OTC Dermatologic Topical Corticosteroids Michael L. Koenig, Ph.D. Interdisciplinary Scientist...
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Transcript of 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
3Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulation of OTC DrugsRegulation of OTC Drugs
• NDA (New Drug Application)– Drug product-specific– Confidential
• Monograph– Active ingredient-specific– Public
4Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
OTC MonographsOTC Monographs
• OTC Drug Review initiated in 1972
• > 200,000 OTC drug products
• 700 active ingredients in 26 therapeutic categories
5Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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
6Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
OTC MonographsOTC Monographs
• Category I: GRASE• Category II: not GRASE• Category III: cannot determine if safe and
effective ANPR
7Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
OTC MonographsOTC Monographs
ANPRTFM
Comments
8Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
OTC MonographsOTC Monographs
TFM
Comments
Data
FM
9Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
10Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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)
11Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
ANPR (1979)
• Lack of adverse local effects– Striae
– Telangiectasia
– Pustular eruptions and crusting
12Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
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
13Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
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
14Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
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
15Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
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
16Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
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
17Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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
18Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Regulatory History of Regulatory History of HydrocortisoneHydrocortisone
FM (20??)
• Pending
• Manufacturers generally comply with TFM and amended TFM
• Continuing review of data
19Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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
20Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
Current Labeling of Current Labeling of HydrocortisoneHydrocortisone
21Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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.
22Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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.
23Joint DODAC/NDAC Meeting Joint DODAC/NDAC Meeting March 24, 2005March 24, 2005
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