# Presentation: 791900

## Clinical Wrap-Up

**Denise Cook, M.D.**
**Medical Officer**
**Division of Dermatology and Dental Drug Products**

## Other Information on the Safety and Efficacy of the Chemical Moiety

**Drug use trends of topical tazarotene**
**Adverse events with topical tazarotene**
**Efficacy of topical tazarotene**
**Efficacy of oral tazarotene**

## Drug Use Trends for Topical Tazarotene

- Total number of tazarotene (Tazorac®, Avage®) prescriptions dispensed increasing
- 226,000 (1999)
- 937,000 (2003)1* *
- In 2003, most commonly prescribed by
- dermatologists (67%)
- family practitioners (7%)1
- In 2003, most common diagnoses associated with use
- acne (75%)
- psoriasis (13%)2
- 	1**IMS Health, National Prescription Audit *****Plus*********,  Data Extracted  June  2004**
**	****2****IMS Health, National Disease and Therapeutic Index********, 6 yr CD-Rom, Jan 1998 – Dec 2003  Extracted 6/2004**

## 58% of all dispensing to women1

46.5% of all claims for women of childbearing age (12-44 years)1

1AdvancePCS Dimension Rx, Data Extracted June 2004

- 46.5% of all claims for women of childbearing age (12-44 years)1
**	**
**1****AdvancePCS******** Dimension Rx, Data Extracted June 2004**
**	**

**Drug Use Trends for Topical Tazarotene****Year 2003**

## 125 AERS Reports Associated with Topical Tazarotene (June 1997 to May 24, 2004)

| Most Common AEs: | Pruritus, rash erythematous, dermatitis exfoliative, burning sensation, drug ineffective, erythema |
| --- | --- |
| Systemic AEs: | Liver enzyme elevation (3), gastrointestinal (3), hot flashes and perspiration (1), ↑ triglycerides (1) |
| Indications for Use: | Psoriasis (91), Acne (8), Other Skin (10), NR (16) |
| Gender: | Female (69), Male (52), NR (4) |
| Serious Outcomes: | Hospitalizations (2), Congenital Anomaly (1) |

## 113 Worldwide Pregnancy Exposures Associated with Topical Tazarotene ** 

| US – 107, Foreign – 6 |  |
| --- | --- |
| Age Range: | 17 to 38 years, median = 29 years, n = 24 |
| Indications for topical tazarotene: | Acne (60)
Psoriasis (20)
Facial Wrinkling (2)
Other (5), NR (26) |
| Pregnancy and Fetal Outcomes: | Spontaneous Abortion (4)
Chromosomal Abnormalities (2)
Trisomy 18, Cornelia de Lange
“No adverse outcome or Unknown” (107) |

- **Data Obtained from Sponsor December 4, 1996 to May 15, 2004

**Notes:**
The Agency has knowledge of 113 reports worldwide of pregnancies exposed to topical tazarotene.  The majority of the exposures occurred in the United States.  For the women who provided age information, the women ranged in age from 17 to 38 years, with a median age of 29 years.  

Topical tazarotene was used primarily for labeled indications, including acne, psoriasis and facial wrinkles.  A small number of the women who were pregnant while using topical tazarotene, used the product for other skin conditions.  

In this subset of patients, six women reported adverse pregnancy outcomes, including four spontaneous abortions and two fetuses with chromosomal abnormalities.  The chromosomal abnormalities included Trisomy 18 defect, and Cornelia de Lange defect.  Neither of these chromosomal abnormalities are consistent with retinoid embryopathy.

There was a sizable number of reports categorized by the sponsor as “no adverse outcome, or outcome unknown”.  It is important to note that we do not know how many of these reports were “no adverse outcome”, or unknown.  And we also do not know the outcomes of those pregnancies.

## Efficacy of the Chemical Moiety in the Treatment of Plaque Psoriasis

**Topical Tazarotene**
**Clinical Trials – Success ****≥75% improvement**
**0.05% gel**
**30% and 18%**
**0.1% gel**
**38% and 25%**
**Placebo**
**13% and 10%**
**Oral Tazarotene**
**Clinical Trials – Success – no or minimum disease**
**15.2% and 18.7%**
**Placebo – 1.2% and 4.8%**
**Clinical Trials - 2**** ̊ efficacy parameter – Success ≥75% improvement (or marked improvement or better)**
**30.1% and 30.8%**
**Placebo – 8.2% and 9.1%**