The percutaneous penetration of AzA was shown to be approximately
8-fold greater after application of AzA 15% gel
compared with AzA 20% cream based on results from an in
vitro Franz flow-through diffusion cell test in murine skin.25Skin Barrier Effects
Sensitive skin is common in rosacea patients, with increased
centrofacial transepidermal water loss reported in those with
centrofacial erythema both with and without papulopustular
lesions.1,5,13,43
Application-site stinging and/or burning, reported in a
subset of patients treated with AzA 15% gel, are usually
transient in duration, mild to moderate in severity, no longer
occurring after the first week to a few weeks of use
in many patients, and not commonly resulting in discontinued
use of the AzA 15% gel.19,25,26,28,36,44 These symptoms
are not associated with visible skin changes suggestive of
contact dermatitis or contact urticaria, but rather are neurosensory
and idiosyncratic in nature.38
Regular proper skin care with a gentle cleanser and wellformulated
moisturizer has been shown to reduce the
likelihood, frequency, and intensity of stinging and burning
after application of AzA 15% gel in most rosacea patients
who experience these idiosyncratic effects.15,24,25,44,45
An in vitro modified Franz diffusion chamber test performed
with human skin showed that applying 1 of 3
studied brand moisturizer lotions (CeraVe® Moisturizing
Lotion, Cetaphil® Moisturizing Lotion, Dove® lotions) before
applying AzA 15% gel did not reduce the percutaneous
penetration of AzA, and in some cases resulted in an incremental
increase in percutaneous penetration compared
with applying the moisturizer after applying the AzA 15%
gel. The study results suggested that any of the 3 tested
moisturizers may be applied either before or after AzA 15%
gel without a major change in the percutaneous penetration/
absorption profile of AzA.39
In a split-face, investigator-blinded, 12-week study of 40 subjects with PPR, the idiosyncratic neurocutaneous
symptoms of stinging and burning that affect a subset of
rosacea patients treated with AzA 15% gel were shown not
to be related to worsening of the epidermal permeability
barrier function by the medication.46 One side of the face
was treated with AzA 15% gel twice daily, and the other
side remained untreated. The results were as follows:
Decline in skin hydration measured by corneometry
was greater on the untreated side. There was
an increase in skin hydration at week 1 compared
with baseline on the AzA-treated side (P=.009).
Investigator assessments of parameters such as
facial erythema, desquamation, and overall facial
appearance were scored using a 6-point ordinal
scale (Table 1). Subjects used this same scale to
report symptoms.
A statistically significant decrease in overall facial
erythema was also noted on the treated side at
week 2 (P=.003) and week 4 (P<.001) (Figure 1).
Overall facial appearance assessment was statistically
superior on the treated side at week 2 (P=.005)
and week 4 (P<.001).
A statistically significant decrease in desquamation
was noted on the treated side over the untreated
side at each time point (P<.001) (Figure 2).
Longitudinal analysis showed an increase in desquamation
on the untreated side at 48 hours, week
1, week 2, and week 4 (Figure 2).
There was no increase noted in facial stinging and
itching at any time point on the treated side. By week
4, there was a reduction in itching in both groups.
This study supports that AzA 15% gel does not appear to induce
impairment of the epidermal permeability barrier, and improves
signs and symptoms of rosacea, including skin changes inherent
to rosacea-prone facial skin. This supports that the disease state
itself is associated with epidermal permeability barrier impairment
that is often not visibly evident or may present with visible
signs such as fine facial scaling (“rosacea dermatitisâ€).5,43-46
Efficacy and Safety
The efficacy and safety of AzA 15% gel for PPR have been
demonstrated in multiple studies, both as monotherapy and
in combination with oral therapy (ie, doxycycline); no major
cutaneous or systemic safety issues have been associated
with AzA 15% gel.19,26-29,31-34,36,37
