erythema, flushing, rosacea, skin warm, skin discomfort and
irritation/dermatitis. Table 1 presents the frequency of those adverse
events in the phase III trials.13
The discontinuation rate for dermatological adverse events occurring
in >1% of total subjects was 0.8%. The time to onset
of dermatological adverse events and discontinuations due to
these events during the 12-month long-term study of brimonidine
gel are shown in Figure 2.13
As detailed in Figure 2 and Table 2, the majority of these adverse
events occurred in the first two weeks of the long-term study,
and were mild to moderate in severity.13, 16 The data show no clear relationship between baseline numbers of papules/pustules
and frequency of adverse events. Of interest, the majority
of dermatologic events were not observed by investigators or
documented with photographs, but rather were reported in patient
diaries.13 It is important to note that discontinuation due to
dermatologic adverse events occurred at a low and relatively
steady rate throughout the study.16
Reports of “Rebound†in the Literature
In 2014, Ilkovitch et al18 published one case and Routt et al19 reported three cases of “rebound†in patients treated with brimonidine gel. The events reported in these instances happened within 24 hours after the first application of brimonidine gel and as such do not fit the traditional definition of “rebound†as occurring after a treatment course has finished.18, 19 Each could, however, potentially be considered an exaggerated recurrence of erythema. In the single case reported by Ilkovitch et al, brimonidine gel effectively relieved redness but erythema recurred 10-12 hours after application (an expected return); unexpectedly, the erythema was worse than baseline.18 The worsened erythema persisted for 12-14 hours then resolved spontaneously.18 Continued use of brimonidine gel resulted in similar outcomes.18 In our opinion, this should be called exaggerated recurrence of erythema, indicating an erythema that occurs after the drug effect subsides and has severity greater than baseline.
In 2014, Ilkovitch et al18 published one case and Routt et al19 reported three cases of “rebound†in patients treated with brimonidine gel. The events reported in these instances happened within 24 hours after the first application of brimonidine gel and as such do not fit the traditional definition of “rebound†as occurring after a treatment course has finished.18, 19 Each could, however, potentially be considered an exaggerated recurrence of erythema. In the single case reported by Ilkovitch et al, brimonidine gel effectively relieved redness but erythema recurred 10-12 hours after application (an expected return); unexpectedly, the erythema was worse than baseline.18 The worsened erythema persisted for 12-14 hours then resolved spontaneously.18 Continued use of brimonidine gel resulted in similar outcomes.18 In our opinion, this should be called exaggerated recurrence of erythema, indicating an erythema that occurs after the drug effect subsides and has severity greater than baseline.
The cases reported by Routt et al also involved worsening erythema
after the first application of brimonidine gel.19 In these cases,
erythema improved for 1-6 hours but then worsening redness occurred.
In two cases, the patients continued use of brimonidine
for several days until additional symptoms were noticed (burning
