Table 5.
Adverse events classified as nervous system disorders or psychiatric disorders reported across the entire tafenoquine development programme classified by total tafenoquine dose [74]
| Adverse event, n (%) | All placeboa (N = 794) | Total TQ 300 mg ≤ 3 days (N = 807) | Total TQ > 300 mg ≤ 3 days (N = 1482) | Total TQ > 300 mg > 3 days (N = 1445) | All TQb (N = 4129) |
|---|---|---|---|---|---|
| Any nervous system disorder | 170 (21) | 142 (18) | 240 (16) | 269 (19) | 734 (18) |
| Headache | 149 (19) | 98 (12) | 164 (11) | 211 (15) | 544 (13) |
| Migraine | 4 (< 1) | 3 (< 1) | 0 | 3 (< 1) | 8 (< 1) |
| Sinus headache | 1 (< 1) | 0 | 0 | 4 (< 1) | 4 (< 1) |
| Tension headache | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Head discomfort | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Visual field defect | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Lethargy | 0 | 0 | 28 (2) | 28 (2) | 56 (1) |
| Somnolence | 1 (< 1) | 3 (< 1) | 21 (1) | 1 (< 1) | 25 (< 1) |
| Amnesia | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Depressed level of consciousness | 0 | 1 (< 1) | 0 | 0 | 1 (< 1) |
| Disturbance in attention | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Dysgeusia | 1 (< 1) | 0 | 17 (1) | 1 (< 1) | 18 (< 1) |
| Paraesthesia | 0 | 0 | 3 (< 1) | 4 (< 1) | 8 (< 1) |
| Hypoaesthesia | 1 (< 1) | 0 | 3 (< 1) | 1 (< 1) | 4 (< 1) |
| Hyperaesthesia | 0 | 0 | 0 | 1 (< 1) | 2 (< 1) |
| Burning sensation | 0 | 0 | 0 | 0 | 1 (< 1) |
| Coordination abnormal | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Balance disorder | 0 | 1 (< 1) | 0 | 0 | 1 (< 1) |
| Dizziness | 24 (3) | 62 (8) | 56 (4) | 33 (2) | 171 (4) |
| Syncope | 0 | 2 (< 1) | 1 (< 1) | 2 (< 1) | 5 (< 1) |
| Presyncope | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Dizziness postural | 1 (< 1) | 0 | 0 | 0 | 0 |
| Loss of consciousness | 1 (< 1) | 0 | 0 | 0 | 0 |
| Tremor | 0 | 1 (< 1) | 1 (< 1) | 2 (< 1) | 4 (< 1) |
| Muscle contractions involuntary | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Sciatica | 0 | 0 | 0 | 2 (< 1) | 3 (< 1) |
| Post herpetic neuralgia | 0 | 0 | 1 (< 1) | 1 (< 1) | 2 (< 1) |
| Trigeminal neuralgia | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Any psychiatric disorder | 8 (1) | 16 (2) | 19 (1) | 37 (3) | 79 (2) |
| Insomnia | 8 (1) | 15 (2) | 12 (< 1) | 15 (1) | 48 (1) |
| Abnormal dreams | 0 | 1 (< 1) | 0 | 6 (< 1) | 7 (< 1) |
| Sleep disorder | 0 | 0 | 0 | 3 (< 1) | 3 (< 1) |
| Nightmare | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Agitation | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Anxiety | 0 | 2 (< 1) | 0 | 0 | 2 (< 1) |
| Anxiety disorder | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Irritability | 0 | 0 | 1 (< 1) | 0 | 2 (< 1) |
| Neurosis | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Panic attack | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Psychotic disorder | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Stress | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Euphoric mood | 0 | 0 | 1 (< 1) | 2 (< 1) | 3 (< 1) |
| Depressed mood | 0 | 0 | 1 (< 1) | 1 (< 1) | 2 (< 1) |
| Depression | 0 | 0 | 0 | 2 (< 1) | 2 (< 1) |
| Bipolar disorder | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Disinhibition | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Mood altered | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
| Alcoholic hangover | 0 | 0 | 0 | 1 (< 1) | 1 (< 1) |
| Tic | 0 | 0 | 1 (< 1) | 0 | 1 (< 1) |
aThe placebo group includes healthy volunteers treated with placebo and P. vivax subjects treated with chloroquine alone in P. vivax relapse prevention
bAlso includes 392 subjects who received < 300 mg total dose and 3 subjects who received 300 mg total dose > 3 days