Increases in indirect bilirubin are primarily associated with extravascular hemolysis.29 G6PD-unrelated, extravascular hemolytic mechanisms have been suggested for the primaquine metabolite 6-methoxy-8-hydroxylaminoquinoline, contributing to its overall hemolytic potential and to methemoglobin formation.30 In contrast, there are no detectable major metabolites of tafenoquine in human plasma or urine (detection limit 1–2 ng/mL), and tafenoquine causes less methemoglobinemia compared with primaquine. This evidence concerns the gene G6PD and methemoglobinemia.