Regulatory Focus™ > News Articles > Malaria Drug Given Boxed Warning by FDA in Light of Side Effects, Link to Massacre

Malaria Drug Given Boxed Warning by FDA in Light of Side Effects, Link to Massacre

Posted 29 July 2013 | By Alexander Gaffney, RAC

US regulators have issued a warning regarding the safety of the drug mefloquine hydrochloride, an antimalarial drug widely given to US soldiers and other citizens traveling abroad, saying the drug is associated with a risk of serious psychiatric and nerve side effects.


The drug has notably been associated with the case of US Army Staff Sgt. Robet Bales, now accused of killing 16 Afghani civilians during a "rampage" in 2012. An adverse event report submitted to FDA regarding the incident indicated that mefloquine may have-in combination with other factors, including stress and a traumatic brain injury-resulted in "homicidal behavior."

The drug was originally developed by the US military at Walter Reed Army Medical Center in 1989 under new drug application (NDA) #019578. That particular drug has since been discontinued, but several generic equivalents manufactured by Sandoz, Barr and Roxane remain on the market.

However, as with other drugs in similar circumstances, this has made updating the label problematic, as only the NDA holder may submit labeling changes. Holders of an abbreviated new drug application (ANDA)-the application most often used to obtain approval for a generic equivalent of an NDA-may not submit labeling change requests without the permission of the NDA holder, leaving it up to FDA to require changes. As in the case of Mutual Pharmaceutical Co. v. Bartlett, this can result in serious problems for patients for whom there is little recourse available.

The particular drug implicated in the case of Bales, Roche's Lariam (NDA #019591), was discontinued in the US as of August 2009, several months after Bales' rampage is alleged to have occurred.

Stronger Warnings

Now, in light of Bales' adverse event and many others, FDA has issued a new warning regarding the drug's neurologic and psychiatric side effects, which must now be contained in a "boxed" (also known as a "black box") warning on the drug's packaging.

FDA explained the side effects can include dizziness, loss of balance, ringing in the ears, anxiety, mistrust, depression and hallucinations, the latter four of which can occur at "any time during drug use, and can last for months to years after the drug is stopped or can be permanent."

"FDA will continue to evaluate the safety of mefloquine and will communicate with the public again if additional information becomes available," regulators said in a statement.

The labeling changes affect the last three generic versions of mefloquine on the market, manufactured by Sandoz, Barr and Roxane.

FDA's Mefloquine Warning

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