Lariam

Generic Name: Mefloquine Hydrochloride
Class: Antimalarials
VA Class: AP101
Chemical Name: (R*,S*)-(±)-α-2-Piperidinyl-2,8-bis(trifluoromethyl)-4-quinolinemethanol
Molecular Formula: C₁₇H₁₆F₆N₂O
CAS Number: 53230-10-7

REMS:

FDA approved a REMS for mefloquine to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antimalarial; 4-quinolinemethanol derivative; quinine analog.^{1 2 3 7}

Uses for Lariam

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium vivax or P. falciparum, including chloroquine-resistant P. falciparum;^{1 2 3 11 17 50 51 54 55 56 57 58 59 60 61 62 63 64 113 130 134} designated an orphan drug by FDA for this use.⁵⁶ A drug of choice for prophylaxis in those traveling to areas where chloroquine-resistant P. falciparum has been reported^{17 134} and an alternative for prophylaxis in those traveling to areas where chloroquine-resistant P. falciparum malaria has not been reported.¹⁷

Treatment of uncomplicated malaria caused by mefloquine-susceptible P. falciparum, including chloroquine-susceptible and -resistant P. falciparum;^{1 2 3 11 134 143} designated an orphan drug by FDA for this use.⁵⁶ CDC and others consider mefloquine an alternative that should be used only when the regimens of choice cannot be used.^{134 143 144}

One of several regimens recommended by CDC for treatment of uncomplicated chloroquine-resistant P. vivax malaria.¹⁴⁴

Active only against the asexual erythrocytic forms of Plasmodium and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure;^{1 2 3 11 17 34} primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.^{1 2 3 11 17 34 58 64 143 144}

Detailed recommendations regarding prevention of malaria available from CDC 24 hours a day from the voice information service (877-394-8747) or at .¹⁷

Assistance with diagnosis or treatment of malaria available from CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.^{143 144}

Lariam Dosage and Administration

General

• 
  

  A mefloquine medication guide and information wallet card is available from the manufacturer to help individuals understand the risks of malaria, risks and benefits of taking mefloquine to prevent malaria, and the rare but potentially serious psychiatric adverse effects associated with the drug.^{1 142}

  
  


• 
  

  As required by law, a copy of the mefloquine medication guide must be supplied to patients each time mefloquine is dispensed for prevention of malaria.^{1 142}

  
  


• 
  

  The mefloquine medication guide is intended only for individuals taking mefloquine to preventmalaria; information in the guide may not apply to patients receiving the drug for the treatmentof malaria.¹⁴²

  
  

Administration

Oral Administration

Administer orally with ample water (at least 8 oz [240 mL] of water for an adult).¹

Do not administer on an empty stomach;¹ administration on a full stomach minimizes nausea and vomiting.¹⁷

If patient receiving mefloquine for treatment of malaria vomits within 30 minutes after receiving a dose, give a full dose as replacement; if vomiting occurred within 30–60 minutes of the dose, give 50% of the dose as replacement.^{1 115 129} If vomiting recurs, monitor patient closely and consider alternative malaria treatment if improvement is not observed within a reasonable period of time.¹

For administration in children and others who are unable to swallow tablets, mefloquine tablets may be crushed and mixed with a small amount of liquid (e.g., water, milk, other beverage)^{1 17 22 129} or food (e.g., applesauce, chocolate syrup, jelly) or enclosed in gelatin capsules to mask the bitter taste.¹⁷

Gelatin capsules containing the calculated pediatric dosage may be prepared extemporaneously in advance (preferably by a pharmacist) and each dose administered by mixing the contents of the opened capsule with a sweet-tasting food (e.g., applesauce, chocolate syrup, or jelly).¹⁷

Dosage

Available as mefloquine hydrochloride; dosage usually expressed in terms of the salt.¹ In the US, each 250 mg of mefloquine hydrochloride is equivalent to 228 mg of mefloquine base.¹

Dosage in children is based on body weight.¹

Pediatric Patients

Malaria

Prevention of P. vivax or P. falciparum Malaria

Oral

Children weighing ≤45 kg: Approximately 5 mg/kg once weekly on the same day each week.¹ (See Table.) Experience in infants <3 months of age or weighing <5 kg is limited.^{1 134}

Children weighing >45 kg: 250 mg once weekly on the same day each week.^{1 134}

Dosage for Prevention of Malaria in Children Weighing ≤45 kg1134

Weight (kg)	Dosage Once Weekly
30–45	187.5 mg (¾ of a 250-mg tablet)
20–30	125 mg (½ of a 250-mg tablet)
10–20	62.5 mg (¼ of 250-mg tablet)
5–10	31.25 mg (1/8 of a 250-mg tablet)

Initiate prophylaxis 1–2 weeks prior to entering a malarious area and continue for 4 weeks after leaving the area.^{1 17 57 58 60 113 134} If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.^{1 17}

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of mefloquine prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.^{17 134}

Treatment of Uncomplicated P. vivax or P. falciparum Malaria

Oral

Children ≥6 months of age: 20–25 mg/kg; dividing the dosage into 2 doses given 6–8 hours apart may reduce incidence and severity of adverse effects.¹ Alternatively, CDC and some clinicians recommend that children weighing <45 kg may receive an initial dose of 15 mg/kg followed by a single dose of 10 mg/kg 6–12 hours later.^{134 143 144}

If a response is not attained within 48–72 hours, an alternative antimalarial agent should be given; mefloquine should not be used for retreatment.¹

For those with P. vivax malaria, a 14-day regimen of oral primaquine also may be indicated to provide a radical cure and prevent delayed attacks or relapse.^{134 143 144}

Adults

Malaria

Prevention of P. vivax or P. falciparum Malaria

Oral

250 mg once weekly on the same day each week.^{1 2 17 57 60 113 134}

Initiate prophylaxis 1–2 weeks prior to entering a malarious area and continue for 4 weeks after leaving the area.^{1 17 57 58 60 113 134} If there are concerns about tolerance or drug interactions, it may be advisable to initiate prophylaxis 3–4 weeks prior to travel in individuals receiving other drugs to ensure that the combination of drugs is well tolerated and to allow ample time if a switch to another antimalarial is required.^{1 17}

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of mefloquine prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.^{17 134}

Treatment of Uncomplicated P. vivax or P. falciparum Malaria

Oral

A single dose of 1250 mg.¹ Alternatively, CDC and others recommend an initial dose of 750 mg followed by 500 mg given 6–12 hours later (total dose of 1250 mg).^{115 134 143 144}

If a response is not attained within 48–72 hours, an alternative antimalarial agent should be given; mefloquine should not be used for retreatment.¹

For those with P. vivax malaria, a 14-day regimen of oral primaquine also may be indicated to provide a radical cure and prevent delayed attacks or relapse.^{134 143}

Prescribing Limits

Pediatric Patients

Malaria

Prevention of P. vivax or P. falciparum Malaria

Oral

Maximum 1250 mg daily.¹⁴³

Special Populations

Hepatic Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with hepatic impairment.¹ Increased mefloquine plasma concentrations may occur because of decreased elimination.¹

Renal Impairment

No specific recommendations available regarding need for dosage adjustment in individuals with renal impairment.¹

When used for prevention of malaria, limited data indicate that dosage adjustment is not necessary in patients undergoing hemodialysis.^{1 49}

Cautions for Lariam

Contraindications

• 
  

  Hypersensitivity to mefloquine, structurally related agents (e.g., quinine, quinidine), or any ingredient in the formulation.^{1 17 57}

  
  


• 
  

  Malaria prevention in patients with active depression, recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders.¹

  
  


• 
  

  History of seizures.¹

  
  

Warnings/Precautions

Warnings

Severe Malaria

Not recommended for treatment of life-threatening, serious or overwhelming malaria caused by P. falciparum.¹ These infections should be treated with an IV antimalarial; mefloquine may be used as follow-up after completion of the IV regimen.¹

Neuropsychiatric Effects

Severe neuropsychiatric disorders have been reported occasionally with mefloquine,^{1 63 78 86} including sensory and motor neuropathies (paresthesia, tremor, ataxia), seizures,^{1 18 62 64 74 78 84 85 88 113} agitation or restlessness, anxiety, depression, mood changes, panic attacks, forgetfulness, confusion, hallucinations, aggression, psychotic or paranoid reactions, and encephalopathy.¹ In some patients, these symptoms have been reported to continue long after mefloquine was discontinued.¹

Although a causal relationship has not been established, there have been rare cases of suicidal ideation and suicide in patients receiving mefloquine.¹

To minimize risk of psychiatric symptoms, use of mefloquine for prevention of malaria is contraindicated in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia or other major psychiatric disorders.¹ In addition, use with caution in individuals with a previous history of depression.¹

In patients receiving mefloquine for prevention of malaria, if neuropsychiatric manifestations (e.g., acute anxiety, depression, restlessness, confusion) occur, they may be considered prodromal for a serious psychiatric event and mefloquine should be discontinued and an alternative drug substituted.¹

Interactions

Concomitant use with certain other antimalarials not recommended (chloroquine, quinine, quinidine) because of possible increased risk of ECG abnormalities and seizures.¹ In addition, concomitant or sequential use with halofantrine not recommended because of possible increased risk of prolongation of QT interval.¹ (See Interactions.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious cutaneous reactions, including Stevens-Johnson syndrome,^{1 2 93 99} erythema multiforme,^{1 2} and cutaneous vasculitis,⁹⁷ have been reported rarely.^{1 2} Reactions ranging from mild cutaneous events to anaphylaxis cannot be predicted.¹

General Precautions

Epilepsy Patients

Increased risk of seizures in epilepsy patients.¹ Do not use for prevention of malaria in epilepsy patients; may be used for treatment of malaria only if there are compelling reasons for its use.¹

Cardiac Effects

Mefloquine is a myocardial depressant, and mefloquine-induced changes in several cardiac parameters have been described.^{1 2} Bradycardia,^{1 2 76 94} extrasystoles,^{1 2} reversible sinus arrhythmia,^{2 94 100} aberrant cardiac conduction,⁹⁸ first degree AV-block,¹ hypotension,¹ hypertension,¹ flushing,¹ and syncope¹ have been reported.

Substantial changes in PR or QRS intervals have not been reported,^{2 94} but the drug has been associated with prolongation of the QT_c interval and abnormal T waves.^{1 117}

The benefits of mefloquine should be weighed against the possibility of adverse effects in patients with cardiac disease.¹ Some experts state the drug should not be used in patients with cardiac conduction abnormalities.¹³⁴

Ocular Effects

Visual disturbances have been reported infrequently.^{1 50 63 64 77 103} Dose-related ocular lesions (retinal degeneration, retinal edema, lenticular opacity) reported in long-term animal studies.¹

Periodic ophthalmic examinations recommended.¹

Laboratory Monitoring

If used for prolonged periods (e.g., for malaria prophylaxis), evaluate liver function periodically.¹

Specific Populations

Pregnancy

Category C.¹

Women of childbearing potential should use effective contraceptive measures while receiving mefloquine prophylaxis and for up to 3 months following the last mefloquine dose.¹ In the event of an unplanned pregnancy, use of mefloquine for prevention of malaria is not considered an indication for pregnancy termination.¹

Because of the potential risk of stillbirth associated with mefloquine exposure, CDC and other clinicians state that the drug should not be used for treatment of malaria during pregnancy unless no other treatment option exists and benefits outweigh risks.^{134 136 143}

Lactation

Distributed into milk.^{1 2 102 107} Discontinue nursing or the drug.¹

Pediatric Use

Only limited experience for prevention of malaria in infants <3 months of age or weighing <5 kg.¹

Safety and efficacy not established for treatment of malaria in children <6 months of age.¹

Use in children for treatment of acute uncomplicated malaria caused by P. falciparum is supported by evidence from adequate and well-controlled studies in adults and from published open-label and comparative studies in children <16 years of age.^{1 100 101 102} Experience is limited regarding use of mefloquine for treatment of malaria in children <3 months of age or weighing <5 kg.¹

Children of any age can contract malaria, and the indications for prophylaxis and treatment of malaria are the same for children as for adults.^{22 57 58 100 101 102 113 115 129}

Children ≤6 years of age being treated for malaria have experienced early vomiting (within 1 hour of drug administration) more frequently than individuals 7–50 years of age;^{18 68 70 76} early vomiting has been cited as a possible cause of treatment failure in some children.¹ If a second dose is not tolerated, the child should be closely monitored, and alternative antimalarial treatment considered if the child does not improve within a reasonable period of time.¹

Geriatric Use

Response in patients ≥65 years of age does not appear to differ from that in younger adults.¹

Because mefloquine therapy is associated with ECG abnormalities, the greater frequency of cardiac disease observed in the elderly should be considered and the benefit of mefloquine therapy in geriatric individuals should be weighed against the possibility of adverse cardiac effects.¹

Hepatic Impairment

Mefloquine elimination may be prolonged resulting in higher plasma concentrations.¹

Common Adverse Effects

GI effects (nausea, vomiting, loose stools or diarrhea, abdominal pain); CNS effects (dizziness, vertigo); neuropsychiatric events (headache, somnolence, sleep disorders); rash; pruritus.^{1 2 50 51 61 63 76 113 138}

Interactions for Lariam

Drugs Affecting QT Interval

Possibility of prolongation of QT interval if used concomitantly with other drugs that alter cardiac conduction, including antiarrhythmic agents, β-adrenergic blocking agents, calcium channel blocking agents, antihistamines, tricyclic antidepressants, and phenothiazines.¹ Some experts state that mefloquine may be used concomitantly with β-adrenergic blocking agents in patients without an underlying arrhythmia.^{58 134}

Specific Drugs

Drug	Interaction	Comments
Anticonvulsants (carbamazepine, phenobarbital, phenytoin, valproic acid)	Possible decreased concentrations of the anticonvulsant and loss of seizure control1 2 74	Mefloquine generally contraindicated in patients with history of seizures;57 if used in an individual receiving an anticonvulsant agent, monitor concentrations of the anticonvulsant and adjust dosage as necessary1
Antimalarial agents	Possibility of ECG abnormalities and increased risk of seizures with quinine, quinidine, or chloroquine1 Use of halofantrine after mefloquine has resulted in potentially fatal prolongation of the QTc interval; data not available regarding use of mefloquine after halofantrine1	If quinine, quinidine, or chloroquine is used in initial treatment of severe malaria, mefloquine should not be administered until ≥12 hours after the last dose of any of these drugs1 2 If mefloquine administered in the 12 hours preceding initiation of parenteral therapy for severe malaria, a loading dose of quinidine gluconate should not be administered143 Concomitant or sequential use with halofantrine not recommended1 17 57 112
Typhoid Vaccine	Possibility of interference with immune response to typhoid vaccine live oral since mefloquine has in vitro activity against Salmonella typhi108 109 110	Vaccination with typhoid vaccine live oral should be delayed for 24 hours after mefloquine dose;58 108 complete typhoid vaccination ≥3 days before initiating mefloquine prophylaxis1 2 57

Lariam Pharmacokinetics

Absorption

Bioavailability

Mefloquine is a racemic mixture of 2 erythro enantiomers whose rates of release, absorption, transport, action, degradation, and elimination may differ.^{1 2 4 30 41 42 43 44}

Slowly absorbed from GI tract; peak concentrations in blood or plasma are attained within 6–24 hours and appear to be proportional to dose.^{2 30 31 35 36 37 38 39 40 45}

Food

Limited evidence indicates that bioavailability is greater when administered with food than when administered in the fasting state.^{2 3 49}

Special Populations

Some evidence that peak blood or plasma concentrations of mefloquine are substantially higher in Asians than in other ethnic groups.^{2 30 37 38} The reason for this ethnic variation has not been determined, but may involve differences in the volume of distribution secondary to the relatively lower body fat in Asians or differences in the enterohepatic circulation of mefloquine in Asians.^{2 40}

Distribution

Extent

Widely distributed into body tissues and fluids.^{1 2 30 31 37 38 39 45 46 107}

Concentrates in erythrocytes to a greater extent than in plasma.^{1 2 7 8 30 31 33 41 44 122 123}

Distributed into CNS.^{74 83} Because GI absorption may be incomplete and erratic in patients with severe malaria, oral mefloquine therapy should not be relied on for CNS infections.^{1 115}

Distributed into milk in low concentrations.^{1 2 102 107}

Plasma Protein Binding

98% bound to plasma proteins.^{1 2 3 30 31 33 44 45}

Elimination

Metabolism

Metabolized in the liver, but metabolic fate has not been fully determined.^{1 2 3} Plasma concentrations of the principal metabolite, the 4-carboxylic acid derivative, exceed those of mefloquine.^{1 3 31 44}

Elimination Route

Mefloquine and its metabolites are excreted in feces, with only small amounts (<13% combined) eliminated in urine.^{1 2 3 42 48}

Undergoes biliary excretion and extensive enterohepatic circulation;³⁰ some evidence suggests that enterohepatic circulation and fecal elimination may be increased in patients with malaria compared with those in healthy adults.³⁰

Mefloquine and its 4-carboxylic acid metabolite are not removed by hemodialysis.⁴⁹

Half-life

Terminal elimination half-life shows considerable interindividual variation, ranging from 13–33 days (mean: 21 days) in healthy adults and about 10–15 days in patients with uncomplicated malaria.^{1 2 30 31 35 37 38 39 41 42 45 47}

Faster elimination in patients with uncomplicated malaria relative to healthy individuals may result from decreased enterohepatic recirculation and increased fecal elimination.³⁰

In Thai children with uncomplicated malaria, a terminal elimination half-life of 9.8–10.7 days was reported in those 6–24 months of age and 5–12 years of age.^{120 121}

Special Populations

Mefloquine elimination may be prolonged in patients with hepatic impairment, resulting in higher plasma concentrations.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions and Spectrum

• 
  

  A blood schizonticidal agent^{1 2 11} active against asexual erythrocytic forms of most strains of Plasmodium falciparum, P. malariae, P. ovale, and P. vivax, including chloroquine-resistant and pyrimethamine-sulfadoxine-resistant strains of P. falciparum.^{2 11 113} Not active against mature gametocytes or against intrahepatic stages of plasmodial development.^{2 11}

  
  


• 
  

  Also active in vitro against Entamoeba histolytica,¹³ Giardia lamblia,¹⁵ and against the larval and adult stages of Brugia patei and B. malayi.¹⁴

  
  


• 
  

  Mefloquine-resistant Plasmodium has been reported in geographic areas where mefloquine has been used.^{2 3 7 17 18 19 20 21 22 113 114} In addition, P. falciparum strains with in vitro resistance to mefloquine have been identified in areas before introduction of the drug (i.e., intrinsic resistance).^{2 7 23 25 26}

  
  


• 
  

  P. falciparum resistant to mefloquine also may be resistant to halofantrine.^{2 24} Cross-resistance between mefloquine and quinine has been reported in some areas.¹

  
  

Advice to Patients

• 
  

  Importance of reading the medication guide supplied with mefloquine.¹ Advise patients to carry the information wallet card with them when they are taking mefloquine.¹

  
  


• 
  

  For prevention of malaria, necessity of starting mefloquine prophylaxis ≥1 week before arriving in an area with malaria.¹

  
  


• 
  

  Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).^{1 17 57 60 113}

  
  


• 
  

  Possibility of contracting malaria during travel, regardless of prophylactic regimen used.^{1 17 57 60 113}

  
  


• 
  

  Advise travelers who plan presumptive self-treatment in the event of a possible malarial infection to keep an amount of mefloquine sufficient for self-treatment in their possession during travel and to take it promptly in the event of a febrile illness during or after their travel if professional medical care is not readily available.¹³⁴

  
  


• 
  

  Advise travelers that presumptive self-treatment of malaria is an interim measure and that they should seek medical evaluation as soon as possible.¹³⁴

  
  


• 
  

  Importance of seeking medical attention as soon as possible if febrile illness develops during or after return from a malaria-endemic area and of informing clinician of possible malaria exposure, including instances when such illness was self-treated as malaria during travel.^{1 17 57 60 113 134}

  
  


• 
  

  Advise patients that a small percentage of people are unable to take mefloquine because of adverse effects and that it may be necessary to change medications if this occurs.¹

  
  


• 
  

  Potential for mefloquine to cause dizziness, loss of balance, or other disorders of the CNS or peripheral nervous system; use caution with regard to activities requiring alertness and fine motor coordination (driving, piloting aircraft, operating machinery, deep-sea diving).¹

  
  


• 
  

  Advise patients that psychiatric symptoms (e.g., acute anxiety, depression, restlessness, confusion) may be considered prodromal to more serious events.¹ If these effects occur, the drug should be discontinued and an alternative substituted.¹

  
  


• 
  

  Warn women of childbearing potential against becoming pregnant if they will be traveling to areas where malaria is endemic.¹ Advise women of childbearing potential to practice contraception during mefloquine prophylaxis and for up to 3 months after the drug is discontinued.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Mefloquine Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	250 mg	Lariam (scored)	Roche

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Mefloquine HCl 250MG Tablets (ROXANE): 25/$251.50 or 75/$675.09

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Roche. Lariam (mefloquine hydrochloride) tablets prescribing information. Nutley, NJ; 2004 May.

2. Palmer KJ, Holliday SM, Brogden RN. Mefloquine: a review of its antimalarial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1993; 45:430-75. [PubMed 7682911]

3. Tracy JW, Webster LT Jr. Drugs used in the chemotherapy of protozoal infections: malaria. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1995:978-98..

4. Gimenez F, Pennie RA, Koren G et al. Stereoselective pharmacokinetics of mefloquine in healthy Caucasians after multiple doses. J Pharm Sci. 1994; 83:824-7. [IDIS 330679] [PubMed 9120814]

5. Reber-Liske R. Note on the stability of mefloquine hydrochloride in aqueous solution. Bull World Health Organ. 1983; 61:525-7. [PubMed 6349842]

6. Basco LK, Gillotin C, Gimenez F et al. In vitro activity of the enantiomers of mefloquine, halofantrine and enpiroline against Plasmodium falciparum. Br J Clin Pharmacol. 1992; 33:517-20. [IDIS 297355] [PubMed 1524966]

7. Foley M, Tilley L. Quinoline antimalarials: mechanisms of action and resistance. Int J Parasitol. 1997; 27:231-40. [PubMed 9088993]

8. Desneves J, Thorn G, Berman A et al. Photoaffinity labelling of mefloquine-binding proteins in human serum, uninfected erythrocytes and Plasmodium falciparum-infected erythrocytes. Mol Biochem Parasitol. 1996; 82:181-94. [PubMed 8946384]

9. Berman A, Shearing LN, Ng KF et al. Photoeffinity labeling of Plasmodium falciparum proteins involved in phospholipid transport. Mol Biochem Parasitol. 1994:67:235-43.

10. Geary TG, Divo AA, Jensen JB. Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture. Am J Trop Med Hyg. 1989; 40:240-4. [PubMed 2648881]

11. Krogstad DJ. Plasmodium species (malaria). In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995:2415-26.

12. Basco LK, Gillotin C, Gimenez F et al. Absence of antimalarial activity or interaction with mefloquine enantiomers in vitro of the main human metabolite of mefloquine. Trans R Soc Trop Med Hyg. 1991; 85:208-9. [PubMed 1887471]

13. Osisanya JOS. Comparative in vitro activity of mefloquine, diloxanide furoate and other conventionally used amoebicides against entamoeba histolytica. E Afr Med J. 1986; 63:263-8.

14. Walter RD, Wittich RM, Kuhlow F. Filaricidal effect of mefloquine on adults and microfilariae of Brugia patei and Brugia malayi. Trop Med Parsitol. 1987; 38:55-6.

15. Crouch AA, Seow WK, Thong YH. Effect of twenty-three chemotherapeutic agents on the adherence and growth of Giardia lamblia in vitro. Trans R Soc Trop Med Hyg. 1986; 80:893-6. [PubMed 3603639]

16. Karle JM, Karle IL. Crystal structure and molecular structure of mefloquine methylsulfonate monohydrate: implications for a malaria receptor. Antimicrob Agents Chemother. 1991; 35:2238-45. [PubMed 1803997]

17. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website ().

18. Nosten F, ter Kuile F, Chongsuphajaisiddhi T et al. Mefloquine-resistant falciparum malaria on the Thai-Burmese border. Lancet. 1991; 337:1140-3. [IDIS 280801] [PubMed 1674024]

19. Sowunmi A, Oduola AMJ, Salako LA et al. The relationship between the response of Plasmodium falciparum malaria to mefloquine in African children and its sensitivity in vitro. Trans R Soc Trop Med Hyg. 1992; 86:368-71. [PubMed 1440804]

20. Lambros C, Notsch JD. Plasmodium falciparum: mefloquine resistance produced in vitro. Bull World Health Organ. 1984; 62:433-7. [IDIS 260490] [PubMed 6380785]

21. Oduola AMJ, Milhous WK, Weatherly NF et al. Plasmodium falciparum: induction of resistance to mefloquine in cloned strains by continuous drug exposure in vitro. Exp Parasitol. 1988; 67:354-60. [PubMed 3056740]

22. Nosten F, ter Kuile F, Chongsuphajaisiddhi T et al. Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria. Br J Clin Pharmacol. 1991; 31:556-9. [IDIS 282555] [PubMed 1888626]

23. White NJ. Mefloquine: in the prophylaxis and treatment of falciparum malaria. BMJ. 1994; 308:286-7. [IDIS 325041] [PubMed 8124114]