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Efavirenz response

MedGen UID:
482783
Concept ID:
C3281153
Finding
Synonyms: Efavirenz central nervous system toxicity, susceptibility to; Efavirenz, poor metabolism of
Drug:
efavirenz
MedGen UID:
194090
Concept ID:
C0674428
Pharmacologic Substance
A synthetic non-nucleoside reverse transcriptase (RT) inhibitor with antiviral activity. Efavirenz binds directly to the human immunodeficiency virus type 1 (HIV-1) RT, an RNA-dependent DNA polymerase, blocking its function in viral DNA replication. In combination with other antiretroviral drugs, this agent has been shown to significantly reduce HIV viral load, retarding or preventing damage to the immune system and reducing the risk of developing AIDS. Efavirenz induces activity of the cytochrome P450 system, accelerating its own metabolism. [from NCI]
 
Gene (location): CYP2B6 (19q13.2)
 
Monarch Initiative: MONDO:0800431
OMIM®: 614546

Definition

Efavirenz is a non-nucleoside reverse transcriptase inhibitor widely used worldwide to treat HIV-1 infection. It is predominantly metabolized into inactive metabolites by cytochrome P450-2B6 (CYP2B6). Genetic variants in CYP2B6 (e.g. CYP2B6*6 and *18), along with other genetic and non-genetic factors, are known to influence variability in efavirenz response. Patients with certain CYP2B6 genetic polymorphisms may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. [from PharmGKB]

Additional description

From OMIM
Highly active antiretroviral therapy (HAART) has reduced mortality associated with acquired immunodeficiency syndrome (AIDS; see 609423) by at least 70%. Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. However, during the first weeks of therapy, up to half of patients who receive efavirenz experience CNS side effects, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, and such side effects may reflect varying efavirenz plasma concentrations. Plasma clearance of efavirenz appears slower in African Americans than in European Americans, and studies have suggested earlier virologic failure on efavirenz for both African Americans and Hispanics compared with European Americans. Efavirenz is metabolized primarily by hepatic CYP2B6, with some involvement of CYP3A (CYP3A4; 124010) (summary by Haas et al., 2004).  http://www.omim.org/entry/614546

Professional guidelines

PubMed

Stockdale AJ, Khoo S
Curr Opin HIV AIDS 2022 Jan 1;17(1):4-14. doi: 10.1097/COH.0000000000000709. PMID: 34740228
Lagathu C, Béréziat V, Gorwood J, Fellahi S, Bastard JP, Vigouroux C, Boccara F, Capeau J
Expert Opin Drug Saf 2019 Sep;18(9):829-840. Epub 2019 Jul 19 doi: 10.1080/14740338.2019.1644317. PMID: 31304808
Hill A
Curr Opin HIV AIDS 2013 Jan;8(1):34-40. doi: 10.1097/COH.0b013e32835b7f28. PMID: 23143139

Curated

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services.

DailyMed Drug Label, SUSTIVA- efavirenz, 2020

Recent clinical studies

Etiology

Jiang HY, Zhang MN, Chen HJ, Yang Y, Deng M, Ruan B
Int J Infect Dis 2014 Aug;25:130-5. Epub 2014 Jun 6 doi: 10.1016/j.ijid.2014.04.020. PMID: 24911886
Sanford M
Drugs 2012 Mar 5;72(4):525-41. doi: 10.2165/11208590-000000000-00000. PMID: 22356290
Roca B
Recent Pat Antiinfect Drug Discov 2008 Jun;3(2):132-5. doi: 10.2174/157489108784746650. PMID: 18673126
Maggiolo F
Expert Opin Pharmacother 2007 Jun;8(8):1137-45. doi: 10.1517/14656566.8.8.1137. PMID: 17516877
Cheer SM, Goa KL
Drugs 2002;62(18):2667-74; discussion 2675-6. doi: 10.2165/00003495-200262180-00013. PMID: 12466009

Diagnosis

Nyangulu W, Mungwira RG, Divala TH, Nampota-Nkomba N, Nyirenda OM, Buchwald AG, Miller J, Earland DE, Adams M, Plowe CV, Taylor TE, Mallewa JE, van Oosterhout JJ, Parikh S, Laurens MB, Laufer MK; TSCQ Study Team
Malar J 2023 Jan 27;22(1):32. doi: 10.1186/s12936-023-04466-w. PMID: 36707795Free PMC Article
Variava E, Sigauke FR, Norman J, Rakgokong M, Muchichwa P, Mochan A, Maartens G, Martinson NA
J Acquir Immune Defic Syndr 2017 Aug 15;75(5):577-579. doi: 10.1097/QAI.0000000000001451. PMID: 28520619Free PMC Article
Yu Y, Loi CM, Hoffman J, Wang D
J Clin Pharmacol 2017 Feb;57(2):173-184. Epub 2016 Aug 22 doi: 10.1002/jcph.792. PMID: 27402157
Palombi L, Pirillo MF, Marchei E, Jere H, Sagno JB, Luhanga R, Floridia M, Andreotti M, Galluzzo CM, Pichini S, Mwenda R, Mancinelli S, Marazzi MC, Vella S, Liotta G, Giuliano M
J Antimicrob Chemother 2016 Apr;71(4):1027-30. Epub 2015 Dec 17 doi: 10.1093/jac/dkv435. PMID: 26679247
Parra J, Portilla J, Pulido F, Sánchez-de la Rosa R, Alonso-Villaverde C, Berenguer J, Blanco JL, Domingo P, Dronda F, Galera C, Gutiérrez F, Kindelán JM, Knobel H, Leal M, López-Aldeguer J, Mariño A, Miralles C, Moltó J, Ortega E, Oteo JA
Clin Drug Investig 2011;31(8):527-542. doi: 10.2165/11590700-000000000-00000. PMID: 21595497

Therapy

Sanford M
Drugs 2012 Mar 5;72(4):525-41. doi: 10.2165/11208590-000000000-00000. PMID: 22356290
Tozzi V
Antiviral Res 2010 Jan;85(1):190-200. Epub 2009 Sep 8 doi: 10.1016/j.antiviral.2009.09.001. PMID: 19744523
Liedtke MD, Rathbun RC
Ann Pharmacother 2009 Feb;43(2):322-8. Epub 2009 Feb 5 doi: 10.1345/aph.1L497. PMID: 19196837
Roca B
Recent Pat Antiinfect Drug Discov 2008 Jun;3(2):132-5. doi: 10.2174/157489108784746650. PMID: 18673126
Maggiolo F
Expert Opin Pharmacother 2007 Jun;8(8):1137-45. doi: 10.1517/14656566.8.8.1137. PMID: 17516877

Prognosis

Bienczak A, Denti P, Cook A, Wiesner L, Mulenga V, Kityo C, Kekitiinwa A, Gibb DM, Burger D, Walker AS, McIlleron H
J Acquir Immune Defic Syndr 2016 Oct 1;73(2):161-8. doi: 10.1097/QAI.0000000000001032. PMID: 27116047Free PMC Article
Cottrell ML, Hadzic T, Kashuba AD
Clin Pharmacokinet 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. PMID: 23824675Free PMC Article
Croxtall JD
Drugs 2012 Apr 16;72(6):847-69. doi: 10.2165/11209110-000000000-00000. PMID: 22512366
Rekić D, Röshammar D, Mukonzo J, Ashton M
Br J Clin Pharmacol 2011 Apr;71(4):536-43. doi: 10.1111/j.1365-2125.2010.03883.x. PMID: 21395646Free PMC Article
Maggiolo F
J Antimicrob Chemother 2009 Nov;64(5):910-28. Epub 2009 Sep 18 doi: 10.1093/jac/dkp334. PMID: 19767318Free PMC Article

Clinical prediction guides

Boyle A, Moss CE, Marzolini C, Khoo S
Clin Pharmacokinet 2019 Dec;58(12):1553-1565. doi: 10.1007/s40262-019-00806-9. PMID: 31388941
Cottrell ML, Hadzic T, Kashuba AD
Clin Pharmacokinet 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. PMID: 23824675Free PMC Article
McNicholl IR
Drugs 2013 Mar;73(3):207-12. doi: 10.1007/s40265-013-0022-6. PMID: 23420097
Tozzi V
Antiviral Res 2010 Jan;85(1):190-200. Epub 2009 Sep 8 doi: 10.1016/j.antiviral.2009.09.001. PMID: 19744523
Dando TM, Wagstaff AJ
Drugs 2004;64(18):2075-82; discussion 2083-4. doi: 10.2165/00003495-200464180-00005. PMID: 15341498

Recent systematic reviews

Amaro-Álvarez L, Cordero-Ramos J, Calleja-Hernández MÁ
Farm Hosp 2024 Nov-Dec;48(6):T299-T309. Epub 2024 Jun 8 doi: 10.1016/j.farma.2024.03.010. PMID: 38851909
Amaro-Álvarez L, Cordero-Ramos J, Calleja-Hernández MÁ
Farm Hosp 2024 Nov-Dec;48(6):299-309. Epub 2024 Feb 9 doi: 10.1016/j.farma.2023.12.004. PMID: 38341366
Jiang HY, Zhang MN, Chen HJ, Yang Y, Deng M, Ruan B
Int J Infect Dis 2014 Aug;25:130-5. Epub 2014 Jun 6 doi: 10.1016/j.ijid.2014.04.020. PMID: 24911886
Omeje I, Okwundu CI
Cochrane Database Syst Rev 2012 May 16;2012(5):CD007276. doi: 10.1002/14651858.CD007276.pub3. PMID: 22592718Free PMC Article
Omeje I, Okwundu CI
Cochrane Database Syst Rev 2012 Feb 15;(2):CD007276. doi: 10.1002/14651858.CD007276.pub2. PMID: 22336829

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • PAGAA, 2024
      Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services.
    • DailyMed Drug Label, 2020
      DailyMed Drug Label, SUSTIVA- efavirenz, 2020

    Consumer resources

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