Lariam: Why is this high-risk drug still prescribed to consumers now that safer anti-malaria drugs exist?

I am interviewing Sue Rose and Jeanne Lese, Co-Directors of a grass roots health advocacy organization called Lariam Action USA (www.lariaminfo.org). Lariam (mefloquine) is a widely prescribed anti-malarial drug that for many years was the CDC’s “drug of choice” for malaria prevention. But ever since it came on the market (1989), there have been nagging questions about the drug’s safety for healthy travelers—questions the medical community has largely ignored. For the past ten years, Sue and Jeanne have provided information to the public and helped people suffering from Lariam’s severe side effects, information they couldn’t get anywhere else. They do this work on a volunteer basis.  Neither of them has ever taken Lariam. Sue is an adjunct assistant professor at the School of Public Health and Health Services, George Washington University, Washington, DC.  She is also an attorney who litigated some of the early Lariam cases against Roche. Jeanne has a Master’s degree and has taught at colleges and universities. She has also worked as a writer in banking, mutual funds, medical information, and pharmaceutical advertising.

1. Why was Lariam (mefloquine) developed?

During the Vietnam war, malaria was a huge problem for U.S. ground troops as the parasite had developed resistance to the old standard drug, chloroquine. Mefloquine was the result of Walter Reed Army Institute of Research (WRAIR)’s program to discover a new compound to protect the troops from chloroquine-resistant malaria. Walter Reed later gave Hoffmann-La Roche the license to market Lariam on a commercial basis.

2. What are Lariam’s side effects?

Adverse heart, kidney, liver, skin, central and peripheral nervous system and psychiatric effects are listed on the label as side effects from Lariam use. Neuropsychiatric side effects such as damage to the central nervous system, dizziness, depression, acute anxiety, mania, aggression, rage, psychosis, confusion and memory loss are common. Physical effects such as seizures, insomnia, visual disturbances, ringing in the ears, impaired balance, and severe skin lesions are also well documented.

Alarmingly, mefloquine can also cause suicides, suicidal ideation, and brain damage. These adverse effects present an unacceptable risk in a drug primarily given to healthy people.

3.  When were these side effects first brought to public awareness?

In 1991, a paper detailing Lariam’s “severe and alarming” neurological and psychiatric side effects was published jointly by the World Health Organization and Roche.. The report concluded with several recommendations for future research studies. None of the studies were ever performed.

4.  What has research found about the true frequency of Lariam toxicity?

In 2001 a report of randomized, blinded clinical trials conducted at 15 travel clinics in The Netherlands, Germany, the United Kingdom, Canada, and South Africa was published.  Lariam was compared to another anti-malarial drug (Malarone).  The results: Lariam-treated patients showed a 29% frequency of neuropsychiatric adverse events, 19% rated moderate to severe.

In 2003, the British Medical Journal published research by Swiss scientists comparing Lariam to three other anti-malarial drugs.  They found that 41.6% of the patients taking Lariam experienced moderate to severe neuropsychiatric side effects, almost twice as many as those taking doxycycline or Malarone.

5.  I’ve heard that “serious” side effects from Lariam occur only in 1 in 10,000 cases. Where did this number come from?

Before we talk about numbers, let’s look at “serious.” Roche uses the drug industry’s standard definition— “serious” effects are fatal, life threatening, lead to or prolong a hospital stay, or result in severe disability. This definition is inappropriate for Lariam’s effects. People with Lariam toxicity typically do not die, become disabled, or land in the hospital. But they often become incapacitated—so that they are forced to shorten their holiday or spend the time confined to bed. Even after returning home, many are unable to work, sometimes for years. A better definition comes from a 1996 British study, which says an adverse effect is “significant” [if it] prevents the traveler from undertaking the activity for which he or she had made the journey.”

As for numbers, Roche is also less than candid when it says serious effects from Lariam happen only in “1 in 10,000” cases. This figure is an estimate, not the result of research. It first appeared in the 1991 WHO/Roche paper (see #3). The authors arrived at the estimate by assuming a 50% adverse reaction reporting rate – a rate with no bearing on reality. The FDA says reports of adverse reaction are made between 1 and 10% of the time. If we apply this information to the 1991 paper, the incidence of these “serious” side effects jumps to 1 in 2000.

6.  Is there any evidence that mefloquine damage can be permanent?

Yes. Lariam causes neurotoxicity, as reported by Dow et al. at WRAIR in 2004 and 2006. Their study of laboratory animals concludes that this damage is permanent and notes that this fact should be of significance to clinicians.

Since the early 1990s human patients have been diagnosed with damage to their central vestibular system, in the brain. This raises the disturbing question of why animal research such as Dow’s was not done prior to the licensing of the drug. In fact, “[H]ad this understanding of mefloquine been available prior to licensing, as it should have been, it is certain that the FDA and other national licensing authorities . . . would not have endorsed this drug,” says Dr. Ashley Croft, a world expert on Lariam in “A Lesson Learnt: the rise and fall of Lariam and Halfan,” a prize-winning essay published in the Journal of the Royal Society of Medicine in April 2007. http://www.lariaminfo.org/pages/pdfs/alessonlearntlariamhalfancroft.pdf

7. Lariam prescriptions must be accompanied by a “Consumer Medication Guide.” That’s unusual, isn’t it?

It is.  Significantly, Roche has updated its warnings for Lariam four times recently, each time strengthening the warnings. In 2002, the word “suicide” was added to Lariam’s label. The U.S. was the first country to require this addition to the label.

Perhaps public response to these label changes and publicity about Lariam as a factor in the murders and suicides at Ft. Bragg involving soldiers returned from Afghanistan made the FDA act. In July 2003 the FDA required that patients be given a plain-English consumer guide with easy to understand warnings. (Such patient medication guides have only been required of 18 drugs.) The new guide says Lariam has been associated with “serious psychiatric adverse events” that “may persist even after stopping the medication.” It also notes “rare reports have claimed that Lariam users think about killing themselves” and “rarer reports of suicides.” One major omission, however is the total lack of information about the scientifically established frequency of neuropsychiatric side effects caused by this drug—details that any reasonable person would want to know before deciding what drug to take for anti-malarial protection (see #4).

8.  What are the main goals of Lariam Action USA?

a.  To provide information about mefloquine and support to people suffering from mefloquine’s adverse effects.

b. To create awareness in the medical community and among the public that mefloquine (Lariam) use can result in significant physical and mental adverse effects that can be long-lasting, even permanent.

c. To promote the re-evaluation of the use of mefloquine by Congress, the Pentagon, and the FDA. The drug should be reserved to treat malaria, not used to prevent it.  It is unreasonable to continue to market a drug with a well-known toxic history when other equally effective drugs are available.

d. To inform the public that there are effective and safer alternatives to mefloquine.

e. To inform the public that Lariam (mefloquine) is a “chemical cousin” to the fluoroquinolone antibiotics (such as Cipro, Levaquin, Tequin, Avelox, Floxin, Noroxin, and generics like ciprofloxacin, levafloxacin and gatifloxacin). The FQ antibiotics cause adverse reactions strikingly similar to those of Lariam. People who have adverse reactions to Lariam should NEVER take a fluoroquinolone, and vice versa. (For info on FQ antibiotics, see https://www.medicationsense.com/articles/may_aug_05/warning_antibiotics_052205.html).

9. Lots of travelers go to exotic places to sail, surf, and scuba dive. Should they take Lariam?

No, Lariam is a very bad choice for them. Lariam’s label says it shouldn’t be used by people doing things that require fine eye/hand coordination. Also, because one of Lariam’s most frequent side effects is dizziness, an adverse reaction might be confused with the bends. The Divers Alert Network (DAN) cautions divers against Lariam, as does Dr. David Wright:  “As diving medical physicians at the Royal New Zealand Naval hyperbaric medicine unit we would strongly advise that mefloquine should not be used as chemoprophylaxis for … scuba diving ….”  Doxycycline and Malarone are much safer anti-malarial drugs for people engaging in these sports.

10. How has Lariam Action USA advocated against mefloquine? What methods have you used?

Lariam Action USA is an unfunded advocacy organization run by two volunteer co-directors who do the work and pay the bills! We have used email, a listserv, newsalerts, and a website to spread the word.  Thanks to requests from some individuals associated with the group, Senator Dianne Feinstein has sent six official letters requesting the Pentagon, State Department, FDA and CDC reassess the use of this troublesome drug.

Reporters from radio, TV, print and the internet have covered the mefloquine story both in the US and internationally. Unfortunately, not much has changed in the U.S.  “Taken As Directed,” a documentary film, is our latest effort to broadcast the truth about mefloquine and its toxic effects on healthy people. You can view the trailer at www.takenasdirected.com. At this time the only way to see the film is to purchase a DVD through the website.

11. I’m surprised that after all you’ve done, “Lariam” isn’t a household word (like Cipro!). What can readers do to learn more and help spread the word about the problems you’ve described?

The easiest way to learn more is to visit www.lariaminfo.org and start reading. To receive occasional emails about Lariam news, sign up for our NewsAlerts on the website. People may also join the support group on Yahoo—that link is also on the website.

To see what Lariam can do to healthy people, purchase a copy of “Taken As Directed.” While the film focuses on 5 people suffering major adverse effects from Lariam who were completely healthy until they took the first dose, it also documents what happens when dangerous drug side effects are not taken as seriously as they should be.  We tend to treat drug side effects far too cavalierly in this country and too many people suffer needlessly.  Sadly, some people even pay with their lives.

NOTE TO READERS: The purpose of this E-Letter is solely informational and educational. The information herein should not be considered to be a substitute for the direct medical advice of your doctor, nor is it meant to encourage the diagnosis or treatment of any illness, disease, or other medical problem by laypersons. If you are under a physician’s care for any condition, he or she can advise you whether the information in this E-Letter is suitable for you. Readers should not make any changes in drugs, doses, or any other aspects of their medical treatment unless specifically directed to do so by their own doctors.