Released by FDA: 6/27/01.  Posted by FDA:  7/31/01

Edward G Brann 
Assistant Director, Regulatory Affairs 
Janssen Research Foundation 
1125 Trenton Harbourton Road 
Titusville, NJ 008560-0200

RE:    NDA#20-083 
          Sporanox (Itraconazole) Capsules 
          MACMIS ID # 10159

Dear Mr. Brann:

This letter concerns violative promotional activities by the Janssen Research Foundation (Janssen).   As a part of the Division of Drug Marketing, Advertising, and Communications’ (DDMAC) routine surveillance, we have identified false or misleading statements made by a Janssen sales representative about Sporanox (itraconazole) Capsules for the treatment of onychomycosis.   The statements were made at Janssen’s booth in the commercial exhibit hail of the American Society of Health-System Pharmacists’ (ASHP) annual meeting in June 2001.   We find the statements in violation of the Federal Food, Drug, and Cosmetic Act and its applicable regulations. Specifically, we object to the following:

Failure to Disclose Risk Information

At the ASHP annual meeting, a Janssen sales representative stated, “Sporanox does not have any hepatic effects and you do not need to monitor liver function tests (LFT’s).”   This statement was made by the representative while promoting pulse dosing of Sporanox Capsules for the treatment of onychomycosis.   In addition, when asked about potential cardiac risks associated with Sporanox, the sales representative stated, “I am not aware of any cardiac risks associated with Sporanox.”   These statements are violative because they fail to present the hepatic risks associated with Sporanox use, as well as recent additions to the boxed warning for Sporanox Capsules regarding cardiac effects, specifically congestive heart failure.   Additionally, cardiac risk has been associated with drug-drug interactions, which are also included in the boxed warning for Sporanox Capsules.

The approved product labeling (PI) for Sporanox contains specific warnings and precautions about hepatic and cardiac effects for Sporanox including:

• Boxed Warning: Sporanox (itraconazole) Capsules should not be administered for the treatment of onychornycosis in patients with evidence of ventricular dysfunction such as congenstive heart failure (CHF) or a history of CHF.  Coadniinistration of cisapride, pimozide, quinidine, or dofetilide with Sporanox (itraconazole) Capsules, injection, or Oral Solution is contraindicated.   Serious cardiovascular events, including QT  prolongation, torsades de pointes, ventricular tachycardia, cardiac arrest, and/or sudden death have occurred in patients using cisapride, pmiozide, or quinidine, concurrently with Sporanox and/or other CYP3A4 inhibitors.

• Warnings: Sporanox has been associated with rare cases of serious hepatotoxicity, including liver failure and death.   Some of these cases had neither pre-existing liver disease nor a serious underlying medical condition.

• Precautions: Hepatic enzyme test values should be monitored in patients with pre-existing hepatic function abnormality or those who have experienced liver toxicity with other medications.   Hepatic enzyme test values should be monitored periodically in all patients receiving continuous treatment for more than I month, or at any time a patient develops signs or symptoms suggestive of liver dysfunction.

Requested Action

We request that Janssen representatives immediately cease making such false or misleading statements.   We request that you submit a written response by July 12, 2001 describing your intent and plans to comply with the above.   Your response should include your method of ceasing such oral statements.

You should direct your response to the undersigned by facsimile at (301) 594-6771, or in writing to the Food and Drug Administration, Division of Drug Marketing, Advertising, and Communications, HFD-42, Rm 17-B-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 # 10159 in addition to the NDA number.

Sincerely,

 

James R. Rogers, Pharm.D. 
Regulatory Review Officer 
Division of Drug Marketing, 
  Advertising, and Communications