A proposed management algorithm for lateonset efavirenz neurotoxicity

A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causin...

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Main Authors: H Cross, S Chetty, M Asukile, H Hussey, E Lee Pan, L Tucker
Format: Article
Language:English
Published: South African Medical Association 2018-03-01
Series:South African Medical Journal
Online Access:http://www.samj.org.za/index.php/samj/article/download/12261/8444
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author H Cross
S Chetty
M Asukile
H Hussey
E Lee Pan
L Tucker
author_facet H Cross
S Chetty
M Asukile
H Hussey
E Lee Pan
L Tucker
author_sort H Cross
collection DOAJ
description A high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Concomitant INH use therefore affects plasma levels of EFV. EFV is well known to cause neuropsychiatric side-effects on initiation, and a recent adult case series described late-onset neurotoxicity in the form of subacute ataxia and encephalopathy in patients treated with EFV for a median of 2 years, in association with toxic plasma levels of the drug. We have seen an increase in cases of EFV toxicity presenting to our neurology referral unit. All cases have been in the context of recent initiation of concomitant INH. We therefore conducted a retrospective case record audit to describe these seven cases with the additional advantage of tertiary-level assessment. We outline the clinical features and investigation results, as well as outcomes after EFV was stopped. Our main objectives are to highlight the probable role of concomitant INH use in the development of this syndrome, and to suggest that only limited work-up may be warranted in suspected cases.
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spelling doaj.art-05ef8b5bc0bf4856b8e7aa92039bd61e2024-01-02T08:06:27ZengSouth African Medical AssociationSouth African Medical Journal0256-95742078-51352018-03-01108427127410.7196/SAMJ.2018.v108i4.12914A proposed management algorithm for lateonset efavirenz neurotoxicityH CrossS ChettyM AsukileH HusseyE Lee PanL TuckerA high proportion of HIV-positive patients in South Africa receive concomitant efavirenz (EFV) and isoniazid (INH) therapy. EFV is metabolised in the liver via CYP2B6, and genetic polymorphism of CYP2B6 is known to result in slowed metabolism of the drug. INH is also metabolised in the liver, causing inhibition of a pathway that plays an important role in slow EFV metabolisers. Concomitant INH use therefore affects plasma levels of EFV. EFV is well known to cause neuropsychiatric side-effects on initiation, and a recent adult case series described late-onset neurotoxicity in the form of subacute ataxia and encephalopathy in patients treated with EFV for a median of 2 years, in association with toxic plasma levels of the drug. We have seen an increase in cases of EFV toxicity presenting to our neurology referral unit. All cases have been in the context of recent initiation of concomitant INH. We therefore conducted a retrospective case record audit to describe these seven cases with the additional advantage of tertiary-level assessment. We outline the clinical features and investigation results, as well as outcomes after EFV was stopped. Our main objectives are to highlight the probable role of concomitant INH use in the development of this syndrome, and to suggest that only limited work-up may be warranted in suspected cases.http://www.samj.org.za/index.php/samj/article/download/12261/8444
spellingShingle H Cross
S Chetty
M Asukile
H Hussey
E Lee Pan
L Tucker
A proposed management algorithm for lateonset efavirenz neurotoxicity
South African Medical Journal
title A proposed management algorithm for lateonset efavirenz neurotoxicity
title_full A proposed management algorithm for lateonset efavirenz neurotoxicity
title_fullStr A proposed management algorithm for lateonset efavirenz neurotoxicity
title_full_unstemmed A proposed management algorithm for lateonset efavirenz neurotoxicity
title_short A proposed management algorithm for lateonset efavirenz neurotoxicity
title_sort proposed management algorithm for lateonset efavirenz neurotoxicity
url http://www.samj.org.za/index.php/samj/article/download/12261/8444
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