E-DRUG: MSF on amodiaquine
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[a response from MSF on the debate whether amodiaquine is safe or not, and
whether it should be added to the WHO EDL for a third time. WB]
dear E-druggers,
M�decins Sans Fronti�res (MSF) on the use of amodiaquine for the
treatment of uncomplicated falciparum malaria
The WHO/EDL expert committee decision not to include amodiaquine on
the Essential Medicines List, pending further safety data, conflicts
with the recommendations of WHO's April 2001 technical consultation.
The report of this consultation puts forward four drug combinations
for use in malaria control programmes, including artesunate plus
amodiaquine and SP plus amodiaquine (in areas where efficacy of both
amodiaquine and SP remains high) [WHO/CDS/RBM/2001.35].
Amodiaquine was first deleted from WHO recommendations and the EDL in
1990 because of serious adverse reactions when used in prophylaxis,
and no advantage over chloroquine in terms of efficacy and price [WHO
Tech Rep Series No.805, 1990]. However, this decision was later
reviewed and amodiaquine use allowed in cases where the benefits
outweigh the risks [WHO 19th Expert Committee, 1993]. Subsequently,
based on the results of a systematic review, amodiaquine was
re-instated in WHO treatment guidelines in 1996 [WHO/MAL/96.1075].
Current evidence on the efficacy and safety of amodiaquine submitted
to the EDL committee was based on the Cochrane Systematic Review (1996
& 2002 update) [Olliaro et al, Lancet 1996], the meta-analysis of
three double-blind randomised controlled trials (RCTs) of single-agent
amodiaquine versus its combination with artesunate [Adjuik et al,
Lancet 2002], and experience of sub-district deployment of artesunate
plus amodiaquine in Senegal (2000-2001) [Agnamey et al, unpublished].
In these analyses, amodiaquine - either alone or in combination with
artesunate - was found to be effective and well tolerated. Its safety
profile was similar to chloroquine and SP in the systematic review,
and in the RCTs, no clinical hepatitis was reported (instead, there
was an overall downward trend in liver function tests). The same
trends were reported in Senegal. In both the systematic review and the
meta-analysis, there was a decline in mean neutrophil counts which, in
the systematic review, was similar to chloroquine and SP. In the RCTs,
9 out of 153 patients developed asymptomatic neutropenia by day 28.
In conclusion, amodiaquine is an efficacious and well tolerated
antimalarial drug. The real prevalence and clinical significance of
neutropenia and the effects of repeat treatments are unclear - when
amodiaquine plus artesunate is used widely, a sound pharmacovigilance
system should therefore be in place.
M�decins Sans Fronti�res (MSF) is strongly advocating for the use of
artemisinin-based combination therapy in African countries facing
increased resistance to chloroquine and SP. Artesunate plus
amodiaquine and artemether-lumefantrine (Coartem�) are the current
best options for malaria treatment [WHO/CDS/RBM/2001.35]. Artesunate
plus amodiaquine currently costs US$1-1.30 per adult dose and Coartem�
US$2.40 per adult dose. Where increased cost of switching to
combination therapy is an issue, artesunate plus amodiaquine may
therefore be the more appropriate choice.
MSF has applied WHO recommendations by implementing artesunate plus
amodiaquine combination therapy in several field projects in Africa.
Some African regions and countries have also already opted for
amodiaquine-containing combinations (e.g Zanzibar) or are considering
them (e.g. Rwanda and Burundi). Amodiaquine is also widely used in the
private sector in West Africa, and as second-line treatment in Kenya.
MSF looks forward to rapid inclusion of amodiaquine on the Essential
Medicines List. Given the limited choice of safe and effective
antimalarial drugs, it is essential to make full use of all options
available to fight the leading killer of children in Africa.
Jean Rigal
M�decins Sans Fronti�res
Paris
France
JRIGAL@paris.msf.org
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