&AGING

Supplement to the June 2010

®

The Relevance of Vehicle in Low-Potency Topical Steroids: 2 Case Studies of Pruritic Condition

Series: Relevance of Low-Potency Topical Steroids in Dermatology

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Supplement to Skin & Aging � June 2010 3

Vehicle selection in treating dermatologic disorders isas important as the formulation you choose, as vehiclegreatly influences both treatment efficacy and patient

satisfaction. Lotions, gels, foams, creams and other vehiclesoffer different benefits and drawbacks and, as a result, are ap-propriate for different conditions. This article will exploreconsiderations for vehicle selection in treating dermatologicdisorders and the importance of vehicle in topical steroidtherapy, as well as present two case studies.

DIFFERENTIATING THE VEHICLESVehicles such as ointments, creams and lotions are consid-

ered the gold standard for the treatment of atopic dermatitis(AD) and other dry conditions because of their ability tosoothe and moisturize skin.1 Ointments are thought to be themost hydrating of the three.1 Gels, solutions and powders aremore appropriate for “moist” conditions, such as contact der-matitis and infection.2 Foam-vehicle formulations are some-times preferred for their easy spreadability.Emollients will be the focus, as the case studies center on

AD and psoriasis.

• Ointment. With a high oil content, ointment tends to begreasy, which helps replace skin’s barrier function.3 Ideally,this vehicle would be the basis of treatment for many derma-tologic conditions. However, patients don’t like to use it —often, they don’t like the feel, or find that ointments interferewith their everyday activities. As such, it is generally recom-mended that this vehicle be prescribed only for chronic, thick-ened lesions.4,5 Ointments are often preservative-free, makingthem less likely than certain other vehicles to cause allergy insensitive patients.3 However, patient preference scores for oint-ments are low, because they are greasy and messy.6

• Cream. Creams are less greasy and more spreadable thanointments, so patients tend to like them better. This vehi-cle is more appropriate than ointments, but less so thanlotions, for use on weeping lesions in intertiginous zonesand on skin that is covered by hair.4,5 The greater watercontent of creams usually requires additions to the for-mulation, which may be irritating to some patients.3

• Lotion. The high water content of lotions makes them easilyspreadable over large areas and tender areas, and less prone tostain than ointments (and some creams).3,4 For these reasons,

The Relevance of Vehicle in Low-Potency Topical Steroids: 2 Case Studies of Pruritic ConditionHarold F. Farber, MDPhiladelphia, PA

CASE 1. After: Topical steroid therapy including PramosoneETM

Cream reduced the PGA of patient No. 1's lesions fromsevere to excellent. His itch by VAS went from about 9 toabout 2.5.

CASE 1. Before: The patient presented with severe pruritusand a severe flare limited to the forearms and dorsal sur-faces of the hands. Cold weather, stress and exposure ofthe extremities were contributing factors in the flare.

lotions are well-accepted by patients. Lotions are also the idealvehicle for use on weeping lesions in intertiginous zones andon skin that is covered by hair.4,5 However, as the water in alotion evaporates, it tends to dry the skin, so it may be impor-tant to add moisturizer to a regimen that will involve lotion.7

Patient satisfaction is tied closely to the treatment vehicle.For example, asking a patient to use an ointment on AD in in-tertiginous areas can lead to a patient’s non-adherence with thetreatment plan, because the vehicle may be uncomfortable. Sev-eral vehicle characteristics have been shown to affect patientpreference, including ease or difficulty of use, messiness, odorand staining.8 Further, studies show that patient preference andadherence to the treatment regimen are linked more closely tooutcomes than the formulation of the therapy prescribed.2

VEHICLE AND TOPICAL STEROIDSPatients are also less likely to adhere if they don’t feel the pre-

scribed therapy is working. This is important with regard to ve-hicle selection, because the right choice can enhance the efficacyof treatment with topical steroids.9This means that vehicle affectsthe disease process and, in turn, may affect patient compliance.8

The occlusion, bioavailability and lipid solubility are among thevehicle factors that influence the potency of a steroid applied top-ically.5The common wisdom is that steroid potency is highest inoinment preparations, followed by creams and lotions.5The knock-on effect is that less steroid has to be used in the preparation, whichdecreases the potential for steroid-related undesirable effects.1

The low-potency topical steroid (LPS) formulation ofPramosone ETM Cream 2.5% combines hydrocortisone acetateand pramoxine HCl to help treat conditions such as AD andpsoriasis. The low-strength hydrocortisone acetate inPramosone E Cream is a safe and effective LPS that acts as ananti-inflammatory agent.10,11 Pramoxine hydrochloride is atopical anesthetic with low irritation and sensitization poten-tial that helps relieve the pain and pruritus associated withthese conditions, which helps break the itch-scratch cycle.10,11

The result is rapid onset and extended duration of itch re-lief that patients desire.12,13Whenever possible and appropri-ate, use of a steroid-sparing agent is recommended.

CASE STUDY NO. 1: SEVERE, LIMITED FLAREPatient No. 1, a 48-year-old male, has a 10-year history of atopic

dermatitis, including periods of moderate to severe flares. He pre-

sented with severe pruritus and a severe flare limited to the fore-arms and dorsal surfaces of the hands. Cold weather, stress andexposure of the extremities were determined to be contributingfactors in the flare. On a visual analog scale (VAS), the patientrated his pruritus intensity at 8 of 10 at baseline (see Table 1).14

Because of the severity of this flare, a high-potency topicalsteroid was deemed appropriate. However, in order to minimizepotential steroid-related side effects, the high-potency steroid’s usewas pulsed with an LPS. Due to the isolated nature of this flare,Pramosone ETM Cream was used for the latter purpose of mini-mizing steroid use. Potential secondary infection was checked for. In terms of vehicle, cream provided the most concentrated

moisture in a vehicle that this particular patient found accept-able; i.e., it was unobtrusive and didn’t interfere with his workand other daily activities. Because of its consistency, PramosoneE Cream stays where it’s applied, which maximizes the benefitfor the affected areas and minimizes steroid effect on non-af-fected skin. (It’s important to note that the low-potency natureof Pramosone E Cream means that undesirable effects such ascutaneous atrophy are rare; however, it’s generally good prac-tice to use steroid-sparing therapy wherever possible.) The patient was started on combination therapy of potent

topical steroid pulsed with Pramosone E Cream. For the first2 weeks, he used about 5 g of the potent topical steroid for 5days, and 5 g of the Pramosone E Cream for 2 days, before re-peating the cycle. For the second 2 weeks, the cycle was flipped:Pramosone E Cream for 5 days, potent steroid for 2 days. Overthe last 2 weeks of treatment, the patient used Pramosone ECream 5 days a week and moisturizers every day.At the end of 6 weeks’ treatment, the improvement in the

severity of his lesions, rated by physician’s global assessment(PGA), was excellent (see Table 2), and the patient self-assessedpruritus as mild (VAS 2 to 3).15 He uses moisturizers as thebulk of his maintenance regimen. The patient also continuesto use the Pramosone E Cream on a strictly as-needed basis,such as when triggers are present, or he starts to feel thetwinge that pruritus and a flare are imminent.

CASE STUDY NO. 2: MODERATE FLARE Patient No. 2 is a 24-year-old male with a history of rela-

tively mild whole-body atopic dermatitis. He presented witha moderate flare over the legs and arms and a pruritus VAS of6. Because of the diffuseness of his condition, Pramosone®

4 June 2010 � Supplement to Skin & Aging

EMOLLIENT LOW-POTENCY STEROIDS IN ATOPIC DERMATITIS

TABLE 1. VISUAL ANALOG SCALE (VAS) — MODIFIED

THE VAS IS A TOOL THAT ALLOWS PATIENTS TO ASSIGN QUANTITATIVE VALUES TO THEIR QUALITATIVEEVALUATIONS OF THEIR SYMPTOMS, IN THIS CASE PRURITUS INTENSITY. THIS IS THE SCALE THAT WAS USED:

No pruritus Mild Moderate Severe Most severe pruritus1 2 3 4 5 6 7 8 9 10

Note: Adapted from Aitken.10

Lotion, which is easier to spread over large areas than an oint-ment, was deemed most appropriate. In addition, ointmentson large areas often inconvenience patients, as they take a longtime to dry and can make putting on clothes uncomfortable.Along with minimizing triggers, the patient was started on

Pramosone® Lotion for 2 weeks: Pramosone Lotion BID, alongwith a focus on using moisturizer. The following 2 weeks, low-potent steroid therapy was tapered; the patient used Pramosonelotion once a day for 5 days and kept up with moisturizer. Forthe final 2 weeks, he used the Pramosone Lotion once everyother day and focused on moisturizing as often as possible.At the end of 6 weeks’ treatment, the patient had achieved

almost-clear over the whole body, with little to no pruritus(1 on the VAS). The patient’s maintenance therapy after thispoint included using gentle cleanser and moisturizer, andPramosone lotion on a strictly as-needed basis.

CONCLUSIONLow-potency topical steroids such as the Pramosone line

are a key part of a maintenance regimen in which patientsshould try to avoid triggers, use gentle cleansers, moisturizeadequately, and avoid hot showers and excessive water expo-sure. Patients who take all these steps are more likely to suc-ceed, and patients are more likely to comply with treatmentif they have been well-educated by the clinician.Many of the pruritic conditions we dermatologists see are

chronic and long-term, so patients must be involved in and ed-ucated to take ownership of their care. They know better thananyone when they get those twinges that tell them they’re aboutto have a flare — and they can use an LPS such as PramosoneETM Cream, for example, proactively rather than reactively. When choosing among treatment options and vehicles, it’s

important to pick a product that’s safe for long-term use, withminimal undesirable effects. Products in the Pramosone linehelp reduce pruritus and reduce inflammation with a steroid-sparing formulation that can be used solo or in combinationwith other topical agents. The variety of vehicles lets you ac-commodate hydration needs, body geography and patientpreference for cosmetic acceptability.

There of course must be physician supervision, but enlistingpatients to join in the process can only help control their con-ditions. In teaching patients to prevent flares, there is a furtheropportunity for dermatologists to offer patients the servicethey desire — to not just treat them, but also enlist them inminimizing their discomfort and the disruption of their dailyactivities and in promoting quality of life. �

References1. Peterson JD, Chan LS. A Comprehensive management guide for atopicdermatitis. Dermatol Nurs. 2006;18(6):531–542.2. Marco CA. A Common Sense Guide to Dermatologic Therapy. Pre-sented at: Scientific Assembly of the American College of EmergencyPhysicians. Chicago, IL: October 29, 2008.3. White GM, Cox NH. Diseases of the Skin: A Color Atlas and Text, 2nd Edi-tion. St. Louis, MO: Mosby; 2005.4. Tadicherla S, Ross K, Shenefelt PD, Fenske NA. Topical corticosteroidsin dermatology. J Drugs Dermatol. 2009;8(12):1093–105. Review. 5. Fitzpatrick JE, Aeling JL. Dermatology Secrets in Color, 2nd Edition.Philadelphia, PA: Hanley and Belfus, Inc.; 2000.6. Zivkovich AH, Feldman SR. Are ointments better than other vehicles forcorticosteroid treatment of psoriasis? J Drugs Dermatol. 2009;8(6):570–572.7.Buck M, Roberts RJ, Hendrick AE, Rogers D. Topical corticosteroids inchildren. Pediatric Pharmacotherapy. 1996;2(1):1–7.8. Feldman SR, Housman TS. Patients’ vehicle preference for corticos-teroid treatments of scalp psoriasis. Am J Clin Dermatol. 2003;4(4):221–224.9. Ference JD, Last AR. Choosing topical corticosteroids. Am Fam Physi-cian. 2009;79(2):135–140.10. Littz J. Treatment of itching without corticosteroids. In: Bernhard J, editor. Itchmechanisms and management of pruritus. New York: McGraw Hill; 1994, p. 383–397.11. Mösges R, Domröse CM, Löffler J. Topical treatment of acute otitis ex-terna: clinical comparison of an antibiotics ointment alone or in combinationwith hydrocortisone acetate. Eur Arch Otorhinolaryngol. 2007;264(9):1087–1094. 12. University of Maryland Medical Center. Complimentary and Alterna-tive Medicine Index: Pramoxine. 2009. Accessed April 10, 2010 athttp://www.umm.edu/altmed/drugs/pramoxine-104850.htm.13. University of Maryland Medical Center. Complimentary and Alterna-tive Medicine Index: Hydrocortisone. 2009. Accessed April 10, 2010 athttp://www.umm.edu/altmed/drugs/hydrocortisone-063400.htm.14. Aitken RC. Measurement of feeling using visual analogue scales. ProcRSocMed. 1969;62(10):989–993.15. Ashcroft D, Li Wan Po A, Williams H, Griffiths C. Clinical measures ofdisease severity and outcome in psoriasis: a critical appraisal of their quality.Br J Dermatol. 1999;141(2):185–191.

Supplement to Skin & Aging � June 2010 5

TABLE 2. PHYSICAN’S GLOBAL ASSESSMENT

THE PGA IS A FIVE-TIER SYSTEM IN WHICH A PHYSICIAN ASSIGNS A DEGREE OF IMPROVEMENT TO SUMMA-RIZE THE OVERALL QUALITY (ERYTHEMA, SCALING AND THICKNESS) AND EXTENT (BODY SURFACE AREA) OFPLAQUES RELATIVE TO THE BASELINE ASSESSMENT.

Poor 0% to 24%

Fair 25% to 49%

Good 50% to 74%

Excellent 75% to 99%

Cleared 100%

Note: Adapted from Ashcroft.15

Item #6957IRev.: 09/09

Information for the Patient: Patients using topical corticosteroids should receive the following information and instructions:1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed.3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.4. Patients should report any signs of local adverse reactions especially under occlusive dressings.5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.

Laboratory Tests: The following tests may be helpful in evaluating the HPA axis suppression: Urinary free cortisol test ACTH stimulation test

Carcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone and hydro- cortisone have revealed negative results.

Pregnancy: Teratogenic Effects: Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on preg- nant patients, in large amounts, or for prolonged periods of time.

Nursing Mothers: It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Sys- temically administered corticosteroids are secreted into breast milk in quantities NOT likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Pediatric Use: Pediatric patients may demonstrate greater susceptibility to topical corti- costeroid induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio.Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and intra- cranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may inter- fere with the growth and development of children.

ADVERSE REACTIONS: The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dres- sings. These reactions are listed in an approximate decreasing order of occurrence:

OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)

DOSAGE AND ADMINISTRATION: Topical corticosteroids are generally applied to the affected area as a thin film three to four times daily depending on the severity of the condition. Occlusive dressings may be used for the management of psoriasis or recal- citrant conditions. If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.

HOW SUPPLIED: Pramosone E™ Cream 2.5% 1 oz tube (NDC 0496-0708-04) 2 oz tube (NDC 0496-0708-03)

Storage Conditions: Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF) [see USP Controlled Room Temperature].

Pramosone E™ and Hydrolipid™ are trademarks of Ferndale IP, Inc. Protected under U.S. Patent No. 5,635,497

DESCRIPTION: Pramosone E™ Cream 2.5% is a topical preparation containing hydro- cortisone acetate 2.5% w/w and pramoxine hydrochloride 1% w/w in a Hydrolipid™ base containing cetostearyl alcohol, ceteth 20, mineral oil, white petrolatum, propylparaben, triethanolamine lauryl sulfate, citric acid, sodium citrate, and purified water.Topical corticosteroids are anti-inflammatory and anti-pruritic agents. The structural formula, the chemical name, molecular formula and molecular weight for active ingredients are presented below.

Burning Hypertrichosis Maceration of the skin Itching Acneiform eruptions Secondary infection Irritation Hypopigmentation Skin atrophyDryness Perioral dermatitis StriaeFolliculitis Allergic contact dermatitis Miliaria

CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man. Pramoxine hydrochloride is a topical anesthetic agent which provides temporary relief from itching and pain. It acts by stabilizing the neuronal membrane of nerve endings with which it comes into contact.

Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings sub- stantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resistant dermatoses. (See DOSAGE AND ADMINISTRATION.)Once absorbed through the skin, topical corticosteroids are handled through pharmaco- kinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

INDICATIONS AND USAGE: Topical corticosteroids are indicated for the relief of the inflam- matory and pruritic manifestations of corticosteroid-responsive dermatoses.

CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

PRECAUTIONS: General: Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cush- ing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings.Therefore, patients receiving a large dose of a potent topical steroid applied to a large sur- face area and under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. 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 steroid.Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See Precau- tions-Pediatric Use.)If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.In the presence of dermatological infections, the use of an appropriate antifungal or anti- bacterial agent should be instituted. If a favorable response does not occur promptly the corticosteroid should be discontinued until the infection has been adequately controlled.

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Item # 0726IRev.: 01/07

DESCRIPTION: Pramosone® Lotion is a topical preparation containing hydrocortisone acetate 1% w/w or 2.5% w/w and pramoxine hydrochloride 1% w/w in a hydrophilic lotion base containing stearic acid, cetyl alcohol, FORLAN-L (Contains: petrolatum, lan-olin, hydrogenated coconut oil, sorbitan sesquioleate, stearyl alcohol, and cetyl alcohol), glycerin, trolamine, polyoxyl 40 stearate, di-isopropyl adipate, povidone, dimethicone, potassium sorbate, sorbic acid, and purified water.Topical corticosteroids are anti-inflammatory and anti-pruritic agents. The structural formula, the chemical name, molecular formula and molecular weight for active ingred-ients are presented below.

CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.Pramoxine hydrochloride is a topical anesthetic agent which provides temporary relief from itching and pain. It acts by stabilizing the neuronal membrane of nerve endings with which it comes into contact. Pharmacokinetics: The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids. Thus, occlusive dressings may be a valuable therapeutic adjunct for treatment of resis-tant dermatoses. (See DOSAGE AND ADMINISTRATION.) Once absorbed through the skin, topical corticosteroids are handled through pharma-cokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.INDICATIONS AND USAGE: Topical corticosteroids are indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.CONTRAINDICATIONS: Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation. PRECAUTIONS: General: Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area and under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimula-tion tests. 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 steroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity. (See PRECAUTIONS-Pediatric Use.) If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted. In the presence of dermatological infections, the use of an appropriate antifungal or anti-bacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Information for the Patient: Patients using topical corticosteroids should receive the following information and instructions:1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed.3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.4. Patients should report any signs of local adverse reactions especially under occlu- sive dressings.5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.Laboratory Tests: The following tests may be helpful in evaluating the HPA axis sup-pression: Urinary free cortisol test ACTH stimulation testCarcinogenesis, Mutagenesis, and Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.Pregnancy: Teratogenic Effects: Pregnancy Category C: Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.Nursing Mothers: It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable amounts in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities NOT likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman. Pediatric Use: Pediatric patients may demonstrate greater susceptibility to topical corticosteroid induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and intra-cranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, head-aches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.ADVERSE REACTIONS: The following local adverse reactions are reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence:

Burning Hypertrichosis Maceration of the skinItching Acneiform eruptions Secondary infection Irritation Hypopigmentation Skin atrophy Dryness Perioral dermatitis Striae Folliculitis Allergic contact dermatitis Miliaria

OVERDOSAGE: Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)DOSAGE AND ADMINISTRATION: Topical corticosteroids are generally applied to the affected area as a thin film three to four times daily depending on the severity of the condition. Lotion should be shaken well before use. Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions. If an infection develops, the use of occlusive dressings should be discontinued and appropriate antimicrobial therapy instituted.HOW SUPPLIED: Pramosone® Lotion 1% 2 fl oz (NDC 0496-0729-06) 4 fl oz (NDC 0496-0729-04) 8 fl oz (NDC 0496-0729-03) Pramosone® Lotion 2.5% 2 fl oz (NDC 0496-0726-06) 4 fl oz (NDC 0496-0726-04)Storage Conditions: Store at controlled room temperature 59º - 86ºF (15º - 30ºC).

Pramosone® is a registered trademark of Ferndale IP, Inc.