Table 6.
Details of subjects with severe, serious or medically important psychiatric adverse events following tafenoquine [74]
| Study identification (indication) [refs.] | Study design | Dose | Event preferred term (severity or verbatim terms) | Onset | Duration | Resolution | Relationship to study drug by the Investigator | Intervention/action taken | Medical history |
|---|---|---|---|---|---|---|---|---|---|
| SB252263/043 (prophylaxis) [89] | R, DB, PC | 750 mg cumulative | Suicidal behaviour (associated with alcohol intoxication)a | Day 8 | 1 day after tafenoquine discontinued | Resolved | Related (chloroquine co-suspect)b | Hospitalized and required corrective therapy (intervention unknown)/withdrawn due to unstable mental state | Family reported history of marital difficulties and previous suicide threat; no other relevant history or concomitant medications reported at screening |
| SB252263/050 subject A (volunteers) [90] | R, DB, PC | 350 mg single dose | Acute psychotic episode (severe) | Day 24 | 25 days | Recovered | Possibly related | Hospitalized following progressive emotional distress | Two previous episodes of psychosis (not disclosed at screening) |
| SB252263/050 subject B (volunteers) [90] | R, DB, PC | 500 mg single dose | Psychotic episode (severe) | Day 8 | 9 days | Recovered | Remotely related | Hospitalized for a pre-scheduled psychiatric admission | Recent diagnosis of schizophrenia (not disclosed at screening) |
| SB252263/014 (volunteers) [unpublished] | R, O, PG | 1200 mg cumulative | Paranoid hallucinotic psychosis (serious) | Day 27 | 3 days | Not resolved | Unrelated | Hospitalized and treated with olanzapine and lorazepam/none | History of “hallucinotic psychosis” 6 months earlier (not disclosed at screening); no obvious signs of psychosis at screening; negative drug screen |
| TAF112582 part 1 (P. vivax relapse prevention) [9] | R, DB, PC | 600 mg single dose | Depressed mood | Day 6 | Unknown | Resolved | Unrelated (chloroquine co-suspect)b | Hospitalized (on day 88 for 2 days) with nausea, epigastric pain, diarrhoea, and depression; treated with fluoxetine; consulted with psychiatric specialist (findings unknown) | History of depression but no suicidal tendencies; irregular psychiatric consults; frequent but irregular use of diazepam (10 mg) |
| TAF114582 (volunteers) [91] | R, SB, PC, AC | 600 mg single dose | Depressed mood (mild) | Day 4 | 3 days | Resolved | Related | None | No relevant past medical history or concomitant medications were reported; at the time of the event, subject also reported abdominal pain, diarrhoea, and palpitations |
| SB252263/033 (prophylaxis) [7] | R, DB, AC | 1200 mg cumulative | Depression (moderate) | Day 24 | 87 days | Resolved | Related | Required corrective therapy (paroxetin)/withdrawn from study | Closed head injury 3 years prior to study |
| SB252263/057 subject B (volunteers) [92] | R, DB, PC | 1600 mg cumulative | Depressed mood (mild) | Day 37 | 15 days | Resolved | Unlikely related | None | No relevant past history; treated for a UTI with sulfamethoxazole starting on day 13 (co-suspect) |
| SB252263/057 subject A (volunteers) [92] | R, DB, PC | 5200 mgc cumulative | Bipolar depression (mild); depression (mild) | Day 223 (62 days since last dose) | Lost to follow-up | Unknown | Unlikely related | Bupropion and lithium started on study day 223 (ongoing)/excluded due to a positive hepatitis/HIV screen | No relevant past history or concomitant medications |
UTI urinary tract infection, R randomised, SB single blind, DB double blind, PC placebo controlled, AC active controlled, O open label, PG parallel group
aFamily reported that subject had taken “poison.” The event was not assigned a body system and therefore does not appear in the pooled output for adverse events within the psychiatric disorders classification
bThe sponsor considered chloroquine co-suspect
cLoading dose 200 mg/day for 3 days plus 200 mg weekly for 23 weeks