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

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H46N5O7S2.Na
Molecular Weight 771.921
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SIMEPREVIR SODIUM

SMILES

[Na+].[H][C@@]12C[C@]1(NC(=O)[C@]3([H])C[C@H](C[C@@]3([H])C(=O)N(C)CCCCC=C2)OC4=CC(=NC5=C4C=CC(OC)=C5C)C6=NC(=CS6)C(C)C)C(=O)[N-]S(=O)(=O)C7CC7

InChI

InChIKey=LLXQGDWGCCKOQP-MVZLLIIPSA-M
InChI=1S/C38H47N5O7S2.Na/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,(H2,41,42,44,46);/q;+1/p-1/b10-8-;/t23-,24-,27-,28-,38-;/m1./s1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C38H46N5O7S2
Molecular Weight 748.931
Charge -1
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Simeprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor approved for the treatment of Chronic Hepatitis C (genotype 1 and 4). Inhibiting NS3/4A, simeprevir blocks viral replication. In in vitro assays simeprevir was potent against HCV genotype 1a and 1b. Simeprevir must not be administered as monotherapy and should only be prescribed with both peginterferon alfa and ribavirin.

CNS Activity

Curator's Comment: There was minimal penetration of the blood-brain barrier.

Originator

Curator's Comment: Patent application WO2008092954A2 is a formulation patent, originally filed by Tibotec Pharmaceuticals, now part of Janssen Pharmaceuticals. The application claims a crystalline form of a substituted macro cyclic compound, preferably a variant of simeprevir, useful for the treatment of HCV infections.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.36 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
OLYSIO

Approved Use

Indicated for the treatment of chronic hepatitis C (CHC) genotype 1 or 4 infection as a component of a combination antiviral treatment regimen. OLYSIO monotherapy is not recommended.

Launch Date

1.38507846E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
11470 ng/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2304 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
4067 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6172 ng/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
206000 ng × h/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
24630 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
56430 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
79710 ng × h/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
41.32 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
16.04 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SIMEPREVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Other AEs: Headache, Diarrhoea...
Other AEs:
Headache (13.5%)
Diarrhoea (10.8%)
Fatigue (10.8%)
Pruritus (10.8%)
Anorexia (8.1%)
Back pain (8.1%)
Myalgia (8.1%)
Sources:
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
healthy, 24.0 years(range: 20-44 years)
n = 9
Health Status: healthy
Age Group: 24.0 years(range: 20-44 years)
Sex: M+F
Population Size: 9
Sources:
600 mg single, oral
Highest studied dose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
healthy, 38.0 years (range: 23-55 years)
n = 9
Health Status: healthy
Age Group: 38.0 years (range: 23-55 years)
Sex: M
Population Size: 9
Sources:
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
healthy, 38.0 years (range: 25-54 years)
n = 9
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Population Size: 9
Sources:
Other AEs: Photosensitivity reaction, Diarrhea...
Other AEs:
Photosensitivity reaction (3 patients)
Diarrhea (2 patients)
Abdominal pain upper (2 patients)
Sources:
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Disc. AE: Pruritus, Psoriasis...
AEs leading to
discontinuation/dose reduction:
Pruritus (<1%)
Psoriasis (<1%)
Rash (1%)
Rash erythematous (<1%)
Skin burning sensation (<1%)
Aggression (<1%)
Blood bilirubin increased (<1%)
Major depression (<1%)
Stomatitis (<1%)
Headache (<1%)
Pain (<1%)
Sources: Page: p. 57
AEs

AEs

AESignificanceDosePopulation
Diarrhoea 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Fatigue 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Pruritus 10.8%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Headache 13.5%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Anorexia 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Back pain 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Myalgia 8.1%
200 mg 1 times / day multiple, oral
Dose: 200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 200 mg, 1 times / day
Sources:
unhealthy, 18–70 years
n = 37
Health Status: unhealthy
Condition: HCV genotypes 2–6 infection
Age Group: 18–70 years
Sex: M+F
Population Size: 37
Sources:
Abdominal pain upper 2 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
healthy, 38.0 years (range: 25-54 years)
n = 9
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Population Size: 9
Sources:
Diarrhea 2 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
healthy, 38.0 years (range: 25-54 years)
n = 9
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Population Size: 9
Sources:
Photosensitivity reaction 3 patients
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
healthy, 38.0 years (range: 25-54 years)
n = 9
Health Status: healthy
Age Group: 38.0 years (range: 25-54 years)
Sex: M+F
Population Size: 9
Sources:
Rash 1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Aggression <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Blood bilirubin increased <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Headache <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Major depression <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Pain <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Pruritus <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Psoriasis <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Rash erythematous <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Skin burning sensation <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
Stomatitis <1%
Disc. AE
150 mg 1 times / day steady, oral
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: steady
Dose: 150 mg, 1 times / day
Sources: Page: p. 57
unhealthy, 49 years (range: 18-73 years)
n = 781
Health Status: unhealthy
Age Group: 49 years (range: 18-73 years)
Sex: M+F
Population Size: 781
Sources: Page: p. 57
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [IC50 42.9 uM]
moderate [IC50 49.1 uM]
moderate [IC50 59.7 uM]
no
no
no
no
no
weak [IC50 131 uM]
likely (co-administration study)
Comment: Concomitant use of OLYSIO with these antiarrhythmics may result in mild increases in concentrations of these antiarrhythmics due to intestinal CYP3A4 inhibition by simeprevir
Page: 37.0
weak [IC50 86.1 uM]
yes [IC50 1.67 uM]
yes [IC50 25 uM]
yes (co-administration study)
Comment: Concomitant use of OLYSIO with rosuvastatin resulted in increased plasma concentrations of rosuvastatin due to inhibition of OATP1B1 by simeprevir
Page: 38.0
yes [IC50 3.47 uM]
yes [IC50 6.4 uM]
yes [IC50 85.9 uM]
yes (co-administration study)
Comment: Concomitant use of OLYSIO with digoxin resulted in increased concentrations of digoxin due to inhibition of P-gp by simeprevir
Page: 38.0
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes
yes
yes
yes
yes
likely (co-administration study)
Comment: Concomitant use of OLYSIO with carbamazepine, oxcarbazepine, phenobarbital or phenytoin may result in significantly decreased plasma concentrations of simeprevir due to strong CYP3A induction by these anticonvulsants; Concomitant use of OLYSIO with clarithromycin or telithromycin may result in increased plasma concentrations of simeprevir due to CYP3A inhibition by these antibiotics
Page: 37.0
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.
2009 Apr
Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.
2015 Aug 5
Patents

Sample Use Guides

The recommended dose is one 150 mg capsule taken once daily with food. OLYSIO should be administered with both peginterferon alfa and ribavirin. The recommended treatment duration of OLYSIO with peginterferon alfa and ribavirin is 12 weeks, followed by either 12 or 36 additional weeks of peginterferon alfa and ribavirin depending on prior response status.
Route of Administration: Oral
The median simeprevir EC50 and EC90 values against a HCV genotype 1b replicon were 9.4 nM (7.05 ng/mL) and 19 nM (14.25 ng/mL), respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:31:27 UTC 2023
Edited
by admin
on Sat Dec 16 09:31:27 UTC 2023
Record UNII
16U7H60184
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SIMEPREVIR SODIUM
WHO-DD  
Common Name English
TMC-435 SODIUM SALT
Code English
OLYSIO
Brand Name English
Simeprevir sodium [WHO-DD]
Common Name English
SIMEPREVIR SODIUM [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS OLYSIO (AUTHORIZED: HEPATITS C, CHRONIC)
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
Code System Code Type Description
PUBCHEM
46866715
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
EVMPD
SUB169848
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
FDA UNII
16U7H60184
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
DRUG BANK
DBSALT001485
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
SMS_ID
100000159513
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
RXCUI
1484518
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY RxNorm
ChEMBL
CHEMBL501849
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
PRIMARY
CAS
1241946-89-3
Created by admin on Sat Dec 16 09:31:27 UTC 2023 , Edited by admin on Sat Dec 16 09:31:27 UTC 2023
NON-SPECIFIC STOICHIOMETRY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY