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

Table 5 Clinical neurologic toxicity is not observed following short or long-term dosing in humans [18]

Neurologic symptom associated with plasmocid, pamaquine or pentaquine in rhesus monkeys or humans	MEDRA code	Number of subjects affected (%)
		Tafenoquine (total dose)				Placebo
		Phase 1 [44] (4–600 mg)	200 mg × 3 (600 mg)	400 mg × 3 (1200 mg)	200 mg × 3 then 200 mg weekly (average duration 21 weeks) (3000 mg)	Placebo
		N = 45	N = 491	N = 713	N = 825	N = 396
NystagmusLoss of motor	Nystagmus—10029864	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Coordination	Coordination abnormal—10010947	0 (0.0)	0 (0.0)	0 (0.0)	2 (0.2)^a	0 (0.0)
Loss of equilibrium	Balance disorder—10049848	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Loss of pupillary reflexes	Pupillary reflex impaired—10037352	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Death	Death—10011906	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Syncope	Syncope—10042772	0 (0.0)	0 (0.0)	0 (0.0)	2 (0.2)^b	0 (0.0)
Postural hypotension or Hypotension	Postural hypotension or hypotension—10021097 or 10036433	0 (0.0)	0 (0.0)	1 (0.1)	0 (0.0)	0 (0.0)
Erectile dysfunction	Erectile dysfunction—10061461	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.1)	1 (0.3)
Paralyzed palate	Araflexia—1003084	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
Eye movements disturbed	Ophthalmoplegia—10030875 or	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	Extraocular muscle paresis—10015829 or	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
	Diplopia—10013036	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)

^aBoth subjects reported abnormal coordination at the beginning of the study (Day 0), suggesting pre-existing factors were at play. One subject had a history of spinal surgery, while the other had been using loratadine for 7 years
^bIn both cases, there was a single episodes of syncope that was considered mild and unrelated to tafenoquine

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