U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Hertz DL, Bousman CA, McLeod HL, Monte AA, Voora D, Orlando LA, Crutchley RD, Brown B, Teeple W, Rogers S, Patel JN
Am J Health Syst Pharm 2024 Aug 12;81(16):672-683. doi: 10.1093/ajhp/zxae110. PMID: 38652504
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
Schafer JJ, Short WR
Antivir Ther 2012;17(8):1495-502. Epub 2012 Aug 10 doi: 10.3851/IMP2254. PMID: 22878339

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

Greig JM, Anderson J
Curr Opin Infect Dis 2014 Feb;27(1):46-52. doi: 10.1097/QCO.0000000000000033. PMID: 24322593
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

Niklasson B, Klitz W, Juntti-Berggren L, Berggren PO, Lindquist L
Viral Immunol 2020 Nov;33(9):594-599. Epub 2020 Aug 4 doi: 10.1089/vim.2020.0039. PMID: 32758075
Tabb ZJ, Mmbaga BT, Gandhi M, Louie A, Kuncze K, Okochi H, Shayo AM, Turner EL, Cunningham CK, Dow DE
AIDS 2018 Jun 1;32(9):1115-1123. doi: 10.1097/QAD.0000000000001788. PMID: 29438196Free PMC Article
Nicot F, Sauné K, Raymond S, Jeanne N, Carcenac R, Lefebvre C, Cuzin L, Marchou B, Delobel P, Izopet J
J Clin Virol 2015 Jan;62:20-4. Epub 2014 Nov 20 doi: 10.1016/j.jcv.2014.10.020. PMID: 25542465
Shah I
Indian Pediatr 2012 May;49(5):409-10. doi: 10.1007/s13312-012-0077-6. PMID: 22700667Free PMC Article
Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F
Proc Natl Acad Sci U S A 2009 Jun 9;106(23):9403-8. Epub 2009 May 22 doi: 10.1073/pnas.0903107106. PMID: 19470482Free PMC Article

Therapy

van Heeswijk RP, Beumont M, Kauffman RS, Garg V
Antivir Ther 2013;18(4):553-60. Epub 2013 Jan 23 doi: 10.3851/IMP2527. PMID: 23344266
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
Roca B
Recent Pat Antiinfect Drug Discov 2008 Jun;3(2):132-5. doi: 10.2174/157489108784746650. PMID: 18673126
Wynn HE, Brundage RC, Fletcher CV
CNS Drugs 2002;16(9):595-609. doi: 10.2165/00023210-200216090-00002. PMID: 12153332

Prognosis

Yee KL, Cabalu TD, Kuo Y, Fillgrove KL, Liu Y, Triantafyllou I, McClain S, Dreyer D, Wenning L, Stoch SA, Iwamoto M, Sanchez RI, Khalilieh SG
J Clin Pharmacol 2021 Mar;61(3):394-405. Epub 2020 Sep 28 doi: 10.1002/jcph.1747. PMID: 32989795
Burgess KS, Ipe J, Swart M, Metzger IF, Lu J, Gufford BT, Thong N, Desta Z, Gaedigk R, Pearce RE, Gaedigk A, Liu Y, Skaar TC
Clin Pharmacol Ther 2018 Jul;104(1):130-138. Epub 2017 Oct 25 doi: 10.1002/cpt.892. PMID: 28960269Free PMC Article
Nicot F, Sauné K, Raymond S, Jeanne N, Carcenac R, Lefebvre C, Cuzin L, Marchou B, Delobel P, Izopet J
J Clin Virol 2015 Jan;62:20-4. Epub 2014 Nov 20 doi: 10.1016/j.jcv.2014.10.020. PMID: 25542465
Greig JM, Anderson J
Curr Opin Infect Dis 2014 Feb;27(1):46-52. doi: 10.1097/QCO.0000000000000033. PMID: 24322593
Reddy YS, Gotzkowsky SK, Eron JJ, Kim JY, Fiske WD, Fiscus SA, Petch L, Cohen MS, Kashuba AD
J Infect Dis 2002 Nov 1;186(9):1339-43. Epub 2002 Oct 7 doi: 10.1086/344311. PMID: 12402205

Clinical prediction guides

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
Penrose KJ, Brumme CJ, Scoulos-Hanson M, Hamanishi K, Gordon K, Viana RV, Wallis CL, Harrigan PR, Mellors JW, Parikh UM
Antivir Chem Chemother 2018 Jan-Dec;26:2040206618762985. doi: 10.1177/2040206618762985. PMID: 29566538Free PMC Article
Burgess KS, Ipe J, Swart M, Metzger IF, Lu J, Gufford BT, Thong N, Desta Z, Gaedigk R, Pearce RE, Gaedigk A, Liu Y, Skaar TC
Clin Pharmacol Ther 2018 Jul;104(1):130-138. Epub 2017 Oct 25 doi: 10.1002/cpt.892. PMID: 28960269Free PMC Article
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):299-309. Epub 2024 Feb 9 doi: 10.1016/j.farma.2023.12.004. PMID: 38341366
Verrest L, Wilthagen EA, Beijnen JH, Huitema ADR, Dorlo TPC
Clin Pharmacokinet 2021 Sep;60(9):1149-1169. Epub 2021 Jun 1 doi: 10.1007/s40262-021-01031-z. PMID: 34060020Free PMC Article
Nickel K, Halfpenny NJA, Snedecor SJ, Punekar YS
BMC Infect Dis 2021 Feb 26;21(1):222. doi: 10.1186/s12879-021-05850-0. PMID: 33637050Free PMC Article
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 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