NEVIRAPINE

First approved in 1996

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H14N4O
Molecular Weight	266.2979
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=NC2=C1NC(=O)C3=C(N=CC=C3)N2C4CC4

InChI

InChIKey=NQDJXKOVJZTUJA-UHFFFAOYSA-N

InChI=1S/C15H14N4O/c1-9-6-8-17-14-12(9)18-15(20)11-3-2-7-16-13(11)19(14)10-4-5-10/h2-3,6-8,10H,4-5H2,1H3,(H,18,20)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00238
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/nevirapine.html

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (nNRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). HIV-2 RT and eukaryotic DNA polymerases (such as human DNA polymerases alpha, beta, or sigma) are not inhibited by nevirapine. Nevirapine is, in general, only prescribed after the immune system has declined and infections have become evident. It is always taken with at least one other HIV medication such as Retrovir or Videx. The virus can develop resistance to nevirapine if the drug is taken alone, although even if used properly, nevirapine is effective for only a limited time. Nevirapine binds directly to reverse transcriptase (RT) and blocks the RNA-dependent and DNA-dependent DNA polymerase activities by causing a disruption of the enzyme's catalytic site. The activity of nevirapine does not compete with template or nucleoside triphosphates. Nevirapine is used for use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
BXPC-3 2 Target ID: CHEMBL614530 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26086472	Inhibitor 8297	239.0 µM [EC50]
Human immunodeficiency virus 1 33 Target ID: CHEMBL378 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25240095	Inhibitor 8297	0.31 nM [EC50]
Human immunodeficiency virus type 1 reverse transcriptase 67 Target ID: CHEMBL247 Sources: http://www.drugbank.ca/drugs/DB00238	Inhibitor 8297	250.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020933s022,020636s032lbl.pdf	Primary		Approved 8429	Viramune Approved Use VIRAMUNE is an NNRTI indicated for combination antiretroviral treatment of HIV-1 infection Launch Date 1995

C_max

Value	Dose	Co-administered	Analyte	Population
2060 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		NEVIRAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
82000 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NEVIRAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
96700 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg 1 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	NEVIRAPINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
161000 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	NEVIRAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
45 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		NEVIRAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/201152s013lbl.pdf	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:		NEVIRAPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg single, oral Overdose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17605042	unhealthy, 8-days-old n = 1 Health Status: unhealthy Age Group: 8-days-old Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17605042	Other AEs: Neutropenia, Hyperlactatemia... Other AEs: Neutropenia (mild) Hyperlactatemia Sources: https://pubmed.ncbi.nlm.nih.gov/17605042
200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56	unhealthy, >18 years n = 506 Health Status: unhealthy Age Group: >18 years Sex: M+F Population Size: 506 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56	Disc. AE: Rash, Stevens-Johnson syndrome... AEs leading to discontinuation/dose reduction: Rash (2%) Stevens-Johnson syndrome (1%) Transaminases increased (1%) ALT increased (1%) GGT increased (<1%) AST increased (<1%) Hepatic enzyme increased (<1%) Hepatitis (1%) Hepatotoxicity (1%) Hepatitis acute (<1%) Hepatitis toxic (<1%) Nausea (1%) Malaise (1%) Pyrexia (1%) Fatigue (1%) Vascular disorders (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56
400 mg 1 times / day steady, oral Recommended Dose: 400 mg, 1 times / day Route: oral Route: steady Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56	unhealthy, >18 years n = 505 Health Status: unhealthy Age Group: >18 years Sex: M+F Population Size: 505 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56	Disc. AE: Rash, Drug rash with eosinophilia and systemic symptoms... AEs leading to discontinuation/dose reduction: Rash (2%) Drug rash with eosinophilia and systemic symptoms (<1%) Transaminases increased (1%) ALT increased (<1%) GGT increased (<1%) AST increased (<1%) Hepatic enzyme increased (<1%) Hepatitis (1%) Hepatotoxicity (<1%) Hepatitis acute (<1%) Hepatitis toxic (<1%) Nausea (<1%) Malaise (<1%) Pyrexia (<1%) Fatigue (<1%) Vascular disorders (<1%) Musculoskeletal and connective tissue disorders (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/201152Orig1s000MedR.pdf Page: p. 56
800 mg 1 times / day multiple, oral Overdose Dose: 800 mg, 1 times / day Route: oral Route: multiple Dose: 800 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf	Disc. AE: Hepatotoxicity, Reaction skin... AEs leading to discontinuation/dose reduction: Hepatotoxicity (grade 5) Reaction skin (severe) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020636s050,020933s040lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63613	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63613
ChemicalBook	CB9743074	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9743074
MolPort	MolPort-002-507-817	https://www.molport.com/shop/molecule-link/MolPort-002-507-817
MolPort	MolPort-046-594-170	https://www.molport.com/shop/molecule-link/MolPort-046-594-170
Selleck Chemicals	Nevirapine(Viramune)	http://www.selleckchem.com/products/Nevirapine(Viramune).html
ZINC	ZINC000000004778	http://zinc15.docking.org/substances/ZINC000000004778
eMolecules	766252	https://www.emolecules.com/cgi-bin/more?vid=766252

PubMed

Title	Date	PubMed
Sensitivity and resistance to (+)-calanolide A of wild-type and mutated forms of HIV-1 reverse transcriptase.	1999	10723499
Synthesis and anti-HIV activity of 1,1,3-trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazines (TTDs): a new family of HIV-1 specific non-nucleoside reverse transcriptase inhibitors.	1999 Dec	10658585
Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1.	1999 Dec	10582878
N'-[2-(2-thiophene)ethyl]-N'-[2-(5-bromopyridyl)] thiourea as a potent inhibitor of NNI-resistant and multidrug-resistant human immunodeficiency virus-1.	1999 Dec 20	10617082
Structure-based design of non-nucleoside reverse transcriptase inhibitors of drug-resistant human immunodeficiency virus.	1999 Sep	10574178
Long-term exposure of HIV type 1-infected cell cultures to combinations of the novel quinoxaline GW420867X with lamivudine, abacavir, and a variety of nonnucleoside reverse transcriptase inhibitors.	2000 Apr 10	10777142
Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy.	2000 Dec 15	11141242
Human immunodeficiency virus type 1 reverse transcriptase dimer destabilization by 1-[Spiro[4"-amino-2",2" -dioxo-1",2" -oxathiole-5",3'-[2', 5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]]]-3-ethylthy mine.	2000 Feb 15	10684624
1-[2-(Diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole: a potent lead for the design of novel NNRTIs.	2000 Feb 7	10698447
Novel 2,2-dioxide-4,4-disubstituted-1,3-H-2,1,3-benzothiadiazines as non-nucleoside reverse transcriptase inhibitors.	2000 Jan 17	10673109
Drug resistance and drug combination features of the human immunodeficiency virus inhibitor, BCH-10652 [(+/-)-2'-deoxy-3'-oxa-4'-thiocytidine, dOTC].	2000 Jul	10950391
Non-nucleoside HIV-1 reverse transcriptase inhibitors: synthesis and biological evaluation of novel quinoxalinylethylpyridylthioureas as potent antiviral agents.	2000 Mar	10819438
[Methadone withdrawal syndrome induced by nevirapine].	2000 Mar 18	10786356
Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives.	2000 Mar 9	10715167
Mutational analysis of trp-229 of human immunodeficiency virus type 1 reverse transcriptase (RT) identifies this amino acid residue as a prime target for the rational design of new non-nucleoside RT inhibitors.	2000 May	10779379
Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine.	2000 May	10770740
Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.	2000 May 4	10794705
Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors.	2000 Oct 19	11052800
Computer-assisted design, synthesis and biological evaluation of novel pyrrolyl heteroaryl sulfones targeted at HIV-1 reverse transcriptase as non-nucleoside inhibitors.	2000 Sep	11026542
The tolerability of efavirenz after nevirapine-related adverse events.	2000 Sep	11017835
Stereochemistry of halopyridyl and thiazolyl thiourea compounds is a major determinant of their potency as nonnucleoside inhibitors of HIV-1 reverse transcriptase.	2000 Sep 18	10999473
The emerging roles of non-nucleoside reverse transcriptase inhibitors in antiretroviral therapy.	2001	11217868
Rwanda to receive cheaper anti-HIV drugs for chronic treatment and free viramune to prevent viral transmission from mother to child.	2001 Apr	11436238
Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles.	2001 Apr	11264389
Resolution of chronic parvovirus b19-induced anemia, by use of highly active antiretroviral therapy, in a patient with acquired immunodeficiency syndrome.	2001 Apr 1	11264051
Long-term safety and efficacy of nevirapine, stavudine and lamivudine in a real-world setting.	2001 Apr 13	11371699
Determination of serum levels of thirteen human immunodeficiency virus-suppressing drugs by high-performance liquid chromatography.	2001 Apr 13	11355843
[Results of the AIDS-In-Europe Study. Non-nucleoside reverse transcriptase inhibitor does not equal non-nucleoside reverse transcriptase inhibitor].	2001 Apr 2	11373776
Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine.	2001 Feb	11174414
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.	2001 Feb	11159797
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.	2001 Jan	11225565
Sex differences in nevirapine rash.	2001 Jan	11118391
Estimation of binding affinities for HEPT and nevirapine analogues with HIV-1 reverse transcriptase via Monte Carlo simulations.	2001 Jan 18	11170624
Nevirapine should not be prescribed for needlestick injuries.	2001 Jan 20	11159560
From the Centers for Disease Control and Prevention. Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures--worldwide, 1997-2000.	2001 Jan 24-31	11263401
Need for increased dose of warfarin in HIV patients taking nevirapine.	2001 Jan 26	11216940
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Distribution of K103N and/or Y181C HIV-1 mutations by exposure to zidovudine and non-nucleoside reverse transcriptase inhibitors.	2001 Jul	11418520
Development of drug resistance in patients receiving combinations of zidovudine, didanosine and nevirapine.	2001 Jul 6	11426071
Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.	2001 Jul 6	11426070
Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.	2001 Jun	11368826
Saliva as an alternative body fluid for therapeutic drug monitoring of the nonnucleoside reverse transcription inhibitor nevirapine.	2001 Jun	11360034
The effect of nevirapine in combination with nelfinavir in heavily pretreated HIV-1-infected patients: a prospective, open-label, controlled, randomized study.	2001 Jun 1	11404533
Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377).	2001 Jun 15	11372025
Pharmacokinetics of ritonavir and nevirapine in peritoneal dialysis.	2001 Mar	11239054
International perspectives on antiretroviral resistance. Nonnucleoside reverse transcriptase inhibitor resistance.	2001 Mar 1	11264999
Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir-experienced subjects: AIDS Clinical Trials Group protocol 373.	2001 Mar 1	11181147
[Cutaneous adverse events related to simultaneous nevirapine treatment and pneumococcal vaccination in HIV-infected patients].	2001 Mar 31	11333714
An in vivo model for HIV resistance development.	2001 May 1	11375059
Mismatched double-stranded RNA (polyI-polyC(12)U) is synergistic with multiple anti-HIV drugs and is active against drug-sensitive and drug-resistant HIV-1 in vitro.	2001 Sep	11448730

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose for Nevirapine is one 200 mg tablet daily for the first 14 days, followed by one 200 mg tablet twice daily, in combination with other antiretroviral agents.

Route of Administration: Oral

In Vitro Use Guide

The IC50 value for inhibition by nevirapine against immunodeficiency virus type 1 (HIV) nucleoside reverse transcriptase (RT) in removal assay was 3 uM

Name

Type

Language

NEVIRAPINE

Official Name

English

NEVIRAPINE ANHYDROUS [USP-RS]

Common Name

English

VIRAMUNE

Brand Name

English

NEVIRAPINE [MI]

Common Name

English

NEVIRAPINE [EP MONOGRAPH]

Common Name

English

NEVIRAPINE TEVA

Brand Name

English

NEVIRAPINUM ANHYDROUS [WHO-IP LATIN]

Common Name

English

NSC-641530

Code

English

NEVIRAPINE [MART.]

Common Name

English

nevirapine [INN]

Common Name

English

Nevirapine [WHO-DD]

Common Name

English

NEVIRAPINE ANHYDROUS [WHO-IP]

Common Name

English

NEVIRAPINE, ANHYDROUS

Common Name

English

BIRG-0587

Code

English

NEVIRAPINE [EMA EPAR]

Common Name

English

NEVIRAPINE [VANDF]

Common Name

English

NEVIRAPINE [USP IMPURITY]

Common Name

English

BIRG0587

Code

English

NEVIRAPINE [JAN]

Common Name

English

11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO(3,2-B:2',3'-E)(1,4)DIAZEPIN-6-ONE

Systematic Name

English

NEVIRAPINE [USP MONOGRAPH]

Common Name

English

6H-DIPYRIDO(3,2-B:2',3'-E)(1,4)DIAZEPIN-6-ONE, 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-

Systematic Name

English

NEVIRAPINE [HSDB]

Common Name

English

NEVIRAPINE [USAN]

Common Name

English

NEVIRAPINE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

NEVIRAPINE TEVA (AUTHORIZED: HIV INFECTIONS)