Label: CLOBETASOL PROPIONATE emulsion
Contains inactivated NDC Code(s)
NDC Code(s): 54868-6305-0
- Packager: Physicians Total Care, Inc.
- This is a repackaged label.
- Source NDC Code(s): 50383-270
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: Abbreviated New Drug Application
Updated June 4, 2010
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- SPL UNCLASSIFIED SECTION
Clobetasol Propionate Cream-Emollient, 0.05% contains the active compound clobetasol propionate, a synthetic corticosteroid, for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity.
Chemically, clobetasol propionate is (11ß,16ß)-21- chloro-9-fluoro-11-hydroxy-16-methyl-17-(1-oxopropoxy)- pregna-1,4-diene-3,20-dione, and it has the following structural formula:
Clobetasol propionate has the molecular formula C25H32CIFO5 and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water.
Clobetasol propionate cream-emollient contains clobetasol propionate 0.5 mg/g in an emollient base of cetomacrogol 1000, cetostearyl alcohol, citric acid, dimethicone 360, imidurea as a preservative, isopropyl myristate, propylene glycol, purified water, and sodium citrate.
Like other topical corticosteroids, clobetasol propionate has antiinflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and integrity of the epidermal barrier. Occlusive dressing with hydrocortisone for up to 24 hours has not been demonstrated to increase penetration; however, occlusion of hydrocortisone for 96 hours markedly enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption.
Studies performed with clobetasol propionate cream-emollient indicate that it is in the super-high range of potency as compared with other topical corticosteroids.
INDICATIONS AND USAGE
Clobetasol propionate cream-emollient is a super-high potency corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Treatment beyond 2 consecutive weeks is not recommended, and the total dosage should not exceed 50 g/week because of the potential for the drug to suppress the hypothalamic-pituitary- adrenal (HPA) axis. Use in pediatric patients under 12 years of age is not recommended.
In the treatment of moderate to severe plaque-type psoriasis, clobetasol propionate cream-emollient applied to 5% to 10% of body surface area can be used up to 4 consecutive weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. Treatment beyond 4 consecutive weeks is not recommended. Patients should be instructed to use clobetasol propionate cream-emollient for the minimum amount of time necessary to achieve the desired results (see PRECAUTIONS and INDICATIONS AND USAGE). Use in pediatric patients under 16 years of age has not been studied.
Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g/day.
Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy.
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. Patients receiving super-potent corticosteroids should not be treated for more than 2 weeks at a time, and only small areas should be treated at any one time due to the increased risk of HPA suppression.
In a controlled clinical trial involving patients with moderate to severe plaque-type psoriasis, clobetasol propionate cream-emollient applied to 5% to 10% of body surface area resulted in additional benefits in the treatment of patients for 4 consecutive weeks. In this trial, there were no clobetasol-treated patients with clinically significant decreases in morning cortisol levels after 4 weeks of treatment; however, morning cortisol levels may not identify patients with adrenal dysfunction. Therefore, the additional benefits of extending treatment beyond 2 weeks should be weighed against the potential for HPA suppression. Therapy should be discontinued when control has been achieved. Treatment beyond 4 consecutive weeks is not recommended.
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 that require 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). The use of clobetasol propionate cream-emollient for 4 consecutive weeks has not been studied in pediatric patients under 16 years of age.
Clobetasol propionate cream-emollient contains the excipient imidurea which releases traces of formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.
If irritation develops, clobetasol propionate cream-emollient 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 clobetasol propionate cream-emollient should be discontinued until the infection has been adequately controlled.
Clobetasol propionate cream-emollient should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.
Information for Patients
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, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.
- Patients should report any signs of local adverse reactions to the physician.
- Patients should inform their physicians that they are using clobetasol propionate cream-emollient if surgery is contemplated.
- This medication should not be used on the face, underarms, or groin areas.
- As with other corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, contact the physician.
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
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
Studies in the rat following subcutaneous administration at dosage levels up to 50 mcg/kg/day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose.
Clobetasol propionate was nonmutagenic in 3 different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test.
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 to laboratory animals.
Clobetasol propionate has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent.
Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate cream-emollient. Abnormalities seen included cleft palate and skeletal abnormalities.
In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate cream-emollient. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.
There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol propionate cream-emollient should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 clobetasol propionate cream-emollient is administered to a nursing woman.
Safety and effectiveness of clobetasol propionate cream-emollient in pediatric patients have not been established. Use in pediatric patients under 12 years of age is not recommended. For continued use beyond 2 consecutive weeks, the safety of clobetasol propionate cream-emollient has not been studied. 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 syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children.
HPA axis suppression, Cushing syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in children 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.
A limited number of patients at or above 65 years of age (n = 34) have been treated with clobetasol propionate cream-emollient in US clinical trials. While the number of patients is too small to permit separate analysis of efficacy and safety, the single adverse reaction reported in this population was similar to those reactions reported by younger patients. Based on available data, no adjustment of dosage of clobetasol propionate cream-emollient in geriatric patients is warranted.
In controlled trials with all clobetasol propionate formulations, the following adverse reactions have been reported: burning/stinging, pruritus, irritation, erythema, folliculitis, cracking and fissuring of the skin, numbness of the fingers, tenderness in the elbow, skin atrophy, and telangiectasia. The incidence of local adverse reactions reported in the trials with clobetasol propionate cream-emollient was <2% of patients treated with the exception of burning/stinging, which occurred in 5% of treated patients.
Cushing syndrome has been reported in infants and adults as a result of prolonged use of other topical clobetasol propionate formulations.
The following additional local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with super-high potency corticosteroids such as clobetasol propionate cream-emollient. These reactions are listed in an approximately decreasing order of occurrence: dryness, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, and miliaria.
To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Topically applied Clobetasol Propionate Cream-Emollient, 0.05% can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).
DOSAGE AND ADMINISTRATION
Apply a thin layer of clobetasol propionate cream-emollient, 0.05% to the affected skin areas twice daily and rub in gently and completely (see INDICATIONS AND USAGE).
Clobetasol propionate cream-emollient is a super-high potency topical corticosteroid; therefore, treatment should be limited to 2 consecutive weeks and amounts greater than 50 g/week should not be used.
In moderate to severe plaque-type psoriasis, clobetasol propionate cream-emollient applied to 5% to 10% of body surface area can be used up to 4 weeks. The total dosage should not exceed 50 g/week. When dosing for more than 2 weeks, any additional benefits of extending treatment should be weighed against the risk of HPA suppression. As with other highly active corticosteroids, therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary. Treatment beyond 4 consecutive weeks is not recommended. Use in pediatric patients under 16 years of age has not been studied.
Clobetasol propionate cream-emollient should not be used with occlusive dressings.
In studies where geriatric patients (65 years of age or older, see PRECAUTIONS) have been treated with clobetasol propionate cream-emollient, safety did not differ from that in younger patients; therefore, no dosage adjustment is recommended.
Clobetasol Propionate Cream-Emollient, 0.05% is supplied in 30-g tubes (NDC 54868-6305-0).
Store between 15° and 30° C (59° and 86° F).
Clobetasol propionate cream-emollient should not be refrigerated.
Hi-Tech Pharmacal Co., Inc.
Amityville, NY 11701
DPT Laboratories Ltd
San Antonio, TX 78215
Rev. 270:00 10/09
Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, OK 74146
- PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
INGREDIENTS AND APPEARANCE
clobetasol propionate emulsion
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-6305(NDC:50383-270) Route of Administration TOPICAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength CLOBETASOL PROPIONATE (UNII: 779619577M) (CLOBETASOL - UNII:ADN79D536H) CLOBETASOL PROPIONATE 0.5 mg in 1 g Inactive Ingredients Ingredient Name Strength CETETH-20 (UNII: I835H2IHHX) CETOSTEARYL ALCOHOL (UNII: 2DMT128M1S) ANHYDROUS CITRIC ACID (UNII: XF417D3PSL) DIMETHICONE 350 (UNII: 2Y53S6ATLU) IMIDUREA (UNII: M629807ATL) ISOPROPYL MYRISTATE (UNII: 0RE8K4LNJS) PROPYLENE GLYCOL (UNII: 6DC9Q167V3) WATER (UNII: 059QF0KO0R) SODIUM CITRATE (UNII: 1Q73Q2JULR) Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:54868-6305-0 1 in 1 CARTON 1 30 g in 1 TUBE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA075325 09/07/2011 Labeler - Physicians Total Care, Inc. (194123980) Establishment Name Address ID/FEI Business Operations Physicians Total Care, Inc. 194123980 relabel, repack