Included as part of the PRECAUTIONS section.
Hypersensitivity reactions, including cases of
angioedema, eye swelling, facial swelling, dyspnea, urticaria, and adverse skin
reactions, have been reported during post marketing surveillance.
Avoid the use of FINACEA Gel in patients with known
hypersensitivity to any component of the gel. If hypersensitivity develops
during treatment, discontinue FINACEA Gel and institute appropriate therapy.
Skin irritation (i.e. pruritus, burning or stinging) may
occur during use of FINACEA Gel, usually during the first few weeks of
treatment. If sensitivity or severe irritation develops and persists,
discontinue treatment and institute appropriate therapy.
There have been isolated reports of hypopigmentation
after use of azelaic acid. Since azelaic acid has not been well studied in
patients with dark complexion, monitor these patients for early signs of
Eye And Mucous Membranes Irritation
Avoid contact with the eyes, mouth and other mucous
membranes. If FINACEA Gel does come in contact with the eyes, wash the eyes
with large amounts of water and consult a physician if eye irritation persists [see
Exacerbation Of Asthma
Worsening of asthma has been reported in patients using
azelaic acid formulations including FINACEA Gel. Consult a physician if asthma
is exacerbated with use of FINACEA Gel.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Systemic long-term animal studies have not been performed
to evaluate the carcinogenic potential of azelaic acid. In a 26-week dermal
carcinogenicity study using transgenic (Tg.AC) mice, FINACEA Gel and the gel
vehicle, when applied once or twice daily, did not increase the number of
female Tg.AC animals with papillomas at the treatment site. No statistically
significant increase in the number of animals with papillomas at the treatment
site was observed in male Tg.AC animals after once daily application. After
twice daily application, FINACEA Gel and the gel vehicle induced a
statistically significant increase in the number of male animals with
papillomas at the treatment site when compared to untreated males. This
suggests that the positive effect may be associated with the vehicle
application. The clinical relevance of the findings in animals to humans is not
Azelaic acid was not mutagenic or clastogenic in a
battery of in vitro [Ames assay, HGPRT in V79 cells (Chinese hamster lung
cells), and chromosomal aberration assay in human lymphocytes] and in vivo (dominant
lethal assay in mice and mouse micronucleus assay) genotoxicity tests.
Oral administration of azelaic acid at dose levels up to
2500 mg/kg/day (162 times the MRHD based on BSA) did not affect fertility or
reproductive performance in male or female rats.
Use In Specific Populations
Pregnancy Category B
There are no adequate and well-controlled studies in
pregnant women. Therefore, FINACEA Gel should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Dermal embryofetal developmental toxicology studies have
not been performed with azelaic acid, 15% gel. Oral embryofetal developmental
studies were conducted with azelaic acid in rats, rabbits, and cynomolgus
monkeys. Azelaic acid was administered during the period of organogenesis in
all three animal species. Embryotoxicity was observed in rats, rabbits, and
monkeys at oral doses of azelaic acid that generated some maternal toxicity.
Embryotoxicity was observed in rats given 2500 mg/kg/day [162 times the maximum
recommended human dose (MRHD) based on body surface area (BSA)], rabbits given
150 or 500 mg/kg/day (19 or 65 times the MRHD based on BSA) and cynomolgus
monkeys given 500 mg/kg/day (65 times the MRHD based on BSA) azelaic acid. No
teratogenic effects were observed in the oral embryofetal developmental studies
conducted in rats, rabbits and cynomolgus monkeys.
An oral peri- and post-natal developmental study was
conducted in rats. Azelaic acid was administered from gestational day 15
through day 21 postpartum up to a dose level of 2500 mg/kg/day. Embryotoxicity
was observed in rats at an oral dose of 2500 mg/kg/day (162 times the MRHD
based on BSA) that generated some maternal toxicity. In addition, slight
disturbances in the post-natal development of fetuses was noted in rats at oral
doses that generated some maternal toxicity (500 and 2500 mg/kg/day; 32 and 162
times the MRHD based on BSA). No effects on sexual maturation of the fetuses
were noted in this study.
It is not known whether azelaic acid is excreted in human
milk; however, in vitro studies using equilibrium dialysis were conducted to
assess the potential for human milk partitioning. The studies demonstrated
that, at an azelaic acid concentration of 25 μg/mL, the milk/plasma
distribution coefficient was 0.7 and the milk/buffer distribution was 1.0.
These data indicate that passage of drug into maternal milk may occur. Since
less than 4% of a topically applied dose of 20% azelaic acid cream is
systemically absorbed, the uptake of azelaic acid into maternal milk is not
expected to cause a significant change from baseline azelaic acid levels in the
milk. Nevertheless, a decision should be made to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the
Safety and effectiveness of FINACEA Gel in pediatric
patients have not been established.
Clinical studies of FINACEA Gel did not include
sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger subjects.