Bulletin of the Canadian Network for Human Health and the Environment Number 15 November 2009 Welcome to the fifteenth Bulletin of the Canadian Network for Human Health and the Environment! Visit us at If you have new information that would be useful to others on any aspect of human health and the environment, please forward it to us for inclusion in the next Bulle
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What are the contraindications?
• Mefloquine (Lariam®) is an anti-malarial drug effectively Contraindications for mefloquine include those with a known used to prevent malaria. It is FDA-approved for use in hypersensitivity or allergy to mefloquine or related regions where local strains of malaria have developed a compounds (other quinoline methanol derivatives such as resistance to other anti-malarial agents such as chloroquine. quinine, quinidine); current or past depressive disorder, • Mefloquine is prescribed to over 350,000 Americans each general anxiety disorder, psychosis, schizophrenia, or other year and has a relatively safe and efficacious record of significant psychiatric illness; a cardiac conduction abnormality or dysrythmia, liver disease, or history of • Provide service members a medication guide detailing possible side effects of this medication before taking Providers should not prescribe mefloquine for patients • Advise service members to avoid using alcohol while taking taking medications that alter cardiac conduction (especially mefloquine because the more serious side effects occur beta-blockers such as propranolol, atenolol, and metoprolol), among those who consume alcohol while taking the anticonvulsant medications, drugs related to mefloquine (e.g. chloroquine, quinine, quinidine, and halofantrine), • While rare, suicides have been reported, but not proved aurothioglucose,ampicillin, ampicil in/sulbactam, or the scientifically, as a result of taking mefloquine. Remain alert to talk or signs of suicide and evaluate as necessary. • Advise female service members not to use mefloquine if Some occupational groups (e.g., aviators) may be restricted they are pregnant and not to become pregnant for three from taking prophylactic mefloquine because of certain side effects described later. No anti-malarial medication provides 100% effective prevention. Therefore, critical prevention When should mefloquine be prescribed?
efforts include properly wearing the uniform and use of Mefloquine should be prescribed for patients traveling to regions in which malaria is present and the parasite is resistant to chloroquine. Alternatives to prophylactic mefloquine include What are the common side effects?
doxycycline and Malarone® (atovaquone with proguanil), but For most patients, mefloquine is well tolerated and offers the these require daily dosing instead of mefloquine’s weekly dosing. best protection in regions with chloroquine-resistant malaria. Side effects occur in 3 to 25 per cent of patients, rates For adults, the usual oral dosing regimen is 250 mg each week similar to chloroquine. Most side effects do not necessitate beginning at least one week before travel, continuing weekly altering the type of prophylactic drug. Potential side effects during travel, and for 4 weeks after leaving an endemic area, that can impair reaction time and thinking include sensory generally with an additional antimalarial prophylaxis medication. and motor neuropathies, encephalopathy, convulsions, Doses should be taken on the same day of each week. psychosis, nightmares, dizziness, and confusion. Mefloquine should be taken with food and at least 8 oz. (240 ml) of water to enhance bioavailability and to minimize side effects, Side effects can include insomnia, unusual dreams, particularly an upset stomach or vomiting. Steady state drug lightheadedness, headache, vertigo, visual disturbances, levels are reached after seven to eight weeks of consistent ringing in the ear, rash, irritability, and gastrointestinal weekly dosing. Thus, side effects are more likely to occur within symptoms, such as nausea, vomiting, and diarrhea. Vomiting is the most common side effect, affecting 3 percent of users. Other complaints affect less than 1 percent of The elimination half-life is relatively long, lasting from 13 to 24 users. If any of these effects occur, individuals should seek medical advice about the safety of operating heavy Your Suggestions
equipment or carrying a weapon while remaining on the How can I report adverse drug events potentially
medication. If these effects persist or significantly impair related to mefloquine?
functioning, consideration should be given to stopping the drug Health care providers are encouraged to document and report known or suspected patient adverse drug events. What about neuropsychiatric side effects?
The FDA has the primary responsibility for assuring the Rare instances of suicide in patients taking mefloquine have safety and efficacy of all regulated drug products. been reported but no studies have demonstrated a statistical MedWatch, the FDA Safety Information and Adverse Event association between mefloquine use and suicide, suicidal ideas, Reporting Program, serves both health care professionals suicide attempts, or any other violent behavior. Patients with a and the public. MedWatch facilitates voluntary and history of psychiatric il ness may be vulnerable to mefloquine- confidential reporting of adverse events potentially related to related psychiatric symptoms, and the package insert various medications. Reporting can be done via the FDA recommends against prescribing to patients with a history of telephone (1-800-FDA-1088), fax (1-800-FDA-0178) or mail. FDA MedWatch Form 3500 may also be completed online. Often, potential neuropsychiatric side effects are the greatest It is also appropriate to notify the local Medical Treatment concern for patients. Side effects may include anxiety, paranoia, Facility Pharmacy and Therapeutics Committee of adverse depression, agitation, restlessness, mood changes, panic events potentially due to prescribed or dispensed attacks, forgetfulness, hallucinations, aggression, and psychotic medications. This committee can review the event and forward the report to the FDA (see AR 40-3, Chapter 11, Studies indicate that these may occur in 1 in 2,000 to 1 in 13,000 people who receive prophylactic mefloquine. Neuropsychiatric What medical tests are indicated?
side effects may occur more commonly among those who Baseline liver function tests are ideal though potential y consume alcohol while taking mefloquine, so patients should be impractical before deployment and should be repeated if careful y instructed to avoid alcoholic beverages. clinical signs or symptoms suggest possible liver problems. An EKG should be performed for signs or symptoms Symptoms may continue long after mefloquine use has been suggestive of a potential cardiac problem. Animal studies stopped. If neuropsychiatric symptoms occur, mefloquine use have suggested changes in vision may occur with long-term should be discontinued in favor of other prophylactic medications mefloquine administration. Therefore, baseline vision testing is recommended and patients should be told to report vision problems to their provider. Repeat vision testing and eye What neuropsychiatric red flags should precipitate a
examinations should be performed if the patient reports referral?
vision changes or if administration is prolonged (twelve In the event a patient who is taking mefloquine experiences suicidal ideation, depression, acute psychosis, or any of the other above-mentioned neuropsychiatric symptoms, the clinician should initiate an urgent medical referral including psychiatric assessment by a specialist. Under some deployed conditions, a psychiatric consultation may not be possible. In this situation, medical consultation with careful patient observation may be substituted. Mefloquine should be discontinued and replaced with another appropriate anti-malarial medication. Can mefloquine be used during pregnancy or
CDC has advised that mefloquine can be used during pregnancy
and breastfeeding, but its use in the first trimester should be
based on assessment of benefits versus risks. Pregnant women
or those desiring to become pregnant while in malarial regions
should be advised against travel to such locations. Women of
childbearing age should use a reliable contraceptive during
prophylaxis and for three months after the last dose to avoid
conceiving. Consultation with a travel medicine or infectious
disease expert is recommended for these patients.
Where Do I Get More Information?
Air Force Institute for Operational Health
DoD Deployment Health Support
U.S. Army Center for Health Promotion and Preventive Medicine
DoD Deployment Health Clinical Center
Navy Environmental Health Center (NEHC)
Food and Drug Administration
Egr. Dott. Marco Tronchetti ProveraPirelli & C spaVia G. Negri 1020123 MilanoFusione Pirelli S.p.a. – Pirelli & C Luxembourg S.p.a. - Pirelli & C S.a.p.a. La presente per richiederle, a nome e per conto della signora XXXXXXXX, già azionista di Sip e di Pirellis.p.a. il risarcimento dei danni subiti dalla incongrua determinazione del rapporto di cambio proposto evoluto dal consigli