Released by FDA:  11/9/04.  Posted by FDA:  11/17/04

Mr. Daniel Glassman
Chief Executive Officer
Bradley Pharmaceuticals, Inc.
383 Route 46
West Fairfield, NJ 07004

Re:  NDA # 08-848, 08-848/S-024
        Pamine® (methscopolamine bromide) 2.5 mg Tablets
        Pamine® Forte (methscopolamine bromide) 5 mg Tablets
        MACMIS ID # 12413

Dear Mr. Glassman:

The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a professional sales aid (PA589) for Pamine® (methscopolamine bromide) 2.5 mg Tablets and a patient brochure (PA630) for Pamine® Forte (methscopolamine bromide) 5 mg Tablets submitted by Kenwood Therapeutics (Kenwood), a Division of Bradley Pharmaceuticals, Inc., under cover of Form FDA 2253. In addition, DDMAC has reviewed a page of the Bradley Pharmaceuticals, Inc. website that promotes Pamine (www.bradpharm.com/pamine.htm).  The professional sales aid, patient brochure, and website contain numerous effectiveness claims for Pamine and Pamine Forte that are not, to our knowledge, supported by substantial evidence or substantial clinical experience.  They also omit risk information for these drugs.  Finally, the professional sales aid and website misrepresent the safety of Pamine.  The professional sales aid, patient brochure, and website are, therefore, false or misleading under the Federal Food, Drug, and Cosmetic Act (Act), see 21 U.S.C. §§ 352(a), (n); 321(n); 21 CFR 202.1(e)(5), and pose a potential risk to the public health because they suggest Pamine and Pamine Forte are safer and more effective than has been demonstrated. In addition, the website was not submitted to DDMAC under cover of Form FDA 2253 at the time of initial dissemination or publication, as required by 21 CFR 314.81(b)(3)(i).

Background

According to the FDA-approved labeling (PI), Pamine and Pamine Forte are indicated as "Adjunctive therapy for the treatment of peptic ulcer."  Although the Clinical Pharmacology section of the PI states that methscopolamine bromide possesses most of the pharmacologic actions of the drug class anticholinergics, including inhibition of gastrointestinal motility, Pamine and Pamine Forte have not been found by FDA to be safe and effective in the treatment of gastrointestinal motility symptoms, such as diarrhea, cramping, and bloating.

Pamine and Pamine Forte are associated with numerous risks, as described in the "Warnings," "Precautions," and "Adverse Reactions" sections of the PI.  These risks include:

According to the "Pharmacokinetics" section of the PI, "Methscopolamine bromide has limited ability to cross the blood-brain barrier."

Unsubstantiated Effectiveness Claims

The professional sales aid, patient brochure, and website suggest that Pamine and Pamine Forte are effective in treating gastrointestinal motility symptoms and in improving patients' control of their lives.  For example, the professional sales aid for Pamine states:

The patient brochure asks the following questions, suggesting that such conditions can be effectively treated with Pamine Forte:

The patient brochure also states:

The website states:

Moreover, the professional sales aid, patient brochure, and website claim that Pamine and Pamine Forte relieve symptoms of bloating, despite the fact that the "Adverse Reactions" section of the PI states that a "bloated feeling" has been associated with the use of the drugs.

We are not aware of substantial evidence or substantial clinical experience to support any of the preceding claims. If you have data to support the claims, please submit them for review.

Omission of Risk Information

The professional sales aid, patient brochure, and website are false or misleading because they present effectiveness claims for Pamine and Pamine Forte but fail to provide ny risk information about the drugs.  As described above, Pamine and Pamine Forte are associated with many risks.

The professional sales aid is accompanied by the PI, and the website provides a link to the PI (although not from the page containing the effectiveness claims reproduced above). For promotional materials to be truthful and non-misleading, they must contain risk information in each part as necessary to qualify any safety or effectiveness claims made in that part.

False or Misleading Safety Claims

The professional sales aid and website state, respectively:

These statements suggest that Pamine is not likely to produce central nervous system side effects because it does not penetrate the blood-brain barrier. This is false or misleading.  As noted, Pamine is associated with several CNS side effects, including drowsiness, blurred vision, headache, nervousness, mental confusion, and dizziness, and limited ability to cross the blood-brain barrier.

Finally, the professional sales aid states:

This professional sale aid thus implies that, because Pamine is lactose-free, patients using it will have no added gastrointestinal problems, unlike dicyclomine hydrochloride and glycopyrrolate. FDA is not aware of substantial evidence supporting this claim. Moreover, as noted, Pamine is associated with gastrointestinal side effects, such as nausea, vomiting, constipation, and bloated feeling.

Failure to Submit Under Form FDA 2253

FDA regulations require you to submit specimens of mailing pieces and any other labeling or advertising devised for promotion of a prescription drug product at the time of initial dissemination of the labeling and at the time of initial publication of the advertisement for a prescription drug product.  Each submission is required to be accompanied by a completed transmittal Form FDA-2253 (Transmittal of Advertisements and Promotional Labeling for Drugs for Human Use) and is required to include a copy of the product's current professional labeling.  You did not submit the website to DDMAC under cover of Form FDA 2253 as required by 21 CFR 314.81(b)(3)(i).

Conclusion and Requested Action

For the reasons discussed above, the professional sales aid, patient brochure, and website misbrand Pamine and Pamine Forte in violation of the Federal Food, Drug, and Cosmetic Act (Act). _See 21 U.S.C. §§ 352(a), (n); § 321(n); 21 CFR 202.1(e)(5). Furthermore, the website was not submitted to DDMAC under cover of Form FDA 2253 at the time of initial dissemination or publication, as required by 21 CFR 314.81(b)(3)(i).

DDMAC requests that Bradley Pharmaceuticals, Inc. immediately cease the dissemination of violative promotional materials for Pamine and Pamine Forte such as those described above.  Please submit a written response to this letter on or before November 23, 2004, stating whether you intend to comply with this request, listing all violative promotional materials for Pamine and Pamine Forte such as those described above, and explaining your plan for discontinuing use of such materials.  Because the violations described above are serious, we request, further, that your submission include a plan of action to disseminate truthful, non-misleading, and complete information to the audience(s) that received the violative promotional materials.  Please direct your response to me at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, BFD-42, Room 81345, 5600 Fishers Lane, Rockville, MD 20857, facsimile at 301-594-6771. In all future correspondence regarding this matter, please refer to MACMIS ID # 12413 in addition to the NDA numbers.  We remind you that only written communications are considered official.

The violations discussed in this letter do not necessarily constitute an exhaustive list.  It is your responsibility to ensure that your promotional materials for Pamine and Pamine Forte comply with each applicable requirement of the Act and FDA implementing regulations.

Failure to correct the violations discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.

Sincerely,

Thomas W. Abrams, R.Ph., MBA
Director
Division of Drug Marketing, Advertising, and
Communications