otc dermatologic topical corticosteroids michael l. koenig, ph.d. interdisciplinary scientist...

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

otc dermatologic topical corticosteroids michael l. koenig, ph.d. interdisciplinary scientist...

Documents

joint dodacndac meeting

hydrocortisone grase

insulin slide

crusting slide

research slide

hydrocortisone acetate

otc monographs otc drug

otc monographs category