Statement |

Médecins Sans Frontières (MSF) on the use of amodiaquine for the treatment of uncomplicated falciparum malaria

Response to the WHO’s decision not to include amodiaquine on the Essential Medicines List (EML), and the debate regarding its safety.

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2002], and experience of sub-district deployment of artesunate plus amodiaquine in Senegal (2000-2001) [Agnamey et al, unpublished].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.

Médecins Sans Frontières (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.