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Identification
NameSimeprevir
Accession NumberDB06290
TypeSmall Molecule
GroupsApproved
Description

Simeprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated in patient’s with HCV genotype 1 for the treatment of chronic hepatitis as a combination therapy, which includes peginterferon alfa and ribavirin. It was approved by the FDA in November 2014 and is marketed under the brand name Olysio.

Structure
Thumb
Synonyms
SynonymLanguageCode
TMC435EnglishInvestigational name
TMC435350EnglishInvestigational name
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Olysiocapsule150 mgoralJanssen Products LP2013-11-22Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Galexoscapsule150 mgoralJanssen IncNot AvailableNot AvailableCanada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number923604-59-5
WeightAverage: 749.939
Monoisotopic: 749.291690263
Chemical FormulaC38H47N5O7S2
InChI KeyJTZZSQYMACOLNN-RCSAWCOCNA-N
InChI
InChI=1/C38H47N5O7S2/c1-21(2)30-20-51-35(40-30)29-18-32(26-13-14-31(49-5)22(3)33(26)39-29)50-24-16-27-28(17-24)36(45)43(4)15-9-7-6-8-10-23-19-38(23,41-34(27)44)37(46)42-52(47,48)25-11-12-25/h8,10,13-14,18,20-21,23-25,27-28H,6-7,9,11-12,15-17,19H2,1-5H3,(H,41,44)(H,42,46)/b10-8-/t23-,24?,27+,28+,38+/s2
IUPAC Name
(1R,4R,6R,7Z,15R)-N-(cyclopropanesulfonyl)-17-({7-methoxy-8-methyl-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.0⁴,⁶]octadec-7-ene-4-carboxamide
SMILES
[H][C@]12C[C@]1(NC(=O)[C@]1([H])CC(C[C@@]1([H])C(=O)N(C)CCCC\C=C/2)OC1=CC(=NC2=C(C)C(OC)=CC=C12)C1=NC(=CS1)C(C)C)C(=O)NS(=O)(=O)C1CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as macrolactams. These are cyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. They are nitrogen analogues (the a nitrogen atom replacing the o atom of the cyclic carboxylic acid group ) of the naturally occurring macrolides.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassMacrolactams
Sub ClassNot Available
Direct ParentMacrolactams
Alternative Parents
Substituents
  • Macrolactam
  • Alpha-amino acid amide
  • Quinoline
  • Anisole
  • Alkyl aryl ether
  • 2,4-disubstituted 1,3-thiazole
  • Benzenoid
  • Pyridine
  • Cyclopropanecarboxylic acid or derivatives
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Thiazole
  • Tertiary carboxylic acid amide
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Azole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Lactam
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationSimeprevir is indicated in patient's with hepatitis C virus (HCV) genotype 1 for the treatment of chronic hepatitis as a combination therapy, which includes peginterferon alfa and ribavirin.
PharmacodynamicsSimeprevir is a protease inhibitor for HCV NS3/4A protease, which is required for replication of the virus.
Mechanism of actionSimeprevir functions as a direct-acting antiviral agent because it inhibits hepatitis C viral replication by binding to and inhibiting the protease, hepatitis C virus (HCV) NS3/4A.
AbsorptionAfter oral administration, simeprevir reaches its maximum plasma concentrations in 4-6 hours.
Volume of distribution

The volume of distribution for simeprevir has yet to be determined.

Protein bindingSimeprevir is >99.9% plasma protein bound with albumin being the main plasma protein.
Metabolism

Simeprevir is mainly metabolized by CYP3A enzymes.

Route of eliminationSimeprevir is mainly eliminated through biliary excretion (91%). Elimination through the urine is insignificant (1%).
Half lifeThe half-life of simeprevir is about 41 hours in HCV patients.
Clearance

The clearance of simeprevir has yet to be determined.

ToxicityIn patients receiving the combination therapy, the most common adverse reactions were nausea, pruritus, photosensitivity, and rash.
Affected organisms
  • Hepatitis C virus, RSV and other RNA/DNA viruses
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 2C19 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Capsuleoral150 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00303 mg/mLALOGPS
logP4.69ALOGPS
logP4.56ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)3.77ChemAxon
pKa (Strongest Basic)1.62ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area156.89 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity206.95 m3·mol-1ChemAxon
Polarizability79.98 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
References
Synthesis Reference

Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24.

General Reference
  1. Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24. Pubmed
  2. FDA label.
External Links
ATC CodesJ05AE14
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (85.3 KB)
Interactions
Drug Interactions
Drug
AbacavirMay decrease the serum concentration of Abacavir.
AbirateroneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
ado-trastuzumab emtansineMay increase the serum concentration of CYP3A4 Substrates.
AfatinibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib.
AlfentanilMay increase the serum concentration of CYP3A4 Substrates.
AlfuzosinMay increase the serum concentration of Alfuzosin.
AlprazolamMay increase the serum concentration of ALPRAZolam.
AminophyllineMay decrease the serum concentration of Theophylline Derivatives. Exceptions: Fosamprenavir.
AmiodaroneMay increase the serum concentration of CYP3A4 Substrates.
AmitriptylineMay increase the serum concentration of Tricyclic Antidepressants.
AmlodipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
AmoxapineMay increase the serum concentration of Tricyclic Antidepressants.
ApixabanMay increase the serum concentration of CYP3A4 Substrates.
AprepitantCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
AripiprazoleMay increase the serum concentration of CYP3A4 Substrates.
armodafinilMay increase the serum concentration of CYP3A4 Substrates.
AtazanavirMay increase the serum concentration of other Protease Inhibitors.
AtorvastatinMay increase the serum concentration of AtorvaSTATin.
AvanafilMay increase the serum concentration of CYP3A4 Substrates.
AxitinibMay increase the serum concentration of CYP3A4 Substrates.
BatimastatSimeprevir may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Simeprevir.
BenzphetamineMay increase the serum concentration of CYP3A4 Substrates.
BicalutamideCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
BiotinCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
BisoprololMay increase the serum concentration of CYP3A4 Substrates.
BoceprevirBoceprevir may decrease the serum concentration of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Boceprevir.
BosentanCYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir.
BosutinibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib.
Brentuximab vedotinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.
BromocriptineMay increase the serum concentration of Ergot Derivatives.
BuprenorphineMay increase the serum concentration of CYP3A4 Substrates.
BuspironeMay increase the serum concentration of CYP3A4 Substrates.
CabazitaxelMay increase the serum concentration of CYP3A4 Substrates.
CabozantinibMay increase the serum concentration of CYP3A4 Substrates.
CalcitriolMay increase the serum concentration of CYP3A4 Substrates.
CarbamazepineCarBAMazepine may increase the metabolism of Protease Inhibitors. Protease Inhibitors may decrease the metabolism of CarBAMazepine.
ChlordiazepoxideMay increase the serum concentration of CYP3A4 Substrates.
ChloroquineMay increase the serum concentration of CYP3A4 Substrates.
CilostazolMay increase the serum concentration of CYP3A4 Substrates.
CimetidineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
CinacalcetMay increase the serum concentration of CYP3A4 Substrates.
CisaprideMay increase the serum concentration of Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias.
CitalopramMay increase the serum concentration of CYP3A4 Substrates.
ClarithromycinMay diminish the therapeutic effect of Clarithromycin. Specifically, certain protease inhibitors may decrease formation of the active 14-hydroxy-clarithromycin metabolite, which may negatively impact clarithromycin effectiveness vs. H. influenzae and other non-MAC infections. Clarithromycin may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Clarithromycin. Clarithromycin dose adjustment in renally impaired patients may be needed.
ClidiniumMay increase the serum concentration of CYP3A4 Substrates.
ClomipramineMay increase the serum concentration of Tricyclic Antidepressants.
ClonazepamMay increase the serum concentration of CYP3A4 Substrates.
ClotrimazoleCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
CocaineMay increase the serum concentration of CYP3A4 Substrates.
ColchicineP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased.
ConivaptanCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
CrizotinibCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
CyclophosphamideMay enhance the adverse/toxic effect of Cyclophosphamide. Specifically, the incidences of neutropenia, infection, and mucositis may be increased.
Cyproterone acetateMay increase the serum concentration of CYP3A4 Substrates.
Dabigatran etexilateP-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate.
DabrafenibCYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir.
DantroleneMay increase the serum concentration of CYP3A4 Substrates.
DarifenacinMay increase the serum concentration of CYP3A4 Substrates.
DarunavirMay increase the serum concentration of other Protease Inhibitors.
DasatinibMay increase the serum concentration of CYP3A4 Substrates.
DeferasiroxMay decrease the serum concentration of CYP3A4 Substrates.
DelavirdineDelavirdine may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may decrease the serum concentration of Delavirdine.
DesipramineMay increase the serum concentration of Tricyclic Antidepressants.
DesogestrelMay decrease the serum concentration of Contraceptives (Estrogens).
DiazepamMay increase the serum concentration of CYP3A4 Substrates.
DigoxinMay increase the serum concentration of Digoxin. Increased serum concentrations of digoxin may increase risk of AV nodal blockade.
DihydroergotamineMay increase the serum concentration of Ergot Derivatives.
DiltiazemMay decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased serum concentrations of the calcium channel blocker may increase risk of AV nodal blockade.
DisopyramideMay increase the serum concentration of CYP3A4 Substrates.
DocetaxelMay increase the serum concentration of CYP3A4 Substrates.
DomperidoneMay increase the serum concentration of CYP3A4 Substrates.
DoxazosinMay increase the serum concentration of CYP3A4 Substrates.
DronedaroneCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
EletriptanMay increase the serum concentration of CYP3A4 Substrates.
EliglustatMay increase the serum concentration of CYP3A4 Substrates.
EltrombopagMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
EnfuvirtideEnfuvirtide may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Enfuvirtide.
EnzalutamideCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
EplerenoneMay increase the serum concentration of CYP3A4 Substrates.
Ergoloid mesylateMay increase the serum concentration of Ergot Derivatives.
ErgonovineMay increase the serum concentration of Ergot Derivatives.
ErgotamineMay increase the serum concentration of Ergot Derivatives.
ErlotinibMay increase the serum concentration of CYP3A4 Substrates.
EscitalopramEscitalopram may decrease the serum concentration of Simeprevir.
EszopicloneMay increase the serum concentration of CYP3A4 Substrates.
Ethinyl EstradiolMay decrease the serum concentration of Contraceptives (Estrogens).
EthosuximideMay increase the serum concentration of CYP3A4 Substrates.
EthynodiolMay decrease the serum concentration of Contraceptives (Estrogens).
EtoposideMay increase the serum concentration of CYP3A4 Substrates.
EtravirineEtravirine may increase the serum concentration of Protease Inhibitors. This effect is anticipated with nelfinavir. Protease Inhibitors may decrease the serum concentration of Etravirine. This effect is anticipated with darunavir, saquinavir, and lopinavir (with low-dose ritonavir).
EverolimusP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.
FelbamateMay increase the serum concentration of CYP3A4 Substrates.
FelodipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
FentanylMay increase the serum concentration of CYP3A4 Substrates.
FesoterodineMay increase the serum concentration of CYP3A4 Substrates.
FluconazoleCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
FlurazepamMay increase the serum concentration of CYP3A4 Substrates.
FlutamideMay increase the serum concentration of CYP3A4 Substrates.
Fluticasone furoateMay increase the serum concentration of CYP3A4 Substrates.
FosamprenavirMay increase the serum concentration of other Protease Inhibitors.
FosaprepitantCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
FosphenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
GefitinibMay increase the serum concentration of CYP3A4 Substrates.
GuanfacineMay increase the serum concentration of CYP3A4 Substrates.
HaloperidolMay increase the serum concentration of CYP3A4 Substrates.
HydrocodoneMay increase the serum concentration of CYP3A4 Substrates.
ImipramineMay increase the serum concentration of Tricyclic Antidepressants.
IndinavirMay increase the serum concentration of other Protease Inhibitors.
IrinotecanMay increase the serum concentration of CYP3A4 Substrates.
IsavuconazoniumCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
IsoflurophateSimeprevir may increase the serum concentration of Protease Inhibitors. Protease Inhibitors may increase the serum concentration of Simeprevir.
Isosorbide DinitrateMay increase the serum concentration of CYP3A4 Substrates.
Isosorbide MononitrateMay increase the serum concentration of CYP3A4 Substrates.
IsradipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
ItraconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
IvacaftorMay increase the serum concentration of CYP3A4 Substrates.
IxabepiloneMay increase the serum concentration of CYP3A4 Substrates.
KetamineMay increase the serum concentration of CYP3A4 Substrates.
LapatinibMay increase the serum concentration of CYP3A4 Substrates.
LedipasvirMay increase the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Ledipasvir.
LevomilnacipranMay increase the serum concentration of CYP3A4 Substrates.
LomitapideCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
LopinavirMay increase the serum concentration of other Protease Inhibitors.
LovastatinMay increase the serum concentration of Lovastatin.
LULICONAZOLEMay increase the serum concentration of CYP3A4 Substrates.
LurasidoneMay increase the serum concentration of CYP3A4 Substrates.
MACITENTANMay increase the serum concentration of CYP3A4 Substrates.
MaravirocMay increase the serum concentration of CYP3A4 Substrates.
MefloquineMay increase the serum concentration of CYP3A4 Substrates.
MestranolMay decrease the serum concentration of Contraceptives (Estrogens).
MethadoneMay increase the serum concentration of CYP3A4 Substrates.
MethylergometrineMay increase the serum concentration of Ergot Derivatives.
MidazolamMay increase the serum concentration of Midazolam.
MifepristoneMay increase the serum concentration of CYP3A4 Substrates.
MirtazapineMay increase the serum concentration of CYP3A4 Substrates.
ModafinilCYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir.
NafcillinCYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir.
NateglinideMay increase the serum concentration of CYP3A4 Substrates.
NefazodoneMay increase the serum concentration of Nefazodone.
NelfinavirMay increase the serum concentration of other Protease Inhibitors.
NifedipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
NilotinibCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
NimodipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
NisoldipineMay decrease the metabolism of Calcium Channel Blockers (Dihydropyridine).
NorelgestrominMay decrease the serum concentration of Contraceptives (Estrogens).
NorfloxacinCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
NortriptylineMay increase the serum concentration of Tricyclic Antidepressants.
OxycodoneMay increase the serum concentration of CYP3A4 Substrates.
PanobinostatMay increase the serum concentration of CYP3A4 Substrates.
PazopanibP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.
PethidineMay enhance the adverse/toxic effect of Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine. Concentrations of the toxic Normeperidine metabolite may be increased.
PhenobarbitalCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
PhenytoinCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
PimozideMay increase the serum concentration of Pimozide.
PipotiazineMay increase the serum concentration of CYP3A4 Substrates.
PitavastatinSimeprevir may increase the serum concentration of Pitavastatin.
PomalidomideMay increase the serum concentration of CYP3A4 Substrates.
PorfimerPhotosensitizing Agents may enhance the photosensitizing effect of Porfimer.
PosaconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
PravastatinMay increase the serum concentration of Pravastatin.
PraziquantelMay increase the serum concentration of CYP3A4 Substrates.
PrimidoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
ProtriptylineMay increase the serum concentration of Tricyclic Antidepressants.
prucaloprideP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.
QuetiapineMay increase the serum concentration of CYP3A4 Substrates.
QuinidineMay increase the serum concentration of CYP3A4 Substrates.
QuinineMay increase the serum concentration of CYP3A4 Substrates.
RanolazineMay increase the serum concentration of CYP3A4 Substrates.
RegorafenibMay increase the serum concentration of CYP3A4 Substrates.
RifampicinCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
RifapentineCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
RifaximinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rifaximin.
RilpivirineSimeprevir may increase the serum concentration of Rilpivirine.
RiociguatMay increase the serum concentration of Riociguat.
RitonavirMay increase the serum concentration of other Protease Inhibitors.
RivaroxabanP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rivaroxaban.
RosuvastatinMay increase the serum concentration of Rosuvastatin.
RuxolitinibMay increase the serum concentration of CYP3A4 Substrates.
SalmeterolMay increase the serum concentration of CYP3A4 Substrates.
SaquinavirMay increase the serum concentration of other Protease Inhibitors.
SaxagliptinMay increase the serum concentration of CYP3A4 Substrates.
SildenafilMay increase the serum concentration of Sildenafil.
SilodosinP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.
SiltuximabMay decrease the serum concentration of CYP3A4 Substrates.
SimvastatinMay increase the serum concentration of Simvastatin.
SolifenacinMay increase the serum concentration of CYP3A4 Substrates.
SpiramycinMay increase the serum concentration of CYP3A4 Substrates.
SufentanilMay increase the serum concentration of CYP3A4 Substrates.
SulfisoxazoleErythromycin (Systemic) may increase the serum concentration of Simeprevir.
SunitinibMay increase the serum concentration of CYP3A4 Substrates.
SuvorexantMay increase the serum concentration of CYP3A4 Substrates.
TadalafilMay increase the serum concentration of CYP3A4 Substrates.
TamoxifenMay increase the serum concentration of CYP3A4 Substrates.
TamsulosinMay increase the serum concentration of CYP3A4 Substrates.
TelaprevirCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
TelithromycinCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
TemsirolimusMay enhance the adverse/toxic effect of Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely due to inhibition of CYP-mediated metabolism.
TeniposideMay increase the serum concentration of CYP3A4 Substrates.
TenofovirMay increase the serum concentration of Tenofovir. Tenofovir may decrease the serum concentration of Simeprevir.
TeriflunomideMay increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
TetracyclineCYP3A4 Inhibitors (Moderate) may increase the serum concentration of Simeprevir.
TheophyllineMay decrease the serum concentration of Theophylline Derivatives. Exceptions: Fosamprenavir.
TiagabineMay increase the serum concentration of CYP3A4 Substrates.
TipranavirTipranavir may decrease the serum concentration of Protease Inhibitors. Exceptions: Ritonavir.
TocilizumabMay decrease the serum concentration of CYP3A4 Substrates.
TofacitinibMay increase the serum concentration of CYP3A4 Substrates.
TolterodineMay increase the serum concentration of CYP3A4 Substrates.
TolvaptanMay increase the serum concentration of CYP3A4 Substrates.
TopotecanP-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.
TrabectedinMay increase the serum concentration of CYP3A4 Substrates.
TramadolMay increase the serum concentration of CYP3A4 Substrates.
TriazolamMay increase the serum concentration of Triazolam.
TrimipramineMay increase the serum concentration of CYP3A4 Substrates.
Valproic AcidMay decrease the serum concentration of Valproic Acid and Derivatives.
VardenafilMay increase the serum concentration of CYP3A4 Substrates.
VemurafenibMay increase the serum concentration of CYP3A4 Substrates.
VenlafaxineMay increase the serum concentration of CYP3A4 Substrates.
VerteporfinPhotosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
VinblastineMay increase the serum concentration of CYP3A4 Substrates.
VincristineMay increase the serum concentration of CYP3A4 Substrates.
VinorelbineMay increase the serum concentration of CYP3A4 Substrates.
VoriconazoleCYP3A4 Inhibitors (Strong) may increase the serum concentration of Simeprevir.
ZidovudineMay decrease the serum concentration of Zidovudine.
ZolpidemMay increase the serum concentration of CYP3A4 Substrates.
ZonisamideMay increase the serum concentration of CYP3A4 Substrates.
ZopicloneMay increase the serum concentration of CYP3A4 Substrates.
Food Interactions
  • Simeprevir should be taken with food.

Targets

1. NS3 protease

Kind: protein

Organism: Hepatitis C virus

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
NS3 protease Q91RS4 Details

References:

  1. FDA label.
  2. Raboisson P, de Kock H, Rosenquist A, Nilsson M, Salvador-Oden L, Lin TI, Roue N, Ivanov V, Wahling H, Wickstrom K, Hamelink E, Edlund M, Vrang L, Vendeville S, Van de Vreken W, McGowan D, Tahri A, Hu L, Boutton C, Lenz O, Delouvroy F, Pille G, Surleraux D, Wigerinck P, Samuelsson B, Simmen K: Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350. Bioorg Med Chem Lett. 2008 Sep 1;18(17):4853-8. doi: 10.1016/j.bmcl.2008.07.088. Epub 2008 Jul 24. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: no

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. FDA label.
  2. Lexicomp

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Lexicomp

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Actions: binder

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label.

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: no

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. FDA label.
  2. Lexicomp.

2. Solute carrier organic anion transporter family member 1B1

Kind: protein

Organism: Human

Pharmacological action: no

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

References:

  1. FDA label.
  2. Lexicomp.

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Drug created on March 19, 2008 10:22 / Updated on May 04, 2015 17:01