Advances 5: Tafenoquine
For over 60 years primaquine has been the only widely available drug in
the 8-aminoquinoline class. In the past year, after a long and difficult
gestation, the slowly eliminated 8-AQ tafenoquine was registered and
launched. Tafenoquine is a well tolerated single dose treatment which
solves the problem of potentially poor adherence (51,52). Like the other
8-aminoquinolines tafenoquine also causes oxidant haemolysis in G6PD
deficiency. However the rapidly eliminated primaquine can be stopped in
case of haemolysis in a G6PD deficient patient, thereby limiting the
consequent anaemia – whereas tafenoquine continues to cause haemolysis
for weeks. Thus tafenoquine has the advantage of simplicity and
reliability of dosing, but at the expense of an increased risk of
serious haemolysis. Currently available rapid screening tests identify
individuals who have 30-40% of normal erythrocyte G6PD activity which
identifies all male hemizygotes and female homozygotes, but they do not
identify the majority of female heterozygotes (whose blood contains a
mixture of G6PD deficient and normal erythrocytes). Safe use of
tafenoquine therefore requires development and deployment of simple
quantitative G6PD screening tests which can identify individuals with
<70% of normal red G6PD activity in blood samples. These are
under development, but they are not yet ready for roll out. In East Asia
and Oceania relapse is the main cause of vivax illness, a major
contributor to morbidity and mortality, and a major obstacle to
elimination. The dose of tafenoquine currently recommended (300mg adult
dose) is too low for this populous region, where a large proportion of
the world’s relapses occur. In the pre-registration clinical trials
tafenoquine 300mg proved inferior to a sub-optimal dose of primaquine
(52) (Figure 5). Unfortunately there are no plans currently to rectify
this.