A lesson learnt: the rise and fall of Lariam and Halfan.

Lariam (pharmacological name mefloquine) is an antimalaria drug discovered by the US Army shortly after the Vietnam War, and subsequently marketed worldwide by F. Hoffmann-La Roche. The first reported trials of mefloquine were in prisoners, and were performed at the Joliet Correctional Center, Illinois, in 1975, and at the Maryland House of Correction in 1976.1,2 Halfan (pharmacological name halofantrine) is an antimalaria drug chemically related to mefloquine and quinine. Like Lariam, Halfan emerged from the US Army’s huge post-Vietnam antimalaria drug discovery programme.3 Halfan was first described in the literature in November 1982.4 During the 1980s and 1990s, Halfan was marketed by Smith Kline Beecham. There is no question that safe and effective antimalaria drugs were needed in the second half of the twentieth century, once it became apparent that the Plasmodium had developed resistance to the mainstay of antimalaria therapy, namely chloroquine. Chloroquine resistance was observed first in Thailand in 1957, then on the ColombianVenezuelan border in 1959, and in Kenya and Tanzania in 1978.5 Within a decade of Lariam and Halfan being marketed, however, the safety of both these novel agents was in doubt. This essay looks at the unusual developmental history of Lariam and Halfan, explains the circumstances under which both drugs rose in esteem with policy makers and prescribers and then fell into disfavour with consumers, and summarizes the lessons learnt in the process. These lessons need to be recorded and acted upon, to prevent a repetition of the same mistakes with the next generation of antimalaria compounds.