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N7GCW > VETS 23.03.05 23:43l 154 Lines 8248 Bytes #999 (0) @ WW
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Subj: Mefloquine (Lariam) causes long-term effects.
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Sent: 050323/1738z @:WA7V.#SEWA.WA.USA.NOAM [Walla Walla] $:40217_WA7V
UNDER SECRETARY FOR HEALTH'S INFORMATION LETTER POSSIBLE LONG-TERM HEALTH
EFFECTS FROM THE MALARIAL PROPHYLAXIS MEFLOQUINE (LARIAM)
1. Purpose. This Under Secretary for Health Information Letter provides
information to clinicians who examine and provide care to veterans who may
have taken mefloquine as a malaria prophylaxis while on active duty in
Southwest Asia during Operation Iraqi Freedom (OIF) and Operation Enduring
Freedom (OEF).
2. Background
a. During OIF and OEF, the United States (U.S.) Department of Defense (DO
D)
provided mefloquine (Lariam) to some U.S. service members to protect them
against endemic malaria.
b. Mefloquine is approved by the U.S. Health and Human Services Food and
Drug Administration (FDA) for protection against malaria, and since the late
1980s it has become widely recommended for malaria chemoprophylaxis.
Mefloquine can cause common mild side effects including vivid dreams and
mild psychiatric symptoms, which can be sufficiently uncomfortable as to
affect compliance. In addition, a number of anecdotal and media reports have
suggested that mefloquine has caused more serious effects, including violent
and suicidal behavior, and symptoms similar to Post-traumatic Stress
Disorder (PTSD). These media accounts link reports of such behavior to
mefloquine use among returning OIF and OEF veterans, for example, homicides
and suicides among five service members returning to Ft. Bragg, NC, in the
Summer of 2002. Concerns that mefloquine might cause violent behavior is not
new; a Canadian soldier accused of homicide claimed that taking mefloquine,
while deployed to Somalia in 1992, had caused his violent behavior.
c. Adding to this concern, the DOD warning label Information for
Clinicians for mefloquine (taken essentially from the equivalent FDA
label), includes the following: Rare instances of suicide in patients
taking mefloquine have been reported but no studies have demonstrated a
statistical association between mefloquine use and suicide, suicidal ideas,
suicide attempts, or any other violent behavior. Patients with a history of
psychiatric illness may be vulnerable to mefloquine-related psychiatric
symptoms, and the package insert recommends against prescribing (it) to
patients with a history of psychiatric or alcohol problems. Often, potential
neuropsychiatric side effects are the greatest concern for patients. Side
effects may include anxiety, paranoia, depression, agitation, restlessness,
mood changes, panic attacks, forgetfulness, hallucinations, aggression, and
psychotic behavior. Symptoms may continue long after mefloquine use has been
stopped. If neuropsychiatric symptoms occur, mefloquine use should be
discontinued in favor of other prophylactic medications or
measures. Potential side effects that can impair reaction time and thinking
include sensory and motor neuropathies, encephalopathy, convulsions,
psychosis, nightmares, dizziness, and confusion. Studies indicate that these
may occur in 1 in 2,000 to 1 in 13,000 people who receive prophylactic
mefloquine.
d. VHA held a meeting April 13, 2004, to discuss possible responses to this
issue. The meeting included representatives from the Office of Public Health
and Environmental Hazards and Office of Patient Care Services,
Medical-Surgical, Mental Health, and Pharmacy Benefits & Management, and
other VHA leaders and experts in neurology, mental health, infectious
disease, and toxicology. The group concluded that the Department of Veterans
Affairs (VA) needed a well-grounded response to current concerns among
veterans, their families, Congress, the media, VA health care providers, and
others about possible long-term health effects and disability among OIF and
OEF veterans from taking mefloquine. In particular, VHA health care
providers will need concise and accurate medical information about
mefloquine health effects to answer questions and concerns of veterans who
are returning from deployments in Southwest Asia.
e. To develop guidance on possible long-term and chronic health effects from
mefloquine, this group conducted a literature review of more than sixty
reports that included eight surveys of travelers, 34 case reports of adverse
events, two Cochrane reviews, seven epidemiological studies including
clinical trials and prospective studies, and nine general reviews of
multiple case reports, which included manufacturer and FDA warning label
summaries. The most recent Cochrane review (2004) examined ten clinical
trials involving 2750 adult participants, five of which were field trials,
mainly of male soldiers.
3. Guidance
a. The following summary is to assist VA health care providers when they are
providing care to veterans who may have taken mefloquine while on active
duty. Since there are no practical tests for mefloquine, nor are there any
specific tests that can be recommended specifically for veterans who took
mefloquine while on active duty, medical care needs to focus upon
occupational health issues: e.g., taking a thorough military and medical
history, including taking of mefloquine, along with a basic medical
examination that includes appropriate laboratory tests relating to the
veteran's complaints and medical findings.
b. Review of available literature (see Att.A for references and summaries)
suggests that certain health effects may be associated with mefloquine, some
of which may persist after the drug is stopped. Self-reported symptoms in
travelers surveys include: insomnia, mood impairment, depression, strange
thoughts, altered spatial perception, sleeping disturbances, fatigue,
dizziness and other neuropsychiatric effects, lasting in some instances more
than 2 months. Clinical trials and epidemiological studies suggest that
reported side effects are not common, are self-limiting, and include:
depression, panic attacks, anxiety, insomnia, vertigo, nausea and headache,
and strange or vivid dreams. However, such studies have only limited power
to detect more rare and serious adverse events.
c. The most severe and persistent adverse effects appear in case reports.
In those instances, consistent with the nature of a case report, the
relevant signs and symptoms began while mefloquine was being taken, and
persisted in some reports for weeks, months or even years after the drug was
stopped.
NOTE: Mefloquine has a long half-life in humans of 15 to 30 days. Adverse
effects that are reported to persist for significant periods after the drug
is stopped, or that could be associated with long-term health effects,
include the following which lists in decreasing frequency the cases;
NOTE:
The reported number of individual cases and the number of published reports
for that health effect are shown in parenthesis; i.e., 16/12 means that
there were sixteen reported cases and twelve published reports.
(1) Anxiety, paranoia, hallucinations, depression, suicidal ideation,
cognitive and other neuropsychiatric symptoms (16/12),
(2) Acute and paranoid psychosis (10/9),
(3) Convulsions, grand mal seizures, coma and abnormal
electroencephalography (EEG) (9/4),
(4) High frequency sensorineural hearing loss and tinnitus, with partial or
no remission (3/1),
(5) Acute lung injury with diffuse alveolar damage (2/1), (6) Elevated liver
function tests or fatty liver (2/2),
(7) Multifocal myoclonus (1/1),
(8) Fatal toxic epidermal necrolysis (1/1),
(9) Trigeminal sensory neuropathy (1/1),
(10) Atrial flutter (1/1), and
(11) Mefloquine overdose induced encephalopathy (1/1).
d. Veterans need to be informed that seeking care for possible
mefloquine-related conditions does not constitute a claim for compensation.
NOTE: Veterans wishing to file a compensation claim need to be referred to a
Veterans Benefits Counselor, or advised to contact the appropriate VA
Regional Office at 1-800-827-1000.
4. Contact. Questions regarding this information letter may be addressed to
the Environmental Agents Service (131) at (202) 273-8579. S/ Arthur S.
Hamerschlag for Jonathan B. Perlin, MD, PhD, MSHA, FACP Acting Under
Secretary for Health DISTRIBUTION: CO: E-mailed 6/23/04 FLD: VISN, MA, DO,
OC, OCRO, and 200 E-mailed 6/23/04
ATTACHMENT A SUMMARY OF LITERATURE ON POSSIBLE LONG-TERM CHRONIC HEALTH
EFFECTS FROM MEFLOQUINE
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