John Cummins, M.P. Delta-South Richmond

News Release

FOR IMMEDIATE RELEASE
November 14, 1994

Possible Adverse Effects of Mefloquine

OTTAWA—The manufacturer on July 30, 1993 provided the Health Protection Branch at Health Canada, quite possibly as a result of the events in Somalia, data "regarding the incidence of psychiatric adverse events with Lariam and the possible interaction of Lariam and alcohol":

July 30, 1993

PERSONAL & CONFIDENTIAL

[Deleted]
Infection and Immunology Division
Bureau of Human Prescription Drugs
Health and Welfare Canada
Place Vanier, Tower "B"
355 River Road
Vanier, Ontario
KlA 1B8

Dear [deleted]:

Incidence of Psychiatric Adverse Events

The following is further to your conversation of July 22, 1993 with [deleted] regarding the incidence of psychiatric adverse events with Lariam and the possible interaction of Lariam and alcohol.

Psychiatric Adverse Events:

The Canadian Safety Monitoring Study ended in mid March 1993. The total number of subjects involved in the study from November 1990 to March 1993 is estimated at about 55,000 (Appendix 1). At this time we have just completed entering the safety data received from the Monitoring Study into our database. The enclosed information is preliminary since it has not been fully analyzed and therefore this should be viewed as a draft document. This data is presented in various tabular formats for your review (Appendix 2):

1. Adverse Event vs. Causality

2.     Organ Category vs. Causality

3. Adverse Event by Organ Category - Totals only

4. Adverse Event Category and the Event - Totals Only

The causality of the 302 psychiatric disorders were reported as follows: 199 probable 95 possible, 7 remote and 1 insufficient information. Of these 8 cases were reported as serious events. The extended summaries for these eight cases have been previously submitted to the Branch (July 15, 1992) but are enclosed (Appendix 3) for quick reference. The adverse events and the causality are as follows:

We are also providing you with a listing of all spontaneous adverse events reported worldwide, excluding Canada (Appendix 4).

Two publications have come to our attention on the effect and tolerability of Lariam compared to other chemoprophylactic regimens. The effectiveness and tolerability were evaluated for short-term use (Steffen et al.) and long term use (Lobel et. al.). The duration of the stay in the malarious areas in the short-term study was 1-4 weeks whereas in the long-term study, it averaged 32 months. A table has been prepared to facilitate the review of the two publications. The table and the publications are in Appendix 5 of this volume. With regards to the incidence of neuropsychiatric adverse events, the incidence reported with Lariam was very comparable to that reported with other agents. Dizziness was the only adverse event which was slightly higher in the Lariam group than in the other comparative groups, in both studies.

Possible Interaction of Lariam and Alcohol:

Regarding the issue of the possible interaction between Lariam and alcohol, a search of the following databases was done and no references were reported: Medline, RoPu, Embase, REPG, Current Contents. A search of the Lariam safety database was done and the cases in which alcohol was reported as a comedication are enclosed (Appendix 6). A brief list of the adverse events reported in these cases and the causality follows:

The preclinical and/or clinical information included in this document is submitted in confidence. None of this information is to be provided to a third party without our being given written notification in accordance with the Access to Information Act and Regulations and the Treasury Board of Canada - Interim Policy Guide - Access to Information Act.

I trust that all is in order. If you have any questions or require further information please do not hesitate to contact the undersigned at [deleted].

Yours truly,

[Deleted]

-30-

For more information, please contact:

John Cummins, M.P.
(604) 940-8040 or 970-0937 (cell)