Rapid responses are electronic comments to the editor. They enable our users
to debate issues raised in articles published on bmj.com. A rapid response
is first posted online. If you need the URL (web address) of an individual
response, simply click on the response headline and copy the URL from the
browser window. A proportion of responses will, after editing, be published
online and in the print journal as letters, which are indexed in PubMed.
Rapid responses are not indexed in PubMed and they are not journal articles.
The BMJ reserves the right to remove responses which are being
wilfully misrepresented as published articles or when it is brought to our
attention that a response spreads misinformation.
From March 2022, the word limit for rapid responses will be 600 words not
including references and author details. We will no longer post responses
that exceed this limit.
The word limit for letters selected from posted responses remains 300 words.
EDITOR-We read with interest Wise et al’s article on neuropsychiatric
complications of nevirapine treatment1. This described 3 patients
developing a delirium, an organic affective state and an organic
psychosis, respectively, within 2 weeks of starting nevirapine therapy.
They went on to infer that nevirapine was the agent responsible by virtue
of the fact that all symptoms resolved on its withdrawal. However, they
make no reference to any concommittant medication the patients may have
been taking, thereby discounting either another drug or a drug interaction
being the cause of the symptoms observed. Nevirapine is usually given in
combination with other medication as part of a highly active
antiretroviral therapy (HAART) regimen. HIV positive individuals on HAART
often take additional antibiotics eg cotrimoxazole, azithromycin, for
prophylaxis against opportunistic infections. It is therefore highly
likely that the patients in Wise’s article were taking other medication in
addition to nevirapine.
In our recently published article2, we propose that an interaction
between clarithromycin and nevirapine was responsible for the
neuropsychiatric reaction observed in our patient on HAART. This started
10 days after the introduction of a course of clarithromycin 500mg bd for
a bacterial chest infection and stopped 72 hours after the antibiotic was
withdrawn. Continuation of nevirapine in this patient resulted in no
adverse events. Clarithromycin, a macrolide antibiotic, and nevirapine, a
non nucleoside reverse transcriptase inhibitor, are principally
metabolised in the liver by the cytochrome P450 isoenzymes of the CYP3A
family. Clarithromycin is an inhibitor of CYP3A and its use in patients
concurrently taking drugs metabolised by the cytochrome P450 system may be
associated with elevations in their serum levels. Nevirapine acts as a
mild to moderate enzyme inducer of CYP3A, thereby reducing plasma
concentrations of other drugs metabolised by the same system. The
principal side effects of clarithromycin are gastrointestinal, however
less commonly CNS side effects have been reported3. At the time of
writing, the Committee on Safety of Medicines (CSM)/Medicines Control
Agency (MCA) had received 219 reports of suspected Clarithromycin-induced
psychiatric disorders including psychosis (n=5), depersonalisation (n=5)
and suicidal ideation (n=4) (CSM-personal communication). Nevirapine had
not previously been reported to cause serious CNS adverse effects4.
We wish to raise the possibility that the neuropsychiatric reactions
observed by Wise et al may have been due to a drug interaction with
nevirapine or indeed another drug altogether. We would also like to raise
awareness of the CSM/MCA/MRC blue card HIV drug toxicity reporting scheme.
It acts as an early warning system for the identification of previously
unrecognised adverse reactions associated with antiretrovirals and is an
important means of monitoring drug safety of these newer agents.
1 Wise MEJ, Mistry K, Reid S. Neuropsychiatric complications of
nevirapine treatment. BMJ 2002; 7342: 879.
2 Prime KP, French P. Neuropsychiatric reaction induced by
clarithromycin in a patient taking highly active antiretroviral therapy
(HAART). Sex Transm Inf 2001; 77: 297-298.
3 Abbott Laboratories, 2000. Clarithromycin: Summary of Product
Characteristics. Available from the ABPI compendium of data sheets and
SPCs 1999-2000.
Neuropsychiatric reactions in HIV positive patients-Accurate documentation of drug history is needed
EDITOR-We read with interest Wise et al’s article on neuropsychiatric
complications of nevirapine treatment1. This described 3 patients
developing a delirium, an organic affective state and an organic
psychosis, respectively, within 2 weeks of starting nevirapine therapy.
They went on to infer that nevirapine was the agent responsible by virtue
of the fact that all symptoms resolved on its withdrawal. However, they
make no reference to any concommittant medication the patients may have
been taking, thereby discounting either another drug or a drug interaction
being the cause of the symptoms observed. Nevirapine is usually given in
combination with other medication as part of a highly active
antiretroviral therapy (HAART) regimen. HIV positive individuals on HAART
often take additional antibiotics eg cotrimoxazole, azithromycin, for
prophylaxis against opportunistic infections. It is therefore highly
likely that the patients in Wise’s article were taking other medication in
addition to nevirapine.
In our recently published article2, we propose that an interaction
between clarithromycin and nevirapine was responsible for the
neuropsychiatric reaction observed in our patient on HAART. This started
10 days after the introduction of a course of clarithromycin 500mg bd for
a bacterial chest infection and stopped 72 hours after the antibiotic was
withdrawn. Continuation of nevirapine in this patient resulted in no
adverse events. Clarithromycin, a macrolide antibiotic, and nevirapine, a
non nucleoside reverse transcriptase inhibitor, are principally
metabolised in the liver by the cytochrome P450 isoenzymes of the CYP3A
family. Clarithromycin is an inhibitor of CYP3A and its use in patients
concurrently taking drugs metabolised by the cytochrome P450 system may be
associated with elevations in their serum levels. Nevirapine acts as a
mild to moderate enzyme inducer of CYP3A, thereby reducing plasma
concentrations of other drugs metabolised by the same system. The
principal side effects of clarithromycin are gastrointestinal, however
less commonly CNS side effects have been reported3. At the time of
writing, the Committee on Safety of Medicines (CSM)/Medicines Control
Agency (MCA) had received 219 reports of suspected Clarithromycin-induced
psychiatric disorders including psychosis (n=5), depersonalisation (n=5)
and suicidal ideation (n=4) (CSM-personal communication). Nevirapine had
not previously been reported to cause serious CNS adverse effects4.
We wish to raise the possibility that the neuropsychiatric reactions
observed by Wise et al may have been due to a drug interaction with
nevirapine or indeed another drug altogether. We would also like to raise
awareness of the CSM/MCA/MRC blue card HIV drug toxicity reporting scheme.
It acts as an early warning system for the identification of previously
unrecognised adverse reactions associated with antiretrovirals and is an
important means of monitoring drug safety of these newer agents.
Katia Prime
specialist registrar in HIV Medicine
Mortimer Market Centre, London WC1E 6AU
Katiaprime@hotmail.com
Patrick French
consultant in HIV Medicine
Mortimer Market Centre, London WC1E 6AU
pfrench@gum.ucl.ac.uk
1 Wise MEJ, Mistry K, Reid S. Neuropsychiatric complications of
nevirapine treatment. BMJ 2002; 7342: 879.
2 Prime KP, French P. Neuropsychiatric reaction induced by
clarithromycin in a patient taking highly active antiretroviral therapy
(HAART). Sex Transm Inf 2001; 77: 297-298.
3 Abbott Laboratories, 2000. Clarithromycin: Summary of Product
Characteristics. Available from the ABPI compendium of data sheets and
SPCs 1999-2000.
4 Boehringer Ingelheim International, April 2000. Viramune: Summary
of Product Characteristics. Available from
http://www.eudra.org/humandocs/humans/EPAR/Viramune/Viramune.htm
Competing interests: No competing interests