Safety of 8-aminoquinoline antimalarial medicines
Written by external authors, this document was prepared for and discussed at a 2012 meeting of the WHO evidence review group on the safety and effectiveness of single-dose primaquine as a P. falciparum gametocytocide. It reviews published and unpublished studies and reports about the safety of primaquine and its precursors, with particular attention to haemolytic anaemia in G6PD-deficient individuals.
Primaquine is an antimalarial drug of the 8-aminoquinoline class. It provides prophylaxis and radical cure for malaria infections caused by Plasmodium vivax and P. ovale parasites, and is a potent gametocytocide in P. falciparum infections. In recent years, the use of single-dose primaquine has received renewed interest because of its transmission-blocking effects in falciparum malaria.
However, a significant obstacle to its use for the treatment of vivax malaria has been concern about its safety in populations with G6PD deficiency, in whom it may precipitate acute haemolytic anaemia. G6PD deficiency is relatively common in malaria-endemic countries, and its prevalence is highest in sub-Saharan Africa and the Arabian Peninsula.
The review spans nearly a century, during which research methodology has changed substantially and knowledge in biology and pharmacology has made great advances. The data reported are heterogeneous and not readily amenable to pooling (or weighting) as in standard meta-analyses. Therefore, the information is presented chronologically.