretion. <2% of the drug is recovered in feces and <0.1% is expired as CO2.
Volume of Distribution
The volume of distribution of acyclovir is 0.6L/kg.
Clearance
The renal clearance of acyclovir is 248mL/min/1.73m2. The total clearance in neonates if 105-122mL/min/1.73m2.
Absorption of acyclovir from the GI tract is variable and incomplete. 15-30% of an oral dose of the drug is absorbed. Some data suggest that GI absorption of acyclovir may be saturable; in a crossover study in which acyclovir was administered orally to healthy adults as 200 mg capsules, 400 mg tablets, or 800 mg tablets 6 times daily, the extent of absorption decreased with increasing dose, resulting in bioavailabilities of 20, 15, or 10%, respectively. ... This decrease in bioavailability appears to be a function of increasing dose, not differences in dosage forms. In addition, steady-state peak and trough plasma acyclovir concentrations were not dose proportional over the oral dosing range of 200-800 mg 6 times daily, averaging 0.83 and 0.46, 1.21 and 0.63, or 1.61 and 0.83 ug/ml for the 200, 400, or 800 mg dosing regimens, respectively. Peak plasma concentrations usually occur within 1.5-2.5 hours after oral administration.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769
In a multiple dose study in neonates up to 3 months of age, IV infusion over 1 hour of 5, 10, or 15 mg/kg of acyclovir every 8 hours resulted in mean steady state peak serum concentrations of 6.8, 13.9, and 19.6 ug/ml, respectively, and mean steady state trough serum concentration of 1.2, 2.3, and 3.1 ug/ml, respectively. In another multiple dose study in pediatric patients, IV infusion over 1 hour of 250 or 500 mg/sq m of acyclovir every 8 hours resulted in mean steady state peak serum concentrations of 10.3 and 20.7 ug/ml, respectively.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769
Acyclovir is widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, cerebrospinal fluid, and herpetic vesicular fluid. The drug also is distributed into semen, achieving concentrations about 1.4 and 4 times those in plasma during chronic oral therapy at dosages of 400 mg and 1 g daily, respectively. The apparent volume of distribution of acyclovir is reported to be 32.4-61.8 liter/1.73 sq m in adults and 28.8, 31.6, 42, or 51.2-53.6 liter/1.73 sq m in neonates up to 3 months of age, children 1-2 years; 2-7 years; or 7-12 years of age, respectively.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769
Acyclovir crosses the placenta. Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769
For more Absorption, Distribution and Excretion (Complete) data for ACYCLOVIR (13 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Acyclovir is <15% oxidized to 9-carboxymethoxymethylguanine by alcohol dehydrogenase and aldehyde dehydrogenase and 1% 8-hydroxylated to 8-hydroxy-acyclovir by aldehyde oxidase. Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase.
Acyclovir is metabolized partially to 9-carboxymethoxymethylguanine and minimally to 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. In vitro, acyclovir also is metabolized to acyclovir monophosphate, diphosphate, and triphosphate in cells infected with herpes viruses, principally by intracellular phosphorylation of the drug by virus coded thymidine kinase and several cellular enzymes.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769

8.7 Biological Half-Life

The clearance of acyclovir varies from 2.5-3 hours depending on the creatinine clearance of the patient. The plasma half life of acyclovir during hemodialysis is approximately 5 hours. The mean half life in patients from 7 months to 7 years old is 2.6 hours.
Plasma concentrations of acyclovir appear to decline in a biphasic manner. In adults with normal renal function, the half-life of acyclovir in the initial phase averages 0.34 hours and the half-life in the terminal phase averages 2.1-3.5 hours. In adults with renal impairment, both half-life in the initial phase and half-life in the terminal phase may be prolonged, depending on the degree of renal impairment. In a study in adults with anuria, the half-life in the initial phase of acyclovir averaged 0.71 hours. In several studies, the half-life in the terminal phase of acyclovir averaged 3,3.5, or 19.5 hours in adults with creatinine clearances of 50-80 or 15-50 ml/minute per 1.73 sq m or with anuria, respectively. In patients undergoing hemodialysis, the half-life in the terminal phase of acyclovir during hemodialysis averaged 5.4-5.7 hours.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769
In neonates, the half-life of acyclovir depends principally on the maturity of renal mechanisms for excretion as determined by gestational age, chronologic age, and weight. In children older than 1 year of age, the half-life of the drug appears to be similar to that of adults. The half-life in the terminal phase averages 3.8-4.1, 1.9, 2.2-2.9, or 3.6 hours in neonates up to 3 months of age, children 1-2 years, 2-12 years, or 12-17 years of age, respectively.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 769

8.8 Mechanism of Action

Acyclovir is becomes acyclovir monophosphate due to the action of viral thymidine kinase. Acyclovir monophosphate is converted to the diphosphate form by guanylate kinase. Acyclovir diphosphate is converted to acyclovir triphosphate by nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, phosphoglycerate kinase, succinyl-CoA synthetase, phosphoenolpyruvate carboxykinase and adenylosuccinate synthetase. Acyclovir triphosphate has higher affinity for viral DNA polymerase than cellular DNA polymerase and incorporates into the DNA where the missing 2' and 3' carbons causes DNA chain termination. In other cases acyclovir triphosphate competes so strongly for viral DNA polymerase that other bases cannot associate with the enzyme, inactivating it.
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of acyclovir is highly selective due to is affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase adn into triphosphate by a number of cellualr enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1650
Acyclovir inhibits viral DNA synthesis ... . Its selectivity of action depends on interaction with two distinct viral proteins. Cellular uptake and initial phosphorylation are facilitated by HSV thymidine kinase. The affinity of acyclovir for HSV thymidine kinase is about 200-fold greater than for the mammalian enzyme. Cellular enzymes convert the monophosphate to acyclovir triphosphate, which is present in 40- to 100-fold higher concentrations in HSV-infected than in uninfected cells, and competes for endogenous deoxyguanosine triphosphate (dGTP). The immunosuppressive agent mycophenolate mofetil potentiates the antiherpes activity of acyclovir and related agents by depleting intracellular dGTP pools. Acyclovir triphosphate competitively inhibits viral DNA polymerases and, to a much smaller extent, cellular DNA polymerases. Acyclovir triphosphate also is incorporated into viral DNA, where it acts as a chain terminator because of the lack of 3'-hydroxyl group. By a mechanism termed suicide inactivation, the terminated DNA template containing acyclovir binds the enzyme and leads to irreversible inactivation of the DNA polymerase.
Brunton, L. Chabner, B, Knollman, B. Goodman and Gillman's The Pharmaceutical Basis of Therapeutics, Twelth Edition, McGraw Hill Medical, New York, NY. 2011, p. 1594
The concentration of the endogenous neurotoxin quinolinic acid (QA) is increased in the central nervous system of mice with herpes simplex encephalitis. /The authors/ have previously shown that the antiherpetic agent acyclovir (AC) has the ability to reduce QA-induced neuronal damage in rat brain, by attenuating lipid peroxidation. The mechanism by which QA induces lipid peroxidation includes the enhancement of the iron (Fe)-mediated Fenton reaction and the generation of free radicals, such as the superoxide anion (O(2)(-)). Thus, the present study determined whether AC has the ability to reduce Fe(2+)-induced lipid peroxidation, O(2)(-) generation and QA-induced superoxide anion generation, and to bind free Fe. O(2)(-) and Fe(2+) are also cofactors of the enzymes, indoleamine-2,3-dioxygenase (IDO) and 3-hydroxyanthranilate-3,4-dioxygenase (3-HAO) respectively. These enzymes catalyse steps in the biosynthesis of QA; thus, the effect of AC on their activity was also investigated. AC significantly attenuates Fe(2+)-induced lipid peroxidation and O(2)(-) generation. AC reduces O(2)(-) generation in the presence of QA and strongly binds Fe(2+) and Fe(3+). It also reduces the activity of both IDO and 3-HAO, which could be attributed to the superoxide anion scavenging and iron binding properties, respectively, of this drug.
Muller AC et al; Life Sci 80 (10): 918-25 (2007)

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Cytoplasm
  • Membrane

8.10 Biochemical Reactions

8.11 Transformations

9 Use and Manufacturing

9.1 Uses

Aciclovir is used intravenously in the treatment of severe initial and recurrent mucocutaneous infections caused by HSV-1, HSV-2 and varicella-zoster virus (chickenpox virus) in adults and children. It is also the drug of choice for treatment of herpes simplex encephalitis.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V76: 51
THERAPEUTIC CATEGORY (VETERINARY): Antiviral
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
MEDICATION
Antiviral Agents
National Library of Medicine's Medical Subject Headings. Acyclovir. Online file (MeSH, 2014). Available from, as of November 19, 2013: https://www.nlm.nih.gov/mesh/2014/mesh_browser/MBrowser.html

Use (kg) in Switzerland (2009): >250

Use (kg; approx.) in Germany (2009): >10000

Use (kg; exact) in Germany (2009): 15729

Use (kg) in USA (2002): 21300

Consumption (g per capita) in Switzerland (2009): 0.032

Consumption (g per capita; approx.) in Germany (2009): 0.12

Consumption (g per capita; exact) in Germany (2009): 0.19

Consumption (g per capita) in the USA (2002): 0.076

Excretion rate: 0.9

Calculated removal (%): 22

9.1.1 Use Classification

Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9.2 Methods of Manufacturing

Guanine is alkylated with 2-(chloromethoxy)ethylbenzoate and the resulting ester hydrolyzed to the product.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1676
Reaction of 2,6-dichloro-9-(2-benzoyloxyethoxymethyl) purine with methanolic ammonia, followed by treatment with nitrous acid and then with methanolic ammonia yields acyclovir.
Actor P et al; Chemotherapeutics. Ullmann's Encyclopedia of Industrial Chemistry 7th ed. (1999-2013). NY, NY: John Wiley & Sons. Online Posting Date: June 15, 2000

9.3 Formulations / Preparations

Topical: Ointment: 5%, Zovirax (Biovail)
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 3328
Oral: Capsules: 200 mg Zovirax (with parabens), (GlaxoSmithKline); Suspension: 200 mg/5mL Acyclovir Suspension (with parabens), (Alpharma), Zovirax (with glycerin parabens and sorbitol), (GlaxoSmithKline); Tablets: 400 mg Zovirax (with povidone), GlaxoSmithKline, 800 mg Zovirax (with povidone), GlaxoSmithKline.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 775
Acyclovir sodium: Parenteral: For injection, concentrate, for IV infusion only: 25 mg (of acyclovir) per mL (500 mg, 1 g) Acyclovir Sodium Injection (Mayne), 50 mg (of acyclovir) per mL (500 mg, 1 g) Acyclovir Sodium Injection (American Pharmaceutical Partners), For Injection, for IV infusion only: 500 mg (of acyclovir) Acyclovir Sodium for Injection (Abbott, American Pharmaceutical Partners, Bedford), Zovirax (GlaxoSmithKline), 1 g (of acyclovir) Acyclovir Sodium for Injection (Abbott, Bedford), Zovirax (GlaxoSmithKline).
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 775

10 Identification

10.1 Clinical Laboratory Methods

Determination of acyclovir in human serum by high-performance liquid chromatography. Detection limit of 0.3 ug/ml.
Cronqvist J, Nilsson-Ehle I; J Liq Chromatogr 11 (12): 2593-601 (1988)
Determination of acyclovir in human plasma and urine with ion-pair high performance liquid chromatography with ultraviolet detection at a wavelength of 254 nm. The min detectable quantity and concn were 5 ug and 0.5 ug/ml, resp, and the recovery was > 94%.
Guan R et al; Yiyao Gongye 17 (7): 309-12 (1986)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

1 of 2
View All
Note
Pictograms displayed are for 85.3% (81 of 95) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 14.7% (14 of 95) of reports.
Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H315 (77.9%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (77.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (71.6%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P271, P280, P302+P352, P304+P340, P305+P351+P338, P319, P321, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

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

ECHA C&L Notifications Summary

Aggregated GHS information provided per 95 reports by companies from 20 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 14 of 95 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 18 notifications provided by 81 of 95 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Skin Irrit. 2 (77.9%)

Eye Irrit. 2A (77.9%)

STOT SE 3 (71.6%)

Acute Tox. 4 (100%)

Acute Tox. 4 (100%)

Carc. 2 (100%)

11.1.3 Fire Potential

Not flammable or combustible.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

11.1.4 Skin, Eye, and Respiratory Irritations

May cause eye irritation. May be harmful if inhaled. May cause respiratory tract irritation. May be harmful if absorbed through skin. May cause skin irritation.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

11.2 Fire Fighting

11.2.1 Fire Fighting Procedures

Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

11.3 Accidental Release Measures

11.3.1 Cleanup Methods

Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

11.3.2 Disposal Methods

Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US
SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

11.3.3 Preventive Measures

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

11.4 Handling and Storage

11.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place.
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

11.5 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Acyclovir: Does not have an individual approval but may be used under an appropriate group standard

11.5.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including acyclovir, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of November 15, 2013: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including acyclovir sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Acyclovir sodium/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of November 15, 2013: https://www.fda.gov/cder/ob/

11.6 Other Safety Information

Chemical Assessment

IMAP assessments - 6H-Purin-6-one, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-: Environment tier I assessment

IMAP assessments - 6H-Purin-6-one, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-: Human health tier I assessment

11.6.1 Toxic Combustion Products

Hazardous decomposition products formed under fire conditions. - Carbon oxides, nitrogen oxides (NOx)
Sigma-Aldrich; Material Safety Data Sheet for Acyclovir, Product Number: PHR1254, Version 5.0 (Revision Date 09/21/2012). Available from, as of November 25, 2013: https://www.sigmaaldrich.com/catalog/product/fluka/phr1254?lang=en&region=US

12 Toxicity

12.1 Toxicological Information

12.1.1 USGS Health-Based Screening Levels for Evaluating Water-Quality

Chemical
Acyclovir
Chemical Classes
Pharmaceutical
Reference
Smith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP

12.1.2 Hepatotoxicity

Despite widespread use, there is little evidence that acyclovir when given orally causes significant liver injury. Serum enzyme levels generally do not change during oral acyclovir therapy. High dose intravenous administration of acyclovir is associated with renal dysfunction and thrombocytopenia, and occasionally with transient mild-to-moderate elevations in serum ALT levels, which have been asymptomatic and self-limited. There have rare instances of acute, clinically apparent liver injury reported that were attributed to acyclovir or valacyclovir (a prodrug of acyclovir with better oral absorption), but these have not been particularly convincing. Some degree of liver injury and even jaundice can occur during the course of herpes simplex or varicella zoster infection, and these complications could be mistaken for drug induced liver injury. Furthermore, in the reported cases, patients were receiving other medications and had other unlying comorbidities that may have been responsible for the liver injury.

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

12.1.3 Drug Induced Liver Injury

Compound
aciclovir
DILI Annotation
Less-DILI-Concern
Severity Grade
5
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

12.1.4 Evidence for Carcinogenicity

Evaluation: There is inadequate evidence in humans for the carcinogenicity of acyclovir. There is inadequate evidence in experimental animals for the carcinogenicity of aciclovir. Overall evaluation: Acyclovir is not classifiable as to its carcinogenicity to humans (Group 3).
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V76 66 (2000)

12.1.5 Carcinogen Classification

IARC Carcinogenic Agent
Aciclovir
IARC Carcinogenic Classes
Group 3: Not classifiable as to its carcinogenicity to humans
IARC Monographs
Volume 76: (2000) Some Antiviral and Antineoplastic Drugs, and Other Pharmaceutical Agents

12.1.6 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Even with the highest maternal dosages, the dosage of acyclovir in milk is only about 1% of a typical infant dosage and would not be expected to cause any adverse effects in breastfed infants. Topical acyclovir applied to small areas of the mother's body away from the breast should pose no risk to the infant. Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.

◉ Effects in Breastfed Infants

The mother of a 4-month-old infant noticed no adverse effects in her breastfed infant while she was taking an acyclovir dosage of 800 mg orally 5 times daily.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.7 Acute Effects

12.1.8 Interactions

Acyclovir has been used concomitantly with zidovudine ... without evidence of increased toxicity; however, neurotoxicity (profound drowsiness and lethargy), which recurred on rechallenge, has been reported in at least one patient with acquired immunodeficiency syndrome (AIDS) during concomitant therapy with the drugs. Neurotoxicity was evident within 30-60 days after initiation of IV acyclovir therapy, persisted with some improvement when acyclovir was administered orally, and resolved following discontinuance of acyclovir in this patient.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 767
This study reports the effects of a combination of azidothymidine plus acyclovir on both pluripotent (spleen colony forming units) and committed (granulocyte-macrophage colony forming units; erythroid burst forming units) murine hemopoietic progenitors. Administration of azidothymidine alone was associated with severe hematotoxicity, as shown by the marked decrease of all the hemopoietic progenitor populations tested, that is, spleen colony forming units, granulocyte-macrophage colony forming units, and erythroid burst forming units. This, however, was followed by a prompt recovery of hemopoiesis. Administration of acyclovir alone did not modify the hematological parameters studied, whereas the combined administration of azidothymidine and acyclovir led to changes in peripheral blood cells and bone marrow hemopoietic progenitors that were, on the whole, not significantly different from those observed with azidothymidine alone. Only the decrease in spleen colony forming units was significantly more severe, but their recovery was as rapid as that of the committed progenitors. Thus, in this experimental setting, the addition of acyclovir to azidothymidine does not appear to increase the hematotoxicity of the latter.
Bogliolo G et al; Exp Hematol 19 (8): 838-41 (1991)
The combined effect of acyclovir and chlorhexidine on the replication and DNA synthesis of herpes simplex virus was studied. Acyclovir and chlorhexidine showed synergism in the inhibition of the viral replication by enhancing in part the reduction of viral DNA synthesis. These data indicate that combined therapy with acyclovir and chlorhexidine might be beneficial for the control of intraoral herpetic infections.
Park NH et al; Oral Surg Oral Med Oral Pathol 71 (2): 193-6 (1991)
Acyclovir may decrease the renal clearance of other drugs eliminated by active renal secretion, such as methotrexate.
Brunton, L. Chabner, B, Knollman, B. Goodman and Gillman's The Pharmaceutical Basis of Therapeutics, Twelth Edition, McGraw Hill Medical, New York, NY. 2011, p. 1598
For more Interactions (Complete) data for ACYCLOVIR (6 total), please visit the HSDB record page.

12.1.9 Antidote and Emergency Treatment

There are no clinical data to guide management of acyclovir overdose. Treatment is supportive. Adequate urine flow should be maintained to prevent precipitation of acyclovir in the renal tubules. Hemodialysis is generally not recommended because even very large overdoses do not usually result in major toxicity.
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 29
/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 ACYCLOVIR (7 total), please visit the HSDB record page.

12.1.10 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ In a controlled study in men receiving chronic oral acyclovir (400 mg or 1 g daily) therapy, there was no evidence of clinically important effects on sperm count, motility, or morphology during 6 months of therapy and 3 months of post-treatment follow-up.
American Society of Health-System Pharmacists 2013; Drug Information 2013. Bethesda, MD. 2013, p. 767
/HUMAN EXPOSURE STUDIES/ Acyclovir is used to treat herpes infections in preterm and term infants; however, the influence of maturation on drug disposition and dosing requirements is poorly characterized in this population. /The authors/ administered intravenous acyclovir to preterm and term infants <31 days postnatal age and collected plasma samples. /Researchers/ performed a population pharmacokinetic analysis. The primary pharmacodynamic target was acyclovir concentration >/= 3 mg/L for >/=50% of the dosing interval. The final model was simulated using infant data from a clinical database. The analysis included 28 infants (median 30 weeks gestation). Acyclovir pharmacokinetics was described by a 1-compartment model: clearance (L/hr/kg) = 0.305 x (postmenstrual age (PMA)/31.3 weeks). This equation predicts a 4.5-fold increase in clearance from 25 to 41 weeks PMA. With proposed dosing, the pharmacodynamic target was achieved in 91% of infants: 20 mg/kg every 12 hr in infants <30 weeks PMA; 20 mg/kg every 8 hours in infants 30 to <36 weeks PMA; 20 mg/kg every 6 hr in infants 36-41 weeks PMA. Acyclovir clearance increased with infant maturation. A dosing strategy based on PMA accounted for developmental changes in acyclovir disposition to achieve the surrogate pharmacodynamic target in the majority of infants.
Sampson MR et al; Pediatr Infect Dis J (2013 Sep 23) (Epub ahead of print)
/SIGNS AND SYMPTOMS/ Overdoses involving ingestions of up to 100 capsules (20 g) have been reported. Adverse events that have been reported in association with overdosage include agitation, coma, seizures, and lethargy. Precipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. Overdosage has been reported following bolus injections or inappropriately high doses, and in patients whose fluid and electrolyte balance were not properly monitored. This has resulted in elevated BUN and serum creatinine, and subsequent renal failure. In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored.
Physicians Desk Reference 65th ed. PDR Network, LLC, Montvale, NJ. 2011, p. 1652
/SIGNS AND SYMPTOMS/ Aciclovir, like other anti-HIV nucleoside analogues, has been associated with a rare (1 in 10(+5) to 1 in 10(+6) patients) idiosyncratic syndrome of a progressive increase in the activity of liver enzymes in serum, fulminating hepatic steatosis and lactic acidosis. Failure to discontinue the drug can lead to death.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V76 57 (2000)
For more Human Toxicity Excerpts (Complete) data for ACYCLOVIR (16 total), please visit the HSDB record page.

12.1.11 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ Acyclovir, an antiviral, has been tested as a 3% ophthalmic ointment, and clinically has evidenced low toxicity, with only occasional stinging. In rabbits, it has not interfered with healing of corneal wounds. Injected into the vitreous body it is toxic to the retina, but a dose of 80 ug/0.1 mL is tolerable.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 52
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ ... High doses of aciclovir given to dogs by infusion over a short time were more nephrotoxic than lower doses given over a longer time. Beagle dogs given rapid intravenous injections of 10, 20, 25, 50 or 100 mg/kg bw aciclovir twice a day for one month showed marked dose-related toxic effects, including death, at the two higher doses. At doses of 20-50 mg/kg bw, decreased ability to concentrate urine, increased blood urea nitrogen concentration and renal tubular damage were observed.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V76 58 (2000)
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Life-time bioassays in rats and mice given daily doses of up to 450 mg/kg of body weight by gavage did not increase the incidence of tumors or shorten the latency of tumor formation. Maximum plasma concentrations were three to six times the human plasma concentration in the mouse bioassay and one to two times the human plasma concentration in the rat bioassay. However, one of two in vitro cell transformation assays resulted in morphologically transformed cells that formed tumors when inoculated into immunosuppressed, syngeneic, weanling mice.
Thomson.Micromedex. Drug Information for the Health Care Professional. 24th ed. Volume 1. Plus Updates. Content Reviewed by the United States Pharmacopeial Convention, Inc. Greenwood Village, CO. 2004., p. 27
/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a one-year study of toxicity, aciclovir was given orally to beagle dogs at a dose of 15, 45 or 150 mg/kg bw per day. Because of vomiting, diarrhea and weight loss, the two higher doses were reduced to 60 and 30 mg/kg bw early in the study. The only other reported toxic effects were sore paws due to erosion of the footpads and splitting of the nails at the two higher doses.
IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V76 58 (2000)
For more Non-Human Toxicity Excerpts (Complete) data for ACYCLOVIR (14 total), please visit the HSDB record page.

12.1.12 Non-Human Toxicity Values

LD50 Mouse oral > 10,000 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26
LD50 Mouse ip 1000 mg/kg
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 26

12.1.13 Populations at Special Risk

SRP: Acyclovir in elderly patients may cause CNS reactions (eg, decrease level of consciousness, speech disorders, psychotic episodes with visual and auditory hallucinations).
The drug is excreted primarily by the kidney, which may require smaller doses in patients with decreased kidney function.
King DH; J Am Acad Dermatol 18 (1 Pt 2): 176-9 (1988)

12.1.14 Protein Binding

Acyclovir is 9-33% protein bound in plasma.

12.2 Ecological Information

12.2.1 Environmental Fate / Exposure Summary

Acyclovir's production and use as an antiviral may result in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 5.4X10-15 mm Hg at 25 °C indicates acyclovir will exist solely in the particulate phase in the atmosphere. Particulate-phase acyclovir will be removed from the atmosphere by wet or dry deposition. Acyclovir contains chromophores that absorb at wavelengths >290 nm and, therefore, may be susceptible to direct photolysis by sunlight. If released to soil, acyclovir is expected to have very high mobility based upon an estimated Koc of 10. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 3.2X10-22 atm-cu m/mole. Acyclovir is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation of acyclovir may be important in soil and water based on a half-life of 5.3 hours using activated sludge. If released into water, acyclovir is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. 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 groups that hydrolyze under environmental conditions. Occupational exposure to acyclovir may occur through dermal contact with this compound at workplaces where acyclovir is produced or used. The general population may be exposed to acyclovir via medical administration of this compound for the treatment of viral infection. (SRC)

12.2.2 Artificial Pollution Sources

Acyclovir's production and use as an antiviral(1) may result in its release to the environment through various waste streams(SRC).
(1) O'Neil MJ, ed; The Merck Index. 15th ed., Cambridge, UK: Royal Society of Chemistry, p. 26 (2013)

12.2.3 Environmental Fate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acyclovir is expected to have very high mobility in soil(SRC). Volatilization of acyclovir from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.2X10-22 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Acyclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(4). A biodegradation half-life of 5.3 hours using activated sludge(5) suggests that biodegradation may be an important environmental fate process in soil(SRC).
(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 Nov 18, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(4) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(5) Prasse C et al; Environ Sci Technol 45:2761-9 (2011)
AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acyclovir is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.2X10-22 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from its log Kow of -1.56(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolysis is not expected to be an important environmental fate process since this compound lacks groups that hydrolyze under environmental conditions(3). A biodegradationhalf-life of 5.3 hours using activated sludge(7) suggests that biodegradation may be an important environmental fate process in water(SRC).
(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 Nov 18, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 15-1 to 15-29 (1990)
(4) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(5) Franke C et al; Chemosphere 29: 1501-14 (1994)
(6) Meylan WM, Howard PH; J Pharm Sci 84: 83-92 (1995)
(7) Prasse C et al; Environ Sci Technol 45: 2761-9 (2011)
ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acyclovir, which has an estimated vapor pressure of 5.4X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase acyclovir may be removed from the air by wet or dry deposition(SRC). Acyclovir contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).
(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988)
(2) Lyman WJ; p. 31 in Environmental Exposure From Chemicals Vol I, Neely WB, Blau GE, eds, Boca Raton, FL: CRC Press (1985)
(3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 8-12 (1990)

12.2.4 Environmental Biodegradation

AEROBIC: Acyclovir, at an initial concentration of 4 ug/L, was biodegraded with activated sludge, a half-life of 5.3 hours was measured, with a degradation product of carboxy-acyclovir(1). Carboxy-acyclovir was found to be recalcitrant(1).
(1) Prasse C et al; Environ Sci Technol 45: 2761-9 (2011)

12.2.5 Environmental Abiotic Degradation

Acycloviris not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Acyclovir contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).
(1) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5, 8-12 (1990)

12.2.6 Environmental Bioconcentration

An estimated BCF of 3 was calculated in fish for acyclovir(SRC), using a log Kow of -1.56(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) Kristl A et al; Pharmazie 48: 608-10 (1993)
(2) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 18, 2013: h ttp://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(3) Franke C et al; Chemosphere 29: 1501-14 (1994)]

12.2.7 Soil Adsorption / Mobility

Using a structure estimation method based on molecular connectivity indices(1), the Koc of acyclovir can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that acyclovir is expected to have very high mobility in soil.
(1) US EPA; Estimation Program Interface (EPI) Suite. Ver. 4.1. Jan, 2011. Available from, as of Nov 18, 2013: https://www.epa.gov/oppt/exposure/pubs/episuitedl.htm
(2) Swann RL et al; Res Rev 85: 17-28 (1983)]

12.2.8 Volatilization from Water / Soil

The Henry's Law constant for acyclovir is estimated as 3.2X10-22 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that acyclovir is expected to be essentially nonvolatile from moist soil and water surfaces(2). Acyclovir is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.4X10-15 mm Hg(SRC), determined from a fragment constant method(3).
(1) Meylan WM, Howard PH; Environ Toxicol Chem 10: 1283-93 (1991)
(2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990)

12.2.9 Environmental Water Concentrations

SURFACE WATER: Acyclovir was detected in rivers and streams in the Hessian Ried Region of Germany at 2.2-190 ng/L, in the Ruhr River at 2.6-8.9 ng/L and in the Ruhr River tributaries at 3.5-31 ng/L; all samples were collected in September 2009(1).
(1) Prasse C et al; Environ Sci Technol 44: 1728-35 (2010)

12.2.10 Effluent Concentrations

Acyclovir was detected in influent and effluent of two waste water treatment plants in Germany at 1780 and 27.3-53.3 ng/L, respectively; all samples were collected in September 2009(1).
(1) Prasse C et al; Environ Sci Technol 44: 1728-35 (2010)

12.2.11 Milk Concentrations

Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 774

12.2.12 Probable Routes of Human Exposure

Occupational exposure to acyclovir may occur through dermal contact with this compound at workplaces where acyclovir is produced or used. The general population may be exposed to acyclovir via medical administration of this compound for the treatment of viral infection. (SRC)

12.2.13 Body Burden

Limited data indicate that the drug is distributed into milk, generally in concentrations greater than concurrent maternal plasma concentrations, possibly via an active transport mechanism.
McEvoy, G.K. (ed.). American Hospital Formulary Service- Drug Information 2004. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 2004 (Plus Supplements)., p. 774

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Chemical Co-Occurrences in Literature

14.7 Chemical-Gene Co-Occurrences in Literature

14.8 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 FDA Orange Book Patents

15.4 Chemical Co-Occurrences in Patents

15.5 Chemical-Disease Co-Occurrences in Patents

15.6 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Drug-Food Interactions

  • Drink plenty of fluids. Dehydration with acyclovir predisposes patients to nephrotoxicity.
  • Take with or without food. The absorption is unaffected by food.

16.5 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

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

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: Drug

19.5 KEGG: USP

19.6 KEGG: ATC

19.7 KEGG: JP15

19.8 KEGG: Risk Category of Japanese OTC Drugs

19.9 KEGG: OTC drugs

19.10 KEGG: Drug Groups

19.11 KEGG : Antimicrobials

19.12 KEGG: Drug Classes

19.13 WHO ATC Classification System

19.14 FDA Pharm Classes

19.15 ChemIDplus

19.16 ChEMBL Target Tree

19.17 UN GHS Classification

19.18 NORMAN Suspect List Exchange Classification

19.19 CCSBase Classification

19.20 EPA DSSTox Classification

19.21 International Agency for Research on Cancer (IARC) Classification

19.22 LOTUS Tree

19.23 FDA Drug Type and Pharmacologic Classification

19.24 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
    6H-Purin-6-one, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy)methyl]-
    https://services.industrialchemicals.gov.au/search-assessments/
  2. CAS Common Chemistry
    LICENSE
    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/
  3. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  4. 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
  5. DTP/NCI
    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
  6. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  7. 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
    2-amino-9-[(2-hydroxyethoxy)methyl]-6,9-dihydro-1H-purin-6-one
    https://echa.europa.eu/substance-information/-/substanceinfo/100.159.615
    2-amino-9-[(2-hydroxyethoxy)methyl]-6,9-dihydro-1H-purin-6-one (EC: 631-369-1)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/164434
  8. 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
  9. Hazardous Substances Data Bank (HSDB)
  10. 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
  11. New Zealand Environmental Protection Authority (EPA)
    LICENSE
    This work is licensed under the Creative Commons Attribution-ShareAlike 4.0 International licence.
    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  12. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  13. ChEBI
  14. 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
  15. 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
  16. LiverTox
  17. 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/
  18. 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
  19. Open Targets
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    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  20. ChEMBL
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    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
  21. 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
  22. 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
  23. Therapeutic Target Database (TTD)
  24. 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/
    ACYCLOVIR
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  25. 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
  26. Crystallography Open Database (COD)
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    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  27. The Cambridge Structural Database
  28. DailyMed
  29. Drug Induced Liver Injury Rank (DILIrank) Dataset
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  30. European Medicines Agency (EMA)
    LICENSE
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    https://www.ema.europa.eu/en/about-us/legal-notice
  31. Drugs and Lactation Database (LactMed)
  32. Drugs@FDA
    LICENSE
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  33. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  34. EU Clinical Trials Register
  35. FDA Orange Book
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  36. National Drug Code (NDC) Directory
    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
  37. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  38. International Agency for Research on Cancer (IARC)
    LICENSE
    Materials made available by IARC/WHO enjoy copyright protection under the Berne Convention for the Protection of Literature and Artistic Works, under other international conventions, and under national laws on copyright and neighbouring rights. IARC exercises copyright over its Materials to make sure that they are used in accordance with the Agency's principles. All rights are reserved.
    https://publications.iarc.fr/Terms-Of-Use
    IARC Classification
    https://www.iarc.fr/
  39. Japan Chemical Substance Dictionary (Nikkaji)
  40. 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
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
    Risk category of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08312.keg
    Classification of Japanese OTC drugs
    http://www.genome.jp/kegg-bin/get_htext?br08313.keg
  41. MassBank Europe
  42. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  43. Metabolomics Workbench
  44. NIPH Clinical Trials Search of Japan
  45. SpectraBase
    2-amino-9-((2-hydroxyethoxy)methyl)-1H-purin-6(9H)-one
    https://spectrabase.com/spectrum/4IEXY20hQyP
    9-[(2-HYDROXYETHOXY)-METHYL]-GUANINE;ACYCLOVIR
    https://spectrabase.com/spectrum/9i5uMToolCZ
  46. 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
  47. NMRShiftDB
  48. 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/
  49. Protein Data Bank in Europe (PDBe)
  50. RCSB Protein Data Bank (RCSB PDB)
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    https://www.rcsb.org/pages/policies
  51. Springer Nature
  52. 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/
  53. USGS Health-Based Screening Levels for Evaluating Water-Quality Data
  54. Wikidata
    6H-Purin-6-one, 2-amino-1,9-dihydro-9-[(2-hydroxyethoxy-2-t)methyl]-
    https://www.wikidata.org/wiki/Q90542928
  55. Wikipedia
  56. Wiley
  57. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  58. PubChem
  59. GHS Classification (UNECE)
  60. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  61. PATENTSCOPE (WIPO)
CONTENTS