Mefloquine (Systemic)
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VA CLASSIFICATION
Primary: AP101
Commonly used brand name(s): Lariam.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antimalarial—
Indications
General considerations
Malaria transmission occurs in large areas of Central and South America, Hispaniola, sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania {03}. The estimated risk of a traveler acquiring malaria varies markedly from area to area {03}. Country-specific information on malaria risk can be obtained from the Centers for Disease Control and Prevention (CDC) or from the CDC's web site at http://www.cdc.gov/travel/yellowbk {03} {09} {12}.
Travelers to malarious areas should be advised to use an appropriate drug regimen and personal protection measures to prevent malaria {03}. Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn {03} {09}. Therefore, travelers should take protective measures to reduce contact with mosquitoes especially during these hours (see Patient Consultation ) {03}. However, travelers should be informed that regardless of methods employed, malaria still may be contracted {03}.
Asplenic travelers are at increased risk of severe malaria and should take extra precautions to avoid contracting the disease {05}. These precautions should involve careful use of antimosquito measures, strict compliance with appropriate chemoprophylaxis, and avoidance of unnecessary visits to malarious areas {05}.
Drug resistance to chloroquine has been confirmed or is probable in all countries with Plasmodium falciparum malaria except the Dominican Republic, Haiti, countries in Central America west of the Panama Canal Zone, Egypt, and most countries in the Middle East {03} {11}. In addition, resistance to both chloroquine and sulfadoxine and pyrimethamine is widespread in Thailand, Myanmar, Cambodia, and the Amazon basin area of South America, and resistance also has been reported sporadically in sub-Saharan Africa {03}. Resistance to mefloquine has been confirmed in those areas of Thailand (Thai-Cambodian border) with malaria transmission {03} {06}.
The appropriate chemoprophylactic regimen is determined by the traveler's risk of acquiring malaria in the area to be visited and by the risk of exposure to chloroquine-resistant P. falciparum {02} {03}. Indications for prophylaxis for children are identical to those for adults {02} {03}. Chemoprophylaxis should begin 1 to 2 weeks before arrival in the endemic area, allowing time for development of adequate blood concentration of the chemoprophylactic agent and evaluation of any adverse reactions (see General Dosing Information ) {02} {03}.
Accepted
Malaria (prophylaxis)—Mefloquine is indicated for the prophylaxis of P. falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum and P. vivax {01} {10} {11} {13}.
Malaria (treatment)—Mefloquine is indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by both chloroquine-susceptible and resistant strains of P. vivax {01} {10} {13}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Chemical group—
Mefloquine is a 4-quinolinemethanol derivative {01}. It is a 2-aryl substituted chemical structural analog of quinine {01}.
Molecular weight—
Mefloquine hydrochloride: 414.78 {01}
Mechanism of action/Effect:
Mefloquine is an antimalarial agent that acts as a blood schizonticide. However, the exact mechanism of action is unknown {01}.
Absorption:
Well absorbed from the gastrointestinal tract {01} {04}.
Distribution:
Distributed into blood, urine, cerebrospinal fluid (CSF), and tissues; concentrated in erythrocytes; also distributed into breast milk in low concentrations (approximately 3 to 4% of the ingested dose).
Apparent Vol D—9 to 29 L/kg (median 20 L/kg) {04}.
Protein binding:
Very high (98%) {01} {04}.
Biotransformation:
Hepatic (partial); metabolized primarily to the carboxylic acid metabolite {01}.
Half-life:
Absorption—0.36 to 2 hours {01}.
Elimination—15 to 33 days {01}.
Time to peak concentration:
2 to 12 hours {04}.
Peak plasma concentration
Approximately 1 mcg/mL after a single dose of 1 gram {04}.
Elimination:
Biliary/fecal; eliminated very slowly, primarily through bile into the feces. Subtherapeutic concentrations may persist in the blood for up to several months or more.
Renal; approximately 5% of the oral dose is excreted unchanged in the urine.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients hypersensitive to quinidine, quinine, or related medications may be hypersensitive to this medication also {01} {04}.
Carcinogenicity
Two-year feeding studies in rats and mice, fed doses of up to 30 mg per kg of body weight (mg/kg) daily, have not shown that mefloquine is carcinogenic {01}.
Mutagenicity
Mefloquine has not been shown to be mutagenic in the Ames test, host-mediated assays in mice, fluctuation tests, and mouse micronucleus assays, with or without prior metabolic activation. In addition, mefloquine has not been shown to be mutagenic in modified Ames tests utilizing Salmonella typhimurium strains, with or without microsomal activation {01}.
Pregnancy/Reproduction
Fertility—
Studies in adult human males, at doses of 250 mg once a week for 22 weeks, have not shown that mefloquine causes any adverse effects on spermatozoa {01}.
However, studies in rats given doses of 5, 20, and 50 mg/kg daily have shown that mefloquine causes adverse effects on fertility in males at doses of 50 mg/kg daily and in females at doses of 20 and 50 mg/kg daily {01}. In addition, degenerative lesions in the epididymides of male rats have been reported at doses of 20 and 50 mg/kg daily for 13 weeks {01}.
Pregnancy—
Note: Pregnant women should avoid traveling to areas where chloroquine-resistant Plasmodium falciparum malaria is endemic {12}. If travel to the malarious area and mefloquine chemoprophylaxis are considered necessary, women of childbearing potential should be warned to take reliable contraceptive precautions while taking mefloquine and for 2 months after the last dose {12}.
Adequate and well-controlled studies in humans have not been done. However, a review of data from clinical trials and reports of inadvertent use of mefloquine during pregnancy suggests that its use is not associated with adverse fetal or pregnancy outcomes such as birth defects, stillbirths, or spontaneous abortions {02} {08}.
Malaria in pregnant women results in a higher mortality rate and greater morbidity than in other adults {08}. The risks of malaria in pregnancy may far outweigh any harmful effects of chemoprophylaxis {08}. Therefore, mefloquine may be considered for prophylactic use in women who are pregnant or likely to become pregnant when exposure to chloroquine-resistant P. falciparum is unavoidable {02} {08}.
Mefloquine has been demonstrated to be teratogenic and embryotoxic in rats and rabbits {01}.
FDA Pregnancy Category C {01}.
Breast-feeding
Mefloquine is distributed into breast milk in low concentrations (approximately 3 to 4%) following administration of a 250-mg dose {01} {04}. However, the amount of mefloquine distributed into breast milk is of no prophylactic value to the infant {04}.
Pediatrics
Although the safety and efficacy of mefloquine have not been well studied, it has been effective in preventing and treating malaria caused by P. falciparum in children {01}. Two studies of mefloquine in children living in endemic areas for P. falciparum were conducted {01}. All children in these studies had at least a low level of parasitemia and 18 to 40% had significant parasitemia with or without mild malaria symptoms {01}. When given 20 to 30 mg of mefloquine per kg of body weight as a single dose, all children with fever became afebrile, and 92% of those with significant parasitemia had a satisfactory response to treatment {01}. While incomplete follow-up was obtained in these studies, nausea and vomiting occurred in approximately 10 and 20%, respectively, and dizziness was seen in approximately 40% of children {01}.
Children of any age can contract malaria {03}. Consequently, the indications for prophylaxis are identical to those described for adults {03}. Limited data suggest that mefloquine also is well tolerated by infants and children who weigh less than 15 kg {03}. Therefore, mefloquine may be considered for use when travel to areas with chloroquine-resistant P. falciparum is unavoidable {03}.
Children who cannot take mefloquine or doxycycline can be given chloroquine for prophylaxis in chloroquine-sensitive areas {02} {13}. The combination of chloroquine and proguanil for sub-Saharan Africa has lower efficacy {13}. Children should avoid travel to areas with chloroquine-resistant P. falciparum malaria unless they can take a highly effective antimalarial agent, such as mefloquine, doxycycline, or primaquine {02} {13}. Primaquine is safe and highly effective in children provided that their glucose-6-phosphate dehydrogenase (G6PD) level is normal {13}.
Geriatrics
Appropriate studies on the relationship of age to the effects of mefloquine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
» Quinidine or
» Quinine (concurrent use of these agents with mefloquine may result in sinus bradycardia, prolonged QT intervals, or cardiac arrest; the risk of seizures may also be increased with quinine; if concurrent use is necessary, close monitoring of patient response is recommended; in addition, patients should be advised to take mefloquine at least 12 hours after the last dose of quinidine or quinine {01} {13})
» Halofantrine (data on the use of halofantrine subsequent to administration of mefloquine suggest a significant, potentially fatal, prolongation of the QTc interval of the ECG {01} {04}; therefore, halofantrine should not be given simultaneously with or subsequent to mefloquine {01} {04})
» Chloroquine (concurrent use of chloroquine with mefloquine may increase the risk of seizures {03})
» Divalproex or
» Valproic acid (concurrent use of divalproex or valproic acid with mefloquine may result in low valproic acid serum concentrations and loss of seizure control; monitoring of valproic acid serum concentrations is recommended and dosage adjustments may be necessary during and after therapy with mefloquine {01} {04})
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]), serum, and
Aspartate aminotransferase (AST [SGOT]), serum (values may be transiently increased in patients taking mefloquine {01} {04})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
» Epilepsy or
» Seizure disorder, history of (mefloquine may rarely cause seizures {01} {03})
» Heart block, first or second degree{01}
» Psychiatric disorders, history of (mefloquine may cause psychosis, anxiety, or mental depression {01} {03})
Sensitivity to mefloquine, quinidine, quinine, or related medications{01}
Side/Adverse Effects
Note: Mefloquine is well tolerated and rarely has been associated with serious adverse effects when used for prophylaxis {03}. Serious adverse effects are more frequent with the higher doses of mefloquine used in the treatment of malaria {03}. However, serious side effects of mefloquine may be difficult to distinguish from the symptoms of acute malaria infection {01} {06}.
Although mefloquine is well tolerated when used for prophylaxis, monitoring the occurrence of severe adverse reactions is important because such reactions are possible {03}. Therefore, patients who experience serious adverse reactions following a prophylactic dose of mefloquine should consult their physician, and the reactions should be reported to the Centers for Disease Control and Prevention (CDC) Malaria Section (telephone number: 1-770-488-7760) {03}.
Ocular lesions were observed in rats fed mefloquine daily for 2 years {01}. These lesions were characterized by retinal degeneration, opacity of the lens, and retinal edema {01}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence less frequent
Abnormal dreams {01}{04}
asthenia {01}{04}(unusual tiredness or weakness)
forgetfulness{01}{04}
hypertension {01}{04}(dizziness; severe or continuing headache)
hypotension {01}{04}(unusual tiredness or weakness, severe)
insomnia {01}{04}(trouble in sleeping)
Incidence rare
Arrhythmia {01}{04}(irregular heartbeat)
cardiopulmonary arrest {01}{04}(swelling of ankles, feet, and/or lower legs; shortness of breath and/or wheezing)
central nervous system (CNS) disturbances or neuropsychiatric toxicity {01}{04}(anxiety; confusion; depression; hallucinations; psychotic manifestations, such as mood or mental changes, mental depression, and/or restlessness)
convulsions {01}{04}
encephalopathy {01}{04}{07}(confusion; headache, severe or continuing; irritability; stiff neck; vomiting)
erythema multiforme and/or Stevens-Johnson syndrome {01}{04}(aching joints and muscles; blistering, loosening, peeling, or redness of skin; chills, fever, and/or sore throat; red or irritated eye; sores, ulcers, and/or white spots in mouth or on lips; unusual tiredness or weakness)
leukopenia {01}{04}(cough or hoarseness; fever or chills; lower back or side pain; painful or difficult urination)
thrombocytopenia {01}{04}(unusual bleeding or bruising; black, tarry stools; pinpoint red spots on skin)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Abdominal pain (stomach pain)
arthralgia and/or myalgia (aches and pain in joints and/or muscles)
diarrhea
dizziness
fever
headache
nausea
vomiting {01}{04}{11}
Incidence less frequent
Anorexia {01}{04}(loss of appetite)
Those not indicating need for medical attention
Incidence rare
Alopecia (loss of hair){01}{04}
Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Treatment of overdose
Since there is no known specific antidote, the following procedure is recommended in case of overdose {01} {04}:
To decrease absorption:
Vomiting should be induced or gastric lavage should be performed, as appropriate, to empty the stomach {01} {04}.
Specific treatment:
Cardiac function and neurologic and psychiatric status should be monitored for at least 24 hours {01}. Vomiting and/or diarrhea should be treated with standard fluid therapy {01}. Symptomatic treatment should also be given {01}.
Supportive care:
Supportive measures such as maintaining an open airway, respiration, and circulation may be necessary. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Mefloquine (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Allergies to mefloquine, quinidine, quinine, or related medications
Pregnancy—Pregnant women should postpone travel to malarious areas; however, if travel to high-risk areas is unavoidable, mefloquine should be given to pregnant women because the risk to both the mother and the fetus of complications due to malaria exceeds the risk of the harmful effects of mefloquine
Breast-feeding—Distributed into breast milk in low concentrations; however, the amount of mefloquine distributed into breast milk will not protect the infant from acquiring malaria
Use in children—Children should avoid travel to areas with chloroquine-resistant Plasmodium falciparum malaria, unless they can take a highly effective antimalarial agent, such as mefloquine
Other medications, especially chloroquine, divalproex, halofantrine, quinidine, quinine, or valproic acid
Other medical problems, especially a history of epilepsy, heart block, psychiatric disorders, or seizure disorder
Proper use of this medication
Taking with full glass (240 mL) of water and with food
» Proper storage
For suppression of malaria symptoms
Starting medication 1 to 2 weeks before entering malarious area to ascertain response and allow time to substitute another medication if reactions occur
» Continuing medication while staying in area and for 4 weeks after leaving area
» Checking with physician immediately if fever or “flu-like” symptoms develop while traveling in, or within several months after departure from, endemic area
» Importance of not missing doses and taking medication on a regular schedule
» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses; intermittent dosing may result in less adequate protection
For treatment of malaria
» Compliance with therapy
Precautions while using this medication
» Caution if visual disturbances, dizziness, light-headedness, or hallucinations occur
Mosquito-control measures to help prevent malaria: • Remaining in air-conditioned or well-screened rooms to reduce human-mosquito contact
• Sleeping under mosquito netting, preferably impregnated with pyrethrum-containing insecticide
• Wearing long-sleeved shirts or blouses and long trousers to protect arms and legs when mosquitoes are out
• Applying mosquito repellents containing N,N-diethyl- m-toluamide (DEET) to uncovered areas of skin when mosquitoes are out
• Using a pyrethrum-containing flying insect spray to kill mosquitoes
» Taking mefloquine at least 12 hours after the last dose of quinidine or quinine
For treatment of malaria
Checking with physician if no improvement within a few days
Side/adverse effects
Signs of potential side effects, especially abnormal dreams, asthenia, forgetfulness, hypertension, hypotension, insomnia, arrhythmias, cardiopulmonary arrest, CNS disturbances or neuropsychiatric toxicity, convulsions, encephalopathy, erythema multiforme and/or Stevens-Johnson syndrome, leukopenia, and thrombocytopenia
General Dosing Information
Antimalarial chemoprophylaxis should be recommended depending on the estimated risk of infection {09}. Weekly mefloquine is recommended for most travelers to areas with chloroquine-resistant Plasmodium falciparum {09}. However, chloroquine should be used in areas with chloroquine-sensitive P. falciparum {09}.
Mefloquine prophylaxis preferably should begin 1 to 2 weeks before travel to malarious areas {01} {03} {09}. Any potential side effects should be evaluated and treated by the traveler's physician before departure {03}. Malaria prophylaxis should continue during travel in the malarious areas and for 4 weeks after leaving these areas {03} {09}.
When standard weekly dosing is used, side effects usually occur between the third and seventh dose {13}. Some studies suggest that side effects can be predicted within 1 week of initiating therapy by using a loading dose of 250 mg daily for 3 days, followed by weekly dosing {13}.
For the treatment of mild to moderate malaria caused by Plasmodium vivax or mefloquine-susceptible P. falciparum , a single oral dose of 15 to 25 mg per kg of body weight (maximum, 1250 mg) mefloquine hydrochloride should be given {01} {02}. Alternatively, split dosing (750 mg followed by 500 mg 8 hours later) may be considered {12}. Mefloquine should not be taken on an empty stomach and should be administered with at least 8 oz. (240 mL) of water {01}.
Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites {01}. To avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinolone (e.g., primaquine) {01}. There are insufficient clinical data to document the effect of mefloquine in malaria caused by Plasmodium ovale or Plasmodium malariae {01}.
If a full malaria treatment course with mefloquine has been administered without clinical cure, alternative treatment should be prescribed {01}. Similarly, if previous prophylaxis with mefloquine has failed, mefloquine should not be used for curative treatment {01}.
Mefloquine should not be used for self-treatment because of the frequency of serious side effects (e.g., hallucinations, convulsions) that have been associated with the high doses of mefloquine used for the treatment of malaria {03}.
For travel to areas of risk where chloroquine-resistant P. falciparum exists, mefloquine alone should be used {03}. Mefloquine can be used for long-term prophylaxis {03}. In some countries a fixed combination of mefloquine and sulfadoxine and pyrimethamine is marketed under the name Fansimef {03}. Fansimef should not be confused with mefloquine and is not recommended for prophylaxsis of malaria, because of the potential for severe adverse reactions associated with prophylactic use of sulfadoxine and pyrimethamine {03}.
Persons who travel to areas where drug-resistant P. falciparum is endemic and for whom mefloquine is not recommended should use an alternative regimen, as follows {03}: • Doxycycline alone taken daily is an alternative regimen for travelers who cannot tolerate mefloquine or for whom mefloquine is not recommended {03}. Doxycycline is as effective as mefloquine for travel to most malarious areas {03}. It is also the only available effective prophylactic agent for travelers to malaria-endemic areas of Thailand bordering Myanmar and Cambodia {03}.
• Chloroquine alone taken weekly is recommended only for those travelers to areas with drug-resistant P. falciparum who cannot use mefloquine or doxycycline {03}. Chloroquine with daily proguanil may be more effective than chloroquine alone {03}. However, the combination of chloroquine and proguanil for sub-Saharan Africa has lower efficacy {13}. Therefore, travelers should avoid areas with chloroquine-resistant P. falciparum malaria unless they can take a highly effective antimalarial agent, such as mefloquine, doxycycline, or primaquine {02} {13}.
Primaquine in an adult dose of 30 mg per day (2 tablets daily) has been shown to provide excellent protection against P. falciparum and P. vivax malaria in Indonesia, Kenya, and Colombia {13}. If primaquine is considered for treatment, glucose-6-phosphate dehydrogenase (G6PD) level should be determined prior to primaquine administration {13}.
Oral Dosage Forms
MEFLOQUINE HYDROCHLORIDE TABLETS
Note: The dosing below is based on the product available in the U.S., in which a 250-mg tablet is equivalent to 228 mg of mefloquine base. The product available in Canada and other countries is 250 mg of mefloquine base, equivalent to 274 mg of mefloquine hydrochloride. To avoid confusion, the dosing below is expressed in the salt form (i.e., mefloquine hydrochloride) {13}.
Usual adult and adolescent dose
Malaria (prophylaxis)
Oral, 250 mg once a week, starting one to two weeks before travel, then weekly during travel in malarious areas and for four weeks after leaving those areas {01} {02} {03} {04} {13}.
Malaria (treatment)
Oral, 1250 mg as a single dose, or 16.5 mg per kg of body weight as a single dose {01} {02} {03} {13}. Alternatively, 750 mg followed by 500 mg 8 hours later may be considered {12}.
Usual pediatric dose
Malaria (prophylaxis)
Infants and children up to 15 kg of body weight: Oral, 5 mg per kg of body weight, once a week, starting one to two weeks before travel, then weekly during travel in malarious areas and for four weeks after leaving endemic areas{02} {03} {13}{14}.
Children 15 to 19 kg of body weight—Oral, 62.5 mg (1/4 tablet) once a week, starting one to two weeks before travel, then weekly during travel in malarious areas and for four weeks after leaving endemic areas {02} {03} {13}.
Children 20 to 30 kg of body weight—Oral, 125 mg (1/2 tablet) once a week, starting one to two weeks before travel, then weekly during travel in malarious areas and for four weeks after leaving endemic areas {02} {03} {13}.
Children 31 to 45 kg of body weight—Oral, 187.5 mg (3/4 tablet) once a week, starting one to two weeks before travel, then weekly during travel in malarious areas and for four weeks after leaving endemic areas {02} {03} {13}.
Children over 45 kg of body weight—See Usual adult and adolescent dose {02} {03} {13}.
Malaria (treatment)
See Usual adult and adolescent dose {02} {03}.
Strength(s) usually available
U.S.—
250 mg (228 mg base) (Rx) [Lariam (scored)]{01}
Canada—
274 mg (250 mg base) (Rx) [Lariam (cross-scored [both sides])]{04}
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer {01} {04}.
Auxiliary labeling:
• Take with food and full glass of water {01} {04}.
• May cause dizziness or vision problems {01} {04}.
• Continue medication for full time of treatment {01} {04}.
Revised: 01/24/2001
References
- Lariam package insert (Roche—US), Rev 08/94, Rec 06/98.
- American Academy of Pediatrics. Malaria. In: Peter G, editor. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics; 1997. p. 335-42.
- Centers for Disease Control and Prevention (CDC). Malaria. In: CDC, Health information for international travel 1996–7. U.S. Department of Health and Human Services, Atlanta, GA 1997. p. 128-37.
- Lariam (Roche). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 863-4.
- Bradley DJ, Warhurst DC. Malaria prophylaxis: guidelines for travellers from Britain. BMJ 1995; 310: 709-11.
- Hopperus Buma APCC, van Thiel PPAM, Lobel HO, et al. Long-term malaria prophylaxis with mefloquine in Dutch marines in Cambodia. J Infect Dis 1996; 173: 1506-9.
- Hong Mai NT, Day NPJ, Chuong LV, et al. Post-malaria neurological syndrome. Lancet 1996; 348: 917-21.
- Smoak BL, Writer JV, Keep LW, et al. The effects of inadvertent exposure of mefloquine chemoprophylaxis on pregnancy outcomes and infants of US army servicewomen. J Infect Dis 1997; 176: 831-3.
- Lobel HO, Kozarsky PE. Update on prevention of malaria for travelers. JAMA 1997; 278(21): 1767-71.
- Ohrt C, Richie TL, Widjaja H, et al. Mefloquine compared with doxycycline for prophylaxis of malaria in Indonesian soldiers: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1997; 126(12): 963-72.
- Weiss WR, Oloo AJ, Johnson A, et al. Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil. J Infect Dis 1995; 171: 1569-75.
- Panel comment, 2/99.
- Panel comment, 2/99.
- Product Information: Lariam®, mefloquine. Roche Laboratories Inc., Nutley, NJ, (PI Revised 08/1999) Reviewed 01/2001.
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