Archived - Important Safety Information Regarding PERMAX® (pergolide mesylate) and Cardiac Valvulopathy - Eli Lilly Canada Inc. and Draxis Health Inc. - Health Professional Advisory

IMPORTANT SAFETY INFORMATION REGARDING PERMAX^® (pergolide mesylate) and CARDIAC VALVULOPATHY

April 14, 2003

Dear Health Care Professional,

This letter is being sent out following discussions with Health Canada regarding the use of PERMAX® (pergolide mesylate) for the treatment of Parkinson's Disease. PERMAX^® (pergolide mesylate) is indicated in the treatment of the signs and symptoms of idiopathic Parkinson's disease. We would like to provide you with additional safety information that has become available through post-marketing experience in other countries.

During the post-marketing surveillance for PERMAX, a small number of individuals have been identified as developing cardiac valvulopathy involving one or more valves during PERMAX therapy.

Based on data from the worldwide Eli Lilly safety database and scientific publications the pathological assessment of valves that were surgically removed was consistent with the valvulopathy associated with carcinoid syndrome and with the use of other ergot alkaloid drugs. While a clear causal relationship between pergolide and valvulopathy seen in these patients can not be established, given the nature of the lesions and known similar effects of other ergots, the Warnings section of the Canadian Product Monograph for PERMAX will be modified to reflect these reports.

In the post-marketing reports, aortic, mitral and tricuspid valves were involved. In some cases, the symptoms or manifestations of valvulopathy improved with cessation of pergolide therapy. Valve replacement was required in two patients.

It is not known whether the fibrotic valvular changes are related to retroperitoneal, pleural, and pericardial fibrosis, which are very rare but well-known adverse events seen with PERMAX.

Since PERMAX was first launched in the US in 1989, a very limited number of cases have been reported. Of the estimated 500,000 people who have been treated with pergolide worldwide since 1989, valvulopathy has been reported in less than 1 in 20,000 patients (0.005%). No cases of cardiac valvulopathy have been reported in Canada since PERMAX was introduced in 1991 to this country. Reporting rates determined on the basis of spontaneously reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.

The following revisions to the Warnings section of the Canadian Product Monograph for PERMAX (section related to valvulopathy underlined) have been proposed:

Serous Inflammation and Fibrosis - There have been rare reports of pleuritis, pleural effusion, pleural fibrosis, pericarditis, pericardial effusion, cardiac valvulopathy involving one or more valves, or retroperitoneal fibrosis in patients taking pergolide. In some cases, symptoms or manifestations of cardiac valvulopathy improved after discontinuation of pergolide. Pergolide should be used with caution in patients with a history of these conditions, particularly those patients who experienced the event while taking ergot derivatives. Patients with a history of such events should be carefully monitored clinically and with appropriate radiographic and laboratory studies while taking pergolide.

Proposed revisions to the Product Monograph to reflect this updated safety information in the Warnings, Adverse Reactions, and Patient Information sections are currently under review by Health Canada. The revised Product Monograph will be available following approval by Health Canada.

Draxis Health Inc. and Eli Lilly and Company will continue to monitor pharmacovigilance reports. The safety of patients and our products remains our first priority. Should it be determined that PERMAX is to be discontinued, abrupt discontinuation is not recommended as it might exacerbate Parkinsonism.

The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Health care professionals are asked to report any suspected adverse reactions in patients receiving PERMAX to Draxis Health Inc. at the following address:

Attn: Medical and Regulatory Affairs
Draxis Health Inc.
6870 Goreway Drive
Mississauga, Ontario, L4V 1P1
Telephone: (866) 460-9885 (toll free)
Fax: (905) 677-9263

Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed use of drugs.

If you have additional questions about PERMAX, please call Draxis Health Inc. Medical Information at 1-866-460-9885.

Sincerely,

original signed by

Bernard J. Chiasson, Ph.D.
Executive Director, Medical & Regulatory Affairs
Draxis Health Inc.

Loren D. Grossman, M.D., FRCPC, FACP
Vice President, Research & Development
Eli Lilly Canada Inc.

^® PERMAX is a registered trademark of Eli Lilly and Company, and is licensed exclusively in Canada to Draxis Health Inc.