Systemic absorption of topical corticosteroids can produce
reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the
potential for glucocorticosteroid insufficiency 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.
Patients applying a topical steroid to a large surface area or to areas under
occlusion should be evaluated periodically for evidence of HPA axis suppression.
This may be done by using the ACTH stimulation, A.M. plasma cortisol, and
urinary free cortisol tests.
In a study evaluating the effects of mometasone furoate cream on the
hypothalamic-pituitary-adrenal (HPA) axis, 15 grams were applied twice daily for
7 days to six adult patients with psoriasis or atopic dermatitis. The cream was
applied without occlusion to at least 30% of the body surface. The results show
that the drug caused a slight lowering of adrenal corticosteroid secretion.
If HPA axis suppression is noted, an attempt should be made to 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
corticosteroids. For information on systemic supplementation, see Prescribing
Information for those products.
Pediatric patients may be more susceptible to systemic toxicity from
equivalent doses due to their larger skin surface to body mass ratios (see PRECAUTIONS –
Pediatric Use).
If irritation develops, Mometasone Furoate Cream 0.1% 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.
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 Mometasone Furoate Cream 0.1% should be discontinued
until the infection has been adequately controlled.
Patients using topical corticosteroids should receive the
following information and instructions:
This medication is to be used as directed by the physician. It is
for external use only. Avoid contact with the eyes.
This medication should not be used for any disorder other than
that for which it was prescribed.
The treated skin area should not be bandaged or otherwise covered
or wrapped so as to be occlusive, unless directed by the physician.
Patients should report to their physician any signs of local
adverse reactions.
Parents of pediatric patients should be advised not to use
Mometasone Furoate Cream 0.1% in the treatment of diaper dermatitis. Mometasone
Furoate Cream 0.1% should not be applied in the diaper area as diapers or
plastic pants may constitute occlusive dressing (see DOSAGE and
ADMINISTRATION).
This medication should not be used on the face, underarms, or
groin areas unless directed by the physician.
As with other corticosteroids, therapy should be discontinued
when control is achieved. If no improvement is seen within 2 weeks, contact the
physician.
Other corticosteroid-containing products should not be used with
Mometasone Furoate Cream 0.1% without first consulting with the
physician.
Laboratory TestsThe following tests may be helpful in evaluating patients for HPA
axis suppression:
ACTH stimulation test
A.M. plasma cortisol test
Urinary free cortisol test
Carcinogenesis, Mutagenesis, Impairment of Fertility:Long-term animal studies have not been performed to evaluate the
carcinogenic potential of Mometasone Furoate Cream 0.1%. 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 Mometasone Furoate Cream 0.1% 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
Mometasone Furoate Cream 0.1% 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 Mometasone Furoate Cream
0.1% on a mcg/m2 basis).
Pregnancy:
Teratogenic Effects:
Pregnancy Category C: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 Mometasone Furoate Cream 0.1% 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 Mometasone
Furoate Cream 0.1% on a mcg/m2 basis.)
In rabbits, mometasone furoate caused multiple malformations (eg, 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 Mometasone Furoate Cream 0.1% 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 Mometasone Furoate Cream 0.1% 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 Mometasone Furoate Cream 0.1% on a
mcg/m2 basis.)
There are no adequate and well-controlled studies of teratogenic effects from
topically applied corticosteroids in pregnant women. Therefore, topical
corticosteroids should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers: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 Mometasone Furoate Cream 0.1% is
administered to a nursing woman.
Pediatric Use:Mometasone Furoate Cream 0.1% 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. Use of Mometasone
Furoate Cream 0.1% is supported by results from adequate and well controlled
studies in pediatric patients with corticosteroid responsive dermatoses. Since
safety and efficacy of Mometasone Furoate Cream 0.1% have not been established
in pediatric patients below 2 years of age, its use in this age group is not
recommended.
Mometasone Furoate Cream 0.1% caused HPA axis suppression in approximately
16% of pediatric patients 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% to 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 less than 7 mcg/dL.
Follow-up testing 2 to 4 weeks after study completion, available for 5 of the
patients, demonstrated suppressed HPA axis function in one patient, using these
same criteria. Long-term use of topical corticosteroids has not been studied in
this population (see CLINICAL PHARMACOLOGY –
Pharmacokinetics section).
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 papilledema.
Mometasone Furoate Cream 0.1% should not be used in the treatment of diaper
dermatitis.
Geriatric Use:Clinical studies of Mometasone Furoate Cream 0.1% 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 ruled out.
