Identification
NameSofosbuvir
Accession NumberDB08934
TypeSmall Molecule
GroupsApproved
Description

Sofosbuvir (tradename Sovaldi) is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients [14]. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as sofosbuvir. As a prodrug nucleotide analog, Sofosbuvir is metabolized into its active form as the antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (also known as GS-461203), which acts as a defective substrate for NS5B (non-structural protein 5B) [Synthesis]. NS5B, an RNA-dependent RNA polymerase, is essential for the transcription of Hepatitis C viral RNA and for its high replicative rate and genetic diversity [4]. Sofosbuvir and other direct acting antivirals are therefore very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance [5]. This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Sofosbuvir as first line therapy in combination with other antivirals for all six genotypes of Hepatitis C [14]. Depending on the genotype, sofosbuvir is often used in combination with other antivirals such as Ledipasvir, Velpatasvir, Daclatasvir, Simeprevir, Elbasvir, Grazoprevir, Ribavirin, Peginterferon alfa-2a, or Peginterferon alfa-2b with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality [6]. Treatment with direct acting antivirals such as sofosbuvir is associated with very minimal side effects, with the most common being headache and fatigue [FDA Label]. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects [11].

Since 2014, sofosbuvir has been available as a fixed dose combination product with Ledipasvir (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without Ribavirin depending on the level of liver damage or cirrhosis [FDA Label]. When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment [3]. Its use has also proven successful in the treatment of HCV in patients co-infected with HIV [7].

Sofosbuvir is also available as a fixed dose combination product with Velpatasvir as the commercially available product Epclusa. First approved in June 2016, Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. Epclusa is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis [14]. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV [14, 6].

Notably, sofosbuvir has come under intense scrutiny since its release to market in 2013. With the price per pill set at $1000, a 12-week treatment can cost upwards of $84,000 per patient [12].

Structure
Thumb
Synonyms
S)-Isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)- (phenoxy)phosphorylamino)propanoate
External IDs GI 7977 / GI-7977 / GI7977 / GS 331007 / GS 461203 / GS-331007 / GS-461203 / GS-7977 / GS331007 / GS461203 / GS7977 / PSI 7977 / PSI-7977 / PSI7977
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SovaldiTablet400 mgOralGilead Sciences2014-01-06Not applicableCanada
SovaldiTablet, film coated400 mg/1OralGilead Sciences2013-12-06Not applicableUs
SovaldiTablet, film coated400 mgOralGilead Sciences2014-01-16Not applicableEu
SovaldiTablet, film coated400 mgOralGilead Sciences2014-01-16Not applicableEu
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
HepcinatNatco Pharma Ltd.
HepcvirCipla Limited
ResofHetero Drugs Ltd
SoviHepZydus Cadila
Brand mixtures
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EpclusaTabletOralGilead Sciences2016-08-02Not applicableCanada
HarvoniTabletOralGilead Sciences2014-10-16Not applicableCanada
VoseviTablet, film coatedOralGilead Sciences2017-07-18Not applicableUs
Categories
UNIIWJ6CA3ZU8B
CAS number1190307-88-0
WeightAverage: 529.458
Monoisotopic: 529.162544687
Chemical FormulaC22H29FN3O9P
InChI KeyTTZHDVOVKQGIBA-IQWMDFIBSA-N
InChI
InChI=1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36-/m0/s1
IUPAC Name
SMILES
CC(C)OC(=O)[[email protected]](C)N[[email protected]](=O)(OC[[email protected]]1O[[email protected]@H](N2C=CC(=O)NC2=O)[[email protected]](C)(F)[[email protected]@H]1O)OC1=CC=CC=C1
Pharmacology
Indication

Sofosbuvir is used in combination therapy with other antiviral medications to treat chronic hepatitis C virus (HCV) infected patients with HCV genoptypes 1-6, and to treat HCV and HIV co-infected patients. Depending on the level of cirrhosis or decompensation, combination therapy can also include either ribavirin alone or ribavirin and peg-interferon alfa.

When used in combination with Ledipasvir as the combination product Harvoni, sofosbuvir has the following indications: treatment of genotypes 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis; in combination with Ribavirin for genotype 1 infection with decompensated cirrhosis; or in combination with Ribavirin for the treatment of genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis.

When used in combination with Velpatasvir as the combination product Epclusa, sofosbuvir is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis, or in combination with Ribavirin if associated with decompensated cirrhosis.

Resistance: Reduced susceptibility to sofosbuvir has been associated with the NS5B substitution mutation S282T [10].

Structured Indications
Pharmacodynamics

Sofosbuvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA).

At a dose 3 times the recommended dose, sofosbuvir does not prolong QTc to any clinically relevant extent [FDA Label].

Mechanism of action

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator [Synthesis]. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material [13].

TargetKindPharmacological actionActionsOrganismUniProt ID
RNA-dependent RNA-polymeraseProteinyes
inhibitor
Hepatitis C virusO39930 details
Related Articles
Absorption

When given orally, sofosbuvir reaches its maximum plasma concentration in about 0.5 to 2 hours with a maximal concentration (Cmax) of 567 ng/mL [FDA Label].

Volume of distribution

The volume of distribution for sofosbuvir has yet to be determined [FDA Label].

Protein binding

Sofosbuvir is approximately 61-65% bound to human plasma proteins [FDA Label].

Metabolism

In vitro studies in human liver microsomes showed that sofosbuvir was an efficient substrate for Cathepsin A (Cat A) and carboxyl esterase 1 (CES1). Sofosbuvir was cleaved by CatA and CES1 and subsequent activation steps included amino acid removal by histidine triad nucleotide-binding protein 1 (HINT1) and phosphorylation by uridine monophosphate-cytidine monophosphate (UMP-CMP) kinase and nucleoside diphosphate (NDP) kinase. In vitro data indicated that Cat A preferentially hydrolysed sofosbuvir (the S-diastereomer) while CES1 did not exhibit stereoselectivity [8, 9].

SubstrateEnzymesProduct
Sofosbuvir
GS-56650Details
GS-56650
GS-606965Details
GS-606965
GS-461203Details
Route of elimination

Sofosbuvir is eliminated by three routes: urine ( 80%), feces (14%), and respiration (2.5%); however, elimination through the kidneys is the major route [FDA Label].

Half life

Sofosbuvir has a terminal half life of 0.4 hours [FDA Label].

Clearance

The clearance of sofosbuvir has yet to be determined [FDA Label].

Toxicity

Sofosbuvir, as a single agent, has very mild toxicity. The most common adverse reactions are headache and fatigue. The FDA Label currently warns of a risk of symptomatic bradycardia when Epclusa is used in combination with amiodarone [FDA Label].

Affected organisms
  • Hepatitis C Virus
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcetaminophenThe serum concentration of Sofosbuvir can be increased when it is combined with Acetaminophen.Approved
AfatinibThe serum concentration of Sofosbuvir can be increased when it is combined with Afatinib.Approved
AlbendazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Sofosbuvir can be decreased when it is combined with Aldosterone.Experimental
AlectinibThe serum concentration of Sofosbuvir can be increased when it is combined with Alectinib.Approved
AlfentanilThe serum concentration of Sofosbuvir can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Sofosbuvir can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Sofosbuvir can be increased when it is combined with Aminohippuric acid.Approved
AmiodaroneSofosbuvir may increase the bradycardic activities of Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Sofosbuvir can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Sofosbuvir can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Sofosbuvir can be decreased when it is combined with Amprenavir.Approved
AmsacrineThe serum concentration of Sofosbuvir can be increased when it is combined with Amsacrine.Approved
AstemizoleThe serum concentration of Sofosbuvir can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Sofosbuvir can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Sofosbuvir can be increased when it is combined with Atenolol.Approved
AtorvastatinThe serum concentration of Sofosbuvir can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Sofosbuvir can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Sofosbuvir can be increased when it is combined with Azithromycin.Approved
BenzocaineThe serum concentration of Sofosbuvir can be increased when it is combined with Benzocaine.Approved
BepridilThe serum concentration of Sofosbuvir can be increased when it is combined with Bepridil.Approved, Withdrawn
BiperidenThe serum concentration of Sofosbuvir can be increased when it is combined with Biperiden.Approved
BosutinibThe serum concentration of Sofosbuvir can be increased when it is combined with Bosutinib.Approved
BromocriptineThe serum concentration of Sofosbuvir can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Sofosbuvir can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Sofosbuvir can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Sofosbuvir can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Sofosbuvir can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Sofosbuvir can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Sofosbuvir can be increased when it is combined with Candesartan.Approved
CaptoprilThe serum concentration of Sofosbuvir can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Sofosbuvir can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Sofosbuvir can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Sofosbuvir can be increased when it is combined with Caspofungin.Approved
ChloroquineThe serum concentration of Sofosbuvir can be increased when it is combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe serum concentration of Sofosbuvir can be increased when it is combined with Chlorpromazine.Approved, Vet Approved
ChlorpropamideThe serum concentration of Sofosbuvir can be increased when it is combined with Chlorpropamide.Approved
ChlorprothixeneThe serum concentration of Sofosbuvir can be increased when it is combined with Chlorprothixene.Approved, Withdrawn
CholesterolThe serum concentration of Sofosbuvir can be increased when it is combined with Cholesterol.Experimental
Cholic AcidThe serum concentration of Sofosbuvir can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Sofosbuvir can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Sofosbuvir can be decreased when it is combined with Cimetidine.Approved
CiprofloxacinThe serum concentration of Sofosbuvir can be increased when it is combined with Ciprofloxacin.Approved, Investigational
CitalopramThe serum concentration of Sofosbuvir can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Sofosbuvir can be increased when it is combined with Clarithromycin.Approved
ClofazimineThe serum concentration of Sofosbuvir can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Sofosbuvir can be increased when it is combined with Clomipramine.Approved, Vet Approved
ClotrimazoleThe serum concentration of Sofosbuvir can be decreased when it is combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Sofosbuvir can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Sofosbuvir can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Sofosbuvir can be increased when it is combined with Colforsin.Experimental
CrizotinibThe serum concentration of Sofosbuvir can be increased when it is combined with Crizotinib.Approved
CyclophosphamideThe serum concentration of Sofosbuvir can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Sofosbuvir can be decreased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
DaclatasvirThe serum concentration of Sofosbuvir can be increased when it is combined with Daclatasvir.Approved
DactinomycinThe serum concentration of Sofosbuvir can be increased when it is combined with Dactinomycin.Approved
DasatinibThe serum concentration of Sofosbuvir can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Sofosbuvir can be decreased when it is combined with Daunorubicin.Approved
DesipramineThe serum concentration of Sofosbuvir can be increased when it is combined with Desipramine.Approved
DesloratadineThe serum concentration of Sofosbuvir can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Sofosbuvir can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DextromethorphanThe serum concentration of Sofosbuvir can be increased when it is combined with Dextromethorphan.Approved
DiclofenacThe serum concentration of Sofosbuvir can be increased when it is combined with Diclofenac.Approved, Vet Approved
DigoxinThe serum concentration of Sofosbuvir can be decreased when it is combined with Digoxin.Approved
DihydroergotamineThe serum concentration of Sofosbuvir can be increased when it is combined with Dihydroergotamine.Approved
DiltiazemThe serum concentration of Sofosbuvir can be increased when it is combined with Diltiazem.Approved
DipyridamoleThe serum concentration of Sofosbuvir can be increased when it is combined with Dipyridamole.Approved
DoxazosinThe serum concentration of Sofosbuvir can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Sofosbuvir can be increased when it is combined with Doxepin.Approved
DoxorubicinThe serum concentration of Sofosbuvir can be decreased when it is combined with Doxorubicin.Approved, Investigational
DronabinolThe serum concentration of Sofosbuvir can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Sofosbuvir can be increased when it is combined with Dronedarone.Approved
ElbasvirThe serum concentration of Sofosbuvir can be increased when it is combined with Elbasvir.Approved
EltrombopagThe serum concentration of Sofosbuvir can be increased when it is combined with Eltrombopag.Approved
EnalaprilThe serum concentration of Sofosbuvir can be increased when it is combined with Enalapril.Approved, Vet Approved
EnzalutamideThe serum concentration of Sofosbuvir can be increased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Sofosbuvir can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Sofosbuvir can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Sofosbuvir can be decreased when it is combined with Erythromycin.Approved, Vet Approved
EstramustineThe serum concentration of Sofosbuvir can be increased when it is combined with Estramustine.Approved
EstriolThe serum concentration of Sofosbuvir can be decreased when it is combined with Estriol.Approved, Vet Approved
EstroneThe serum concentration of Sofosbuvir can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Sofosbuvir can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Sofosbuvir can be increased when it is combined with Etravirine.Approved
FelodipineThe serum concentration of Sofosbuvir can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Sofosbuvir can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Sofosbuvir can be increased when it is combined with Fexofenadine.Approved
FidaxomicinThe serum concentration of Sofosbuvir can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Fluconazole.Approved
FluoxetineThe serum concentration of Sofosbuvir can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Sofosbuvir can be increased when it is combined with Flupentixol.Approved, Withdrawn
FluphenazineThe serum concentration of Sofosbuvir can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Sofosbuvir can be increased when it is combined with Flurazepam.Approved, Illicit
FluvoxamineThe serum concentration of Sofosbuvir can be increased when it is combined with Fluvoxamine.Approved, Investigational
GefitinibThe serum concentration of Sofosbuvir can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Sofosbuvir can be increased when it is combined with Genistein.Investigational
GlyburideThe serum concentration of Sofosbuvir can be increased when it is combined with Glyburide.Approved
Gramicidin DThe serum concentration of Sofosbuvir can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Sofosbuvir can be increased when it is combined with Grepafloxacin.Withdrawn
HaloperidolThe serum concentration of Sofosbuvir can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Sofosbuvir can be increased when it is combined with Hydrocortisone.Approved, Vet Approved
IdelalisibThe serum concentration of Sofosbuvir can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Sofosbuvir can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Sofosbuvir can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Sofosbuvir can be decreased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Sofosbuvir can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoniumThe serum concentration of Sofosbuvir can be increased when it is combined with Isavuconazonium.Approved, Investigational
ItraconazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Sofosbuvir can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Sofosbuvir can be increased when it is combined with Ivermectin.Approved, Vet Approved
KetamineThe serum concentration of Sofosbuvir can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Ketoconazole.Approved, Investigational
LansoprazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Sofosbuvir can be increased when it is combined with Lapatinib.Approved, Investigational
LevofloxacinThe serum concentration of Sofosbuvir can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Sofosbuvir can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Sofosbuvir can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Sofosbuvir can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Sofosbuvir can be decreased when it is combined with Liotrix.Approved
LisinoprilThe serum concentration of Sofosbuvir can be increased when it is combined with Lisinopril.Approved, Investigational
LomitapideThe serum concentration of Sofosbuvir can be increased when it is combined with Lomitapide.Approved
LoperamideThe serum concentration of Sofosbuvir can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Sofosbuvir can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Sofosbuvir can be increased when it is combined with Loratadine.Approved
LosartanThe serum concentration of Sofosbuvir can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Sofosbuvir can be increased when it is combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Sofosbuvir can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Sofosbuvir can be increased when it is combined with Maprotiline.Approved
MebendazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Sofosbuvir can be increased when it is combined with Mefloquine.Approved
Megestrol acetateThe serum concentration of Sofosbuvir can be increased when it is combined with Megestrol acetate.Approved, Vet Approved
MeprobamateThe serum concentration of Sofosbuvir can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Sofosbuvir can be increased when it is combined with Methadone.Approved
MetoprololThe serum concentration of Sofosbuvir can be increased when it is combined with Metoprolol.Approved, Investigational
MibefradilThe serum concentration of Sofosbuvir can be increased when it is combined with Mibefradil.Withdrawn
MiconazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Sofosbuvir can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Sofosbuvir can be decreased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Sofosbuvir can be increased when it is combined with Mitomycin.Approved
MitoxantroneThe serum concentration of Sofosbuvir can be decreased when it is combined with Mitoxantrone.Approved, Investigational
ModafinilThe serum concentration of Sofosbuvir can be decreased when it is combined with Modafinil.Approved, Investigational
MorphineThe serum concentration of Sofosbuvir can be increased when it is combined with Morphine.Approved, Investigational
NaltrexoneThe serum concentration of Sofosbuvir can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Sofosbuvir can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Sofosbuvir can be decreased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Sofosbuvir can be decreased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Sofosbuvir can be increased when it is combined with Neostigmine.Approved, Vet Approved
NicardipineThe serum concentration of Sofosbuvir can be increased when it is combined with Nicardipine.Approved
NifedipineThe serum concentration of Sofosbuvir can be decreased when it is combined with Nifedipine.Approved
NilotinibThe serum concentration of Sofosbuvir can be increased when it is combined with Nilotinib.Approved, Investigational
NisoldipineThe serum concentration of Sofosbuvir can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Sofosbuvir can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Sofosbuvir can be increased when it is combined with Nitrendipine.Approved
NorethisteroneThe serum concentration of Sofosbuvir can be decreased when it is combined with Norethisterone.Approved
OmeprazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OxcarbazepineThe serum concentration of Sofosbuvir can be decreased when it is combined with Oxcarbazepine.Approved
P-NitrophenolThe serum concentration of Sofosbuvir can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Sofosbuvir can be increased when it is combined with Paclitaxel.Approved, Vet Approved
Palmitic AcidThe serum concentration of Sofosbuvir can be increased when it is combined with Palmitic Acid.Experimental
PantoprazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Sofosbuvir can be increased when it is combined with Paroxetine.Approved, Investigational
PerindoprilThe serum concentration of Sofosbuvir can be increased when it is combined with Perindopril.Approved
PhenobarbitalThe serum concentration of Sofosbuvir can be decreased when it is combined with Phenobarbital.Approved
PimozideThe serum concentration of Sofosbuvir can be increased when it is combined with Pimozide.Approved
Platelet Activating FactorThe serum concentration of Sofosbuvir can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Sofosbuvir can be increased when it is combined with Ponatinib.Approved
PosaconazoleThe serum concentration of Sofosbuvir can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Sofosbuvir can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Sofosbuvir can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Sofosbuvir can be increased when it is combined with Prednisone.Approved, Vet Approved
ProbenecidThe serum concentration of Sofosbuvir can be increased when it is combined with Probenecid.Approved
ProgesteroneThe serum concentration of Sofosbuvir can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Sofosbuvir can be increased when it is combined with Promethazine.Approved
PropafenoneThe serum concentration of Sofosbuvir can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Sofosbuvir can be increased when it is combined with Propranolol.Approved, Investigational
ProtriptylineThe serum concentration of Sofosbuvir can be increased when it is combined with Protriptyline.Approved
QuercetinThe serum concentration of Sofosbuvir can be increased when it is combined with Quercetin.Experimental
QuinacrineThe serum concentration of Sofosbuvir can be increased when it is combined with Quinacrine.Approved
QuinidineThe serum concentration of Sofosbuvir can be increased when it is combined with Quinidine.Approved
QuinineThe serum concentration of Sofosbuvir can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Sofosbuvir can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Sofosbuvir can be increased when it is combined with Ranolazine.Approved, Investigational
ReboxetineThe serum concentration of Sofosbuvir can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Sofosbuvir can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Sofosbuvir can be decreased when it is combined with Reserpine.Approved
RifabutinThe serum concentration of Sofosbuvir can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Sofosbuvir can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Sofosbuvir can be decreased when it is combined with Rifapentine.Approved
RilpivirineThe serum concentration of Sofosbuvir can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Sofosbuvir can be decreased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Sofosbuvir can be increased when it is combined with Rolapitant.Approved
SaquinavirThe serum concentration of Sofosbuvir can be decreased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Sofosbuvir can be increased when it is combined with Scopolamine.Approved
SelegilineThe serum concentration of Sofosbuvir can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Sofosbuvir can be increased when it is combined with Sertraline.Approved
SimeprevirThe serum concentration of Sofosbuvir can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Sofosbuvir can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Sofosbuvir can be decreased when it is combined with Sirolimus.Approved, Investigational
SorafenibThe serum concentration of Sofosbuvir can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Sofosbuvir can be increased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Sofosbuvir can be decreased when it is combined with St. John's Wort.Nutraceutical
StaurosporineThe serum concentration of Sofosbuvir can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Sofosbuvir can be decreased when it is combined with Streptozocin.Approved
SulfinpyrazoneThe serum concentration of Sofosbuvir can be increased when it is combined with Sulfinpyrazone.Approved
SumatriptanThe serum concentration of Sofosbuvir can be increased when it is combined with Sumatriptan.Approved, Investigational
SunitinibThe serum concentration of Sofosbuvir can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Sofosbuvir can be increased when it is combined with Tacrine.Withdrawn
TacrolimusThe serum concentration of Sofosbuvir can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Sofosbuvir can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Sofosbuvir can be increased when it is combined with Taurocholic Acid.Experimental
TelmisartanThe serum concentration of Sofosbuvir can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Sofosbuvir can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Sofosbuvir can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Sofosbuvir can be increased when it is combined with Terfenadine.Withdrawn
TeriflunomideThe serum concentration of Sofosbuvir can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Sofosbuvir can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Sofosbuvir can be increased when it is combined with Testosterone.Approved, Investigational
TicagrelorThe serum concentration of Sofosbuvir can be increased when it is combined with Ticagrelor.Approved
TolvaptanThe serum concentration of Sofosbuvir can be increased when it is combined with Tolvaptan.Approved
TrazodoneThe serum concentration of Sofosbuvir can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Sofosbuvir can be increased when it is combined with Trifluoperazine.Approved
TriflupromazineThe serum concentration of Sofosbuvir can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Sofosbuvir can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Sofosbuvir can be increased when it is combined with Trimipramine.Approved
VenlafaxineThe serum concentration of Sofosbuvir can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Sofosbuvir can be decreased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Sofosbuvir can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Sofosbuvir can be decreased when it is combined with Vincristine.Approved, Investigational
VinorelbineThe serum concentration of Sofosbuvir can be increased when it is combined with Vinorelbine.Approved, Investigational
ZimelidineThe serum concentration of Sofosbuvir can be increased when it is combined with Zimelidine.Withdrawn
Food Interactions
  • Sofosbuvir can be given with or without food.
References
Synthesis Reference

Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, Rachakonda S, Reddy PG, Ross BS, Wang P, Zhang HR, Bansal S, Espiritu C, Keilman M, Lam AM, Steuer HM, Niu C, Otto MJ, Furman PA: Discovery of a beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. J Med Chem. 2010 Oct 14;53(19):7202-18

General References
  1. Asselah T: Sofosbuvir for the treatment of hepatitis C virus. Expert Opin Pharmacother. 2014 Jan;15(1):121-30. doi: 10.1517/14656566.2014.857656. Epub 2013 Nov 30. [PubMed:24289735 ]
  2. Fung A, Jin Z, Dyatkina N, Wang G, Beigelman L, Deval J: Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase. Antimicrob Agents Chemother. 2014 Jul;58(7):3636-45. doi: 10.1128/AAC.02666-14. Epub 2014 Apr 14. [PubMed:24733478 ]
  3. Molina JM, Orkin C, Iser DM, Zamora FX, Nelson M, Stephan C, Massetto B, Gaggar A, Ni L, Svarovskaia E, Brainard D, Subramanian GM, McHutchison JG, Puoti M, Rockstroh JK: Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015 Mar 21;385(9973):1098-106. doi: 10.1016/S0140-6736(14)62483-1. Epub 2015 Feb 4. [PubMed:25659285 ]
  4. Simmonds P: Genetic diversity and evolution of hepatitis C virus--15 years on. J Gen Virol. 2004 Nov;85(Pt 11):3173-88. [PubMed:15483230 ]
  5. Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [PubMed:28497432 ]
  6. Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [PubMed:25585348 ]
  7. Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Brau N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M: Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21. [PubMed:26196665 ]
  8. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]
  9. Denning J, Cornpropst M, Flach SD, Berrey MM, Symonds WT: Pharmacokinetics, safety, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor for hepatitis C virus, following single ascending doses in healthy subjects. Antimicrob Agents Chemother. 2013 Mar;57(3):1201-8. doi: 10.1128/AAC.01262-12. Epub 2012 Dec 21. [PubMed:23262999 ]
  10. Xu S, Doehle B, Rajyaguru S, Han B, Barauskas O, Feng J, Perry J, Dvory-Sobol H, Svarovskaia ES, Miller MD, Mo H: In vitro selection of resistance to sofosbuvir in HCV replicons of genotype 1 to 6. Antivir Ther. 2017 Mar 1. doi: 10.3851/IMP3149. [PubMed:28248189 ]
  11. Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [PubMed:9305675 ]
  12. Hill A, Simmons B, Gotham D, Fortunak J: Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J Virus Erad. 2016 Jan 1;2(1):28-31. [PubMed:27482432 ]
  13. Eltahla AA, Luciani F, White PA, Lloyd AR, Bull RA: Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance. Viruses. 2015 Sep 29;7(10):5206-24. doi: 10.3390/v7102868. [PubMed:26426038 ]
  14. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
External Links
ATC CodesJ05AX65 — Sofosbuvir and ledipasvirJ05AX15 — Sofosbuvir
AHFS Codes
  • 8:18.40.16
PDB EntriesNot Available
FDA labelDownload (487 KB)
MSDSDownload (616 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionChronic Hepatitis C Virus (HCV) Infection1
0Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Lung Transplant Infection1
0RecruitingTreatmentChronic Hepatitis C Infection / Transplant, Kidney1
1CompletedNot AvailableHealthy Volunteers4
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentChronic Hepatitis C Infection1
1CompletedTreatmentHepatitis / Infection, Human Immunodeficiency Virus I1
1RecruitingTreatmentChronic Hepatitis C Infection / Pregnancy1
1, 2CompletedTreatmentChronic Hepatitis C Infection1
1, 2CompletedTreatmentChronic Hepatitis C Infection / HIV Disease1
2Active Not RecruitingTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentHCV Infections1
2Active Not RecruitingTreatmentHepatitis C Virus Infection2
2Active Not RecruitingTreatmentHepatitis C, Chronic1
2CompletedNot AvailableHepatitis C, Chronic1
2CompletedTreatmentChronic Genotype 4 HCV / Chronic Genotype 5 HCV1
2CompletedTreatmentChronic HCV Infection3
2CompletedTreatmentChronic Hepatitis C Infection14
2CompletedTreatmentChronic Hepatitis C Infection / HIV Disease1
2CompletedTreatmentChronic Hepatitis C Infection / Hepatocellular,Carcinoma1
2CompletedTreatmentChronic Hepatitis C Infection / Infection, Human Immunodeficiency Virus I1
2CompletedTreatmentChronic Hepatitis C Infection / Liver Cirrhosis / Portal Hypertension / With or Without Liver Decompensation1
2CompletedTreatmentChronic Hepatitis C Virus1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection4
2CompletedTreatmentChronic Hepatitis C Virus Infection1
2CompletedTreatmentHCV Infections2
2CompletedTreatmentHepatitis C Infection With HIV Co-Infection1
2CompletedTreatmentHepatitis C Virus (HCV)3
2CompletedTreatmentHepatitis C Virus Infection8
2CompletedTreatmentHepatitis C, Chronic4
2CompletedTreatmentHepatitits C1
2CompletedTreatmentPost Liver Transplant / Recurrent Chronic Hepatitis C Virus1
2CompletedTreatmentTreatment of Hepatitis C1
2Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Porphyria Cutanea Tarda1
2Not Yet RecruitingTreatmentIndolent Lymphoma1
2RecruitingTreatmentChronic Hepatitis C Infection1
2RecruitingTreatmentChronic Hepatitis C Infection / Indolent B-cell Lymphoma1
2RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection4
2RecruitingTreatmentHepatitis C Virus Infection4
2TerminatedTreatmentHepatitis C Infection1
2WithdrawnTreatmentChronic Hepatitis C Infection2
2, 3Active Not RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
2, 3RecruitingTreatmentChronic Hepatitis C Infection2
2, 3RecruitingTreatmentChronic Hepatitis C Infection / Cryoglobulinemia1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
3Active Not RecruitingNot AvailableChronic Hepatitis C Infection1
3Active Not RecruitingTreatmentChronic HCV Infection1
3Active Not RecruitingTreatmentChronic Hepatitis C Infection / Liver Cirrhosis1
3Active Not RecruitingTreatmentChronic Hepatitis C Virus / Hepatitis C Virus (HCV)1
3Active Not RecruitingTreatmentHCV Infections / Infection, Human Immunodeficiency Virus I1
3Active Not RecruitingTreatmentHepatitis C Virus Infection5
3Active Not RecruitingTreatmentHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentChronic HCV Infection3
3CompletedTreatmentChronic Hepatitis C Infection11
3CompletedTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentChronic Hepatitis C Infection / Liver Cirrhosis1
3CompletedTreatmentChronic Hepatitis C Virus3
3CompletedTreatmentChronic Hepatitis C Virus (HCV Infection Genotype 1)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection4
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Genotype 3 Hepatitis C Virus / Hepatitis C Virus (HCV)1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Genotype 4 Chronic Hepatitis C1
3CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV)1
3CompletedTreatmentHepatitis C Virus (HCV) / HIV Disease1
3CompletedTreatmentHepatitis C Infection1
3CompletedTreatmentHepatitis C Virus (HCV)1
3CompletedTreatmentHepatitis C Virus Infection11
3Enrolling by InvitationTreatmentCirrhosis, Decompensated / Hepatitis C, Chronic1
3Enrolling by InvitationTreatmentHepatitis C Genotype 41
3Enrolling by InvitationTreatmentHepatitis C Virus Infection1
3Not Yet RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection1
3RecruitingTreatmentChronic Hepatitis C Infection1
3RecruitingTreatmentHepatitis C Virus Infection1
3RecruitingTreatmentHepatitis C, Chronic / Hepatocellular,Carcinoma1
3TerminatedTreatmentHepatitis C Viral Infection1
4Active Not RecruitingTreatmentChronic Hepatitis C Infection2
4Active Not RecruitingTreatmentChronic Hepatitis C Infection / End-Stage Renal Disease (ESRD)1
4Active Not RecruitingTreatmentChronic Hepatitis C Infection / Liver Cirrhosis1
4Active Not RecruitingTreatmentLiver Diseases1
4CompletedTreatmentChronic Hepatitis C Infection3
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
4CompletedTreatmentHepatitis C Infection / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHepatitis C Virus Infection1
4CompletedTreatmentHepatitis C Virus Infection, Response to Therapy of / Human Immunodeficiency Virus (HIV)1
4CompletedTreatmentHepatitis C, Chronic1
4CompletedTreatmentPT-NANBH1
4Enrolling by InvitationTreatmentHepatitis C, Chronic1
4Not Yet RecruitingHealth Services ResearchHepatitis C, Chronic / Opioid-use Disorder1
4Not Yet RecruitingPreventionChronic Hepatitis C Infection / End Stage Heart Disease1
4Not Yet RecruitingPreventionChronic Hepatitis C Infection / End Stage Liver Diseases1
4Not Yet RecruitingTreatmentChronic Hepatitis C Infection / Hepatitis C, Chronic / Opiate Dependence1
4Not Yet RecruitingTreatmentHepatitis C, Chronic / Lung Transplant1
4RecruitingTreatmentAwaiting Organ Transplant / Chronic Hepatitis C Infection1
4RecruitingTreatmentChronic Hepatitis C Infection4
4RecruitingTreatmentChronic Hepatitis C Infection / HCV1
4RecruitingTreatmentChronic Hepatitis C Infection / HIV Disease / Liver Cirrhosis1
4RecruitingTreatmentChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV)1
4RecruitingTreatmentChronic Hepatitis C Infection / Thalassaemic disorders1
4RecruitingTreatmentChronic Hepatitis C Virus (HCV) Infection3
4RecruitingTreatmentChronic Renal Failure (CRF) / Hepatitis C, Chronic1
4RecruitingTreatmentGenotype 1 Hepatitis C Virus1
4RecruitingTreatmentHCV Coinfection / HIV Disease / Liver Diseases1
4RecruitingTreatmentHeart Failure, Unspecified / Hepatitis C, Chronic / Lung Diseases, Interstitial / Pulmonary Disease, Chronic Obstructive1
4RecruitingTreatmentHematopoietic Stem Cell Transplantation (HSCT)1
4RecruitingTreatmentHepatitis C, Chronic1
4WithdrawnTreatmentHCV1
4WithdrawnTreatmentHepatitis C, Chronic / HIV CDC Category A11
4WithdrawnTreatmentPT-NANBH1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Infection1
Not AvailableActive Not RecruitingNot AvailableChronic Hepatitis C Virus (HCV) Infection / Liver Cirrhosis1
Not AvailableActive Not RecruitingNot AvailableHepatitis C Virus Infection1
Not AvailableApproved for MarketingNot AvailablePost-transplant Hepatitis C1
Not AvailableCompletedNot AvailableChronic Hepatitis C (Disorder)1
Not AvailableCompletedNot AvailableChronic Hepatitis C Infection1
Not AvailableEnrolling by InvitationNot AvailableChronic Hepatitis C Infection1
Not AvailableEnrolling by InvitationNot AvailableHepatitis C Virus Infection2
Not AvailableNo Longer AvailableNot AvailableChronic Hepatitis C Virus (HCV) Infection2
Not AvailableNot Yet RecruitingNot AvailableChronic Hepatitis C Infection3
Not AvailableNot Yet RecruitingTreatmentCardiac Transplant / Chronic Hepatitis C Infection1
Not AvailableNot Yet RecruitingTreatmentChronic Hepatitis C Infection1
Not AvailableRecruitingNot AvailableChronic Hepatitis C Infection2
Not AvailableRecruitingNot AvailableHCV Infections1
Not AvailableRecruitingNot AvailableHepatitis C Virus (HCV)3
Not AvailableRecruitingNot AvailableHepatitis C, Chronic / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingBasic ScienceInsulin Resistance1
Not AvailableRecruitingScreeningHepatitis C, Chronic1
Not AvailableRecruitingTreatmentChronic Hepatitis C Infection / Chronic Kidney Disease (CKD)1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral
Tablet, film coatedOral
TabletOral400 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral400 mg
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8841278 No2010-05-122030-05-12Us
US7964580 No2009-03-262029-03-26Us
US8334270 No2008-03-212028-03-21Us
US8822430 No2010-05-122030-05-12Us
US8633309 No2009-03-262029-03-26Us
US8273341 No2010-05-122030-05-12Us
US8618076 No2010-12-112030-12-11Us
US8735372 No2008-03-212028-03-21Us
US8580765 No2008-03-212028-03-21Us
US8889159 No2009-03-262029-03-26Us
US9085573 No2008-03-212028-03-21Us
US9284342 No2010-09-132030-09-13Us
US8088368 No2010-05-122030-05-12Us
US9393256 No2012-09-142032-09-14Us
US9511056 No2010-05-122030-05-12Us
US9549941 No2009-03-262029-03-26Us
US8940718 No2012-11-162032-11-16Us
US8575135 No2012-11-162032-11-16Us
US8921341 No2012-11-162032-11-16Us
US9585906 No2008-03-212028-03-21Us
US9296782 No2014-07-172034-07-17Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP1.62FDA Label
pKa9.3FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.824 mg/mLALOGPS
logP1.63ALOGPS
logS-2.8ALOGPS
Predicted ADMET featuresNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassPyrimidine 2'-deoxyribonucleosides
Direct ParentPyrimidine 2'-deoxyribonucleosides
Alternative ParentsAlpha amino acid esters / Alanine and derivatives / Phosphoric diester monoamides / Phenoxy compounds / Pyrimidones / Hydropyrimidines / Organic phosphoramides / Vinylogous amides / Tetrahydrofurans / Heteroaromatic compounds
SubstituentsPyrimidine 2'-deoxyribonucleoside / Alpha-amino acid ester / Alanine or derivatives / Alpha-amino acid or derivatives / Phenoxy compound / Phosphoric diester monoamide / Pyrimidone / Monocyclic benzene moiety / Benzenoid / Hydropyrimidine
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorsorganofluorine compound, ring assembly, L-alanyl ester, phosphoramidate ester, nucleotide conjugate (CHEBI:85083 )

Targets

Kind
Protein
Organism
Hepatitis C virus
Pharmacological action
yes
Actions
inhibitor
General Function:
Rna-directed rna polymerase activity
Specific Function:
Not Available
Gene Name:
NS5b
Uniprot ID:
O39930
Uniprot Name:
RNA-dependent RNA-polymerase
Molecular Weight:
65753.05 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]

Enzymes

Kind
Protein
Organism
Pharmacological action
unknown
Actions
substrate
General Function:
Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
Specific Function:
Carboxypeptidase activity
Gene Name:
CTSA
Uniprot ID:
P10619
Uniprot Name:
Lysosomal protective protein
Molecular Weight:
54465.655 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Carboxylic ester hydrolase activity
Specific Function:
Not Available
Gene Name:
CES1A1a
Uniprot ID:
Q6LAP9
Uniprot Name:
Carboxylesterase
Molecular Weight:
1908.25 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein kinase c binding
Specific Function:
Hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, including adenosine 5'monophosphoramidate (AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysy...
Gene Name:
HINT1
Uniprot ID:
P49773
Uniprot Name:
Histidine triad nucleotide-binding protein 1
Molecular Weight:
13801.815 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Uridylate kinase activity
Specific Function:
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.
Gene Name:
CMPK1
Uniprot ID:
P30085
Uniprot Name:
UMP-CMP kinase
Molecular Weight:
22222.175 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Ribosomal small subunit binding
Specific Function:
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities....
Gene Name:
NME1
Uniprot ID:
P15531
Uniprot Name:
Nucleoside diphosphate kinase A
Molecular Weight:
17148.635 Da
References
  1. Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [PubMed:20801890 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Uniprot Name:
Multidrug resistance protein 1
Molecular Weight:
141477.255 Da
References
  1. Tischer S, Fontana RJ: Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting. J Hepatol. 2014 Apr;60(4):872-84. doi: 10.1016/j.jhep.2013.11.013. Epub 2013 Nov 23. [PubMed:24280292 ]
  2. Burgess S, Partovi N, Yoshida EM, Erb SR, Azalgara VM, Hussaini T: Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients. Ann Pharmacother. 2015 Jun;49(6):674-87. doi: 10.1177/1060028015576180. Epub 2015 Mar 13. [PubMed:25770114 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Uniprot Name:
ATP-binding cassette sub-family G member 2
Molecular Weight:
72313.47 Da
Drug created on January 01, 2014 21:48 / Updated on September 01, 2017 12:00