Identification

Name
Famciclovir
Accession Number
DB00426  (APRD00600)
Type
Small Molecule
Groups
Approved, Investigational
Description

Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpes virus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).

Structure
Thumb
Synonyms
  • 2-(2-(2-amino-9H-purin-9-yl)ethyl)-1,3-propanediol diacetate
  • 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine
  • acetic acid 2-acetoxymethyl-4-(2-amino-purin-9-yl)-butyl ester
  • Famciclovir
  • Famciclovirum
  • FCV
External IDs
AV 42810 / BRL 42810 / BRL-42810
Active Moieties
NameKindUNIICASInChI Key
Penciclovirprodrug359HUE8FJC39809-25-1JNTOCHDNEULJHD-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act FamciclovirTablet500 mgOralActavis Pharma Company2008-10-29Not applicableCanada
Act FamciclovirTablet250 mgOralActavis Pharma Company2008-10-29Not applicableCanada
Act FamciclovirTablet125 mgOralActavis Pharma Company2008-10-29Not applicableCanada
FamciclovirTablet500 mgOralPro Doc Limitee2009-10-16Not applicableCanada
FamciclovirTablet250 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
FamciclovirTablet125 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
FamciclovirTablet250 mgOralPro Doc Limitee2009-10-16Not applicableCanada
FamciclovirTablet500 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
FamciclovirTablet125 mgOralPro Doc Limitee2009-10-16Not applicableCanada
FamvirTablet, film coated250 mg/1OralPhysicians Total Care, Inc.1994-06-292011-06-30Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-famciclovirTablet125 mgOralApotex Corporation2007-02-22Not applicableCanada
Apo-famciclovirTablet500 mgOralApotex Corporation2007-02-22Not applicableCanada
Apo-famciclovirTablet250 mgOralApotex Corporation2007-02-22Not applicableCanada
Auro-famciclovirTablet250 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-famciclovirTablet500 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-famciclovirTablet125 mgOralAuro Pharma IncNot applicableNot applicableCanada
Ava-famciclovirTablet500 mgOralAvanstra Inc2011-09-192014-08-21Canada
Ava-famciclovirTablet250 mgOralAvanstra Inc2011-09-192014-08-21Canada
Ava-famciclovirTablet125 mgOralAvanstra Inc2011-09-192014-08-21Canada
Dom-famciclovirTablet500 mgOralDominion PharmacalNot applicableNot applicableCanada
International/Other Brands
Ezovir (Alphapharm) / Fambir (Il Hwa) / Famcino (Daewoong) / Famcir (Kwang Dong) / Famvir Once (Novartis) / Fanclomax (Blausiegel) / Fanle (Jialin) / Microvir (Micro Gratia) / Oravir (Novartis) / Pentavir (Fortbenton) / Penvir (Hetero) / Pixin (Pidi Pharmaceutical) / Virovir (FDC) / Wan Qi (Renfu Pharmaceutical) / Weike (Hisun)
Categories
UNII
QIC03ANI02
CAS number
104227-87-4
Weight
Average: 321.3318
Monoisotopic: 321.143704121
Chemical Formula
C14H19N5O4
InChI Key
GGXKWVWZWMLJEH-UHFFFAOYSA-N
InChI
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)
IUPAC Name
2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate
SMILES
CC(=O)OCC(CCN1C=NC2=CN=C(N)N=C12)COC(C)=O

Pharmacology

Indication

For the treatment of acute herpes zoster (shingles). Also for the treatment or suppression of recurrent genital herpes in immunocompetent patients and treatment of recurrent mucocutaneous herpes simplex infections in HIV infected patients.

Associated Conditions
Pharmacodynamics

Famciclovir is a prodrug that undergoes rapid biotransformation to the active antiviral compound penciclovir. Penciclovir is an anti-viral drug which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Therefore, herpes viral DNA synthesis and replication are selectively inhibited.

Mechanism of action

Famciclovir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.

TargetActionsOrganism
ADNA polymerase catalytic subunit
inhibitor
HHV-1
ADNA polymerase catalytic subunit
inhibitor
HHV-3
Absorption

77 %

Volume of distribution
  • 1.08±0.17 L/kg [healthy male subjects following a single intravenous dose of penciclovir at 400 mg administered as a 1-hour intravenous infusion]
Protein binding

20-25%

Metabolism

Hepatic

Route of elimination

Active tubular secretion contributes to the renal elimination of penciclovir.

Half life

10 hours

Clearance
  • 36.6 +/- 6.3 L/hr [healthy male]
  • 0.48 +/- 0.09 L/hr/kg [healthy male]
Toxicity

Symptoms of overdose include constipation, diarrhea, dizziness, fatigue, fever, headache, nausea, and vomiting.

Affected organisms
  • Human Herpes Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Famciclovir.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Famciclovir.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Famciclovir.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Famciclovir.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Famciclovir.
6-Deoxyerythronolide BThe metabolism of Famciclovir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Famciclovir.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Famciclovir.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Famciclovir.
AcalabrutinibThe metabolism of Famciclovir can be decreased when combined with Acalabrutinib.
Food Interactions
  • Take without regard to meals.

References

Synthesis Reference
US5246937
General References
Not Available
External Links
Human Metabolome Database
HMDB0014570
KEGG Drug
D00317
PubChem Compound
3324
PubChem Substance
46507561
ChemSpider
3207
BindingDB
50066502
ChEBI
4974
ChEMBL
CHEMBL880
Therapeutic Targets Database
DAP000489
PharmGKB
PA449585
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Famciclovir
ATC Codes
S01AD07 — FamciclovirJ05AB09 — Famciclovir
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
FDA label
Download (227 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
2CompletedTreatmentHerpes Simplex1
2, 3CompletedTreatmentHerpes Labialis1
3CompletedTreatmentChickenpox / Herpes Zoster1
3CompletedTreatmentGenital Herpes2
3CompletedTreatmentHerpes Simplex1
3CompletedTreatmentRecurrent Genital Herpes (RGH)1
3RecruitingTreatmentHerpes Zoster1
3TerminatedTreatmentMenière's Disease1
4CompletedTreatmentGenital Herpes2
4CompletedTreatmentRecurrent Genital Herpes (RGH)1
4CompletedTreatmentRecurrent Herpes Labialis1
Not AvailableCompletedTreatmentHerpes / Herpes Nos2
Not AvailableNot Yet RecruitingTreatmentHerpes Zoster / Post-Herpetic Neuralgia (PHN)1

Pharmacoeconomics

Manufacturers
  • Teva pharmaceuticals usa
  • Novartis pharmaceuticals corp
Packagers
  • Apotheca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Redpharm Drug
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
TabletOral125 mg/1
TabletOral250 mg/1
TabletOral500 mg/1
Tablet, film coatedOral500 mg/1
Tablet, film coatedOral125 mg/1
Tablet, film coatedOral250 mg/1
TabletOral125 mg
TabletOral250 mg
TabletOral500 mg
Prices
Unit descriptionCostUnit
Famvir 500 mg tablet14.39USD tablet
Famciclovir 500 mg tablet11.67USD tablet
Famvir 250 mg tablet7.16USD tablet
Famvir 125 mg tablet6.59USD tablet
Famciclovir 250 mg tablet5.81USD tablet
Famciclovir 125 mg tablet5.34USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5246937No1993-09-212010-09-21Us
CA2176392No2005-11-082014-11-11Canada
CA2086756No2003-04-082011-07-03Canada
US5840763Yes1998-11-242016-03-01Us
US5916893Yes1999-06-292016-03-01Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)102-104 °CNot Available
logP0.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.32 mg/mLALOGPS
logP0.13ALOGPS
logP-0.48ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)16.7ChemAxon
pKa (Strongest Basic)5.05ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area122.22 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity81.54 m3·mol-1ChemAxon
Polarizability32.83 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.988
Blood Brain Barrier+0.9429
Caco-2 permeable-0.603
P-glycoprotein substrateSubstrate0.6719
P-glycoprotein inhibitor INon-inhibitor0.9305
P-glycoprotein inhibitor IINon-inhibitor0.9213
Renal organic cation transporterNon-inhibitor0.6392
CYP450 2C9 substrateNon-substrate0.9156
CYP450 2D6 substrateNon-substrate0.8345
CYP450 3A4 substrateNon-substrate0.6545
CYP450 1A2 substrateNon-inhibitor0.5863
CYP450 2C9 inhibitorNon-inhibitor0.7961
CYP450 2D6 inhibitorNon-inhibitor0.8068
CYP450 2C19 inhibitorNon-inhibitor0.8151
CYP450 3A4 inhibitorNon-inhibitor0.8987
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8661
Ames testNon AMES toxic0.5887
CarcinogenicityNon-carcinogens0.9257
BiodegradationNot ready biodegradable0.9495
Rat acute toxicity2.3203 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.797
hERG inhibition (predictor II)Non-inhibitor0.9071
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00dr-1869000000-c198d52e11cc029a313c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-0329000000-cfd0210d7c106403c4fe

Taxonomy

Description
This compound belongs to the class of organic compounds known as purines and purine derivatives. These are aromatic heterocyclic compounds containing a purine moiety, which is formed a pyrimidine-ring ring fused to an imidazole ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Purines and purine derivatives
Alternative Parents
Aminopyrimidines and derivatives / N-substituted imidazoles / Dicarboxylic acids and derivatives / Heteroaromatic compounds / Carboxylic acid esters / Amino acids and derivatives / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organic oxides
show 2 more
Substituents
Purine / Aminopyrimidine / Pyrimidine / Dicarboxylic acid or derivatives / N-substituted imidazole / Azole / Heteroaromatic compound / Imidazole / Amino acid or derivatives / Carboxylic acid ester
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
acetate ester, 2-aminopurines (CHEBI:4974)

Targets

Kind
Protein
Organism
HHV-1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name
Not Available
Uniprot ID
P04293
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
136419.66 Da
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  2. Schmid-Wendtner MH, Korting HC: Penciclovir cream--improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8. [PubMed:15452407]
Kind
Protein
Organism
HHV-3
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rna-dna hybrid ribonuclease activity
Specific Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding pro...
Gene Name
Not Available
Uniprot ID
P09252
Uniprot Name
DNA polymerase catalytic subunit
Molecular Weight
134046.615 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
References
  1. Rashidi MR, Smith JA, Clarke SE, Beedham C: In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver. Drug Metab Dispos. 1997 Jul;25(7):805-13. [PubMed:9224775]
  2. Al-Salmy HS: Inter-strain variability in aldehyde oxidase activity in the mouse. Comp Biochem Physiol C Toxicol Pharmacol. 2002 Jul;132(3):341-7. [PubMed:12161167]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 00:42