Thank you. The product monographs for any drug are routinely updated on the basis of new safety signals and the need to warn the public of drug safety risks.
I am more familiar with the history of the U.S. label, but I believe the Canadian label language closely mirrors that of the United States. I can say that in general, beginning with the first availability of mefloquine in the late eighties, early nineties, the product insert should have said that if during prophylactic use of the drug—meaning for prevention of malaria—anxiety, depression, restlessness or confusion are noted, these either may or must be considered prodromal to a more serious event, and the drug must be discontinued.
In fact, in pretty much every jurisdiction where mefloquine, then marketed as Lariam, was available, this language existed in the product insert. We have known all along that mefloquine can produce a toxic encephalopathy that manifests with these symptoms and that the early manifestation of these symptoms predicts the development of more serious encephalopathy that can over time contribute to this risk of permanent neurotoxicity and disability. I think this is what permitted Roche—the original manufacturer of Lariam—to minimize their legal exposure such that they could with confidence market an inherently dangerous product. I think if you ask lawyers they will say that Roche has some very limited exposure, because they have warned all along that you are to stop taking this drug if you develop anxiety.
But the question remains. How is one supposed to use a drug in a military setting, a drug designed for military use, that has to be discontinued at the onset of anxiety? Isn't anxiety a ubiquitous emotion in deployed settings? How is one realistically to distinguish between anxiety from a toxic encephalopathy from mefloquine and anxiety from being deployed? It suggests the drug is inherently defective for the indications for which it was developed.
Now, that being said, that language was never emphasized. It was never understood by rank-and-file troops. It was never understood by military psychiatrists in the field, and certainly soldiers taking the drug were never told to discontinue the drug at the onset of those symptoms.