Released by FDA: 11/14/01.  Posted by FDA:  11/29/01

Mr. Donald E. Baker
Senior Director, Regulatory Affairs 
Fujisawa Healthcare, Inc.
3 Parkway Center North 
Deerfield, IL 60015

RE:    NDA #50-777
         Protopic (tacrolimus) Ointment 0.03%, 0.1% 
         MACMIS lD# 10491

Dear Mr. Baker:

This letter objects to Fujisawa Healthcare, Inc. (Fujisawa) dissemination of violative promotional materials for Protopic (tacrolimus) Ointment 0.03%, 0.1%.   As part of its monitoring program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has become aware of a direct-to-consumer (DTC) television (TV) broadcast advertisement and DTC print advertisements for Protopic that are false or misleading in violation of the federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.   The DTC television broadcast advertisement ("Awakenings," 60 second spot, PCA88103) and DTC print advertisements (Adult - PT064, Caregiver - PT065), submitted under cover of form FDA 2253, are violative for the reasons described below.

Overstatement of Efficacy

The DTC television broadcast advertisement and DTC print advertisements for Protopic Ointment feature models with smooth, even-colored skin, completely clear of lesions.  These visual presentations imply that all patients treated with Protopic Ointment will experience 100% improvement (complete clearing) of their atopic dermatitis.  However, this outcome is not representative of the typical response that a patient can expect with Protopic therapy.  Specifically, the approved product labeling (Pl) for Protopic Ointment includes data from clinical trials in which only 10% of adult patients treated with Protopic Ointment 0.03% or 0.1% experienced 100% improvement of atopic dermatitis.  Therefore, the TV and print advertisements are misleading because they overstate the efficacy of Protopic Ointment.

Broadening of Indication

The TV advertisement begins by stating:

These claims suggest that Protopic Ointment is indicated as first line therapy to treat all types of atopic dermatitis.   However, the PI states, "PROTOPIC Ointment, both 0.03% and 0.1% for adults, and only 0.03% for children aged 2 to 15 years, is indicated for short-term and intermittent long-term therapy in the treatment of patients with moderate to severe atopic dermatitis in whom the use of alternative, conventional therapies are deemed inadvisable because of potential risks, or in the treatment of patients who are not adequately responsive to or are intolerant of alternative, conventional therapies."  Therefore, the TV advertisement is misleading because it suggests that Protopic Ointment is approved for use in a broader patient population and a broader range of conditions than what has been demonstrated by substantial evidence.

We note that three frames later, the advertisement states, "Protopic Ointment can ease moderate to severe eczema for people who do not respond well or who may have side effects with other treatments.  There is no cure for eczema, but Protopic can help manage it."  However, this disclosure is not sufficient to correct the initial misleading message that Protopic Ointment is indicated as first line therapy to treat all types of atopic dermatitis.  Furthermore, this disclosure inadequately communicates Protopic's approved indication is limited to the specific patient population mentioned (emphasis added).

Similarly, the DTC print advertisements are misleading because they do not adequately communicate the complete product indication.  For example, the Adult and Caregiver DTC print advertisements present the following claims:

Caregiver Ad

Adult Ad

The prominent presentation of these claims suggests that Protopic Ointment is indicated as first line therapy to treat all types of atopic dermatitis.  We note that in small print, toward the bottom of the advertisement, you state "Protopic Ointment can be used for patients with moderate to severe eczema who do not respond well to or who may have side effects with traditional treatments."  However, as stated above, this disclosure is not sufficient to correct the prominent misleading message that Protopic Ointment is indicated as first line therapy to treat all types of atopic dermatitis, nor does it adequately communicate the approved indication.  Furthermore, the claim that the child is "lucky" because "she's the first generation to grow up with eczema and Protopic" is misleading because it implies that Protopic Ointment is superior to other products approved for atopic dermatitis, when such has not been demonstrated by substantial evidence.  Moreover, this claim contributes to the misleading message that Protopic Ointment is indicated as first line therapy to treat all types of atopic dermatitis.

Minimization of Risk

In one segment of the TV advertisement, a female model moves her hand over her shoulder and the voiceover claims, ". . . soothes eczema anywhere on your body" and the supers "eczema" and "soothed" move across the screen.  Similarly, the adult print advertisement presents the claim "soothe your eczema."  These claims of soothing eczema are misleading because they minimize the risk of application site reactions that can occur with Protopic therapy. Specifically, the PI states, "The use of PROTOPIC Ointment may cause local symptoms such as skin burning (burning sensation, stinging, soreness) or pruritis."  The PI also describes adult studies in which there was a 47% incidence of skin burning and 25% incidence of pruntis in patients treated with Protopic Ointment 0.1 %.

Requested Action

Fujisawa should immediately discontinue these and all other promotional materials and activities for Protopic that contain the same or similar claims or presentations.  We request that Fujisawa respond, in writing, with its intent to comply with the above.  This response should list similarly violative materials with a description of the method for discontinuation and the discontinuation date.  As discussed in our November 9, 2001, phone conversation DDMAC should receive your written response no later than November 30, 2001.

If you have any questions, please contact the undersigned by facsimile at 301-594-6771, or by written communication at the Division of Drug Marketing, Advertising and Communications, HFD-42, Room 17B-20, 5600 Fishers Lane, Rockville, MD 20857.  DDMAC reminds you that only written communications are considered official.

In all future correspondence regarding this particular matter, please refer to MACMIS ID# 10491 in addition to the NDA number.

Sincerely,

Rebecca Williams, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
        Advertising, and Communications