E-DRUG: Artesunate- and amodiaquine-associated extrapyramidal reactions
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[Underreporting of adverse drug reactions is common and in particular in
countries where diseases such as malaria are prevalent. It is therefore
worth noting that an association of EPS with combination therapy with
amodiaquine and artesunate that has been established, and even in low doses.
As WHO has now established spontaneous reporting system in many of the
countries with malaria, E-druggers are encouraged to report ADRs to further
verify this association as well as other adverse reactions to antimalarials.
KM]
McEwen J*. Artesunate- and amodiaquine-associated extrapyramidal reactions:
a series of 49 cases in VigiBaseT. Drug Saf 2012 Aug 1;35(8):667-75. doi:
10.2165/11599860-000000000-00000.
* Discipline of Pharmacy, University of Canberra, Canberra, ACT, Australia
http://adisonline.com/drugsafety/Abstract/2012/35080/Artesunate__and_Amodiaq
uine_Associated.7.aspx
Abstract
BACKGROUND:
Acute extrapyramidal reactions have been attributed to amodiaquine. They may
be anticipated with the widely-used combination antimalarial artesunate with
amodiaquine, but the association is very poorly documented.
OBJECTIVE:
The aim of the study was to identify individual case safety reports in the
Uppsala Monitoring Centre's VigibaseT database associating the use of the
combination of artesunate and amodiaquine with extrapyramidal adverse
reactions and to characterize the clinical features in those reports.
METHODS:
Reports of adverse reactions to the combination use of artesunate or
dihydroartemisinin and amodiaquine entered into VigibaseT up to 15 February
2011 were identified. Reports with a causality grading of 'Unlikely' and
probable duplicates of reports were excluded. Reports that included at least
one MedDRAR Preferred Term strongly suggestive of an extrapyramidal reaction
were subject to further detailed analysis.
RESULTS:
Forty-three reports in adults and six reports in children were identified as
associating the use of artesunate with amodiaquine, either as separate
co-packaged or fixed-combination products, with extrapyramidal reactions.
More than half (57%) of the adults had an onset of the reaction within 48
hours of starting treatment. Almost equal numbers of male and female adult
patients were reported - 67% were aged between 14 and 30 years. The most
commonly implicated daily dose was amodiaquine base 600 mg and artesunate
200 mg, but lower doses were implicated in some adult patients.
Identification of very long delays in some reports reaching VigibaseT was an
unexpected observation.
CONCLUSIONS:
This case series supports an association of the use of artesunate and
amodiaquine as combination antimalarial therapy with acute extrapyramidal
reactions. The reactions occurred with recommended, and in some instances
reduced, daily doses. Extrapyramidal reactions are unpleasant and
frightening and the association warrants being more clearly recorded in
official treatment guidelines and Summary of Product Characteristics
documents.
PMID: 22788236
Correspondence: Dr John McEwen, 253 La Perouse Street, Red Hill, ACT 2603
Australia.