Released by FDA: 4/12/00.  Posted by FDA:  5/22/00

Binita Kwankin 
Senior Regulatory Products Manager 
TAP Pharmaceutical Products, Inc. 
2355 Waukegan Road 
Deerfield, Illinois 60015

RE:  NDA#21-118 
        Uprima (apomorphine HCl tablets) sublingual 
        MACMIS ID #8899

Dear Ms. Kwankin:

As part of its routine monitoring an surveillance activities, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has become aware of a press release for Uprima (apomorphine HCl tablets), disseminated by TAP Pharmaceutical Products, Inc. (TAP), that is in violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable regulations.  DDMAC specifically refers to your press release issued on April 10, 2000, entitled “FDA ADVISORY COMMflTEE RECOMMENDS APPROVAL OF UPRIMA (APOMORPHINE HCl TABLETS) SUBLINGUAL FOR THE TREATMENT OF ERECTILE DYSFUNCTION.”  This press release is considered promotional labeling for Uprima and is in violation of the Act for the following reasons.

Omission of Material Facts

“The most commonly reported side effect was nausea.  Of the nausea reported in the NDA clinical studies, most incidences were mild to moderate in severity.”

Promotional materials are in violation of the Act if they fail to reveal facts material in light of representations made about the product.  The two statements above are represent the full extent of risk information about Uprima in your press release.  You fail to disclose, however, material facts relating to significant and potentially life-threatening risks associated with Uprinia that were presented at the Advisory Committee meeting. Specifically, syncope and severe hypotension were seen in some patients taking Uprima in clinical trials.  These serious adverse events prompted the Committee to voice serious concerns about Uprima’s safety profile.  For example one Committee member, a cardiologist, stated “There will be some people who will probably lose their lives because they pass out at the top of the stairs or operating a car.”

“The committee suggested some cautionary recommendations for labeling.  In addition, the committee advised that educational materials be provided to patient at the point of care.”

The Committee recommended that the labeling for Uprima include contraindications for use with concomitant ingestion of alcohol and in patients taking nitrate therapy.  The Committee also recommended a boxed warning describing vaso-vagal events and the potential for syncope and cardiovascular compromise.  These material facts are also omitted from your press release.

Pre-Appoval Promotion

“New class of Erectile Dysfunction (ED) therapy may benefit millions of men with ED.”

“UPRIMA could offer several benefits for patients suffering from ED....data suggest that UPRIMA is safe and effective in men with varying severities of ED.”

“...we feel that UPRIMA would greatly enhance the therapeutic options of millions of men with ED.”

Section 21 CFR 312.7 states, among other things, that an investigational new drug may not be promoted as being safe or effective for the uses under investigation.  Your press release is violative because it includes claims, representations, and conclusions concerning the safety and efficacy of Uprima, an investigational new drug.

In order to address these objections, DDMAC recommends that TAP take the following actions:

1. Immediately discontinue the use of this, and all other promotional materials and activities for Uprima that contain the same or similar violations.

2. Provide to DDMAC, in writing, your intent to comply with #1 above.  Your response should be received by April 26, 2000.

3. This response should include a list of all similarly violative promotional materials and your method for discontinuing their use.

If you have any questions or comments, please contact the undersigned 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 ID #8899 in addition to the NDA number.

Sincerely, 

Mark W. Askine, R.Ph. 
Regulatory Review Officer 
Division of Drug Marketing,
    Advertising and Communications