# Presentation: 536281

## OTCDermatologic Topical Corticosteroids

- Michael L. Koenig, Ph.D.
- Interdisciplinary Scientist
- Division of Over-the-Counter Drug Products

**Center for Drug Evaluation and Research**** **

## Overview

- Regulation of OTC Drugs
- Regulatory History of Hydrocortisone
- Current Labeling of Hydrocortisone

## Regulation of OTC Drugs

- NDA (New Drug Application)
- Drug product-specific
- Confidential
- Monograph
- Active ingredient-specific
- Public

## OTC Monographs

- OTC Drug Review initiated in 1972
- > 200,000 OTC drug products
- 700 active ingredients in 26 therapeutic categories

## OTC Monographs                           

**Category I: GRASE (Generally Recognized as Safe and Effective)**
**Category II: not GRASE**
**Category III: cannot determine if safe and effective**

## OTC Monographs

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

## OTC Monographs

**Comments**

## OTC Monographs

**Comments**

**Data**

## Regulatory History of Hydrocortisone

## Regulatory History of Hydrocortisone

- 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)

## Regulatory History of Hydrocortisone

_**ANPR (1979)**_
- Lack of adverse local effects
- Striae
- Telangiectasia
- Pustular eruptions and crusting

## Regulatory History of Hydrocortisone

_**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

## Regulatory History of Hydrocortisone

_**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

## Regulatory History of Hydrocortisone

_**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

## Regulatory History of Hydrocortisone

_**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

## Regulatory History of Hydrocortisone

_**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 ofHydrocortisone

_**Amended 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**

## Regulatory History of Hydrocortisone

_**FM (20??)**_
- Pending
- Manufacturers generally comply with TFM and amended TFM
- Continuing review of data

## Hydrocortisone Does Not Suppress 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 Hydrocortisone

## Monograph Labeling:  Hydrocortisone

| Drug Facts |
| --- |
| Active ingredient                                              Purpose
Hydrocortisone (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 |
| Warnings
External 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:  Hydrocortisone

| Drug Facts |
| --- |
| Active ingredient                                              Purpose
Hydrocortisone (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 |
| Warnings
External 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 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

**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 of

- minor skin irritations, inflammation
- and rashes...

- 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, ask a doctor