Product information and disease description Product description Product information

Contraindications/Warnings/Precautions/Adverse effects

7 evidence topics · 5 sources

Warnings and precautions

FDA-approved prescribing information, contraindications, and boxed warnings

No evidence found.

Absence of tissue discoloration in the Phase 2b study

“No TEAEs of tissue discoloration were reported. Two nonserious TEAEs of urinary retention were reported in the active treatment groups, 1 of which required a dose reduction; both patients continued to receive the study medication with no other changes or interventions, including no need for catheterization.” (opens the source at this quote in a new tab)
“There were no cardiovascular signals of concern in electrocardiograms or vital signs, no allergic skin rashes, and no deaths in the study. Urinary problems were infrequent and mild; no catheterization was required. Moreover, tissue discoloration was not observed in this limited duration trial nor in an interim analysis of the ongoing 5-year, open-label extension study.” (opens the source at this quote in a new tab)

Urinary retention during long-term open-label treatment

“Three participants reported urinary retention, 1 reported it as mild and 2 as moderate; no dose changes were made in any case.” (opens the source at this quote in a new tab)
“Serious AEs were infrequent at 12.7%, as were TEAEs related to urinary retention (1.1%), which have been reported with the use of KV7 channel openers.” (opens the source at this quote in a new tab)

Urinary retention as a possible class effect of KV7 openers

“Urinary retention has been reported in a small minority of patients receiving chronic treatment with ezogabine and azetukalner” (opens the source at this quote in a new tab)
“urinary retention may be considered a class effect of these medications.” (opens the source at this quote in a new tab)

Absence of the ophthalmological and pigmentary pattern seen with retigabine

“However, azetukalner lacks the recognizable pattern of drug-induced organ toxicity, specifically the urinary retention and ophthalmological abnormalities (e.g., retinal pigmentation and visual acuity changes), that limited the clinical use of retigabine” (opens the source at this quote in a new tab)

Absence of the phenazinium dimers implicated in ezogabine pigmentation

“Azetukalner lacks a secondary aniline structure and reportedly does not generate the phenazinium dimers considered to be responsible for ezogabine-induced pigmentation” (opens the source at this quote in a new tab)

Central nervous system adverse events

“The most common (>10%) TEAEs across all XEN1101 dose groups were dizziness (24.6%), somnolence (15.6%), and fatigue (10.9%).” (opens the source at this quote in a new tab)
“The adverse event of confusional state was reported in 4.7% of the treated groups (2.2% receiving 10 mg, 5.9% receiving 20 mg, and 5.3% receiving 25 mg) and in 0.9% of the placebo group. No allergic rashes occurred.” (opens the source at this quote in a new tab)

Neuropsychiatric adverse events observed in the psychiatry studies

“In addition, the Company announced today that it has implemented a voluntary pause on enrollment for new patients in its ongoing clinical studies in major depressive disorder (MDD) and bipolar depression (BPD), following an analysis of neuropsychiatric adverse events in these studies. Participants currently enrolled in the randomized controlled psychiatry studies and associated OLE studies will continue on study. The observed events, the rate of these events and their severity, are consistent with the known safety and tolerability profile of azetukalner and its mechanism; however, such adverse events had not previously been seen in the Phase 2 X‑NOVA clinical study in MDD.” (opens the source at this quote in a new tab)
“This voluntary action does not impact ongoing epilepsy studies.” (opens the source at this quote in a new tab)