NEVIRAPINE HEMIHYDRATE

First approved in 1996

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C15H14N4O.H2O
Molecular Weight	550.611
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.CC1=CC=NC2=C1NC(=O)C3=C(N=CC=C3)N2C4CC4.CC5=CC=NC6=C5NC(=O)C7=C(N=CC=C7)N6C8CC8

InChI

InChIKey=KMTLSXAXTLQBKJ-UHFFFAOYSA-N

InChI=1S/2C15H14N4O.H2O/c2*1-9-6-8-17-14-12(9)18-15(20)11-3-2-7-16-13(11)19(14)10-4-5-10;/h2*2-3,6-8,10H,4-5H2,1H3,(H,18,20);1H2

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C15H14N4O
Molecular Weight	266.2979
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Effect of nucleoside analogs and non-nucleoside inhibitors of HIV-1 reverse transcriptase on cell-free virions.	1999	10226617
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
5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3, 4-dihydropyrimidin-4(3H)-ones: novel potent and selective dihydro-alkoxy-benzyl-oxopyrimidine derivatives.	1999 Feb 25	10052969
Rational design of N-[2-(2,5-dimethoxyphenylethyl)]-N'-[2-(5-bromopyridyl)]-thiourea (HI-236) as a potent non-nucleoside inhibitor of drug-resistant human immunodeficiency virus.	1999 Jun 7	10386942
A novel genotype encoding a single amino acid insertion and five other substitutions between residues 64 and 74 of the HIV-1 reverse transcriptase confers high-level cross-resistance to nucleoside reverse transcriptase inhibitors. Abacavir CNA2007 International Study Group.	1999 Oct 1	10843527
Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activity.	1999 Oct 21	10543890
Didanosine-induced hepatitis.	2000 Aug	10950090
1-[2-(Diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole: a potent lead for the design of novel NNRTIs.	2000 Feb 7	10698447
Presence of 2',5'-Bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"-oxath iole-2",2"-dioxide) (TSAO)-resistant virus strains in TSAO-inexperienced HIV patients.	2000 Jun 10	10875608
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
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
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
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
Rwanda to receive cheaper anti-HIV drugs for chronic treatment and free viramune to prevent viral transmission from mother to child.	2001 Apr	11436238
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
High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.	2001 Apr 15	11391173
Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion.	2001 Feb	11159797
Indian company offers cheap anti-AIDS drugs.	2001 Feb 15	11236967
Anti-HIV activity of aromatic and heterocyclic thiazolyl thiourea compounds.	2001 Feb 26	11229762
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
Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures--worldwide, 1997-2000.	2001 Jan 5	11198946
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Limits of deep salvage antiretroviral therapy with nelfinavir plus either efavirenz or nevirapine, in highly pre-treated patients with HIV disease.	2001 Jun	11397623
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
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
Prophylaxis with a nevirapine-containing triple regimen after exposure to HIV-1.	2001 Mar 3	11247556
[Cutaneous adverse events related to simultaneous nevirapine treatment and pneumococcal vaccination in HIV-infected patients].	2001 Mar 31	11333714
Jaundice and hepatocellular damage associated with nevirapine therapy.	2001 May	11374701
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 21:18:13 GMT 2023` Edited by `admin` on `Fri Dec 15 21:18:13 GMT 2023`
Record UNII	B7XF2TD73C
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NEVIRAPINE HEMIHYDRATE

Common Name

English

NEVIRAPINE HEMIHYDRATE [WHO-IP]

Common Name

English

NEVIRAPINE HEMIHYDRATE [EP MONOGRAPH]

Common Name

English

Nevirapine hemihydrate [WHO-DD]

Common Name

English

NEVIRAPINE HEMIHYDRATE [USP-RS]

Common Name

English

NEVIRAPINUM HEMIHYDRATE [WHO-IP LATIN]

Common Name

English

NEVIRAPINE HEMIHYDRATE [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-, HYDRATE (2:1)

Systematic Name

English

Code System Code Type Description

RS_ITEM_NUM

1460714