sensations).19 The third patient experienced additional symptoms
(burning, pruritus) with the initial application.19 In all cases, the
adverse events resolved spontaneously within one day.19 Routt et
al recommended several useful strategies for clinicians prescribing
brimonidine gel, including: 1) counseling patients about the
potential for worsening erythema (perhaps showing a photo of
worsening redness) and 2) utilizing a test area before applying
the medication to the full face.19 In our opinion, this relatively
immediate reaction (with or without additional symptoms such
as burning) could be considered a paradoxical erythema.
Pharmacovigilance Data
Following the introduction of a new drug, suspicions of adverse reactions may be reported to the drug’s manufacturer by prescribers or patients. The cases reported to Galderma, manufacturer of brimonidine gel, have been analyzed to evaluate trends in post-marketing safety signals.13 The analysis of case reports qualified as “condition aggravated†or “rebound effect†by the reporter received from launch to end of April 2014 showed that the most frequently associated symptoms were erythema in nearly all cases, flushing, feeling hot/skin burning sensation/skin warmth, and more rarely skin pain. Dermatitis, pruritus, swelling face, and pallor were found in fewer than 10% of reports each. Because these were spontaneous reports, there is limited information about patient characteristics and risk factors, including clinical type of rosacea, exposure to rosacea triggers or exacerbating factors, concomitant treatments, or medical history.13
Following the introduction of a new drug, suspicions of adverse reactions may be reported to the drug’s manufacturer by prescribers or patients. The cases reported to Galderma, manufacturer of brimonidine gel, have been analyzed to evaluate trends in post-marketing safety signals.13 The analysis of case reports qualified as “condition aggravated†or “rebound effect†by the reporter received from launch to end of April 2014 showed that the most frequently associated symptoms were erythema in nearly all cases, flushing, feeling hot/skin burning sensation/skin warmth, and more rarely skin pain. Dermatitis, pruritus, swelling face, and pallor were found in fewer than 10% of reports each. Because these were spontaneous reports, there is limited information about patient characteristics and risk factors, including clinical type of rosacea, exposure to rosacea triggers or exacerbating factors, concomitant treatments, or medical history.13
As shown in Figure 3, “conditions aggravated/rebound effectsâ€
were most likely to occur in the first 15 days after initiation of
therapy, primarily in the first week (when data were available);
in addition, two distinct peaks in time to onset of erythematous
event after application of brimonidine gel have been reported
(3-6 hours and 10-12 hours).13 This allowed identification of two
types of reactions based on the time to onset post application:
appearing within 3-6 hour and observed after 10-12 hours.13
