Dermatological Adverse Events Associated with Topical Brimonidine Gel 0.33% in Subjects with Erythema of Rosacea: A Retrospective Review of Clinical Studies

Abstract

Background: The topical α2 adrenergic receptor agonist brimonidine gel 0.33% is an effective and safe pharmacological treatment for the facial erythema of rosacea. However, adverse events of worsened redness have occasionally been reported with its use.

Objective: A detailed analysis of adverse events is needed to accurately define worsening erythema and the adverse-events profile associated with brimonidine gel treatment.

Methods and measurements: A retrospective review of related dermatological adverse events occurring in subjects enrolled in the two pivotal four-week Phase 3 studies and the 52-week long-term safety study for brimonidine gel was conducted. Measurements included total adverse-event incidences; number of subjects experiencing adverse events; study discontinuation due to adverse events, severity, onset, episodic duration period; and correlation of adverse events to subject disposition, and rosacea profile.

Results: Flushing and erythema were the most commonly reported adverse events, occurring in a total of 5.4 percent of subjects in the Phase 3 studies and in 15.4 percent in the long-term study. Most adverse events were mild or moderate in severity, transient, and intermittent. Adverse events occurred early in treatment, and duration was short-lived in the majority of cases. Adverse-event patterns were not remarkably altered with regard to subject disposition in the long-term study.

Conclusion: Adverse events of worsening redness are not frequent, are transient in nature, and occur early in the course of treatment with brimonidine gel.

Figures

Figure 1

AE incidence and subject discontinuation. Total AE incidence and subject discontinuations due to AEs over time in the Phase 3 studies (A) and long-term safety study (B) are shown. Subjects are represented more than once if they experienced multiple AEs.

Figure 2

Median AE onset and episodic duration period. Median onset and median episodic duration period of AEs occurring in >1% of subjects in the long-term safety study are shown. Boxes represent initial onset day (left border) to terminal resolution day (right border) of each AE; area represents episodic duration period, including periods when no AE symptoms were present. AEs that were not terminally resolved at the time the subject exited the study were recorded as “ongoing.” Ongoing AEs were not included in the duration analysis and are reported separately.