U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C14H19N5O4
Molecular Weight 321.3318
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FAMCICLOVIR

SMILES

CC(=O)OCC(CCN1C=NC2=CN=C(N)N=C12)COC(C)=O

InChI

InChIKey=GGXKWVWZWMLJEH-UHFFFAOYSA-N
InChI=1S/C14H19N5O4/c1-9(20)22-6-11(7-23-10(2)21)3-4-19-8-17-12-5-16-14(15)18-13(12)19/h5,8,11H,3-4,6-7H2,1-2H3,(H2,15,16,18)

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/3040998 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2754699

Penciclovir (DENAVIR®) is a synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Famciclovir (FAMVIR®) is a prodrug form of penciclovir with improved oral bioavailability.

CNS Activity

Curator's Comment: Known to be CNS penetrant in rats. Human data not available.

Originator

Curator's Comment: Beecham Group plc. is a predecessor of GlaxoSmithKline plc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
16.0 µM [Ki]
Target ID: P89453
Gene ID: 1487316.0
Gene Symbol: NA
Target Organism: Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus|||2)
9.5 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DENAVIR

Approved Use

DENAVIR® is a nucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0 ng/mL
1.8 mg single, topical
dose: 1.8 mg
route of administration: Topical
experiment type: SINGLE
co-administered:
PENCICLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0 ng/mL
1.8 mg 1 times / day steady-state, topical
dose: 1.8 mg
route of administration: Topical
experiment type: STEADY-STATE
co-administered:
PENCICLOVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
6.6 μg/mL
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1.6 μg/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.3 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
0.9 μg/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
17.9 μg × h/mL
1000 mg single, oral
dose: 1000 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.48 μg × h/mL
250 mg single, oral
dose: 250 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8.95 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
12.1 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.24 μg × h/mL
125 mg single, oral
dose: 125 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PENCICLOVIR unknown
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 % 12 times / day multiple, topical
Recommended
Dose: 1 %, 12 times / day
Route: topical
Route: multiple
Dose: 1 %, 12 times / day
Sources: Page: Study 024
unhealthy, 39
n = 782
Health Status: unhealthy
Condition: Recurrent Herpes Simplex Labialis
Age Group: 39
Sex: M+F
Population Size: 782
Sources: Page: Study 024
Disc. AE: Dissociative disorder...
AEs leading to
discontinuation/dose reduction:
Dissociative disorder
Sources: Page: Study 024
750 mg 3 times / day multiple, oral
MTD
unhealthy
1500 mg single, oral
Recommended
Dose: 1500 mg
Route: oral
Route: single
Dose: 1500 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Herpes labialis
Sources: Page: p.1
Other AEs: Acute renal failure...
AEs

AEs

AESignificanceDosePopulation
Dissociative disorder Disc. AE
1 % 12 times / day multiple, topical
Recommended
Dose: 1 %, 12 times / day
Route: topical
Route: multiple
Dose: 1 %, 12 times / day
Sources: Page: Study 024
unhealthy, 39
n = 782
Health Status: unhealthy
Condition: Recurrent Herpes Simplex Labialis
Age Group: 39
Sex: M+F
Population Size: 782
Sources: Page: Study 024
Acute renal failure
1500 mg single, oral
Recommended
Dose: 1500 mg
Route: oral
Route: single
Dose: 1500 mg
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Herpes labialis
Sources: Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

Drug as perpetrator​Drug as victim
PubMed

PubMed

TitleDatePubMed
Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.
2001 Apr-Jul
Antiviral drugs: current state of the art.
2001 Aug
Recent developments in herpesvirus therapy.
2001 Mar
Herpes simplex virus: clinical presentation and treatment.
2001 May
Separation methods for acyclovir and related antiviral compounds.
2001 Nov 25
Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8.
2001 Nov-Dec
A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy.
2001 Oct
Comparison of new topical treatments for herpes labialis: efficacy of penciclovir cream, acyclovir cream, and n-docosanol cream against experimental cutaneous herpes simplex virus type 1 infection.
2001 Sep
Viral diseases of the skin: diagnosis and antiviral treatment.
2002
[Local treatments using antiviral and non-antiviral drugs for herpes facialis and genitalis (excluding pregnant females and neonates at risk)].
2002 Apr
[Genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment].
2002 Apr
Temporal pattern of herpes simplex virus type 1 infection and cell death in the mouse brain stem: influence of guanosine nucleoside analogues.
2002 Apr
Studies on the thermal decomposition process and kinetics of purine drugs.
2002 Aug
Comparative analysis of DNA breakage, chromosomal aberrations and apoptosis induced by the anti-herpes purine nucleoside analogues aciclovir, ganciclovir and penciclovir.
2002 Aug 29
New treatments for genital herpes.
2002 Feb
Drugs for non-HIV viral infections.
2002 Feb 4
Herpes simplex virus infection.
2002 Jan
Comparison of methods for identifying resistant herpes simplex virus and measuring antiviral susceptibility.
2002 Jan
Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial.
2002 Jun
Effective treatment of herpes simplex labialis with penciclovir cream: combined results of two trials.
2002 Mar
The A167Y mutation converts the herpes simplex virus type 1 thymidine kinase into a guanosine analogue kinase.
2002 May 21
Assessing the contribution of the herpes simplex virus DNA polymerase to spontaneous mutations.
2002 May 7
Antiviral agents: Non-antiretroviral [correction of Nonantiviral] drugs.
2002 Oct
CL1-SR39: A noninvasive molecular imaging model of prostate cancer suicide gene therapy using positron emission tomography.
2002 Sep
[4'-Thio-5-ethyl-2'-deoxyuridine 5'-phosphonates: synthesis and antiviral activity].
2002 Sep-Oct
Current and potential therapies for the treatment of herpes-virus infections.
2003
MicroPET imaging of prostate cancer in LNCAP-SR39TK-GFP mouse xenografts.
2003 Apr 1
Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo.
2003 Apr 15
Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis.
2003 Apr 15
Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster.
2003 Aug
Novel agents and strategies to treat herpes simplex virus infections.
2003 Feb
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Herpes simplex virus resistance to antiviral drugs.
2003 Jan
Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening.
2003 Jun
The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis.
2003 Mar
Brivudine: a herpes virostatic with rapid antiviral activity and once-daily dosing.
2003 May
Optimization of cellular nucleotide extraction and sample preparation for nucleotide pool analyses using capillary electrophoresis.
2003 May 5
Comparison of [18F]FHBG and [14C]FIAU for imaging of HSV1-tk reporter gene expression: adenoviral infection vs stable transfection.
2003 Nov
Recurrent herpes simplex labialis: selected therapeutic options.
2003 Sep
In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1.
2004 Apr
Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial.
2004 Apr
Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs.
2004 Apr 21
Antiviral properties and cytotoxic activity of platinum(II) complexes with 1,10-phenanthrolines and acyclovir or penciclovir.
2004 Aug
Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.
2004 Feb 17
Therapeutic options for herpes labialis, II: Topical agents.
2004 Jul
Antiviral drugs in current clinical use.
2004 Jun
Penciclovir cream--improved topical treatment for herpes simplex infections.
2004 Sep-Oct
Platinum(II) complexes with antitumoral/antiviral aromatic heterocycles: effect of glutathione upon in vitro cell growth inhibition.
2005 May 5
Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.
2005 Oct 15
In vitro activity of cycloSal-nucleoside monophosphates and polyhydroxycarboxylates against orthopoxviruses.
2005 Sep
Patents

Sample Use Guides

Penciclovir (DENAVIR®) should be applied every 2 hours during waking hours for a period of 4 days. Treatment should be started as early as possible (i.e., during the prodrome or when lesions appear).
Route of Administration: Topical
In cell culture studies, penciclovir has antiviral activity against the following herpes viruses: HSV-1 and HSV-2. The antiviral activity of penciclovir against wild type strains grown on human foreskin fibroblasts was assessed with a plaque reduction assay and staining with crystal violet 3 days postinfection for HSV. The median EC50 values of penciclovir against laboratory and clinical isolates of HSV-1 and HSV-2 were 2 uM (range 1.2 to 2.4 uM, n=7) and 2.6 uM (range 1.6 to 11 uM, n=6), respectively.
Name Type Language
FAMCICLOVIR
INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
FAMCICLOVIR [JAN]
Common Name English
2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol diacetate (ester)
Common Name English
FAMCICLOVIR [MART.]
Common Name English
Famciclovir [WHO-DD]
Common Name English
1,3-PROPANEDIOL, 2-(2-(2-AMINO-9H-PURIN-9-YL)ETHYL)-, DIACETATE (ESTER)
Common Name English
BRL-42810
Code English
NSC-758921
Code English
FAMCICLOVIR [USP MONOGRAPH]
Common Name English
famciclovir [INN]
Common Name English
FAMCICLOVIR [USP-RS]
Common Name English
FAMCICLOVIR [MI]
Common Name English
FAMCICLOVIR [ORANGE BOOK]
Common Name English
FAMCICLOVIR [USAN]
Common Name English
FAMCICLOVIR [VANDF]
Common Name English
FAMVIR
Brand Name English
Classification Tree Code System Code
WHO-ATC J05AB09
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WHO-ATC S01AD07
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NDF-RT N0000020060
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NDF-RT N0000180187
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LIVERTOX NBK547978
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NDF-RT N0000175459
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WHO-VATC QS01AD07
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WHO-VATC QJ05AB09
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NDF-RT N0000175459
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NCI_THESAURUS C29575
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NCI_THESAURUS C281
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NDF-RT N0000175459
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Code System Code Type Description
MESH
C060590
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PRIMARY
MERCK INDEX
m5240
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PRIMARY Merck Index
NCI_THESAURUS
C29044
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EVMPD
SUB07501MIG
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PRIMARY
USAN
EE-84
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PRIMARY
HSDB
8121
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PRIMARY
CHEBI
4974
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DAILYMED
QIC03ANI02
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PRIMARY
INN
6438
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DRUG CENTRAL
1128
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PRIMARY
CAS
104227-87-4
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PRIMARY
NSC
758921
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PRIMARY
SMS_ID
100000092280
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RXCUI
68099
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PRIMARY RxNorm
WIKIPEDIA
FAMCICLOVIR
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PRIMARY
LACTMED
Famciclovir
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DRUG BANK
DB00426
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PRIMARY
FDA UNII
QIC03ANI02
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PRIMARY
ChEMBL
CHEMBL880
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PRIMARY
EPA CompTox
DTXSID0023038
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PRIMARY
RS_ITEM_NUM
1269152
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PRIMARY
PUBCHEM
3324
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PRIMARY