OTC Dermatologic Topical Corticosteroids Michael L. Koenig, Ph.D. Interdisciplinary Scientist Division of Over-the-Counter Drug Products Center for Drug

OTCOTCDermatologic Topical CorticosteroidsDermatologic Topical Corticosteroids

Michael L. Koenig, Ph.D.Michael L. Koenig, Ph.D.Interdisciplinary ScientistInterdisciplinary ScientistDivision of Over-the-Counter Drug ProductsDivision of Over-the-Counter Drug Products

Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research

2Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005

Overview

1. Regulation of OTC Drugs

2. Regulatory History of Hydrocortisone

3. Current Labeling of Hydrocortisone


Regulation of OTC DrugsRegulation of OTC Drugs

• NDA (New Drug Application)– Drug product-specific– Confidential

• Monograph– Active ingredient-specific– Public


OTC MonographsOTC Monographs

• OTC Drug Review initiated in 1972

• > 200,000 OTC drug products

• 700 active ingredients in 26 therapeutic categories


OTC Monographs OTC Monographs

• Category I: GRASE (Generally Recognized as Safe and Effective)

• Category II: not GRASE• Category III: cannot determine if safe and effective

Advisory Review Panel



• Category I: GRASE• Category II: not GRASE• Category III: cannot determine if safe and

effective ANPR



ANPRTFM

Comments



TFM

Comments

Data

FM


Regulatory History of Regulatory History of HydrocortisoneHydrocortisone



• Introduced as Rx drug (1952)

• Rx-to-OTC switch rejected (1957)– Failure to show safety for self-medication– More testing on absorption through the skin

• Included with other active ingredients in review of external analgesics (1973-1978)



ANPR (1979)

• Lack of adverse local effects– Striae

– Telangiectasia

– Pustular eruptions and crusting



ANPR (1979)• Lack of systemic effects

– Percutaneous absorption– Eosinophil count – Urinary levels of 17-hydroxysteroids and 17-

ketosteroids– Blood glucose levels– Serum sodium– Plasma cortisol ↑ in response to insulin



No HPA Axis Suppression

• Munro and Clift, Br. J. Dermatol., 1973 (TAB 5)

– 40 patients with eczema, psoriasis

– Long term treatment (95% > 10 months)

– Corticosteroid combinations

• 10 included 1% hydrocortisone acetate

– 10/10: normal insulin stress response



Serious Adverse Events (1952-1973)• 1960: Temporary growth retardation in 5.5 year old

– 1% hydrocortisone for 16 months

• 1962: Temporary growth retardation in infant– 1% hydrocortisone twice daily for 6 months (total body)

• 1966: Rapid gain in body weight in 3-week old– 0.25% hydrocortisone three times daily for 8.5 days

– 2100 mg/m2 body surface area



Panel Recommendations• 0.25 – 0.5% hydrocortisone GRASE

• Recommended labeling:– Indication – temporary relief of minor skin irritations,

itching, and rashes due to eczema, dermatitis… – Warnings

• Stop use if condition worsens or lasts > 7 days• Do not use on children under 2 years of age

– Directions – Apply to affected area not more than 3 to 4 times daily



TFM (1983)

• FDA position

– Agreed 0.25 – 0.5% hydrocortisone GRASE– Some labeling modifications

• Temporary relief of itching associated with minor skin irritations and rashes due to…

• Stop use if condition worsens or lasts > 7 days or if symptoms clear up and occur again within a few days


Regulatory History ofRegulatory History ofHydrocortisoneHydrocortisoneAmended TFM (1990)

• Citizen Petition requested increase in dosage strength to 1%

• Data and literature review

• 0.25 – 1.0% hydrocortisone GRASE

• Additional labeling modifications– Do not use

• any other hydrocortisone product• for the treatment of diaper rash



FM (20??)

• Pending

• Manufacturers generally comply with TFM and amended TFM

• Continuing review of data


Hydrocortisone Does Not Hydrocortisone Does Not Suppress HPA AxisSuppress HPA Axis

Published Study n Hydrocortisone

(%)

Duration

of Treatment

Munro, 1979 9 1* 14 days

Marten et al., 1980 10 1 28 days

Patel et al., 1995 14 1 3 - 10 years

Lucky et al., 1997 8 2.5 28 days

Ellison et al., 2000 7 1 0.5 – 17.7 years

* Hydrocortisone acetate


Current Labeling of Current Labeling of HydrocortisoneHydrocortisone


Monograph Labeling: HydrocortisoneMonograph Labeling: HydrocortisoneDrug Facts

Active ingredient PurposeHydrocortisone (1%)…………………………………………....Anti-itch

Uses ■ temporarily relieves itching associated with minor skin

irritations, inflammation, and rashes due to:

■ eczema ■ poison ivy, oak, sumac

■ insect bites ■ soaps

■ detergents ■ cosmetics

■ jewelry ■ seborrheic dermatitis

■ psoriasis ■ and for external genital or anal

itching

■ other uses of this product should be only under the advice and

supervision of a doctor

WarningsExternal use only

Do not use

■ for the treatment of diaper rash. Consult a doctor.

■ in the genital area if you have a vaginal discharge. Consult a

doctor.

Drug Facts (continued)

When using this product

■ avoid contact with the eyes

■ do not exceed the recommended daily dosage unless directed by

a doctor

■ do not cover treated skin

■ do not use any other hydrocortisone product

■ do not put directly in rectum using fingers or any mechanical

device

Stop use and ask a doctor if

■ condition worsens

■ symptoms persist for more than 7 days or clear up and occur

again within a few days

■ rectal bleeding occurs

Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

Directions ■ adults and children 2 years of age and older: apply to affected

area not more than 3 to 4 times daily.

■ children under 2 years of age: Do not use. Consult a doctor.


Monograph Labeling: HydrocortisoneMonograph Labeling: HydrocortisoneDrug Facts

Active ingredient PurposeHydrocortisone (1%)…………………………………………....Anti-itch

Uses ■ temporarily relieves itching associated with minor skin

irritations, inflammation, and rashes due to:

■ eczema ■ poison ivy, oak, sumac

■ insect bites ■ soaps

■ detergents ■ cosmetics

■ jewelry ■ seborrheic dermatitis

■ psoriasis ■ and for external genital or anal

itching

■ other uses of this product should be only under the advice and

supervision of a doctor

WarningsExternal use only

Do not use

■ for the treatment of diaper rash. Consult a doctor.

■ in the genital area if you have a vaginal discharge. Consult a

doctor.

Drug Facts (continued)

When using this product

■ avoid contact with the eyes

■ do not exceed the recommended daily dosage unless directed by

a doctor

■ do not cover treated skin

■ do not use any other hydrocortisone product

■ do not put directly in rectum using fingers or any mechanical

device

Stop use and ask a doctor if

■ condition worsens

■ symptoms persist for more than 7 days or clear up and occur

again within a few days

■ rectal bleeding occurs

Keep out of reach of children. If swallowed, get medical help or contact a Poison Control Center right away.

Directions ■ adults and children 2 years of age and older: apply to affected

area not more than 3 to 4 times daily.

■ children under 2 years of age: Do not use. Consult a doctor.

temporarily relieves itching associated with minorskin irritations, inflammation and rashes due to:■ eczema ■ poison ivy, oak, sumac■ insect bites ■ soaps■ detergents ■ cosmetics■ jewelry ■ seborrheic dermatitis■ psoriasis ■ and for external genital or anal itching

Stop use and ask a doctor if■ symptoms persist for more than 7 days or clear up and occur again within a few days

■ apply to affected area not more than 3 to 4 times daily.■ children under 2 years of age: Do not use. Consult a doctor.


temporarily relieves itching ofminor skin irritations, inflammationand rashes…

symptoms persist for morethan 7 days or clear up and occur again within a few days

■ apply to affected area not morethan 3 to 4 times daily■ children under 2 years of age:do not use, ask a doctor

Documents

OTC Dermatologic Topical Corticosteroids Michael L. Koenig, Ph.D. Interdisciplinary Scientist Division of Over-the-Counter Drug Products Center for Drug