Released by FDA: 5/7/01.  Posted by FDA:  5/22/01

Algernon Thomas 
Manager, Post-Marketing Regulatory Affairs 
Shire Pharmaceutical Development, Inc. 
1901 Research Blvd, Suite 500 
Rockville, MD 20850

RE:   NDA # 19-815 
        ProAmatine (midodrine hydrochloride) Tablets 
        MACMIS ID # 9990

Dear Mr. Thomas:

This letter concerns Shire Laboratories Inc.’s (Shire) dissemination of promotional materials for its accelerated approval product, ProAmatine Tablets.   As part of its routine monitoring program, the Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed a sales aid (PRO 509) for ProAmatine. From its review, DDMAC has concluded that this piece is in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.   Specifically, your sales aid overstates the efficacy of ProAmatine and minimizes the serious risk of supine hypertension associated with the drug.

We refer you to our letters dated July 6, 2000, July 19, 2000, January 23, 2001, March 12, 2001, and our teleconference of February 15, 2001, where we outlined objections to similar claims and presentations.

Your sales aid contains the heading “ProAmatine raises patients’ standing systolic blood pressure into the normal range.”   This claim suggests that patients with symptomatic orthostatic hypotension (OH) will maintain a normal standing systolic blood pressure as a result of taking ProAmatine.    However, ProAmatine has not been demonstrated to maintain standing blood pressure in the “normal range” for patients with symptomatic OH.   As stated in the approved product labeling (PI), “The indication is based on ProAmatine’s effect on increases in 1-minute standing blood pressure, a surrogate marker considered likely to correspond to a clinical benefit.   At present, however, clinical benefits of ProAmatine, principally improved ability to perform life activities, have not been established” (emphasis added).   Furthermore, claims that suggest patients with symptomatic OH will have blood pressure in the “normal range” as a result of taking ProAmatine minimize the serious risk of supine hypertension associated with ProAmatine.   As, stated in the bolded Warning of the PI, “Systolic pressure of about 200 mmHg were seen overall in about 13.4% of patients given 10 mg of ProAmatine.” Therefore, the claim is misleading because it overstates the efficacy of ProAmatine, is inconsistent with the PI, and minimizes the serious risk of supine hypertension that is associated with the use of this drug.

Shire should immediately cease dissemination of promotional materials or activities that. contain these and similar claims or presentations concerning ProAmatine.   In addition, Shire should respond in writing no later than May 21, 2001, describing its plan to comply.   Shire should also include a list of materials being discontinued, as well as the date of discontinuation.

Your response should be directed to me by facsimile at 301-594-6771 or at the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm 178-20, 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 #9990 in addition to the NDA number.

Sincerely,

Andrew S.T. Haffer, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
      Advertising, and Communications