p;0
6 (<1%)
0
Hallucinationsa
14 (2%)
2 (<1%)
6 (<1%)
0
aHallucinations includes visual, auditory, and mixed hallucinations.
5.3 Dizziness and Somnolence
POTIGA causes dose-related increases in dizziness and somnolence [see Adverse Reactions (6.1)]. In placebo-controlled trials in patients with epilepsy, dizziness was reported in 23% of patients treated with POTIGA and 9% of patients treated with placebo. Somnolence was reported in 22% of patients treated with POTIGA and 12% of patients treated with placebo. In these trials 6% of patients on POTIGA and 1.2% on placebo discontinued treatment because of dizziness; 3% of patients on POTIGA and <1.0% on placebo discontinued because of somnolence.
Most of these adverse reactions were mild to moderate in intensity and occurred during the titration phase. For those patients continued on POTIGA, dizziness and somnolence appeared to diminish with continued use.
5.4 QT Interval Effect
A study of cardiac conduction showed that POTIGA produced a mean 7.7-msec QT prolongation in healthy volunteers titrated to 400 mg 3 times daily. The QT-prolonging effect occurred within 3 hours. The QT interval should be monitored when POTIGA is prescribed with medicines known to increase QT interval and in patients with known prolonged QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia [see Clinical Pharmacology (12.2)].
5.5 Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including POTIGA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive-therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted relative risk 1.8, 95% confidence interval [CI]: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43% compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately 1 case of suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanism of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed.
Table 3 shows absolute and relative risk by indication for all eva luated AEDs.
Table |
