DRUGS IN DERMATOLOGY
Azelaic Acid in Acne Vulgaris
Mary Caroline Young, Patrick M. Zito
ABSTRACT: By definition, a drug is a medicine or sub-
stance that exerts a physiologic effect on an organism. In
dermatology, various medications and substances are
utilized on a daily basis, ranging from topical treatments
to anesthetics in micrographic surgery. The purpose of this
section was to focus on some of the more common
substances, specifically how they work, how they are
utilized, and routine alternatives (if available). The mech-
anism of action, usage, and alternative options of the
medication azelaic acid are discussed.
Key words: Acne Vulgaris, Melanin, Pregnancy,
Propionibacterium, Rosacea
A cne vulgaris is a common disorder of the pilose-
baceous unit that causes comedones, papules, pus-
tules, and nodules on the face, chest, and back. It
predominately affects adolescents but may be present in
patients through 30 years old or older (Zaenglein, Graber,
& Thiboutot, 2012).
The pathogenesis of acne involves the following four
key elements: (a) follicular epidermal hyperproliferation,
(b) excess sebum production, (c) inflammation, and (d)
Propionibacterium acnes (Zaenglein et al., 2012). Treat-
ment is typically based on the type of acne that is diag-
nosed. However, regardless of the morphology, topical
retinoids are often involved in the first-line treatment
either as monotherapy or in combination with topical or
oral antibiotics or benzoyl peroxide (Zaenglein et al.,
2012). Topical dapsone, azelaic acid, and salicylic acid
are used as alternatives to retinoids.
Topical antibacterials such as erythromycin are not
recommended as monotherapy for acne vulgaris. Azelaic
acid is a safe and appropriate monotherapy treatment
Mary Caroline Young, DO, A.T. Still University, Kirksville College
of Osteopathic Medicine, Kirksville, MO.
Patrick M. Zito, DO, PharmD, RPh, FASCP, FRSPH, College of Health
Sciences, School of Nursing, Walden University, Minneapolis, MN.
The authors declare no conflict of interest.
Correspondence concerning this article should be addressed to
Patrick M. Zito, DO, PharmD, RPh, FASCP, FRSPH, College of
Health Sciences, School of Nursing, Walden University, 100
Washington Ave., S. Suite 900, Minneapolis, MN 55401.
E-mail: Patrick.zito@waldenu.edu
Copyright B 2018 by the Dermatology Nurses’ Association.
DOI: 10.1097/JDN.0000000000000399
VOLUME 00 | NUMBER 0 | MONTH 2018
Copyright © 2018 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited.
option for acne vulgaris. Azelaic acid is a dicarboxylic
acid that is thought to alter follicular epidermal hyper-
proliferation, inflammation, and Propionibacterium acnes,
but not excess sebum production (Allergan, Inc., 2003;
Zaenglein et al., 2012).
MECHANISM OF ACTION
The mechanism of action of azelaic acid is not well un-
derstood. However, in vitro, it possesses antimicrobial
activity against Propionibacterium acnes and Staphylo-
coccus epidermidis, most likely through microbial cellu-
lar protein synthesis inhibition (Allergan, Inc., 2003).
Microcomedones and comedones can arise because of
hyperkeratinization. Azelaic acid produces an anticomedonal
effect by decreasing the amount of hyperkeratinization
(Allergan, Inc., 2003). Biopsies have shown a decrease in
stratum corneum thickness, keratohyalin granules, and
filaggrin in patients treated with azelaic acid cream (Allergan,
Inc., 2003). Azelaic acid also competitively inhibits tyros-
inase, an enzyme involved in the conversion of tyrosine
to melanin (Figure 1). Last, its mechanism of action also
includes the inhibition of DNA synthesis and mitochon-
drial enzymes, thereby inducing direct cytotoxic effects
on the melanocyte (Sarkar et al., 2016). Therefore, azelaic
acid is thought to decrease postinflammatory hyperpig-
mentation (Zaenglein et al., 2016).
USES IN PRACTICE
Topical azelaic acid is Food and Drug Administration
(FDA) approved for mildYmoderate inflammatory acne
vulgaris under the brand name Azelex as 20% cream
(Allergan, Inc., 2003). It is also FDA approved for mild-
to-moderate papulopustular rosacea under the brand
name Finacea as 15% gel and 15% foam (Bayer
HealthCare Pharmaceuticals Inc., 2015). At this time,
azelaic acid is not approved for any other subtype of
rosacea. In clinical studies for azelaic acid gel 15%
(Finacea), there was some reduction of erythema noted
in patients treated for papulopustular rosacea, but no
specific clinical trials were performed to study erythema
in rosacea in the absence of papules and pustules (Bayer
HealthCare Pharmaceuticals Inc., 2015). Azelaic acid is
also used off-label for the treatment of hyperpigmen-
1
 DRUGS IN DERMATOLOGY
FIGURE 1. Competitive inhibition of tyrosinase by azelaic
acid results in a decreased production of melanin.
tation disorders, including melasma, due to its inhibition
of tyrosinase (Figure 1; Mazurek & Pierzchaaa, 2016).
PHARMACOKINETICS
Topical azelaic acid has a bioavailability of up to 10% in
the epidermis and dermis (Allergan, Inc., 2003). Approx-
imately 4% of azelaic acid cream or gel is absorbed systemi-
cally after topical application (Allergan, Inc., 2003; Bayer
HealthCare Pharmaceuticals Inc., 2015). Azelaic acid is a
saturated dicarboxylic acid (HOOC-(CH2)7-COOH) found
in many foods, including animal products and whole
grains. It may undergo some beta-oxidation to shorter-
chain dicarboxylic acids, but it is predominately excreted
in its original form in urine (Allergan, Inc., 2003). The half-
life of topical azelaic acid is approximately 12 hours, and
the patient should apply it to the area of concern twice
daily. Favorable results are typically seen within 4 weeks
in patients with acne vulgaris and within 12 weeks in pa-
tients with papulopustular rosacea (Allergan, Inc., 2003;
Bayer HealthCare Pharmaceuticals Inc., 2015).
ADVERSE EFFECTS
Mild, transient adverse effects have been reported with
topical azelaic acid. Adverse effects of the 15% gel
(Finacea gel) used for rosacea include burning/stinging/
tingling (29%), pruritis (11%), scaling/dry skin (8%),
and erythema/irritation (4%; Bayer HealthCare Phar-
maceuticals Inc., 2015). Adverse effects of the 20%
cream (Azelex) used for acne vulgaris are similar but
less commonly noted in the clinical trials. They include
pruritus, burning, stinging, and tingling in 1%Y5% of
patients and erythema, dryness, rash, peeling, irritation,
dermatitis, and contact dermatitis in less than 1% of
patients (Allergan, Inc., 2003). Clinical trials of the 15%
foam (Finacea foam) reported similar adverse reactions.
2 Journal of the Dermatology Nurses’ Association
Copyright © 2018 Dermatology Nurses' Association. Unauthorized reproduction of this article is prohibited.
All three formulations of topical azelaic acid mention
that hypopigmentation has been reported and recom-
mend monitoring for this in patients with dark complex-
ions, as this has not been well studied in this population.
Azelaic acid can also cause ocular and mucous mem-
brane irritation; thus, contact should be avoided (Bayer
HealthCare Pharmaceuticals Inc., 2015). It should be
noted that hypersensitivity reactions to azelaic acid or its
components have also been reported.
ALTERNATIVES
Currently, there are no other known drugs with the same
mechanism of action as azelaic acid. On the other hand,
there are many other drugs that can be used in the
treatment of acne vulgaris, such as topical and oral reti-
noids, oral and topical antibiotics, benzoyl peroxide, top-
ical dapsone, salicylic acid, photodynamic therapy, lasers,
and peels. Antibiotics develop resistance when not used in
combination with benzoyl peroxide and therefore should
not be used as monotherapy. Azelaic acid is an effective
monotherapy for acne vulgaris in pregnant women
(Chien, Qi, Rainer, Sachs, & Helfrich, 2016).
WARNINGS AND PRECAUTIONS
Hypersensitivity reactions have been reported with the
use of azelaic acid. It should be avoided in patients with
known hypersensitivity reactions to azelaic acid or its
components. Hypopigmentation has been reported with
the use of azelaic acid as well. Skin should be monitored
for signs of hypopigmentation, especially in patients with
dark complexions. In addition, contact with the eyes,
mouth, and other mucous membranes should be avoided.
REFERENCES
Allergan, Inc. (2003). Azelex (azelaic acid) cream label. Irvine, CA:
Allergan. Retrieved from http://www.accessdata.fda.gov/drugsatfda_
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Bayer HealthCare Pharmaceuticals Inc. (2015). Finacea (azelaic acid) foam full
prescribing information. Whippany, NJ: Author. Retrieved from http://
labeling.bayerhealthcare.com/html/products/pi/Finacea_Foam_PI.pdf
Chien, A. L., Qi, J., Rainer, B., Sachs, D. L., & Helfrich, Y. R. (2016).
Treatment of acne in pregnancy. The Journal of the American Board of
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