Included as part of the PRECAUTIONS section.
Effects On The Endocrine System
Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested.
Systemic absorption of topical corticosteroids has caused reversible adrenal suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid.
The effect of clobetasol propionate lotion, 0.05% on HPA axis function was assessed in adults in two trials, one for psoriasis and one for atopic dermatitis. In total, 8 of 10 evaluable subjects with moderate to severe plaque psoriasis experienced adrenal suppression following 4 weeks of clobetasol propionate lotion, 0.05% therapy. In follow-up testing, 1 of 2 subjects remained suppressed after 8 days.
Furthermore, 5 of 9 evaluable subjects with moderate to severe atopic dermatitis experienced adrenal suppression following 2 weeks of clobetasol propionate lotion, 0.05% therapy. Of the 3 subjects that had follow-up testing, one subjects failed to recover adrenal function 7 days post-treatment. The proportion of subjects suppressed may be underestimated because the adrenal glands were stimulated weekly with cosyntropin in these trials.
Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, young age, concomitant use of multiple corticosteroid-containing products and use in patients with liver failure.
Cushingâ€™s syndrome, hyperglycemia, glycosuria, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.
An adrenocorticotropic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. 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 steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.
Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression [see Use In Specific Populations].
Ophthalmic Adverse Reactions
Use of topical corticosteroids, including IMPEKLO, may increase the risks of glaucoma and posterior subcapsular cataract. Glaucoma and cataracts have been reported in postmarketing experience with the use of topical corticosteroid products, including topical clobetasol products.
Avoid contact of IMPEKLO with eyes. Advise patients to report any visual symptoms and consider referral to an ophthalmologist for evaluation.
Local Adverse Reactions With Topical Corticosteroids
Local adverse reactions may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, miliaria, skin atrophy and telangiectasia. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.
Allergic Contact Dermatitis
Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing.
Concomitant Skin Infections
In the presence of dermatologic infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of IMPEKLO lotion should be discontinued until the infection has been adequately controlled.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all administration instructions or all possible adverse or unintended effects.
Advise patients using IMPEKLO lotion of the following information and instructions:
Important Administration Instructions
- This medication is to be used as directed by the physician. It is for external use only. Avoid use on the face or in skin-fold areas, such as the underarms or groin. Avoid contact with the eyes or other mucous membranes. Wash hands after use.
- Therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician. Avoid use of IMPEKLO longer than the prescribed time period.
- Avoid use for more than 50 g per week (i.e., 20 actuations/day for 7 days) of IMPEKLO lotion. [see DOSAGE AND ADMINISTRATION].
Effects On The Endocrine System
IMPEKLO may cause HPA axis suppression. Advise patients that use of topical corticosteroids, including IMPEKLO, may require periodic evaluation for HPA axis suppression. Topical corticosteroids may have other endocrine effects. Concomitant use of multiple corticosteroid-containing products may increase the total systemic exposure to topical corticosteroids. Patients should inform their physician(s) that they are using IMPEKLO if surgery is contemplated [see WARNINGS AND PRECAUTIONS].
Ophthalmic Adverse Reactions
Advise patients to report any visual symptoms to their healthcare providers [see WARNINGS AND PRECAUTIONS].
Local Adverse Reactions
Advise patients that local reactions and skin atrophy are more likely to occur with occlusive use or prolonged use [see WARNINGS AND PRECAUTIONS].
Advise pregnant women of the potential risk to a fetus and to use IMPEKLO on the smallest area of skin and for the shortest duration possible [see Use In Specific Populations].
Advise a woman to use IMPEKLO on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply IMPEKLO directly to the nipple and areola to avoid direct infant exposure [see Use In Specific Populations].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a 2-year carcinogenicity study, clobetasol propionate was topically applied to rats at concentrations up to 0.005%. No drug-related increase in tumor incidence was observed.
Clobetasol propionate was negative in the in vitro mammalian chromosomal aberration test and in the in vivo mammalian erythrocyte micronucleus test.
In a fertility and reproductive toxicity study, clobetasol propionate was administered subcutaneously to rats at doses of 0, 12.5, 25, and 50 μg/kg/day. Males were treated beginning 70 days before mating and females beginning 15 days before mating through day 7 of gestation. A NOEL could not be determined for paternal and maternal toxicity or male reproductive toxicity because of decreased weight gain in both sexes and increased seminal vesicle weights in males.
The female reproductive NOEL was 12.5 μg/kg/day because higher doses reduced the number of estrous cycles during the pre-cohabitation period and increased in the number of nonviable embryos.
Use In Specific Populations
There are no available data for the use of IMPEKLO during pregnancy to inform any drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Published data report an increased risk of low birthweight with the use of greater than 300 grams of potent or very potent topical corticosteroid during a pregnancy. Advise pregnant women of the potential risk to a fetus and to use IMPEKLO on the smallest area of skin and for the shortest duration possible (see Data). In animal reproduction studies, increased malformations, such as cleft palate and skeletal abnormalities, were observed after subcutaneous administration of clobetasol propionate to pregnant mice and rabbits during the period of organogenesis. The available data do not support relevant comparisons of systemic clobetasol propionate exposures achieved in the animal studies to exposures observed in humans after topical use of IMPEKLO.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Multiple observational studies found no significant associations between maternal use of topical corticosteroids of any potency and congenital malformations, preterm delivery, or fetal mortality. However, when the dispensed amount of potent or very potent topical corticosteroid exceeded 300 g during the entire pregnancy, use was associated with an increase in low birth weight infants. In addition, a small cohort study, in which 28 sub-Saharan women using potent topical corticosteroids (27/28 used clobetasol propionate 0.05%) for skin lightening during pregnancy, noted a higher incidence of low birth weight infants in the exposed group. The majority of exposed subjects treated large areas of the body (a mean quantity of 60 g/month (range, 12-170g) over long periods of time.
In embryofetal development studies in mice, subcutaneous administration of clobetasol propionate during the period of organogenesis resulted in malformations at all dose levels, ranging from 0.03 to 1 mg/kg. Malformations included cleft palate and skeletal abnormalities; fetotoxicity was observed at the high dose (1 mg/kg).
In an embryofetal development study in rabbits, subcutaneous administration of clobetasol propionate during the period of organogenesis resulted in malformations at doses of 0.003 and 0.01 mg/kg. Malformations included cleft palate, cranioschisis, and other skeletal abnormalities.
In a prenatal and postnatal development study in rats, clobetasol propionate was administered subcutaneously to female rats twice daily (0, 12.5, 25, and 50 μg/kg/day) from gestation day 7 through lactation day 25. In dams, body weight gain and food consumption were reduced during gestation at all doses and prolonged delivery occurred at the high dose. A maternal no-observedeffect-level (NOEL) could not be determined and the reproductive NOEL for dams was 25 μg/kg/day. In offspring, doses ≥25 μg/kg/day increased incidence of stillbirths, reduced pup body weights on lactation days 1 and 7, increased pup mortality, increased the incidence of umbilical hernia, increased the incidence of cysts on the kidney, and significantly reduced epididymides and testes weights. However, no effects were observed on the mating and fertility of the offspring. The no-observed-adverse-effect-level (NOAEL) for viability and growth in the offspring was 12.5 μg/kg/day.
There is no information regarding the presence of clobetasol propionate in breast milk or its effects on the breastfed infant or on milk production. Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of clobetasol propionate could result in sufficient systemic absorption to produce detectable quantities in human milk. The developmental and health benefits of breastfeeding should be considered along with the motherâ€™s clinical need for IMPEKLO and any potential adverse effects on the breastfed infant from clobetasol propionate or from the underlying maternal condition.
To minimize potential exposure to the breastfed infant via breast milk, use IMPEKLO on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply IMPEKLO directly to the nipple and areola to avoid direct infant exposure.
Use of clobetasol propionate lotion, 0.05% in pediatric patients is not recommended due to the potential for HPA axis suppression [see WARNINGS AND PRECAUTIONS].
The HPA axis suppression potential of clobetasol propionate lotion, 0.05% has been studied in adolescents (12 to 17 years of age) with moderate to severe atopic dermatitis covering a minimum of 20% of the total body surface area. Subjects were treated twice daily for 2 weeks with clobetasol propionate lotion, 0.05%. After 2 weeks of treatment, 9 out of 14 of the subjects experienced adrenal suppression. One out of 4 subjects who were retested remained suppressed two weeks post-treatment.
Because of higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushingâ€™s syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of glucocorticosteroid insufficiency during and/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, Cushingâ€™s 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.
Clinical studies of clobetasol propionate lotion, 0.05% did not include sufficient numbers of subjects aged 65 and over to adequately determine whether they respond differently than younger subjects. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.