Released by FDA: 4/10/01.  Posted by FDA:  5/15/01

Daisy Chhatwal 
US Drug Regulatory Affairs & Compliance 
Aventis Pharmaceuticals, Inc. 
399 Interpace Parkway 
Parsippany, NJ 07054

RE:   Nilandron® (nilutamide) Tablets 
         NDA 20-169 
         MACMIS ID#9904

Dear Ms Chhatwal:

This letter concerns several promotional materials (sales aid 50060164/20199901/4286T0, wholesaler fact sheet 2l01730l/0230A1, and web sites www.aventispharma-us.com/our_products.htm and www.aventispharma-us.com/presskits/nilandro/overview_TXT.hlml) for Nilandron (nilutamide) tablets disseminated by Aventis Pharmaceuticals, Inc. (Aventis).  As part of its monitoring program, the Division of Drug Marketing, Advertising and Communications (DDMAC) has reviewed these materials and has concluded that they are false or misleading, in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations. A description of our objections follows.

Use of Outdated Product Labeling

The web site www.aventispharma-us.com/our_products.htm is violative because it links to an outdated version of the approved product labeling (PI) for Nilandron that lacks serious risk information about the product.  The failure to provide the current PI results in the omission of important safety information as described below.

The Food and Drug Administration (FDA) approved revisions to the Nilandron PI on September 29, 2000.  These revisions included adding risk information in a Boxed Warning and other warnings regarding hospitalization and death due to both interstitial pneumonitis and severe liver injury in patients treated with Nilandron.  Additionally, a warning that Nilandron is not indicated in women and should not be used in this population was included in the revised PI.   Although your web page states that the Aventis web site was updated on April 6, 2001, the “Nilandron Prescribing Information” is linked to a September 1996 version of the PI.   Your failure to provide the most current PI misbrands Nilandron.   DDMAC is especially concerned with this violation since your omission of information concerning these potentially fatal risks associated with Nilandron treatment raises significant safety concerns.

Lack of Fair Balance

Your sales aid, wholesaler fact sheet, and web site www.aventispharma-us.com/presskits/nilandron/overview_TXT.html include claims such as, “Well-tolerated one tablet once a day therapy for patients with advanced prostate cancer,” “Favorable side effect profile,” and “Nilandron is generally well tolerated ...."    These claims are misleading because they minimize the potentially fatal adverse reactions associated with Nilandron, such as hospitalization and death due to interstitial pneumonitis and severe liver injury.   Additionally, your web site states that “Interstitial pneumonitis has been reported in 2% of Nilandron patients.”   However, you fail to mention that in a small study, 17% of Nilandron patients developed interstitial pneumonitis according to the Boxed Warning in the PI.

The statement in your sales aid, “Visual disturbances are generally mild and tend to disappear spontaneously or after planned dosage reduction” is misleading because it minimizes the risk of visual disturbances and is inconsistent with the bolded warning in the PI.  The PI states “In clinical trials, 13% to 57% of patients receiving Nilandron reported a delay in adaptation to dark, ranging from seconds to a few minutes, when passing from a lighted area to a dark area.  This effect sometimes does not abate as drug treatment is continued.”  Furthermore, the PI also states “Patients who experience this effect should be cautioned about driving at night or through tunnels.”

In addition, promotional materials are lacking in fair balance if they fail to present information relating to side effects and warnings with a prominence and readability reasonably comparable with the presentation of information relating to effectiveness of the drug.   Factors impacting prominence and readability include typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis.  Your sales aid is misleading because of the inadequate prominence provided to Nilandron’s risk information.   For example, the Boxed Warning and other warnings are presented in single-spaced paragraph format, whereas the efficacy claims appear as bolded and bulleted statements that are presented in conjunction with large colorful charts and graphs.

Requested Action

Aventis should immediately discontinue these and all other promotional materials for Nilandron that contain the same or similar claims or presentations.  We request that Aventis response in writing, with its intent to comply with the above.   DDMAC should receive your written response no later than April 24, 2001.  This response should list all 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, Rm. l7B-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 II) #9904 in addition to the NDA number.

Sincerely,

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