Released by FDA: 2/15/00.  Posted by FDA: 2/29/00

Richard A. Shupack 
Director Legal Affairs - Regulatory 
Elan Pharmaceuticals 
800 Gateway Blvd. 
South San Francisco, CA 94080

RE: NDA#19-922 
       Corlopam (fenoldopam mesylate) Injection 
       MACMIS 1D  #8423

Dear Mr. Shupack:

Reference is made to Elan Pharmaceuticals’ (Elan) January 7, 2000 letter, in response to a November 12, 1999 letter, from the Division of Drug Marketing, Advertising and Communications (DDMAC).  Reference is also made to letters from Elan, dated November 29, 1999, and December 14, 1999, and a teleconference between Elan and DDMAC on December 20, 1999.  These letters and teleconference concerned the dissemination of three homemade promotional pieces by or on behalf of Elan, that promoted Corlopam (fenoldoparn mesylate) in violation of the Federal Food, Drug and Cosmetic Act and its implementing regulations.  In our November 12, 1999 letter, DDMAC requested that you investigate the extent to which these homemade materials were used to promote Corlopam.

DDMAC has reviewed these materials and has determined that they promote Corlopam for unapproved uses, lack fair balance, and contain unsubstantiated cost effectiveness claims.

Unapproved uses

The Indication and Usage section of the approved product labeling (P1) for Corlopam states the following:

Corlopam is indicated for the in-hospital, short-term (up to 48 hours) management of severe hypertension when rapid, but quickly reversible, emergency reduction of blood pressure is clinically indicated, including malignant hypertension with deteriorating end-organ function.

All of these homemade materials contain claims concerning the use of Corlopam for “renal protection.”  The following claims, although not an exhaustive list, exemplify claims presented in these homemade materials:

•  IV Corlopam is “D-l” for cost-effective renal protection.

•  Corlopam is indicated for short term (48 hrs.) treatment of hypertension and to increase renal blood perfusion; especially for patients with existing impaired renal function or in patients undergoing procedures that impairs [sic] renal function (i.e., patients receiving radiocontrast dyes, cyclosporine, or other vasoconstrictive agents).

•  These beneficial renal effects make fenoldopam a useful agent for patients with renal dysfunction undergoing cardia [sic] or peripheral vascular surgery, both as a potential renoprotective agent and antihypertensive.

•  Fenoldopam has recently gained FDA approval for renal indications.

These claims state, or imply, that Corlopam is useful in treating patients with renal impairment, or for renal protection, especially in those who are undergoing cardiovascular surgery or other procedures.  However, these uses for Corlopam are not approved.  Furthermore, your claim that “Fenoldopam has recently gained FDA approval for renal indications” is false.  Therefore, your dissemination of these homemade promotional pieces constitutes promotion of Corlopam for unapproved uses.

In addition, in these homemade materials, you make dosing recommendations for renal indications.  For example, you claim that “a dose of Corlopam 0.03-0.1 has been shown to increase renal perfusion without altering systemic blood pressure or heart rate in normotensive patients.”  This presentation is misleading because it makes representations that drug dosages recommended for use in the treatment of severe hypertension are safe and effective for the treatment of other classes of patients with different conditions.  In addition, the Precautions section of the PI states that “Corlopam may occasionally produce symptomatic hypotension and close monitoring of blood pressure during administration is essential,” and that “Corlopam causes a dose-related tachycardia, particularly with infusion rates above 0.1 mcg/kg/min.”

Lack of fair balance

Although all of these homemade pieces contain efficacy claims, one of the pieces does not contain any risk information, and the other pieces contain minimal risk information, presented in a manner that is inadequate to convey the risks associated with the drug. Promotional materials must present information about the risks associated with the use of a drug in a manner reasonably comparable to that of claims concerning the drug’s efficacy.  Therefore, these materials are lacking in fair balance because they fail to adequately disclose the risks associated with the use of Corlopain.

Unsubstantiated cost effectiveness claims

Two of these homemade pieces contain claims or implications that Corlopam is cost effective.  For example, one piece presents the claim that “Corlopam is 'D-1' for cost-effective renal protection” and a second piece presents “expected outcomes” such as, decreased cost per discharge.  These pharmacoeconomic outcomes have not been supported by adequate evidence.  Therefore, your presentation of cost effectiveness claims is misleading.

In your January 7, 1999 letter, you acknowledged that certain Elan sales representatives have been involved in the development and/or dissemination of these violative homemade promotional materials.  In addition, you described your policy for prohibiting use of homemade sales pieces, and specified the disciplinary and corrective actions taken to ensure that this activity will not recur.

DDMAC has reviewed your response and actions taken with respect to dissemination of these violative promotional materials.  In light of your actions, DDMAC considers this matter closed.  However, DDMAC will continue to closely monitor this issue and will consider alternative corrective measures if further activities occur.

If you have any questions or comments, please direct them to the undersigned by facsimile at (301) 594-677!, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and Communications, HFD-42, Rm. 17B-20, 5600 Fishers Lane, Rockville, MD 20857. We remind you that on!)’ written communications are considered official.

In all future correspondence regarding the issues raised in this letter, please refer to MACMIS ID # 8423 in addition to the NDA number.

Sincerely,

Janet Norden, MSN, RN 
Regulatory Review Officer 
Division of Drug Marketing, 
  Advertising and Communications