Nevirapine: Difference between revisions

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{{Short description|Chemical compound}}
{{Short description|Non-nucleoside reverse transcriptase inhibitor used in HIV treatment}}
 
{{Infobox drug
{{Infobox drug
| Watchedfields = changed
| Watchedfields = changed
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| IUPAC_name = 11-cyclopropyl-4-methyl-5,11-dihydro-6''H''- dipyrido[3,2-''b'':2′,3′-''e''][1,4]diazepin-6-one
| IUPAC_name = 11-cyclopropyl-4-methyl-5,11-dihydro-6''H''- dipyrido[3,2-''b'':2′,3′-''e''][1,4]diazepin-6-one
| image = Nevirapine.svg
| image = Nevirapine.svg
| alt =
| alt = Structural formula of Nevirapine
| image2 = Nevirapine 3D balls 1fkp.png
| image2 = Nevirapine 3D balls 1fkp.png
| alt2 =
| alt2 = 3D molecular structure of Nevirapine


<!--Clinical data-->
<!-- Clinical data -->
| tradename = Viramune
| tradename = Viramune
| Drugs.com = {{drugs.com|monograph|nevirapine}}
| Drugs.com = {{drugs.com|monograph|nevirapine}}
| MedlinePlus = a600035
| MedlinePlus = a600035
| DailyMedID = Nevirapine
| DailyMedID = Nevirapine
| pregnancy_AU     = B3
| pregnancy_AU = B3
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = [[Oral administration|By mouth]]
| routes_of_administration = [[Oral administration|By mouth]]
| ATC_prefix = J05
| ATC_prefix = J05
Line 22: Line 21:


<!-- Legal status -->
<!-- Legal status -->
| legal_AU         = S4
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_US = Rx-only
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_EU = Rx-only
| legal_BR_comment  =
| legal_status = Prescription only
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  =
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  =
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  =
| legal_UK          = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment  =
| legal_US         = Rx-only
| legal_US_comment  = <ref name="Viramune FDA label" /><ref name="Viramune XR FDA label" />
| legal_EU         = Rx-only
| legal_EU_comment  =
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  =
| legal_status     = <!-- For countries not listed above -->


<!-- Pharmacokinetic data -->
<!-- Pharmacokinetic data -->
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| metabolism = [[Liver]]
| metabolism = [[Liver]]
| elimination_half-life = 45 hours
| elimination_half-life = 45 hours
| excretion = [[Kidney]]: <6% (Parent drug) <br /> [[Bile duct]] <5% (Parent drug)
| excretion = Primarily via [[kidney]] (<6% as parent drug) and [[bile duct]] (<5% as parent drug)


<!--Identifiers-->
<!-- Chemical data -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 129618-40-2
| CAS_number = 129618-40-2
| PubChem = 4463
| PubChem = 4463
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00238
| DrugBank = DB00238
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4308
| ChemSpiderID = 4308
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 99DK7FVK1H
| UNII = 99DK7FVK1H
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00435
| KEGG = D00435
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 57
| ChEMBL = 57
| NIAID_ChemDB = 001856
| NIAID_ChemDB = 001856
<!--Chemical data-->
| C=15 | H=14 | N=4 | O=1
| C=15 | H=14 | N=4 | O=1
| SMILES = O=C2Nc1c(ccnc1N(c3ncccc23)C4CC4)C
| SMILES = O=C2Nc1c(ccnc1N(c3ncccc23)C4CC4)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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)
| StdInChI = 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)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = NQDJXKOVJZTUJA-UHFFFAOYSA-N
| StdInChIKey = NQDJXKOVJZTUJA-UHFFFAOYSA-N
}}
}}
Nevirapine is a nonnucleoside reverse transcriptase inhibitor used in combination with other agents in the therapy of human immunodeficiency virus ([[HIV]]) infection and the acquired immune deficiency syndrome ([[AIDS]]).  
 
{{livtox}}
== Overview ==
Nevirapine is associated with a high rate of serum [[aminotransferase]] elevations during therapy and is a well established cause of acute, clinically apparent [[liver injury]].
'''Nevirapine''' is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretroviral drugs to treat human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). It functions by directly inhibiting the HIV reverse transcriptase enzyme, preventing the replication of viral RNA.
{{moa}}
 
Nevirapine (ne vir' a peen) is a nonnucleoside inhibitor of the [[HIV]] polymerase enzyme and acts by binding to and disrupting the active catalytic site of the viral polymerase, causing a conformational change in the three dimensional structure of the enzyme. Nevirapine is a potent inhibitor of [[HIV]] replication and is a major component of highly reactive antiretroviral therapy (HAART) commonly being given in combination with one or two nucleoside reverse transcriptase inhibitors.  
Nevirapine is commonly included in highly active antiretroviral therapy (HAART) and is known for its efficacy in reducing viral load in HIV-positive individuals.
{{fda}}
 
Nevirapine was approved for use in [[HIV]] infection in the United States in 1996 and is currently used in a high proportion of HAART regimens.  
== Mechanism of Action ==
{{dose}}
Nevirapine inhibits HIV reverse transcriptase, the enzyme necessary for viral RNA conversion into DNA, a key step in HIV replication. Unlike nucleoside reverse transcriptase inhibitors (NRTIs), nevirapine does not require intracellular activation. Instead, it binds directly to the enzyme, causing a conformational change that disrupts its function, preventing viral replication.
Nevirapine is available in generic forms and under the brand name of Viramune in tablets of 200 mg. The usual dose is 200 mg daily for 2 weeks followed by 400 mg daily. Nevirapine is used in combination with other antiretroviral agents and is available in combinations with zidovudine and lamivudine. An oral suspension is also available for use in pediatrics.  
 
{{se}}
== Indications ==
Common side effects include [[rash]] (~20%), [[nausea]], fatigue, [[fever]] and [[headache]].
Nevirapine is indicated for:
* HIV-1 infection in combination with other antiretroviral agents.
* Prevention of mother-to-child transmission (PMTCT) during childbirth.
 
== Dosage and Administration ==
Nevirapine is available in tablet (200 mg) and oral suspension forms. Standard dosing includes:
 
* Initial dose: 200 mg once daily for 14 days.
* Maintenance dose: 200 mg twice daily OR 400 mg once daily (extended-release).
* Pediatric dosing: Adjusted based on weight and age.
 
Nevirapine is always used in combination with other antiretroviral therapy (ART) agents to reduce the risk of HIV resistance.
 
== Side Effects ==
Common side effects include:
* Rash (up to 20% of patients)
* Nausea and vomiting
* Fatigue
* Fever
* Headache
 
Severe adverse effects:
* Hepatotoxicity: Nevirapine is linked to severe liver toxicity, particularly in patients with pre-existing liver conditions.
* Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Severe skin reactions requiring immediate medical attention.
 
== Contraindications and Precautions ==
Nevirapine should not be used in:
* Patients with severe hepatic impairment.
* Individuals with prior hypersensitivity reactions to the drug.
* Women with CD4+ counts >250 cells/mm³ and men >400 cells/mm³ due to increased risk of liver toxicity.
 
== Drug Interactions ==
Nevirapine is a known CYP3A4 inducer, which can decrease plasma concentrations of certain drugs, including:
* Oral contraceptives (may reduce effectiveness).
* Protease inhibitors (PIs) like lopinavir/ritonavir.
* Warfarin and other anticoagulants.
 
It is advised to monitor drug levels when used with other CYP3A4-metabolized drugs.
 
== Pharmacokinetics ==
* Absorption: Well-absorbed orally (93% bioavailability).
* Distribution: Widely distributed with high tissue penetration.
* Metabolism: Primarily hepatic via the CYP3A4 enzyme system.
* Elimination: Half-life of ~45 hours, primarily excreted via urine.
 
== Special Populations ==
* Pregnancy: Classified as Category B3 in Australia. Used cautiously in pregnant women for PMTCT.
* Pediatrics: Dose adjustments required for children based on weight.
* Renal impairment: Minimal renal excretion; dose adjustment typically not required.
 
== Hepatotoxicity ==
Nevirapine has a well-established link to hepatotoxicity, ranging from mild liver enzyme elevations to severe liver failure. Risk factors include:
* Pre-existing liver disease (e.g., Hepatitis B or C).
* Higher baseline CD4+ counts in women (>250) and men (>400).
* Concomitant hepatotoxic medications.
 
== Availability and Market Status ==
Nevirapine is widely available as a generic medication and is part of the World Health Organization’s (WHO) List of Essential Medicines.
 
Brand names include:
* '''[[Viramune]]''' (Boehringer Ingelheim)
* Various generic formulations
 
== Alternatives ==
Nevirapine is part of the NNRTI class of antiretrovirals. Other NNRTI alternatives include:
* [[Efavirenz]]
* [[Etravirine]]
* [[Rilpivirine]]
 
Patients experiencing severe side effects or drug resistance may be switched to integrase inhibitors (INSTIs) or protease inhibitors (PIs).
 
== See Also ==
* [[Highly active antiretroviral therapy (HAART)]]
* [[HIV/AIDS treatment]]
* [[Reverse transcriptase inhibitors]]
* [[Drug-induced liver injury]]
 
== External Links ==
* [https://www.drugs.com/monograph/nevirapine.html Nevirapine Drug Monograph]
* [https://medlineplus.gov/druginfo/meds/a600035.html MedlinePlus Nevirapine Information]
* [https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2021.02 WHO List of Essential Medicines]
 
{{Antiretroviral drug}}
{{Antiretroviral drug}}
{{Xenobiotic-sensing receptor modulators}}
{{Xenobiotic-sensing receptor modulators}}
{{Portal bar | Medicine | Viruses }}
{{Portal bar | Medicine | Viruses }}
{{Stub}}
[[Category:Drugs developed by Boehringer Ingelheim]]
[[Category:Drugs developed by Boehringer Ingelheim]]
[[Category:Cyclopropyl compounds]]
[[Category:Cyclopropyl compounds]]
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[[Category:Non-nucleoside reverse transcriptase inhibitors]]
[[Category:Non-nucleoside reverse transcriptase inhibitors]]
[[Category:Pyridodiazepines]]
[[Category:Pyridodiazepines]]
== Nevirapine ==
<gallery>
File:Nevirapine.svg|Nevirapine
File:Nevirapine 3D balls 1fkp.png|Nevirapine 3D Balls
File:Nevirapine 3D.png|Nevirapine 3D
</gallery>
== Nevirapine ==
<gallery>
File:Nevirapine.svg|Nevirapine
File:Nevirapine 3D balls 1fkp.png|Nevirapine 3D Balls
File:Nevirapine 3D.png|Nevirapine 3D
</gallery>

Latest revision as of 00:50, 20 March 2025

Non-nucleoside reverse transcriptase inhibitor used in HIV treatment



Nevirapine
Structural formula of Nevirapine
INN
Drug class
Routes of administration By mouth
Pregnancy category
Bioavailability 93% ± 9%
Metabolism Liver
Elimination half-life 45 hours
Excretion Primarily via kidney (<6% as parent drug) and bile duct (<5% as parent drug)
Legal status Prescription only
CAS Number 129618-40-2
PubChem 4463
DrugBank DB00238
ChemSpider 4308
KEGG D00435


Overview[edit]

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other antiretroviral drugs to treat human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). It functions by directly inhibiting the HIV reverse transcriptase enzyme, preventing the replication of viral RNA.

Nevirapine is commonly included in highly active antiretroviral therapy (HAART) and is known for its efficacy in reducing viral load in HIV-positive individuals.

Mechanism of Action[edit]

Nevirapine inhibits HIV reverse transcriptase, the enzyme necessary for viral RNA conversion into DNA, a key step in HIV replication. Unlike nucleoside reverse transcriptase inhibitors (NRTIs), nevirapine does not require intracellular activation. Instead, it binds directly to the enzyme, causing a conformational change that disrupts its function, preventing viral replication.

Indications[edit]

Nevirapine is indicated for:

  • HIV-1 infection in combination with other antiretroviral agents.
  • Prevention of mother-to-child transmission (PMTCT) during childbirth.

Dosage and Administration[edit]

Nevirapine is available in tablet (200 mg) and oral suspension forms. Standard dosing includes:

  • Initial dose: 200 mg once daily for 14 days.
  • Maintenance dose: 200 mg twice daily OR 400 mg once daily (extended-release).
  • Pediatric dosing: Adjusted based on weight and age.

Nevirapine is always used in combination with other antiretroviral therapy (ART) agents to reduce the risk of HIV resistance.

Side Effects[edit]

Common side effects include:

  • Rash (up to 20% of patients)
  • Nausea and vomiting
  • Fatigue
  • Fever
  • Headache

Severe adverse effects:

  • Hepatotoxicity: Nevirapine is linked to severe liver toxicity, particularly in patients with pre-existing liver conditions.
  • Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Severe skin reactions requiring immediate medical attention.

Contraindications and Precautions[edit]

Nevirapine should not be used in:

  • Patients with severe hepatic impairment.
  • Individuals with prior hypersensitivity reactions to the drug.
  • Women with CD4+ counts >250 cells/mm³ and men >400 cells/mm³ due to increased risk of liver toxicity.

Drug Interactions[edit]

Nevirapine is a known CYP3A4 inducer, which can decrease plasma concentrations of certain drugs, including:

  • Oral contraceptives (may reduce effectiveness).
  • Protease inhibitors (PIs) like lopinavir/ritonavir.
  • Warfarin and other anticoagulants.

It is advised to monitor drug levels when used with other CYP3A4-metabolized drugs.

Pharmacokinetics[edit]

  • Absorption: Well-absorbed orally (93% bioavailability).
  • Distribution: Widely distributed with high tissue penetration.
  • Metabolism: Primarily hepatic via the CYP3A4 enzyme system.
  • Elimination: Half-life of ~45 hours, primarily excreted via urine.

Special Populations[edit]

  • Pregnancy: Classified as Category B3 in Australia. Used cautiously in pregnant women for PMTCT.
  • Pediatrics: Dose adjustments required for children based on weight.
  • Renal impairment: Minimal renal excretion; dose adjustment typically not required.

Hepatotoxicity[edit]

Nevirapine has a well-established link to hepatotoxicity, ranging from mild liver enzyme elevations to severe liver failure. Risk factors include:

  • Pre-existing liver disease (e.g., Hepatitis B or C).
  • Higher baseline CD4+ counts in women (>250) and men (>400).
  • Concomitant hepatotoxic medications.

Availability and Market Status[edit]

Nevirapine is widely available as a generic medication and is part of the World Health Organization’s (WHO) List of Essential Medicines.

Brand names include:

  • Viramune (Boehringer Ingelheim)
  • Various generic formulations

Alternatives[edit]

Nevirapine is part of the NNRTI class of antiretrovirals. Other NNRTI alternatives include:

Patients experiencing severe side effects or drug resistance may be switched to integrase inhibitors (INSTIs) or protease inhibitors (PIs).

See Also[edit]

External Links[edit]


Antiviral drugs: antiretroviral drugs used against HIV (primarily J05)
Capsid inhibitors
Entry/fusion inhibitors
(Discovery and development)
Integrase inhibitors
(Integrase strand transfer inhibitors (INSTI))
Maturation inhibitors
Protease Inhibitors (PI)
(Discovery and development)
°DHHS recommended initial regimen options. ◊Formerly or rarely used agent.


Xenobiotic-sensing receptor modulators
CAR
PXR
* Agonists: 17α-Hydroxypregnenolone



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