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

Table 3 Neurologic toxicities of 8AQs in humans

8AQ^d	Minimum dose known to be required to induce clinical signs of neurotoxicity in humans^a	Clinical neurologic signs at minimum neurotoxic dose	Onset of neurologic symptoms (days)	Dose-limiting toxicity	Therapeutic dose in humans^a, mg/day (total mg)	Neurologic therapeutic index (NTI)^e
Primaquine [27, 34]	> 240 (> 3360)	None	NA	GI distress	15 (210)	> 16
Pamaquine [35]	1200 (1200)^b	Paralyzed palate/death	≤ 7	GI distress	30 (150)	8
Pentaquine [40]	120 (1680)	Syncope, postural hypotension, erectile dysfunction	≤ 28	GI distress	60 (840)	2
Plasmocid [1, 2]	Not known	Disturbances in eye movement, muscle and equilibrium control	≤ 2	Neurotoxicity^c	Not known	NA

^aExpressed as daily dose in mg with total dose in mg in brackets. For primaquine, pentaquine, and pamaquine this is the dose administered for radical cure of P. vivax malaria in combination with a blood schizonticidal drug
^bBoth clinical neurologic and histopathologic changes (at autopsy) were observed at this dose which was mistakenly consumed on a single day
^cSame symptoms as presented in Column 3
^dReference source of data is indicated in square brackets
^eNTI = Minimum dose known to induce clinical signs of neurotoxicity/therapeutic dose

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