Released by FDA: 3/7/00.  Posted by FDA:  3/16/00

Mark D. Reeth 
Assistant General Counsel 
MEDICIS Pharmaceutical Corp. 
8125 North Hayden Road 
Scottsdale, AZ 85258

Re:      NDA 18-748 
           Loprox (ciclopirox) 0.77% Cream and Lotion 
           MACMIS ID# 8584

Dear Mr. Reeth:

As part of our routine monitoring program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has become aware of promotional materials for Loprox (ciclopirox) 0.77% cream and lotion by Medicis Pharmaceutical Corp. (Medicis) that violate the Federal Food, Drug and Cosmetic Act and its implementing regulations.  Reference is made to visual aids LPX37899 andLPX35998, a product monograph LPX3 6999, and a post-it note pad.

Unapproved Uses

Promotional material for a prescription drug is false, lacking in fair balance, or otherwise misleading if it contains a representation or suggestion, not approved or permitted for use in the labeling, that a drug is better, more effective, or useful in a broader range of conditions or patients than has been demonstrated by substantial evidence.  Throughout your promotional materials you promote Loprox as a treatment against gram negative and gram positive bacteria, a sporicidal with reliable treatment for dormant spores, and an anti-inflammatory agent with reliable treatment for inflamed mycoses without the additional risks of corticosteroid side effects.  These uses for Loprox are not supported by substantial evidence.  Furthermore, your materials make superiority claims over other anifungals.  For example, In your product monograph LPX36999, you state, “Unlike other antifungals, ciclopirox provides additional therapeutic advantages.  It has been shown to have fungistatic, fungicidal, sporicidal, and anti-inflammatory properties and to be active against gram-negative and gram-positive bacteria.”   As stated above, you have not demonstrated that Loprox is effective or superior to other agents for these uses.  Therefore, these presentations promote Loprox for unapproved uses.

Unsubstantiated Superiority Claims

Unique Mode of Action 
In addition, you make claims suggesting that Loprox is superior to other antifungals because it is the only hydroxypyridone antifungal that provides a unique mode of action that makes it effective against a wide range of cutaneous mycoses.  For example, in your product monograph. you state, “Ciciopirox exhibits a unique and complex mode of action.  It is a substituted hydroxypyvidone with a structure different from other antifungal preparations."  Furthermore, you state, “This mode of action makes ciclopirox an appropriate choice for topical treatment alone, or as concomitant treatment when a topical product is indicated in combination with an oral antifungal drug.”   These claims are unsubstantiated and therefore false and misleading.

Penetration and Dose-Response Curve 
You make claims suggesting that Loprox is superior to other antifungals based upon studies regarding the penetrability of the drug and its steep dose-response curve. For example, in a reference to Loprox’s dose-response curve and growth inhibiting capacity at low concentrations, you state in your product monograph, “These features combined with its high penetrability through dry horny tissue suggest that consistent use of ciclopirox results in better pathogen elimination than would occur with antimycotics with flat dose-response curves (partial activity) such as miconazole."   These claims are misleading because they suggest that the drug is more effective than another drug when this has not been demonstrated by substantial evidence.

Lack of Fair Balance

In general, promotional materials are lacking in fair balance, or otherwise misleading if they fall to present the information relating to the contraindications, warnings, precautions, and side effects associated with the use of a drug in a manner reasonably comparable with the presentation of information relating to the effectiveness of the drug. In your promotional materials you prominently promote the efficacy of Loprox using colorful graphics, bar charts and clearly defined headings.  In contrast, your visual aid LPX35998 does not disclose any risk information associated with the drug.  In your product monograph LPX36999, you allot 14 pages to discuss the attributes of Loprox. In contrast, only one paragraph of the 14 pages is dedicated to the risk information regarding the drug.  Similarly, your visual aid LPX37899 contains several pages presenting Loprox’s efficacy, however, presents the risk information in the last paragraph on the last page of the visual aid.  These presentations are lacking in fair balance with respect to both content and prominence of risk information.

Furthermore, your post-it note pad presents the claim “Loprox redefines broad- spectrum”.  However, there is no risk information presented to balance this claim. Therefore, the note pad lacks fair balance.  Furthermore, this piece is in violation of the Act because it was not disseminated with the approved product labeling.

In addition, in your visual aid LPX37899, you claim that clinical studies show a 0.5% incidence of adverse reactions to Loprox.  In the product label, another study is described that shows a higher incidence of adverse reactions.  By choosing to present the lower number, Medicis is selectively presenting the most favorable result, and therefore, suggesting that Loprox is safer than has been demonstrated.

Failure to Submit on Form FDA 2253

You are in violation of the postmarketing reporting requirements because one of your promotional pieces, i.e. LPX3 7899, was not submitted to the FDA on Form FDA 2253 at the time of initial dissemination.

Action Requested

You should immediately cease distribution of these promotional materials and all other promotional materials for Loprox that contain the same or similar claims or presentations commented on in this letter.  You should submit a written response to us, on or before March 21, 2000, describing your intent and plans to comply with the above.  In your letter to us, you should include a list of all promotional materials that were discontinued, and the discontinuation dates.

You should direct your response to me by facsimile at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm. 17B-20, 5600 Fishers Lane, Rockville, MD 20857. We remind you that only written communications are considered official. In all correspondence regarding this particular submission, please refer to MACMIS ID# 7644 in addition to the NDA number.

Sincerely,

Cheryl Y. Roberts 
Regulatory Review Officer 
Division of Drug Marketing, 
    Advertising and Communications