Tafenoquine and primaquine do not exhibit clinical neurologic signs associated with central nervous system lesions in the same manner as earlier 8-aminoquinolines

Background: Tafenoquine was recently approved for Plasmodium vivax radical cure (KRINTAFEL™) and malaria prevention (ARAKODA™).

Methods: A review of the non-clinical and clinical literature was conducted to assess whether tafenoquine (and primaquine) exhibit the same neurologic lesions and associated clinical signs as earlier 8-aminoquinolines, as has been alleged in recent opinion pieces.

Results: Plasmocid, pamaquine and pentaquine damage specific neuro-anatomical structures in Rhesus monkeys and humans leading to corresponding deficits in neurologic function. Neurologic therapeutic indices for these 3 drugs calculated based on monkey data were well correlated with human data. Despite 60 years of use, there is no evidence that primaquine exhibits similar neurotoxicity in humans.

Discussion/conclusions: Extrapolation of data from Rhesus monkeys to humans, and the available clinical data, suggest that tafenoquine also does not exhibit pamaquine, pentaquine or plasmocid-like clinical neurologic signs in humans.

8-aminoquinoline; Brain-stem; Malaria; Monkeys; Neurohistopathology; Neurotoxicity; Pamaquine; Pentaquine; Plasmocid; Primaquine; Tafenoquine.