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Rx Only For Dermatologic Use Only Not for Ophthalmic Use Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 Dist. by: Taro Pharmaceuticals U.S.A., Inc ., Hawthorne, NY 10532 Revised: September 2016 20740-0916-1 88 Pharmacist: Please cut or tear at dotted line and provide this patient package insert to your customer.

DESCRIPTION Betamethasone Valerate Foam, 0.12% contains betamethasone valerate, USP, a synthetic corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory agents. Betamethasone valerate is 9-fluoro11β,17, 21-trihydroxy-16β-methylpregna-1, 4-diene-3, 20-dione 17-valerate, with the empirical formula C 27 H 37 FO 6 , a molecular weight of 476.58. The following is the chemical structure: Betamethasone valerate Betamethasone valerate is a white to practically white, odorless crystalline powder, and is practically insoluble in water, freely soluble in acetone and in chloroform, soluble in alcohol, and slightly soluble in benzene and in ether. Betamethasone valerate foam, 0.12%, contains 1.2 mg betamethasone valerate, USP, per gram in a thermolabile hydroethanolic foam vehicle consisting of alcohol (60.4%), cetyl alcohol, citric acid anhydrous, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol pressurized with a hydrocarbon (propane/butane) propellant. Chemical Structure

<table width="100%" styleCode="Noautorules"><col width="40%" align="left" valign="bottom"/><col width="60%" align="left" valign="bottom"/><tbody><tr><td><paragraph><renderMultiMedia referencedObject="MM1"/></paragraph></td><td>Betamethasone valerate</td></tr></tbody></table>

CLINICAL PHARMACOLOGY Like other topical corticosteroids, betamethasone valerate foam has anti-inflammatory, 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 A 2 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 A 2 . Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

Pharmacokinetics Topical corticosteroids can be absorbed from intact healthy skin. The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusion, inflammation and/or other disease processes in the skin may also increase percutaneous absorption. The use of pharmacodynamic endpoints for assessing the systemic exposure of topical corticosteroids is necessary due to the fact that circulating levels are well below the level of detection. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. They are metabolized, primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile.

CLINICAL STUDIES The safety and efficacy of betamethasone valerate foam, 0.12% has been demonstrated in a four-week trial. An adequate and well-controlled clinical trial was conducted in 190 patients with moderate to severe scalp psoriasis. Patients were treated twice daily for four weeks with betamethasone valerate foam, 0.12%, Placebo foam, a commercially available betamethasone valerate lotion 0.12% (formerly expressed as 0.1% betamethasone), or Placebo lotion. At four weeks of treatment, study results of 159 patients demonstrated that the efficacy of betamethasone valerate foam, 0.12% in treating scalp psoriasis is superior to that of Placebo foam, and is comparable to that of a currently marketed BMV lotion (see Table below). Subjects with Target Lesion Parameter Clear at Endpoint Betamethasone Valerate Foam, 0.12% n (%) BMV lotion n (%) Placebo foam n (%) Scaling 30 (47%) 22 (35%) 2 (6%) Erythema 26 (41%) 16 (25%) 2 (6%) Plaque Thickness 42 (66%) 25 (40%) 5 (16%) Investigator's Global: Subjects Completely Clear or Almost Clear at Endpoint 43 (67%) 29 (46%) 6 (19%)

<table width="75%" ID="table"><col width="30%" align="left" valign="middle"/><col width="25%" align="center" valign="middle"/><col width="23%" align="center" valign="middle"/><col width="22%" align="center" valign="middle"/><thead><tr><th styleCode="Lrule Rrule">Subjects with Target Lesion Parameter Clear at Endpoint</th><th styleCode="Rrule">Betamethasone Valerate Foam, 0.12% n (%) </th><th styleCode="Rrule">BMV lotion n (%) </th><th styleCode="Rrule">Placebo foam n (%) </th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Scaling</td><td styleCode="Rrule">30 (47%)</td><td styleCode="Rrule">22 (35%)</td><td styleCode="Rrule">2 (6%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Erythema</td><td styleCode="Rrule">26 (41%)</td><td styleCode="Rrule">16 (25%)</td><td styleCode="Rrule">2 (6%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Plaque Thickness</td><td styleCode="Rrule">42 (66%)</td><td styleCode="Rrule">25 (40%)</td><td styleCode="Rrule">5 (16%)</td></tr><tr><td styleCode="Lrule Rrule">Investigator&apos;s Global: Subjects Completely Clear or Almost Clear at Endpoint</td><td styleCode="Rrule">43 (67%)</td><td styleCode="Rrule">29 (46%)</td><td styleCode="Rrule">6 (19%)</td></tr></tbody></table>

INDICATIONS AND USAGE Betamethasone valerate foam, 0.12% is a medium potency topical corticosteroid indicated for relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses of the scalp.

CONTRAINDICATIONS Betamethasone valerate foam, 0.12% is contraindicated in patients who are hypersensitive to betamethasone valerate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS General Systemic absorption of topical corticosteroids has caused 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. 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 applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. 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 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. 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 . ) If irritation develops, betamethasone valerate foam, 0.12% 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. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of betamethasone valerate foam, 0.12% should be discontinued until the infection has been adequately controlled. 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 scalp area should not be bandaged or otherwise covered or wrapped so as to be occlusive unless directed by the physician. Patients should report to their physician any signs of local adverse reactions. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician. Laboratory 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 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 betamethasone valerate. Betamethasone was genotoxic in the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation and in the in vivo mouse bone marrow micronucleus assay.

animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of betamethasone valerate. Betamethasone was genotoxic in the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation and in the in vivo mouse bone marrow micronucleus assay. 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. There are no adequate and well-controlled studies in pregnant women. Therefore, betamethasone valerate foam, 0.12% 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 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 breast milk. Because many drugs are excreted in human milk, caution should be exercised when betamethasone valerate foam, 0.12% is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established. 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. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing'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 an 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 interfere with the growth and development of children.

General Systemic absorption of topical corticosteroids has caused 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. 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 applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. 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 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. 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 . ) If irritation develops, betamethasone valerate foam, 0.12% 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. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of betamethasone valerate foam, 0.12% should be discontinued until the infection has been adequately controlled.

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 scalp area should not be bandaged or otherwise covered or wrapped so as to be occlusive unless directed by the physician. Patients should report to their physician any signs of local adverse reactions. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.

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 betamethasone valerate. Betamethasone was genotoxic in the in vitro human peripheral blood lymphocyte chromosome aberration assay with metabolic activation and in the in vivo mouse bone marrow micronucleus assay.

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. There are no adequate and well-controlled studies in pregnant women. Therefore, betamethasone valerate foam, 0.12% 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 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 breast milk. Because many drugs are excreted in human milk, caution should be exercised when betamethasone valerate foam, 0.12% is administered to a nursing woman.

Pediatric Use Safety and effectiveness in pediatric patients have not been established. 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. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing'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 an 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 interfere with the growth and development of children.

ADVERSE REACTIONS The most frequent adverse event was burning/itching/stinging at the application site; the incidence and severity of this event were as follows: Incidence and severity of burning/itching/stinging Maximum severity Product Total incidence Mild Moderate Severe Betamethasone Valerate Foam n=63 34 (54%) 28 (44%) 5 (8%) 1 (2%) Betamethasone valerate lotion n=63 33 (52%) 26 (41%) 6 (10%) 1 (2%) Placebo Foam n=32 24 (75%) 13 (41%) 7 (22%) 4 (12%) Placebo Lotion n=30 20 (67%) 12 (40%) 5 (17%) 3 (10%) Other adverse events which were considered to be possibly, probably, or definitely related to betamethasone valerate foam, 0.12% occurred in 1 patient each; these were paresthesia, pruritus, acne, alopecia, and conjunctivitis. The following additional local adverse reactions have been reported with topical corticosteroids, and they may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximately decreasing order of occurrence: irritation; dryness; folliculitis; acneiform eruptions; hypopigmentation; perioral dermatitis; allergic contact dermatitis; secondary infection; skin atrophy; striae; and miliaria. 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.

<table width="75%" ID="table1"><caption>Incidence and severity of burning/itching/stinging</caption><col width="30%" align="left" valign="middle"/><col width="22%" align="left" valign="middle"/><col width="16%" align="left" valign="middle"/><col width="16%" align="left" valign="middle"/><col width="16%" align="left" valign="middle"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule"/><th styleCode="Rrule"/><th colspan="3" styleCode="Rrule">Maximum severity</th></tr><tr><th styleCode="Lrule Rrule">Product</th><th styleCode="Rrule">Total incidence</th><th styleCode="Rrule">Mild</th><th styleCode="Rrule">Moderate</th><th styleCode="Rrule">Severe</th></tr></thead><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Betamethasone Valerate Foam n=63</td><td styleCode="Rrule">34 (54%)</td><td styleCode="Rrule">28 (44%)</td><td styleCode="Rrule">5 (8%)</td><td styleCode="Rrule">1 (2%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Betamethasone valerate lotion n=63</td><td styleCode="Rrule">33 (52%)</td><td styleCode="Rrule">26 (41%)</td><td styleCode="Rrule">6 (10%)</td><td styleCode="Rrule">1 (2%)</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Placebo Foam n=32</td><td styleCode="Rrule">24 (75%)</td><td styleCode="Rrule">13 (41%)</td><td styleCode="Rrule">7 (22%)</td><td styleCode="Rrule">4 (12%)</td></tr><tr><td styleCode="Lrule Rrule">Placebo Lotion n=30</td><td styleCode="Rrule">20 (67%)</td><td styleCode="Rrule">12 (40%)</td><td styleCode="Rrule">5 (17%)</td><td styleCode="Rrule">3 (10%)</td></tr></tbody></table>

DOSAGE AND ADMINISTRATION Note: For proper dispensing of foam, can must be inverted. For application to the scalp invert can and dispense a small amount of betamethasone valerate foam, 0.12% onto a saucer or other cool surface. Do not dispense directly onto hands as foam will begin to melt immediately upon contact with warm skin. Pick up small amounts of foam with fingers and gently massage into affected area until foam disappears. Repeat until entire affected scalp area is treated. Apply twice daily, once in the morning and once at night. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. Betamethasone valerate foam, 0.12% should not be used with occlusive dressings unless directed by a physician.

HOW SUPPLIED Betamethasone Valerate Foam, 0.12% is supplied in 50 gram (NDC 51672-4188-3) and 100 gram (NDC 51672-4188-7) aluminum cans. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

WARNING FLAMMABLE. AVOID FIRE, FLAME OR SMOKING DURING AND IMMEDIATELY FOLLOWING APPLICATION. Keep out of reach of children. Contents under pressure. Do not puncture or incinerate container. Do not expose to heat or store at temperatures above 120°F (49°C).

PATIENT INFORMATION Betamethasone Valerate (bay'' ta meth' a sone val' er ate) Foam, 0.12% About Betamethasone Valerate Foam, 0.12% Your doctor has prescribed betamethasone valerate foam, 0.12%, for the relief of corticosteroid-responsive skin conditions of the scalp. Betamethasone valerate foam, 0.12% works because its active ingredient is betamethasone valerate, 0.12%. Betamethasone belongs to a group of medicines known as topical corticosteroids. These agents are used to reduce the inflammation, redness, swelling, itching, and tenderness associated with dermatologic conditions. Other ingredients in betamethasone valerate foam, 0.12% include alcohol (60.4%), cetyl alcohol, citric acid anhydrous, polysorbate 60, potassium citrate, propylene glycol, purified water, and stearyl alcohol. The foam is dispensed from an aluminum can that is pressurized by a hydrocarbon propellant (propane and butane). If you answer YES to one or more of the following questions, tell your doctor (or pharmacist) before using this medicine, so you can get advice about what to do. Are you allergic to any of the ingredients contained in betamethasone valerate foam, 0.12%? Are you pregnant? Planning on becoming pregnant while using betamethasone valerate foam, 0.12%? Or are you breastfeeding? Do you think you have an infection on your scalp? How to apply Betamethasone Valerate Foam, 0.12% Turn the can upside down and dispense a small amount of betamethasone valerate foam onto a clean saucer or other cool, clean surface. Do not dispense directly onto hands, as foam will begin to melt immediately upon contact with warm skin. Pick up small amounts of foam with fingers and gently massage into affected area until foam disappears. Repeat until entire affected scalp area is treated. Apply twice daily, once in the morning and once at night. Use sparingly-only enough to cover the affected areas. Gently massage the foam in until it is absorbed and allow the areas to dry naturally. When applying to the scalp, move the hair away so that the foam can be applied directly to each affected area. Wash your hands immediately after applying betamethasone valerate foam, and discard any unused dispensed medication. Do not wash or rinse the treated areas immediately after applying betamethasone valerate foam. Do not use this medication for any condition other than the one for which it was prescribed. Betamethasone valerate foam, 0.12% is for external use only. Keep the foam away from your eyes, as it will sting. If the foam gets into your eyes, rinse well with cold water. If the stinging continues, contact your doctor immediately. WHAT YOU SHOULD KNOW ABOUT BETAMETHASONE VALERATE FOAM, 0.12%: What to do if you miss an application If you forget to apply betamethasone valerate foam, 0.12% at the scheduled time, use it as soon as you remember, and then go back to your regular schedule. If you remember at or about the time of your next daily application, apply that dose and continue with your normal application schedule. If you miss several doses, tell your doctor at your next appointment. About side effects As with all medications, there may be some side effects. The most frequent side effects associated with the use of betamethasone valerate foam, 0.12% include mild burning, stinging, or itching at the site of application. These side effects typically disappear shortly after application.

t appointment. About side effects As with all medications, there may be some side effects. The most frequent side effects associated with the use of betamethasone valerate foam, 0.12% include mild burning, stinging, or itching at the site of application. These side effects typically disappear shortly after application. Let your doctor know if you notice any of the following: Any unusual effects that you do not understand. Affected areas that do not seem to be healing after several weeks of using the foam. Important safety notes The treated areas should not be bandaged or covered unless directed by your doctor. Keep this and all medicines out of the reach of children. Store the can at controlled room temperature 68° to 77°F (20° to 25°C) and protect it from direct sunlight, as this is a pressurized container. Keep away from and do not spray near fire, open flame, or direct heat--this product is flammable. Do not smoke while using or holding the can. Keep the can away from all sources of ignition. Do not pierce or burn the can, and never throw the can in a fire, even if empty. When you have finished your treatment, dispose of the can safely. Do not use the foam after the expiration date shown on the can. Do not give betamethasone valerate foam, 0.12% to anyone else. Your doctor has prescribed this medicine for your use only. Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel, 2624761 Dist. by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532 Revised: September 2016 20740-0916-1 88 Figure Figure Figure Figure

<table width="80%"><col width="35%" align="center" valign="middle"/><col width="65%" align="left" valign="top"/><tbody><tr styleCode="Botrule"><td align="center" colspan="2" styleCode="Lrule Rrule">How to apply Betamethasone Valerate Foam, 0.12%</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><renderMultiMedia referencedObject="MM2"/></td><td styleCode="Rrule"><content styleCode="italics">Turn the can upside down and dispense a small amount of betamethasone valerate foam onto a clean saucer or other cool, clean surface. Do not dispense directly onto hands, as foam will begin to melt immediately upon contact with warm skin.</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><renderMultiMedia referencedObject="MM3"/></td><td styleCode="Rrule"><content styleCode="italics">Pick up small amounts of foam with fingers and gently massage into affected area until foam disappears. Repeat until entire affected scalp area is treated. Apply twice daily, once in the morning and once at night. Use sparingly-only enough to cover the affected areas. Gently massage the foam in until it is absorbed and allow the areas to dry naturally. When applying to the scalp, move the hair away so that the foam can be applied directly to each affected area. </content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><renderMultiMedia referencedObject="MM4"/></td><td styleCode="Rrule"><content styleCode="italics">Wash your hands immediately after applying betamethasone valerate foam, and discard any unused dispensed medication.</content></td></tr><tr><td styleCode="Lrule Rrule"><renderMultiMedia referencedObject="MM5"/></td><td styleCode="Rrule"><content styleCode="italics">Do not wash or rinse the treated areas immediately after applying betamethasone valerate foam.</content></td></tr></tbody></table>

Rx only FOR EXTERNAL USE ONLY. NOT FOR OPHTHALMIC USE. Mfd. by: Sun Pharma Canada Inc., Brampton, Ontario, Canada L6T 1C1 Dist. by: Sun Pharmaceutical Industries, Inc., Cranbury, NJ 08512 Revised: September 2025 5264923-0925-01 372

DESCRIPTION Betamethasone Valerate Cream USP, 0.1% contains betamethasone valerate USP, a synthetic adrenocorticosteroid for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Betamethasone valerate is a white to practically white odorless crystalline powder practically insoluble in water, freely soluble in acetone and chloroform, soluble in alcohol, and slightly soluble in benzene and ether. Chemically it is 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1, 4-diene-3,20-dione 17-valerate. The structural formula is: Molecular Formula: C 27 H 37 FO 6 Molecular Weight: 476.59 Each gram of Betamethasone Valerate Cream USP, 0.1% contains 1.2 mg betamethasone valerate (equivalent to 1 mg betamethasone) in a soft, white, hydrophilic cream of ceteareth-15, cetyl alcohol, mineral oil, polyethylene glycol 1000, propylene glycol, purified water, stearyl alcohol, white petrolatum, phosphoric acid and sodium hydroxide (for pH adjustment); chlorocresol is present as a preservative. Chemical Structure

<table width="100%" styleCode="Noautorules"><col width="35%" align="right" valign="top"/><col width="30%" align="center" valign="top"/><col width="35%" align="left" valign="top"/><tbody><tr><td colspan="3" align="center"><renderMultiMedia referencedObject="MM1"/></td></tr><tr><td>Molecular Formula: C ₂₇H ₃₇FO ₆</td><td/><td>Molecular Weight: 476.59</td></tr></tbody></table>

CLINICAL PHARMACOLOGY Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the 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. 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 resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic 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.

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 resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic 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.

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 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. Pediatric patients 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 antibacterial 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 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. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed. The treated skin should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. Patients should report any signs of local adverse reactions especially under occlusive dressing. 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 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.

togenic 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 quantities 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 intracranial 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 pediatric patients 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.

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 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. Pediatric patients 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 antibacterial 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 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. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed. The treated skin should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician. Patients should report any signs of local adverse reactions especially under occlusive dressing. 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.

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.

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.

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 intracranial 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 pediatric patients 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, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae and miliaria. To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc., at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DESCRIPTION: Betamethasone Valerate Cream, Ointment and Lotion contain betamethasone valerate USP, a synthetic adrenocorticosteroid for dermatologic use. Betamethasone, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Betamethasone valerate is a white to practically white odorless crystalline powder practically insoluble in water, freely soluble in acetone and chloroform, soluble in alcohol, and slightly soluble in benzene and ether. Chemically, it is 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1, 4-diene-3,20-dione 17-valerate. The structural formula is: Each gram of the 0.1% Cream contains 1.2 mg betamethasone valerate (equivalent to 1 mg betamethasone) in a soft, white, hydrophilic cream of purified water, mineral oil, white petrolatum, polyoxyl 20 cetostearyl ether, cetostearyl alcohol, monobasic sodium phosphate and phosphoric acid or sodium hydroxide (to adjust pH, if required); chlorocresol is present as a preservative. Each gram of the 0.1% Ointment contains 1.2 mg betamethasone valerate (equivalent to 1 mg betamethasone) in an ointment base of white petrolatum and mineral oil. Each gram of the 0.1% Lotion contains 1.2 mg betamethasone valerate (equivalent to 1 mg betamethasone) in a vehicle of isopropyl alcohol and water slightly thickened with carbomer 934P. Sodium hydroxide is used to adjust pH. structural formula

CLINICAL PHARMACOLOGY: Topical corticosteroids share anti-inflammatory, antipruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the 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. 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 resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic 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.

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 resistant dermatoses. Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic 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.

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 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 substitute to 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. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity (See Error! Hyperlink reference not valid. ). 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 antibacterial 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 Patients: 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 that 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 dressing. 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 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.

c 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 quantities 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 intracranial 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 pediatric patients 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.

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 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 substitute to 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. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity (See Error! Hyperlink reference not valid. ). 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 antibacterial 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 Patients: 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 that 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 dressing. 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.

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.

DOSAGE AND ADMINISTRATION: Apply a thin film of Betamethasone Valerate Cream or Ointment to the affected skin areas one to three times a day. Dosage once or twice a day is often effective. Apply a few drops of Betamethasone Valerate Lotion to the affected area and massage lightly until it disappears. Apply twice daily, in the morning and at night. Dosage may be increased in stubborn cases. Following improvement, apply once daily. For the most effective and economical use, apply nozzle very close to affected area and gently squeeze bottle.

How Supplied BETAMETHASONE VALERATE OINTMENT USP, 0.1% (Potency expressed as betamethasone) Rx only NET WT 15 grams Store at room temperature 15° - 30°C (59° - 86°F) [see USP Controlled Room Temperature]. E. FOUGERA & CO. A division of Fougera PHARMACEUTICALS INC. Melville, NY 11747 46289058A R06/2021 #57 Relabeled By: Preferred Pharmaceuticals Inc. NDC 68788-8496-1 15 Gram Tube NDC 68788-8496-4 45 Gram Tube