Clodan

Medimetriks Pharmaceuticals

Clodan (clobetasol propionate) Shampoo, 0.05%

FULL PRESCRIBING INFORMATION: CONTENTS*

• CLODAN DESCRIPTION
• CLINICAL PHARMACOLOGY
  • Pharmacokinetics
• CLINICAL STUDIES
• CLODAN INDICATIONS AND USAGE
• CLODAN CONTRAINDICATIONS
• PRECAUTIONS
  • General
  • Information For Patients
  • Laboratory Tests
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• CLODAN ADVERSE REACTIONS
• OVERDOSAGE
• CLODAN DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
  • Storage
• PATIENT INFORMATION
• PRINCIPAL DISPLAY PANEL - 118 mL Bottle Carton

FULL PRESCRIBING INFORMATION

R_x Only

FOR EXTERNAL USE ONLY.

NOT FOR OPHTHALMIC USE.

CLODAN DESCRIPTION

Clodan™ (clobetasol propionate) Shampoo, 0.05% contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. The chemical name of clobetasol propionate is 21-chloro-9-fluoro-11β, 17-dihydroxy-16β-methylpregna-1, 4-diene-3, 20-dione 17-propionate.

Clobetasol propionate has a molecular weight of 466.97 (CAS Registry Number 25122-46-7). The molecular formula is C₂₅H₃₂CIFO₅. Clobetasol propionate is a white to practically white crystalline, odorless powder insoluble in water.

Each mL of Clodan™ contains clobetasol propionate, 0.05%, in a shampoo base consisting of alcohol, coco-betaine, hydrochloric acid, polyquaternium-10, purified water, and sodium laureth sulfate.

CLINICAL PHARMACOLOGY

Like other topical corticosteroids, Clodan™ 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 A₂ inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A₂.

Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion. Topical corticosteroids can be absorbed from normal intact skin, while inflammation and/or other disease processes in the skin may increase percutaneous absorption.

Due to the fact that circulating levels of corticosteroids are usually below the limit of detection following application, there are no human data regarding the pharmacokinetics of topical corticosteroids. In such cases pharmacodynamic end points, including both hypothalamic-pituitary-adrenal (HPA) axis testing and topical vasoconstriction, are used as surrogates in the assessments of systemic exposure and relative potency, respectively.

In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, use of clobetasol propionate shampoo, 0.05%, resulted in demonstrable HPA axis suppression in 5 out of 12 (42%) adolescent patients (see PRECAUTIONS ).

Clobetasol propionate shampoo, 0.05% is in the super-high range of potency in vasoconstrictor studies.

CLINICAL STUDIES

The safety and efficacy of clobetasol propionate shampoo, 0.05% has been evaluated in two clinical trials involving 290 patients with moderate to severe scalp psoriasis. In both trials, patients were treated with either clobetasol propionate shampoo, 0.05% or the corresponding vehicle applied once daily for 15 minutes before lathering and rinsing for a period of four weeks. Efficacy results are presented in the table below.

	Clobetasol Propionate Shampoo, 0.05% n(%)		Clobetasol Propionate Shampoo Vehicle n(%)
	Study A	Study B	Study A	Study B
Total Number of Patients	95	99	47	49
Success RateSuccess rate defined as the proportion of patients with a-0 (clear) or 1 (minimal) on a 0 to 5 point physician's Global Severity Scale for scalp psoriasis.-at EndpointAt four (4) weeks or last observation recorded for a subject during the treatment period (baseline if no post-baseline data were available).	40 (42.1%)	28 (28.3%)	1 (2.1%)	5 (10.2%)
Subjects with Scalp Psoriasis Parameter Clear (None) at Endpoint
ErythemaPatients with 0 (clear) on a 0 to 3 point scalp psoriasis parameter scale.	17 (17.9%)	12 (12.1%)	3 (6.4%)	1 (2.0%)
ScalingPatients with 0 (clear) on a 0 to 3 point scalp psoriasis parameter scale.	21 (22.1%)	15 (15.2%)	0 (0%)	2 (4.1%)
Plaque ThickeningPatients with 0 (clear) on a 0 to 3 point scalp psoriasis parameter scale.	35 (36.8%)	34 (34.3%)	5 (10.6%)	5 (10.2%)

Clinical studies of clobetasol propionate shampoo, 0.05% did not include sufficient numbers of non-Caucasian patients to determine whether they respond differently than Caucasian patients with regards to efficacy and safety.

CLODAN INDICATIONS AND USAGE

Clodan™ is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe forms of scalp psoriasis in subjects 18 years of age and older (see PRECAUTIONS ). Treatment should be limited to four consecutive weeks because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. The total dosage should not exceed 50g (50 mL or 1.75 fl. oz.) per week (see DOSAGE and ADMINISTRATION ).

Patients should be instructed to use Clodan™, for the minimum time period necessary to achieve the desired results (see PRECAUTIONS ).

Use in patients younger than 18 years of age is not recommended due to numerically high rates of HPA axis suppression (see PRECAUTIONS, Pediatric Use ).

There were insufficient numbers of non-Caucasian patients to determine whether they responded differently than Caucasian patients with regards to efficacy and safety.

CLODAN CONTRAINDICATIONS

Use of Clodan™ is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS

General

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 can produce 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 increase systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings or use on occluded areas. 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 and complete 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.

The effect of clobetasol propionate shampoo, 0.05% on HPA axis suppression was evaluated in one study in adolescents 12 to 17 years of age. In this study, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with clobetasol propionate shampoo, 0.05% applied once daily for 15 minutes to a dry scalp before lathering and rinsing.

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, Clodan™ 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 Clodan™ should be discontinued until the infection has been adequately controlled.

Although Clodan™ is intended for the topical treatment of moderate to severe scalp psoriasis, it should be noted that certain areas of the body, such as the face, groin, and axillae, are more prone to atrophic changes than other areas of the body following treatment with corticosteroids. Clodan™ should not be used on the face, groin or axillae. Avoid any contact of the drug product with the eyes and lips. In case of contact, rinse thoroughly with water all parts of the body that came in contact with the shampoo.

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 and should not be used longer than the prescribed time period. 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 scalp area should not be covered while the medication is on the scalp (e.g., shower cap, bathing cap) so as to be occlusive unless directed by the physician.
• Patients should report any signs of local or systemic adverse reactions to their physician.
• As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within four weeks, contact the physician.
• Patients should wash their hands after applying the medication.
• Patients should inform their physician(s) that they are using Clodan™ if surgery is contemplated.
• Patients should not use more than 50 g (50 mL or 1.75 fl. oz.) per week of Clodan™.

Laboratory Tests

The cortrosyn stimulation test may be helpful in evaluating patients for HPA axis suppression.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Clobetasol propionate did not produce any increase in chromosomal aberrations in Chinese hamster ovary cells in vitro in the presence or absence of metabolic activation. Clobetasol propionate was also negative in the micronucleus test in mice after oral administration.

Studies of the effect of clobetasol propionate shampoo, 0.05% on fertility have not been conducted.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals.

A teratogenicity study of clobetasol propionate in rats using the dermal route resulted in dose related maternal toxicity and fetal effects from 0.05 to 0.5 mg/kg/day. These doses are approximately 0.1 to 1.0 times, respectively, the maximum human topical dose of clobetasol propionate from clobetasol propionate shampoo, 0.05%. Abnormalities seen included low fetal weights, umbilical herniation, cleft palate, reduced skeletal ossification and other skeletal abnormalities.

Clobetasol propionate administered to rats subcutaneously at a dose of 0.1 mg/kg from day 17 of gestation to day 21 postpartum was associated with prolongation of gestation, decreased number of offspring, increased perinatal mortality of offspring, delayed eye opening and delayed hair appearance in surviving offspring. Some increase in offspring perinatal mortality was also observed at a dose of 0.05 mg/kg. Doses of 0.05 and 0.1 mg/kg are approximately 0.1 and 0.2 fold the maximum human topical dose of clobetasol propionate from clobetasol propionate shampoo, 0.05%.

There are no adequate and well controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clodan™ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when Clodan™ is administered to a nursing woman.

Pediatric Use

Use of Clodan™, in patients under 18 years old is not recommended due to potential for HPA axis suppression (see PRECAUTIONS - General ).

The effect of clobetasol propionate shampoo, 0.05%, on HPA axis suppression was evaluated in one study in adolescents 12 to 17 years of age. In this study, 5 of 12 evaluable subjects developed suppression of their HPA axis following four weeks of treatment with clobetasol propionate shampoo, 0.05%, applied once daily for 15 minutes to a dry scalp before lathering and rinsing. Only one of the five subjects who had suppression was tested for recovery of HPA axis, and this subject recovered after two weeks.

No studies have been performed in patients under the age of 12. 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.

Therefore, use is not recommended in patients under the age of 18.

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.

Geriatric Use

Clinical studies of clobetasol propionate shampoo, 0.05% did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. 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.

CLODAN ADVERSE REACTIONS

In clinical trials with clobetasol propionate shampoo, 0.05%, the following adverse reactions have been reported: burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia.

The table below summarizes selected adverse events that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis.

The following additional local adverse reactions have been reported infrequently with other topical corticosteroids, and they may occur more frequently with the use of occlusive dressings, especially with higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.

Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

OVERDOSAGE

Topically applied, Clodan™ can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS ).

CLODAN DOSAGE AND ADMINISTRATION

Clodan™ should be applied onto dry (not wet) scalp once a day in a thin film to the affected areas only, and left in place for 15 minutes before lathering and rinsing.

Move the hair away from the scalp so that one of the affected areas is exposed. Position the bottle over the lesion. Apply a small amount of the shampoo directly onto the lesion, letting the product naturally flow from the bottle (gently squeeze the bottle), avoiding any contact of the product with the facial skin, eyes or lips. In case of contact, rinse thoroughly with water. Spread the product so that the entire lesion is covered with a thin uniform film. Massage gently into the lesion and repeat for additional lesion(s). Wash your hands after applying Clodan™.

Leave the shampoo in place for 15 minutes, then add water, lather and rinse thoroughly all parts of the scalp and body that came in contact with the shampoo (e.g., hands, face, neck and shoulders). Avoid contact with eyes and lips. Minimize contact to non-affected areas of the body. Although no additional shampoo is necessary to cleanse your hair, you may use a non-medicated shampoo if desired.

Treatment should be limited to 4 consecutive weeks. As with other corticosteroids, therapy should be discontinued when control is achieved. If complete disease control is not achieved after four weeks of treatment with Clodan™, treatment with a less potent topical steroid may be substituted. If no improvement is seen within 4 weeks, reassessment of the diagnosis may be necessary.

Clodan™ should not be used with occlusive dressings unless directed by a physician.

HOW SUPPLIED

Clodan™ (clobetasol propionate) Shampoo, 0.05% is available as follows:

4 fl oz (118 mL) bottle (NDC 43538-950-04)

Storage

Keep bottle tightly closed. Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature].

Manufactured for: Medimetriks Pharmaceuticals, Inc.
383 Route 46 West, Fairfield, NJ 07004-2402 • www.medimetriks.com

Manufactured by: Perrigo, Yeruham 80500, Israel

Made in Israel

Iss. 4/14
IP035

PATIENT INFORMATION

For External Use Only.
Not for Ophthalmic (Eye) Use.

Rx Only

Clodan™ (clobetasol propionate) Shampoo, 0.05%

Read the Patient Information that comes with Clodan™ (clobetasol propionate) Shampoo, 0.05% before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about Clodan™?

What is Clodan™?

Clodan™ is a medicine called a topical (skin use only) corticosteroid. It is used for a short time to treat forms of scalp psoriasis. Clodan™ is a super-high potent (very strong) topical corticosteroid. It is very important that you use Clodan™ only as directed in order to avoid serious side effects.

Who should not use Clodan™?

Do not use Clodan™ if you are allergic to any of its ingredients, or to any other corticosteroid. The active ingredient is clobetasol propionate. See the end of this leaflet for a complete list of ingredients in Clodan™. Ask your doctor or pharmacist if you need a list of other corticosteroids.

Clodan™ is not recommended for use by patients under 18 years of age. Children have smaller body sizes and have a higher chance of side effects.

What should I tell my doctor before using Clodan™?

Tell your doctor:

• if you are pregnant, think you are pregnant, or plan to be pregnant. Talk with your doctor before using Clodan™ or if you are already using Clodan™. It is not known Clodan™ can harm your unborn baby.
• if you are breastfeeding. It is not known if Clodan™ passes into your milk, and if it can harm your baby.
• if you think you have an infection on your scalp. You may need another medicine to treat the scalp infection before you use Clodan™.

Tell your doctor about all the other medicines and skin products you use, including prescription and non-prescription medicines, vitamins, herbal supplements, and cosmetics. Some medicines and products can cause serious side effects if used while you are using Clodan™.

How should I use Clodan™?

• Use Clodan™ exactly as prescribed by your doctor. Clodan™ is for use on your scalp only.
• Apply Clodan™ on affected areas of the scalp once a day. Use only enough to cover the affected areas of your scalp. Do not use Clodan™ on your face, groin, armpits, lips, or in your eyes.
• Do not wet your hair before using Clodan™. Move the hair away from the scalp so that one of the affected areas is exposed. Apply a small amount of the shampoo directly onto the affected area by gently squeezing the bottle. Gently, rub Clodan™ into the affected area. Repeat for other affected areas on your scalp.
• Do not cover your head with a shower cap or bathing cap while Clodan™ is on your scalp.
• Leave Clodan™ in place for 15 minutes before adding water, lathering and rinsing hair and scalp completely. No other shampoos are necessary. However, you can use a non-medicated shampoo on your hair after using Clodan™ if you want to.
• Wash your hands after applying Clodan™. Wash any other part of your body that came into contact with Clodan™ such as your neck and shoulders.
• If you forget to apply Clodan™ at the scheduled time, use it as soon as you remember. Then go back to your regular schedule. If it is about time for your next dose, apply just that one dose, and continue with your regular schedule. Do not make up the missed dose. If you miss several doses, tell your doctor.
• Do not use more than 50 grams (50 mL or 1.75 fluid ounces) of Clodan™ per week.

What should I avoid while using Clodan™?

Do not do the following while using Clodan™:

• Do not get Clodan™ on your lips or in or near your eyes because this might cause side effects. If you do, use a lot of water to rinse the Clodan™ off your face, lips, or out of your eyes.
  If your eyes keep stinging after rinsing them well with water, contact your doctor right away.
• Do not apply Clodan™ to your face, groin or armpits.
• Do not get Clodan™ in your mouth. If you or a child accidentally swallows Clodan™, call your Poison Control center or local emergency room right away.
• Do not cover your head with a shower or bathing cap while Clodan™ is on your scalp.
• Do not use Clodan™ any longer than four weeks (28 days) for moderate to severe scalp psoriasis.
• Do not use more than 50 mL (1.75 fluid ounces) of Clodan™ per week.

What should I do if I miss an application of Clodan™?

If you forget to apply Clodan™ at the scheduled time, use it as soon as you remember, and then go back to your regular schedule. If you remember at the time of your next application, apply only one dose and continue with your regular schedule. If you miss several doses, tell your doctor.

What are the possible side effects of Clodan™?

Clodan™ can pass through your skin. Too much Clodan™ passing through your skin can shut down your adrenal glands. This may happen if you use too much Clodan™ or if you use it for too long, but it can happen with correct use. If your adrenal glands shut down, they may not start working right away after you stop using Clodan™. Shutting down of the adrenal glands can cause nausea, vomiting, fever, low blood pressure, heart attack and even death because your body cannot adequately respond to stress or illness.

Your doctor may do special blood and urine tests to check your adrenal gland function while you are using Clodan™.

The most common side effects with Clodan™ include burning or itching at the site of application. Other possible side effects include thinning of the skin and widening of small blood vessels in the skin.

If you go to another doctor for illness, injury or surgery, tell that doctor that you are using Clodan™.

Tell your doctor if you:

• are going to have surgery
• get sick or don't feel right. Call your doctor right away.
• have irritation of the treated skin area that does not go away
• have any unusual effects that you do not understand
• have affected areas that do not seem to be healing after four weeks of using Clodan™.

These are not all the possible side effects of Clodan™. For more information, ask your doctor or pharmacist.

How should I store Clodan™?

• Store Clodan™ at room temperature between 20-25°C (68-77°F).
• Keep the bottle tightly closed at all times.
• Do not use Clodan™ after the expiration date shown on bottle.
• Keep Clodan™ and all medicines out of the reach of children.

General information about Clodan™

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use Clodan™ for a condition for which it was not prescribed. Do not give Clodan™ to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Clodan™. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Clodan™ that is written for health professionals.

What are the ingredients in Clodan™?

Active ingredient: clobetasol propionate

Inactive ingredients (shampoo base): alcohol, coco-betaine, hydrochloric acid, polyquaternium-10, purified water, and sodium laureth sulfate.

Manufactured for: Medimetriks Pharmaceuticals, Inc.
383 Route 46 West, Fairfield, NJ 07004-2402 • www.medimetriks.com

Manufactured by: Perrigo, Yeruham 80500, Israel

Made in Israel

Iss. 4/14
IP035

PRINCIPAL DISPLAY PANEL - 118 mL Bottle Carton

NDC 43538-950-04

R_x Only
Clodan _™
(clobetasol propionate)
Shampoo, 0.05%

For External Use Only
Do Not Use in Eyes

4 FL. OZ. (118 mL)

MEDIMETRIKS
PHARMACEUTICALS, INC.