Mometasone Furoate

Harris Pharmaceutical, Inc.
G&W Laboratories, Inc.

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Mometasone Furoate Topical Solution USP, 0.1% (Lotion) safely and effectively. See full prescribing information for Mometasone Furoate Topical Solution USP, 0.1% (Lotion). Mometasone Furoate Topical Solution USP, 0.1% (Lotion) for topical useInitial U.S. Approval: 1987INDICATIONS AND USAGEMometasone Furoate Topical Solution USP, 0.1% (Lotion) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients ≥12 years of age. (1)DOSAGE AND ADMINISTRATION• Apply a few drops to the affected skin areas once daily and massage lightly until it disappears. (2)• Discontinue therapy when control is achieved. (2)• If no improvement is seen within 2 weeks, reassess diagnosis. (2)• Do not use with occlusive dressings unless directed by a physician. (2)DOSAGE FORMS AND STRENGTHS• Topical Solution, 0.1% (Lotion). (3)CONTRAINDICATIONS• None. (4)WARNINGS AND PRECAUTIONS• Reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment, Cushing's syndrome, and hyperglycemia may occur due to systemic absorption. 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. Modify use should HPA axis suppression develop. Pediatric patients may be more susceptible to systemic toxicity. (5.1, 8.4)Side EffectsMost common adverse reactions included are acneiform reaction, burning, itching and folliculitis. (6) To report SUSPECTED ADVERSE REACTIONS, contact G&W Laboratories, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

FULL PRESCRIBING INFORMATION: CONTENTS*

• 1 INDICATIONS & USAGE
• 2 DOSAGE & ADMINISTRATION
• 3 DOSAGE FORMS & STRENGTHS
• 4 MOMETASONE FUROATE CONTRAINDICATIONS
• 5 WARNINGS AND PRECAUTIONS
  • 5.1 Effects on Endocrine System
  • 5.2 Allergic Contact Dermatitis
  • 5.3 Concomitant Skin Infections
• 6 MOMETASONE FUROATE ADVERSE REACTIONS
• 7 DRUG INTERACTIONS
• 8 USE IN SPECIFIC POPULATIONS
  • 8.1 Pregnancy
  • 8.3 Nursing Mothers
  • 8.4 Pediatric Use
  • 8.5 Geriatric Use
• 10 OVERDOSAGE
• 11 MOMETASONE FUROATE DESCRIPTION
• 12 CLINICAL PHARMACOLOGY
  • 12.1 Mechanism of Action
  • 12.2 Pharmacodynamics
  • 12.3 Pharmacokinetics
• 13 NONCLINICAL TOXICOLOGY
  • 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
• 14 CLINICAL STUDIES
• 16 HOW SUPPLIED/STORAGE AND HANDLING
• 17 PATIENT COUNSELING INFORMATION
• PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

1 INDICATIONS & USAGE

Mometasone Furoate Topical Solution USP, 0.1% (Lotion) is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 12 years of age or older.

2 DOSAGE & ADMINISTRATION

Apply a few drops of Mometasone Furoate Topical Solution USP, 0.1% (Lotion) to the affected skin areas once daily and massage lightly until it disappears.

Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

Mometasone Furoate Topical Solution, 0.1% (Lotion) should not be used with occlusive dressings unless directed by a physician.

Mometasone Furoate Topical Solution, 0.1% (Lotion) should not be applied in the diaper area if the patient still requires diapers or plastic pants, as these garments may constitute occlusive dressing.

Mometasone Furoate Topical Solution USP, 0.1% (Lotion) is for topical use only. It is not for oral, ophthalmic, or intravaginal use.

Avoid use on the face, groin, or axillae.

3 DOSAGE FORMS & STRENGTHS

Solution, 0.1% (Lotion). Each gram of Mometasone Furoate Topical Solution USP, 0.1% (Lotion) contains 1 mg of mometasone furoate in a clear solution.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 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 dressing, 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 lotion on the HPA axis, 15 mL were applied without occlusion twice daily (30 mL per day) for 7 days to 4 adult subjects with scalp and body psoriasis. At the end of treatment, the plasma cortisol levels for each of the 4 subjects remained within the normal range and changed little from baseline.

If HPA axis suppression is documented, 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 corticosteroids.

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  (8.4)].

5.2 Allergic Contact Dermatitis

If irritation develops, Mometasone Furoate Topical Solution USP, 0.1% (Lotion) 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. Such an observation should be corroborated with appropriate diagnostic patch testing.

5.3 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 Mometasone Furoate Topical Solution USP, 0.1% (Lotion) should be discontinued until the infection has been adequately controlled.

6 ADVERSE REACTIONS

7 DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with Mometasone Furoate Topical Solution USP, 0.1% (Lotion).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects Pregnancy Category C:

There are no adequate and well-controlled studies in pregnant women. Therefore, Mometasone Furoate Topical Solution USP, 0.1% (Lotion) 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 Mometasone Furoate Topical Solution USP, 0.1% (Lotion) 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 Topical Solution USP, 0.1% (Lotion) 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 Mometasone Furoate Topical Solution USP, 0.1% (Lotion) 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 Topical Solution USP, 0.1% (Lotion)  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 Topical Solution USP, 0.1% (Lotion) on a mcg/m² basis.)

8.3 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 Topical Solution USP, 0.1% (Lotion) is administered to a nursing woman.

8.4 Pediatric Use

Since safety and efficacy of Mometasone Furoate Topical Solution USP, 0.1% (Lotion) have not been established in pediatric patients below 12 years of age, its use in this age group is not recommended.

Mometasone Furoate Topical Solution USP, 0.1% (Lotion) caused HPA axis suppression in approximately 29% 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 40% (range 16%-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 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 Pharmacology (12.2)].

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.

Mometasosne Furoate Topical Solution USP, 0.1% (Lotion) should not be used in the treatment of diaper dermatitis.

8.5 Geriatric Use

Clinical trials of Mometasone Furoate Topical Solution USP, 0.1% (Lotion) 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 usually starting at the low end of the dosing range.

10 OVERDOSAGE

Topically applied Mometasone Furoate Topical Solution, 0.1% (Lotion) can be absorbed in sufficient amounts to produce systemic effects [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Mometasone Furoate Topical Solution, 0.1% (Lotion) contains mometasone furoate, USP for dermatologic use. Mometasone furoate is a synthetic corticosteroid with anti-inflammatory activity.

Chemically, mometasone furoate is 9α,21-dichloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione 17-(2-furoate), with the empirical formula C₂₇H₃₀CI₂O₆, a molecular weight of 521.4 and the following structural formula: