Neurological and psychiatric safety of tafenoquine in Plasmodium vivax relapse prevention: a review

Malaria Journal

Table 4 Frequency of all NPAEs occurring with tafenoquine/chloroquine versus primaquine/chloroquine (day 1 to day 180) [9,10,11]

Event—n (%) patients	Grade^a	Integrated safety summary
Event—n (%) patients	Grade^a	Tafenoquine (N = 483)	Primaquine (N = 264)
Nervous system disorders	Any	105 (22)	60 (23)
	Grade 1	78 (16)	38 (14)
	Grade 2	26 (5)	19 (7)
	Grade 3	0	2 (< 1)
	NA	1 (< 1)	1 (< 1)
Headache	Any	64 (13)	40 (15)
	Grade 1	45 (9)	22 (8)
	Grade 2	18 (4)	16 (6)
	Grade 3	0	2 (< 1)
	NA	1 (< 1)	0
Dizziness	Any	59 (12)	30 (11)
	Grade 1	52 (11)	25 (9)
	Grade 2	7 (1)	4 (2)
	NA	0	1 (< 1)
Migraine	Any	3 (< 1)	1 (< 1)
	Grade 1	2 (< 1)	0
	Grade 2	1 (< 1)	1 (< 1)
Syncope	Any	2 (< 1)	1 (< 1)
	Grade 1	1 (< 1)	1 (< 1)
	Grade 2	1 (< 1)	0
Balance disorder	Any	1 (< 1)	0
Balance disorder	Grade 2	1 (< 1)	0
Somnolence	Any	1 (< 1)	0
Somnolence	Grade 2	1 (< 1)	0
Tremor	Any	1 (< 1)	1 (< 1)
Tremor	Grade 1	1 (< 1)	1 (< 1)
Burning sensation	Any	0	1 (< 1)
Burning sensation	Grade 1	0	1 (< 1)
Dysaesthesia	Any	0	1 (< 1)
Dysaesthesia	Grade 1	0	1 (< 1)
Hypoaesthesia	Any	0	1 (< 1)
Hypoaesthesia	Grade 2	0	1 (< 1)
Psychiatric disorders	Any	15 (3)	12 (5)
	Grade 1	9 (2)	7 (3)
	Grade 2	6 (1)	5 (2)
Insomnia	Any	15 (3)	8 (3)
	Grade 1	9 (2)	4 (2)
	Grade 2	6 (1)	4 (2)
Anxiety	Any	2 (< 1)	3 (1)
	Grade 1	0	2 (< 1)
	Grade 2	2 (< 1)	1 (< 1)
Depression	Any	0	1 (< 1)
Depression	Grade 1	0	1 (< 1)
Expanded definition of NPAEs
Asthenia	Any	8 (2)	5 (2)
	Grade 1	7 (1)	2 (< 1)
	Grade 2	1 (< 1)	3 (1)
Fatigue	Any	3 (< 1)	0
Fatigue	Grade 1	3 (< 1)	0
Labyrinthitis	Any	2 (< 1)	0
Labyrinthitis	Grade 1	2 (< 1)	0
Alcohol intolerance	Any	1 (< 1)	0
Alcohol intolerance	Grade 1	1 (< 1)	0
Vertigo	Any	3 (< 1)	1 (< 1)
	Grade 1	2 (< 1)	1 (< 1)
	Grade 2	1 (< 1)	0
Vestibular disorder	Any	1 (< 1)	0
Vestibular disorder	Grade 1	1 (< 1)	0

Data are from the DETECTIVE phase 2b, DETECTIVE phase 3, and GATHER trials (safety population). Vivax malaria patients were treated with chloroquine plus either single-dose tafenoquine 300 mg or primaquine 15 mg for 14 days. Adverse events of Grade 3 and above in any treatment group are italicized
Note that this includes adverse events that were associated with recurrences after day 29. Subjects that experienced recurrence received further treatment with primaquine. Thus, the comparison of adverse events before day 29 provides a more reliable indicator of potential differences caused by drug treatment (see Fig. 4)
^aCommon Terminology Criteria for Adverse Events v4.0