Included as part of the PRECAUTIONS section.
Effects on Endocrine System
Systemic absorption of topical
corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA)
axis suppression with the potential for glucocorticosteroid insufficiency. This
may occur during treatment or after withdrawal of treatment. Manifestations of
Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some
patients by systemic absorption of topical corticosteroids while on treatment.
Factors that predispose a patient using a topical corticosteroid to HPA axis
suppression include the use of high-potency steroids, large treatment surface
areas, prolonged use, use of occlusive dressings, altered skin barrier, liver
failure and young age.
Because of the potential for
systemic absorption, use of topical corticosteroids may require that patients be
periodically evaluated for HPA axis suppression. This may be done by using the
adrenocorticotropic hormone (ACTH) stimulation test.
In a study evaluating the
effects of mometasone furoate cream on the HPA axis, 15 grams were applied
twice daily for 7 days to six adult subjects with psoriasis or atopic
dermatitis. The results show that the drug caused a slight lowering of adrenal
If HPA axis suppression is
noted, an attempt should be made to gradually withdraw the drug, to reduce the
frequency of application, or to substitute a less potent corticosteroid.
Recovery of HPA axis function is generally prompt upon discontinuation of
topical corticosteroids. Infrequently, signs and symptoms of
glucocorticosteroid insufficiency may occur, requiring supplemental systemic
Pediatric patients may be more
susceptible to systemic toxicity from equivalent doses due to their larger skin
surface to body mass ratios [see Use In Specific Populations].
Allergic Contact Dermatitis
If irritation develops, ELOCON
Cream should be discontinued and appropriate therapy instituted. Allergic
contact dermatitis with corticosteroids is usually diagnosed by observing a
failure to heal rather than noting a clinical exacerbation as with most topical
products not containing corticosteroids. Such an observation should be
corroborated with appropriate diagnostic patch testing.
Concomitant Skin Infections
If concomitant skin infections are present or develop, an
appropriate antifungal or antibacterial agent should be used. If a favorable
response does not occur promptly, use of ELOCON Cream should be discontinued
until the infection has been adequately controlled.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to
evaluate the carcinogenic potential of ELOCON Cream. Long-term carcinogenicity
studies of mometasone furoate were conducted by the inhalation route in rats and
mice. In a 2-year carcinogenicity study in Sprague Dawley rats, mometasone
furoate demonstrated no statistically significant increase of tumors at
inhalation doses up to 67 mcg/kg (approximately 0.04 times the estimated
maximum clinical topical dose from ELOCON Cream on a mcg/m² basis). In a 19-month
carcinogenicity study in Swiss CD-1 mice, mometasone furoate demonstrated no
statistically significant increase in the incidence of tumors at inhalation
doses up to 160 mcg/kg (approximately 0.05 times the estimated maximum clinical
topical dose from ELOCON Cream on a mcg/m² basis).
Mometasone furoate increased chromosomal aberrations in
an in vitro Chinese hamster ovary cell assay, but did not increase chromosomal
aberrations in an in vitro Chinese hamster lung cell assay. Mometasone furoate
was not mutagenic in the Ames test or mouse lymphoma assay, and was not
clastogenic in an in vivo mouse micronucleus assay, a rat bone marrow
chromosomal aberration assay, or a mouse male germ-cell chromosomal aberration
assay. Mometasone furoate also did not induce unscheduled DNA synthesis in vivo
in rat hepatocytes.
In reproductive studies in rats, impairment of fertility
was not produced in male or female rats by subcutaneous doses up to 15 mcg/kg
(approximately 0.01 times the estimated maximum clinical topical dose from
ELOCON Cream, on a mcg/m² basis).
Use In Specific Populations
Teratogenic Effects - Pregnancy Category C
There are no adequate and well-controlled studies in
pregnant women. Therefore, ELOCON Cream should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Corticosteroids have been shown to be teratogenic in
laboratory animals when administered systemically at relatively low dosage
levels. Some corticosteroids have been shown to be teratogenic after dermal
application in laboratory animals.
When administered to pregnant rats, rabbits, and mice,
mometasone furoate increased fetal malformations. The doses that produced
malformations also decreased fetal growth, as measured by lower fetal weights
and/or delayed ossification. Mometasone furoate also caused dystocia and
related complications when administered to rats during the end of pregnancy.
In mice, mometasone furoate caused cleft palate at
subcutaneous doses of 60 mcg/kg and above. Fetal survival was reduced at 180
mcg/kg. No toxicity was observed at 20 mcg/kg. (Doses of 20, 60, and 180 mcg/kg
in the mouse are approximately 0.01, 0.02, and 0.05 times the estimated maximum
clinical topical dose from ELOCON Cream on a mcg/m² basis.)
In rats, mometasone furoate produced umbilical hernias at
topical doses of 600 mcg/kg and above. A dose of 300 mcg/kg produced delays in
ossification, but no malformations. (Doses of 300 and 600 mcg/kg in the rat are
approximately 0.2 and 0.4 times the estimated maximum clinical topical dose
from ELOCON Cream on a mcg/m² basis.)
In rabbits, mometasone furoate caused multiple
malformations (e.g., flexed front paws, gallbladder agenesis, umbilical hernia,
hydrocephaly) at topical doses of 150 mcg/kg and above (approximately 0.2 times
the estimated maximum clinical topical dose from ELOCON Cream on a mcg/m² basis). In an oral study,
mometasone furoate increased resorptions and caused cleft palate and/or head
malformations (hydrocephaly and domed head) at 700 mcg/kg. At 2800 mcg/kg most
litters were aborted or resorbed. No toxicity was observed at 140 mcg/kg.
(Doses at 140, 700, and 2800 mcg/kg in the rabbit are approximately 0.2, 0.9,
and 3.6 times the estimated maximum clinical topical dose from ELOCON Cream on
a mcg/m² basis.)
When rats received subcutaneous doses of mometasone
furoate throughout pregnancy or during the later stages of pregnancy, 15 mcg/kg
caused prolonged and difficult labor and reduced the number of live births,
birth weight, and early pup survival. Similar effects were not observed at 7.5
mcg/kg. (Doses of 7.5 and 15 mcg/kg in the rat are approximately 0.005 and 0.01
times the estimated maximum clinical topical dose from ELOCON Cream on a mcg/m² basis.)
Systemically administered corticosteroids appear in human
milk and could suppress growth, interfere with endogenous corticosteroid
production, or cause other untoward effects. It is not known whether topical
administration of corticosteroids could result in sufficient systemic
absorption to produce detectable quantities in human milk. Because many drugs
are excreted in human milk, caution should be exercised when ELOCON Cream is
administered to a nursing woman.
ELOCON Cream may be used with caution in pediatric
patients 2 years of age or older, although the safety and efficacy of drug use
for longer than 3 weeks have not been established. Since safety and efficacy of
ELOCON Cream have not been established in pediatric patients below 2 years of
age, its use in this age group is not recommended.
In a pediatric trial, 24 atopic dermatitis subjects, of
whom 19 subjects were age 2 to 12 years, were treated with ELOCON Cream once
daily. The majority of subjects cleared within 3 weeks.ELOCON Cream caused HPA
axis suppression in approximately 16% of pediatric subjects ages 6 to 23
months, who showed normal adrenal function by Cortrosyn test before starting
treatment, and were treated for approximately 3 weeks over a mean body surface
area of 41% (range 15%-94%). The criteria for suppression were: basal cortisol
level of ≤ 5 mcg/dL, 30-minute post-stimulation level of ≤ 18
mcg/dL, or an increase of < 7 mcg/dL. Follow-up testing 2 to 4 weeks after
trial completion, available for 5 of the subjects, demonstrated suppressed HPA
axis function in 1 subject, using these same criteria. Long-term use of topical
corticosteroids has not been studied in this population [see CLINICAL
Because of a higher ratio of skin surface area to body
mass, pediatric patients are at a greater risk than adults of HPA axis
suppression and Cushing's syndrome when they are treated with topical
corticosteroids. They are, therefore, also at greater risk of adrenal
insufficiency during and/or after withdrawal of treatment. Pediatric patients
may be more susceptible than adults to skin atrophy, including striae, when
they are treated with topical corticosteroids. Pediatric patients applying
topical corticosteroids to greater than 20% of body surface are at higher risk
of HPA axis suppression.
HPA axis suppression, Cushing's syndrome, linear growth
retardation, delayed weight gain, and intracranial hypertension have been
reported in pediatric patients receiving topical corticosteroids.
Manifestations of adrenal suppression in children include low plasma cortisol
levels and an absence of response to ACTH stimulation. Manifestations of
intracranial hypertension include bulging fontanelles, headaches, and bilateral
ELOCON Cream should not be used in the treatment of
Clinical studies of ELOCON Cream included 190 subjects
who were 65 years of age and over and 39 subjects who were 75 years of age and
over. No overall differences in safety or effectiveness were observed between
these subjects and younger subjects, and other reported clinical experience has
not identified differences in responses between the elderly and younger
patients. However, greater sensitivity of some older individuals cannot be