DOD Mefloquine Policy Mirrors FDA Update on Malaria Drug
By Cheryl Pellerin
American Forces Press Service
WASHINGTON, Sept. 26, 2013 The Defense Department’s policy on the antimalarial drug mefloquine, which has been in use for decades, is consistent with a stronger, updated warning about the drug from the Food and Drug Administration, senior DOD officials said.
On July 29, the FDA posted on its website a public advisory about neurologic and psychiatric side effects associated with mefloquine hydrochloride, a drug used to prevent and treat the deadly mosquito-borne disease.
The regulatory agency added a boxed warning -- the most serious kind -- to modify the drug’s label and revise the patient medication guide and wallet-information card given with each prescription to include the possibility that the neurologic side effects could persist or become permanent if the drug is used.
The FDA uses a boxed warning when an adverse reaction is so serious in proportion to the drug’s potential benefit that prescribers should consider this when evaluating the drug’s risks and benefits. The warning also is used to alert prescribers that they can prevent or reduce a serious adverse reaction in patients by using the drug appropriately.
Neurologic side effects can include dizziness, loss of balance or ringing in the ears. Psychiatric side effects can include anxiety, mistrust, depression, or hallucinations.
At the Defense Department, mefloquine was designated as the antimalarial drug of last resort in April, according to a DOD policy letter issued that month by Dr. Jonathan Woodson, assistant secretary of defense for health affairs.
“According to the April 15, 2013, Health Affairs guidance, mefloquine should be the last drug that’s used. There are other drugs we use first, which would be chloroquine, doxycycline or Malarone, and we save mefloquine for last,” Air Force Col. (Dr.) Scott Stanek, a preventive medicine physician in the Office of Force Health Protection and Readiness, told American Forces Press Service.
Malaria is rare in the United States, Stanek said, adding that about 1,700 cases were reported here in 2010 and all were acquired outside the country, leading to six deaths.
“But we send our service members to areas where there is malaria,” he said. “It’s a serious disease that kills many people around the world, so that’s one of the reasons we go through these steps to make sure our service members are protected, and part of the protection package is to use antimalarial medications.”
Stanek said that when service members find out they are deploying to an area, they come to the clinic to find out if there is malaria in that location, its type and sensitivity to medications, or whether any resistance to certain antimalarial medications may be present in that location as identified by the Centers for Disease Control and Prevention or the National Center for Medical Intelligence.
Air Force Col. (Dr.) Jose Rodriguez-Vazquez, a family practice and aerospace physician and director of medical readiness in the Office of Force Health Protection and Readiness, said no antimalarial drug is 100 percent protective. Every drug should be used along with personal protective measures such as insect repellent, long sleeves, long pants, sleeping in a mosquito-free setting or using an insecticide-treated bed net, he said.
Stanek added that protection is a multipronged approach.
“We try to minimize the amount of activity we do at times when there are high levels of mosquitoes out there. We provide [service members] with permethrin-treated uniforms; DEET, a very effective insect repellent for the exposed areas of their skin; mosquito netting if needed; and then the last one is antimalarial medicine. It’s kind of a package deal,” he said.
In areas of the world where service members need protection from malaria parasites, it’s only 30 or 40 species of the female Anopheles mosquito infected with the parasites whose bite can transmit the Plasmodium falciparum parasites to humans.
The female mosquito bites mainly between 9 p.m. and 5 a.m., which is why sleeping under a mosquito net is so important.
If a mosquito is infected with Plasmodium parasites and bites someone, the parasites enter the body and travel through the blood stream to the liver, where they multiply about 10,000 times, producing no symptoms at first. About two weeks later, the parasites burst into the blood stream and start infecting red blood cells.
This is where the parasites start producing symptoms of the disease, including chills, fever, headache, sweats and nausea. But it’s also where mefloquine works, killing the parasites and keeping them from multiplying.
Mefloquine is effective in preventing malaria, with a demonstrated success rate of 91 percent, according to studies of travelers to East Africa, military health officials said.
“This medication has been around for quite a few years,” Stanek said. “It has been used by tens of thousands of individuals, and it works well. It is well known that there is a risk of side effects in some individuals, and although the number of those people is relatively small, we need to make sure that patients are screened so they’re not inappropriately given the medication.”
On Aug. 12, Woodson notified all military health care providers of the FDA mefloquine boxed warning and labeling change due to potential neurologic and psychiatric side effects associated with the drug.
“This FDA notice focuses on warnings in the prescribing information,” he said, “but does not change the indications for the medication.”
Woodson said the April 2013 DOD guidance reiterated that mefloquine should be reserved for those who can’t take first-line medications and reinforces the need to evaluate each patient for contraindications before starting mefloquine.
Such contraindications include a history of traumatic brain injury and posttraumatic stress disorder, and in those with psychiatric diagnoses, specifically depression, schizophrenia and anxiety disorders, he said.
“As a result of DOD guidance limiting its use,” Woodson added, “the number of active-duty service members who received prescriptions for mefloquine decreased from 17,361 in 2008 to 889 through July 2013. Use in other DOD beneficiaries has also decreased dramatically.”
Mefloquine use at all points of service for all TRICARE beneficiaries during calendar year 2012 was 5,370 prescriptions given to 4,770 individuals, defense officials said. Of these beneficiaries, 2,030 were active-duty personnel.
“Based on the FDA guidance,” Stanek said, “there needs to be a pretty strong reason why somebody uses mefloquine. They either can’t take one of the other medicines because of contraindications, or they can’t take them because they don’t work for that particular [geographical] area.”