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

Details

Stereochemistry ACHIRAL
Molecular Formula C22H18N6.ClH
Molecular Weight 402.8802
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of RILPIVIRINE HYDROCHLORIDE

SMILES

Cc1cc(/C(/[H])=C(\[H])/C#N)cc(C)c1N=c2ccnc(Nc3ccc(cc3)C#N)[nH]2.Cl

InChI

InChIKey=KZVVGZKAVZUACK-BJILWQEISA-N
InChI=1S/C22H18N6.ClH/c1-15-12-18(4-3-10-23)13-16(2)21(15)27-20-9-11-25-22(28-20)26-19-7-5-17(14-24)6-8-19;/h3-9,11-13H,1-2H3,(H2,25,26,27,28);1H/b4-3+;

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H18N6
Molecular Weight 366.4193
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/?term=19933797

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients. It is active against wild-type and NNRTI-resistant HIV-1. Rilpivirine is a diarylpyrimidinethat inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β and γ.

CNS Activity

Curator's Comment:: Common side effects may include Central Nervous System (CNS) related side effects including dizziness, difficulty with concentration, sleep disturbances, vivid dreams, agitation, nausea (upset stomach, feeling sick to the stomach), dizziness, sleep disturbances.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Reverse transcriptase/RNaseH (UniProtKB: Q72547)
14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
EDURANT

Approved Use

In combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-naïve patients with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy.

Launch Date

1.30584963E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.14 μg/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
121 ng/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.38 μg × h/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
1792 ng × h/mL
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.3%
25 mg 1 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RILPIVIRINE plasma
Homo sapiens
population: PREGNANT
age: ADULT
sex: FEMALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources: Page: p.62
Disc. AE: Alanine aminotransferase increase, Aspartate aminotransferase increased...
AEs leading to
discontinuation/dose reduction:
Alanine aminotransferase increase
Aspartate aminotransferase increased
Sources: Page: p.62
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources: Page: p.1
Disc. AE: Depressive disorders, Suicide attempt...
AEs leading to
discontinuation/dose reduction:
Depressive disorders (severe, 1%)
Suicide attempt (0.29%)
Sources: Page: p.1
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.3
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources: Page: p.3
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (0.1%)
Sources: Page: p.3
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Disc. AE: Fat redistribution, Immune reconstitution syndrome...
AEs leading to
discontinuation/dose reduction:
Fat redistribution
Immune reconstitution syndrome
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Alanine aminotransferase increase Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources: Page: p.62
Aspartate aminotransferase increased Disc. AE
150 mg 1 times / day multiple, oral
Highest studied dose
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Sources: Page: p.62
unhealthy, 21–66
n = 91
Health Status: unhealthy
Condition: HIV-1 infection
Age Group: 21–66
Sex: M+F
Population Size: 91
Sources: Page: p.62
Suicide attempt 0.29%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources: Page: p.1
Depressive disorders severe, 1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources: Page: p.1
Rash 0.1%
Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.3
unhealthy
n = 686
Health Status: unhealthy
Condition: HIV-1 infection
Population Size: 686
Sources: Page: p.3
Fat redistribution Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
Immune reconstitution syndrome Disc. AE
25 mg 1 times / day multiple, oral
Recommended
Dose: 25 mg, 1 times / day
Route: oral
Route: multiple
Dose: 25 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: HIV-1 infection
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
A series of diaryltriazines and diarylpyrimidines are highly potent nonnucleoside reverse transcriptase inhibitors with possible applications as microbicides.
2004 Oct
Synthesis of novel diarylpyrimidine analogues and their antiviral activity against human immunodeficiency virus type 1.
2005 Mar 24
Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.
2007 May
Rilpivirine: a novel non-nucleoside reverse transcriptase inhibitor.
2009 Jul
TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1.
2010 Feb
Potential of the novel antiretroviral drug rilpivirine to modulate the expression and function of drug transporters and drug-metabolising enzymes in vitro.
2013 May
In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2013 Nov
Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.
2014
In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
2014
Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses.
2014 Feb 1
Patents

Sample Use Guides

25 mg (one 25 mg tablet) taken once daily with a meal, is not recommended for patients less than 12 years of age. With rifabutin co-administration, the Edurant dose should be increased to 50 mg (two tablets of 25 mg each) taken once daily with a meal.
Route of Administration: Oral
TMC278 (rilpivirine) showed subnanomolar 50% effective concentrations (EC50 values) against wild-type HIV-1 group M isolates (0.07 to 1.01 nM) and nanomolar EC50 values against group O isolates (2.88 to 8.45 nM).
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:11:10 UTC 2021
Edited
by admin
on Sat Jun 26 09:11:10 UTC 2021
Record UNII
212WAX8KDD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RILPIVIRINE HYDROCHLORIDE
MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
RILPIVIRINE HCL
Common Name English
BENZONITRILE, 4-((4-((4-((1E)-2-CYANOETHENYL)-2,6-DIMETHYLPHENYL)AMINO)-2-PYRIMIDINYL)AMINO)-, HYDROCHLORIDE (1:1)
Systematic Name English
JULUCA COMPONENT RILPIVIRINE HYDROCHLORIDE
Brand Name English
EVIPLERA COMPONENT RILPIVIRINE HYDROCHLORIDE
Brand Name English
RILPIVIRINE HYDROCHLORIDE [WHO-DD]
Common Name English
RILPIVIRINE HYDROCHLORIDE COMPONENT OF ODEFSEY
Common Name English
RILPIVIRINE HYDROCHLORIDE [USAN]
Common Name English
RILPIVIRINE HYDROCHLORIDE [VANDF]
Common Name English
RILPIVIRINE HYDROCHLORIDE COMPONENT OF JULUCA
Brand Name English
RILPIVIRINE (AS HYDROCHLORIDE)
Common Name English
TMC-278 HYDROCHLORIDE
Code English
TMC278 HYDROCHLORIDE
Code English
RILPIVIRINE HYDROCHLORIDE [JAN]
Common Name English
ODEFSEY COMPONENT RILPIVIRINE HYDROCHLORIDE
Common Name English
RILPIVIRINE HYDROCHLORIDE COMPONENT OF EVIPLERA
Brand Name English
RILPIVIRINE HYDROCHLORIDE [MI]
Common Name English
RILPIVIRINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS EVIPLERA (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
NCI_THESAURUS C97453
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
EMA ASSESSMENT REPORTS EDURANT (AUTHORIZED: HIV INFECTIONS)
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
Code System Code Type Description
FDA UNII
212WAX8KDD
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
EVMPD
SUB31460
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
RXCUI
1102287
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL175691
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
PUBCHEM
11711114
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
EPA CompTox
700361-47-3
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
DRUG BANK
DBSALT000152
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
CAS
700361-47-3
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
MERCK INDEX
M9619
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C152217
Created by admin on Sat Jun 26 09:11:10 UTC 2021 , Edited by admin on Sat Jun 26 09:11:10 UTC 2021
PRIMARY
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