Released by FDA: 7/12/01.  Posted by FDA:  7/30/01

Susan P. Rinne
Vice President, Regulatory Affairs 
Alza Corporation
1900 Charleston Road 
P.O. Box 7210 
Mountain View, CA 94039-7210

RE:   NDA # 20-897
          Ditropan XL® (oxybutynin chloride) Extended-Release Tablets 
          MACMIS ID # 10196

Dear Ms. Rinne:

This letter objects to Alza Corporation's (Alza) dissemination of violative promotional materials for Ditropan XL (oxybutynin chloride) extended-release tablets.  As part of its monitoring program, the Division of Drug Marketing, Advertising and Communications (DDMAC) has become aware of direct-to-consumer (DTC) broadcast and print advertisements for Ditropan XL that are false or misleading, in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.  The DTC broadcast ("Stop and Go") and print (0011708) advertisements, submitted on Form FDA 2253, are violative for the reasons described below.

Inadequate Communication of Indication

The approved product labeling (Pl) states that "Ditropan XL is a once-daily controlled-release tablet indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency."   Your broadcast advertisement is misleading because it fails to adequately convey the symptoms of overactive bladder.  Specifically, the supers describing these symptoms are displayed too briefly to be comprehended by consumers.

Overstatement of Efficacy

Broadcast Advertisement

Promotional materials are misleading if they suggest that a drug is more effective than has been demonstrated by substantial evidence.  Your broadcast advertisement presents efficacy claims for Ditropan XL stating in the audio that "Ditropan XL is a prescription medication for overactive bladder proven to reduce wetting accidents by up to 90% versus 51 % for a sugar pill" along with the prominent graphic of "90%" in the middle of the screen and the tagline "Reduces accidents by up to 90%."  This overall presentation is unbalanced and, therefore, misleading because it overwhelmingly emphasizes the 90% reduction in wetting accidents with Ditropan XL.  Furthermore, the graphic presenting that Ditropan XL decreased wetting accidents from 16 to 2 per week while the sugar pill decreased wetting accidents from 21 to 11 per week is too complex for consumers to comprehend and assimilate in a 60second broadcast advertisement.

In addition, your broadcast advertisement fails to prominently disclose important facts regarding the limitations of the clinical trials.  Specifically, the clinical trials for Ditropan XL were set up to include only patients who were known to have had improved symptoms on oxybutynin, the active ingredient in Ditropan XL, or other similar medications used to treat overactive bladder.  This qualifying message is not presented with adequate prominence to provide sufficient context to the efficacy claims.  Your small super at the bottom of the screen briefly stating "Studies included patients known to be responsive to oxybutynin" fails to correct this misleading impression regarding the efficacy of Ditropan XL.

Print Advertisement

Similarly, your print advertisement claims that Ditropan XL "Reduces wetting accidents caused by overactive bladder by 83% to 90%" and "Once-a-day Ditropan XL reduced wetting accidents caused by overactive bladder by 83%-90%."  Your print advertisement either fails to acknowledge or fails to prominently disclose that patients randomized to placebo experienced a 51 % reduction in the number of wetting accidents.  Similarly, your print advertisement fails to prominently disclose that the clinical trials were set up to include only patients who the sponsor knew would have improved symptoms on Ditropan XL because they were known to have had improved symptoms on oxybutynin, the active ingredient in Ditropan XL, or other similar medications used to treat overactive bladder.  Again, this qualifying message is not presented with reasonably comparable prominence to the efficacy claims.  Your graphic in the middle column in the print advertisement fails to correct this misleading impression regarding the efficacy of Ditropan XL.

Major Statement

The clutter and distraction of the moving car in the background during the presentation of the major statement in the broadcast advertisement minimizes the asks of Ditropan XL.

Requested Action

Alza should immediately discontinue these and all other promotional materials and activities for Ditropan XL that contain the same or similar claims or presentations.  We request that Alza respond, in writing, with its intent to comply with the above. DDMAC should receive your written response no later than July 26, 2001.  This response should list similarly violative materials with a description of the method for discontinuation and the discontinuation date.

If you have any questions or comments, please contact me by facsimile at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and Communications, HFD42, Rm. 1713-20, 5600 Fishers Lane, Rockville, MD 20857.  We remind you that only written communications are considered official.

In all future correspondence regarding this particular matter, please refer to MACMIS ID #10196 in addition to the NDA number.

Sincerely,

 

Barbara S. Chong, Pharm.D., BCPS 
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising and Communications