Released by FDA: 11/16/00.  Posted by FDA:  12/20/00

Stephen W. Sherman 
Director, Advertising and Labeling 
Regulatory Affairs 
ALZA Corporation 
1900 Charleston Road 
P0 Box 7210 
Mountain View, CA 94039-7210

RE:   Ditropan® XL (oxybutynin chloride) Extended Release Tablets 
        NDA 20-897 
        MACMIS ID#8996

Dear Mr. Sherman:

This letter concerns several promotional pieces (sales aid # 0008699-2, uncoded sales aid, file cards # 0010171, 0010175) for Ditropan XL (oxybutynin chloride) disseminated by ALZA Corporation (ALZA).  As part of its monitoring program, the Division of Drug Marketing, Advertising and Communications (DDMAC) has reviewed these promotional materials and concluded that they are false or misleading. in violation of the Federal Food, Drug, and Cosmetic Act and its implementing regulations.  Our specific objections follow.

Unsubstantiated Superiority Claim

Promotional materials are misleading if they suggest that a drug is superior to other products when such has not been demonstrated by substantial evidence.  In your materials, you present side by side comparisons of Ditropan XI, and Detrol’s mechanism of action. indication, safety, efficacy, and closing under taglines such as “Let your patients try Ditropan XL and be convinced.”  “Compare and be convinced,” or “Ditropan XL delivers a difference.”  These presentations are misleading because they suggest that Ditropan XL is superior to Detrol when such has not been demonstrated by substantial evidence (generally two adequate and well-controlled head-to-head comparative studies).  Rather, your suggestions of Ditropan XL's superiority appear to he based on an “across label” comparison of the two products.

Omission of Material Facts

In file card (0010175), you present several efficacy claims and presentations about Ditropan XI, such as “In one clinical stud, significant reductions in UI episodes were demonstrated at the 5-mg starting dose in only 2 weeks.   This claim is misleading because it omits material facts.  The approved product labeling (Pl) for Ditropan XL states that the controlled studies included patients known to be responsive to oxybutynin or other anticholinergic medications.  That is, the clinical studies were designed 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.  These facts are not disclosed in the file card.

Misleading Efficacy Presentations

File card 0010171 is misleading because it overstates the effectiveness of Ditropan XL.  Specifically, you present the claim "Up to 90% reduction in urge incontinence episodes across four studies along with four prominent graphs depicting efficacy rates between 83-90% on the front of the card.   However, you fail to present that patients randomized to the placebo arm experienced up to a 51% reduction in urge incontinence episodes in the same trials.  Without the presentation of the placebo arm, the efficacy of Ditropan XL is overstated.

Requested Action

In order to address these violations, DDMAC recommends that ALZA immediately discontinue these, and all other promotional materials 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 December 1, 2000.  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, HFD-42, Rim 17B-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 #8996 in addition to the NDA number.

Sincerely.

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