Mometasone furoate precautions

List of precautions
General Lab tests Carcinogenesis Mutagenesis Impairment of fertility Pregnancy Nursing mothers Pediatric use Geriatric use
 * HPA axis suppression
 * Pediatric system toxicity
 * Irritation
 * Skin infections
 * Overview
 * Mouse studies
 * Rat studies
 * Rabbit studies
 * Human studies

HPA axis suppression
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 lotion on the hypothalamic-pituitary-adrenal (HPA) axis, 15 mL were applied without occlusion twice daily (30 mL per day) for 7 days to four adult patients with scalp and body psoriasis. At the end of treatment, the plasma cortisol levels for each of the four patients remained within the normal range and changed little from baseline. 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. Return to top

Pediatric system toxicity
Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. Return to top

Irritation
If irritation develops, Mometasone Furoate Lotion 0.1% (Mometasone furoate topical solution USP) should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing 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. Return to top

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 Mometasone Furoate Lotion 0.1% should be discontinued until the infection has been adequately controlled. Return to top

Lab tests
The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH stimulation test, A.M. plasma cortisol test, urinary free cortisol test. Return to top

Carcinogenesis
Long-term animal studies have not been performed to evaluate the carcinogenic potential of Mometasone Furoate Lotion 0.1% (Mometasone furoate topical solution USP). 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 Lotion 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 Lotion 0.1% on a mcg/m2 basis). Return to top

Mutagenesis
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. Return to top

Impairment of fertility
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 Lotion 0.1% on a mcg/m2 basis). Return to top

Overview
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.Return to top

Mouse studies
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 Lotion 0.1% (Mometasone furoate topical solution USP) on a mcg/m2 basis). Return to top

Rat studies
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 Lotion 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 Lotion 0.1% on a mcg/m2 basis). Return to top

Rabbit studies
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 Mometasone Furoate Lotion 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 Lotion 0.1% on a mcg/m2 basis). Return to top

Human studies
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. Return to top

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 Lotion 0.1% (Mometasone furoate topical solution USP) is administered to a nursing woman. Return to top

Pediatric use
Since safety and efficacy of Mometasone Furoate Lotion 0.1% (Mometasone furoate topical solution USP) have not been established in pediatric patients below 12 years of age, its use in this age group is not recommended. Mometasone Furoate Lotion 0.1% caused HPA axis suppression in approximately 29% 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 40% (range 16% to 90%). 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 stopping treatment, available for 8 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. 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 absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Mometasone Furoate Lotion 0.1% (Mometasone furoate topical solution USP) should not be used in the treatment of diaper dermatitis. Return to top

Geriatric use
Clinical studies of Mometasone Furoate Lotion 0.1% (Mometasone furoate topical solution USP) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious. Return to top