PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
nevirapine

2D structure

Overview

Generic Names: NEV; NVP
Trade Names: Viramune
PharmGKB Accession Id: PA450616

Description

A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. PubChem (source: Drug Bank)

Indication

For use in combination with other antiretroviral drugs in the ongoing treatment of HIV-1 infection. (source: Drug Bank)

ATC Therapeutic Category

  • J05AG:Non-nucleoside reverse transcriptase inhibitors

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

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. (source: Drug Bank)

Pharmacology

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. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. In vivo studies in humans and in vitro studies with human liver microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 3A4 metabolism to several hydroxylated metabolites. (source: Drug Bank)

Protein Binding

60% (source: Drug Bank)

Absorption

90% (absolute bioavailability 93 ± 9%) (source: Drug Bank)

Toxicity

Symptoms of overdose include edema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonaryinfiltrates, rash, vertigo, vomiting, and weight decrease. (source: Drug Bank)

Isomeric SMILES Code:

Cc1ccnc2c1NC(=O)c3cccnc3N2C4CC4 (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs3745274 at chr19:46204681 in CYP2A7P1, CYP2B6
    CYP2B6:516G>T is part of the CYP2B6 haplotype. It has been associated with lower activity and response to NNRTIs. See VIP annotation for more details.
    Variant Name:
    CYP2B6:516G>T; part of CYP2B6*6; CYP2B6:Gln172His
    Related Drugs:
    efavirenz, nevirapine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  2. rs28399499 at chr19:46210061 in CYP2A7P1, CYP2B6
    This variant is the only protein coding change in the CYP2B6*18 allele. Its phenotype with respect to drugs is unclear. See VIP annotation for more details.
    Variant Name:
    CYP2B6:983T>C; CYP2B6:Ile328Thr; part of CYP2B6*18
    Related Drugs:
    bupropion, efavirenz, nevirapine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  3. rs3211371 at chr19:46214555 in CYP2A7P1, CYP2B6
    CYP2B6:1459C>T has been reported to reduce CYP2B6 protein expression in human liver and brain. Impact on drug response is somewhat contradictory, see VIP annotation for details.
    Variant Name:
    CYP2B6:1459C>T; CYP2B6:Arg487Cys; part of CYP2B6*1C, CYP2B6*5, CYP2B6*7
    Related Drugs:
    bupropion, efavirenz, mephenytoin, nevirapine, nicotine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp

Curated Annotations (Curated Annotation)

  1. rs1045642 at chr7:86976581 in ABCB1
    Decreased risk of hepatotoxicity was associated with ABCB1:3435C>T in a study of HIV patients receiving either efavirenz- or nevirapine-containing drug regimens.
    Variant Name:
    ABCB1:3435C>T, MDR1 3435C>T
    Related Drugs:
    efavirenz, nevirapine
    Related Diseases:
    HIV
    Evidence:
    PMID:16912956
  2. rs1045642 at chr7:86976581 in ABCB1
    Risk or phenotype-associated allele: C. Phenotype: This variant is associated with nevirapine-induced hepatotoxicity in patients from Mozambique, with the T allele showing a protective effect. Study size: 156 (78 with nevirapine-induced hepatotoxicity and 78 without adverse events). Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p = 0.038; odds ratio: 0.42. Type of association: GN; CO
    Variant Name:
    c.3435C>T
    Related Drugs:
    nevirapine
    Related Diseases:
    Drug Toxicity, HIV Infections
    Evidence:
    PMID:20017669
  3. rs776746 at chr7:99108475 in CYP3A, CYP3A5
    Risk or phenotype-associated allele: G. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with higher ALT mean value for G genotype carriers. Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p= 0.019. Type of association: GN; CO
    Variant Name:
    g.6986A>G
    Related Drugs:
    nevirapine
    Related Diseases:
    Drug Toxicity, HIV Infections
    Evidence:
    PMID:20017669
  4. rs12721646 at chr19:46139024 in CYP2A7P1, CYP2B7P1
    Risk or phenotype-associated allele: T. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with higher ALT mean value for T genotype carriers. Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p= 0.007. Type of association: GN; CO
    Variant Name:
    c.646-17C>T
    Related Drugs:
    nevirapine
    Related Diseases:
    Drug Toxicity, HIV Infections
    Evidence:
    PMID:20017669
  5. rs58425034 at chr19:46206805 in CYP2A7P1, CYP2B6
    Risk or phenotype-associated allele: C. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with higher ALT mean value for C genotype carriers. Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p= 0.01. Type of association: GN; CO
    Variant Name:
    c.646-159G>C
    Related Drugs:
    nevirapine
    Related Diseases:
    Drug Toxicity, HIV Infections
    Evidence:
    PMID:20017669
  6. rs28399499 at chr19:46210061 in CYP2A7P1, CYP2B6
    Risk or phenotype-associated allele: TC. Phenotype: This variant is statistically correlated with the mean of maximum transaminase values (ALT) in patients from Mozambique, with ALT mean value of 91.68 U/l for TT, and 221.45 U/l for TC genotypes (p < 0.001). Study size: 156. Study population/ethnicity: HIV infected patients from Mozambique. Significance metric(s): p< 0.001. Type of association: GN; CO
    Variant Name:
    c.983T>C
    Related Drugs:
    nevirapine
    Related Diseases:
    Drug Toxicity, HIV Infections
    Evidence:
    PMID:20017669
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available No literature annotations Not annotated
CYP2A7P1
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2B6
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data No literature annotations Not annotated
CYP2B7P1
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  • CO
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
HLA-B
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  • CO
  • PD
  • PK
  • FA
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
NR1I3
  • CO
  • PD
  • PK
  • FA
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
  • CO
  • PD
  • PK
  •   
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
rifampin
  •   
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation Nevirapine decreases the anticoagulant effect (source: Drug Bank)
atazanavir Uncurated Annotation Decreases levels/effect of atazanavir (source: Drug Bank)
atorvastatin Uncurated Annotation The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
dicumarol Uncurated Annotation Nevirapine decreases the anticoagulant effect (source: Drug Bank)
ketoconazole Uncurated Annotation Decreases the effect of ketoconazole (source: Drug Bank)
lovastatin Uncurated Annotation The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
methadone Uncurated Annotation The antiretroviral agent decreases the effect of methadone (source: Drug Bank)
nelfinavir Uncurated Annotation Decreases the effect of nelfinavir (source: Drug Bank)
saquinavir Uncurated Annotation Decreases the effect of saquinavir (source: Drug Bank)
simvastatin Uncurated Annotation The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
warfarin Uncurated Annotation Nevirapine decreases the anticoagulant effect (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Drug Hypersensitivity
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Drug Toxicity
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Epidermal Necrolysis, Toxic
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
HIV
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
HIV Infections
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Leukemia
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Stevens-Johnson Syndrome
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Toxic liver disease
  •   
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00238
KEGG Compound ID:
C07263
KEGG Drug ID:
D00435
PubChem Compound ID:
4463
PubChem Substance ID:
197039

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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