Version May 2024
Mefloquine may cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued.
Mefloquine should not be prescribed for prophylaxis in patients with major psychiatric disorders. During prophylactic use, if psychiatric or neurologic symptoms occur, the drug should be discontinued, and an alternative medication should be substituted.
Note: Dose expressed as mg of mefloquine hydrochloride. Due to geographical resistance and cross-resistance, consult current CDC or World Health Organization guidelines as appropriate.
Malaria, prophylaxis: Oral: 250 mg once weekly starting ≥2 weeks before arrival in endemic area, continuing weekly during travel and for 4 weeks after leaving endemic area (CDC Yellow Book 2020).
Malaria, uncomplicated, treatment (alternative agent):
Note: Use only if no other treatment options are available (CDC 2020). When available, artemisinin-based combination therapy is the preferred treatment for malaria; outside of the United States, mefloquine is available in a fixed-dosed combination product with artesunate (WHO 2022).
Oral: 750 mg as a single dose initially, followed 6 to 12 hours later with 500 mg as a single dose; for P. vivax or Plasmodium ovale malaria, use in combination with primaquine (CDC 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary; only a small amount of mefloquine is renally eliminated.
There are no dosage adjustments provided in the manufacturer's labeling; however, half-life may be prolonged and plasma levels may be higher in patients with hepatic impairment.
Refer to adult dosing.
(For additional information see "Mefloquine: Pediatric drug information")
Dosage guidance:
Dosing: Dose is expressed as mg of mefloquine hydrochloride.
Malaria, prophylaxis: Note: Begin ≥2 weeks before arrival in endemic area and continue weekly during travel (on the same day each week) and for 4 weeks after leaving endemic area. Starting 3 to 4 weeks in advance of travel may allow potential adverse effects to occur prior to travel (CDC 2023).
Weight-directed dosing: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose once weekly; maximum dose: 250 mg/dose (CDC 2023; manufacturer's labeling).
Fixed dosing: Infants, Children, and Adolescents:
>9 to 19 kg: Oral: 62.5 mg (1/4 of 250 mg tablet) once weekly (CDC 2023).
>19 to 30 kg: Oral: 125 mg (1/2 of 250 mg tablet) once weekly (CDC 2023).
>30 to 45 kg: Oral: 187.5 mg (3/4 of 250 mg tablet) once weekly (CDC 2023).
>45 kg: Oral: 250 mg once weekly (CDC 2023).
Malaria, uncomplicated, treatment: Note: Recommended only if no other treatment options are available; not recommended for infections caused by P. falciparum or unknown species acquired in Southeast Asia due to resistance (CDC 2023).
Infants, Children, and Adolescents: Limited data available in ages <6 months: Oral: 15 mg/kg once (maximum dose: 750 mg/dose) followed 6 to 12 hours later with 10 mg/kg once (maximum dose: 500 mg/dose). For treatment of P. vivax or Plasmodium ovale, use in combination with primaquine to prevent relapse (CDC 2023).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants ≥6 months, Children, and Adolescents: No dosage adjustment necessary; only a small amount of mefloquine is renally eliminated; not removed by hemodialysis.
There are no dosage adjustments provided in the manufacturer's labeling; however, half-life may be prolonged and plasma levels may be higher in patients with hepatic impairment; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Nervous system: Abnormal dreams (14%) (Tickell-Painter 2017), insomnia (13%) (Tickell-Painter 2017)
1% to 10%: Gastrointestinal: Vomiting (3%)
<1%:
Cardiovascular: Bradycardia, extrasystoles, syncope
Dermatologic: Alopecia, pruritus, telogen effluvium
Nervous system: Asthenia, dizziness, emotional disturbance
Frequency not defined:
Dermatologic: Skin rash
Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea
Hematologic & oncologic: Decreased hematocrit, leukopenia, thrombocytopenia
Hepatic: Increased serum transaminases (transient)
Nervous system: Chills, fatigue, headache
Neuromuscular & skeletal: Myalgia
Otic: Tinnitus
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Atrioventricular block (including first-degree atrioventricular block), cardiac arrhythmia (including atrial flutter) (Fonteyne 1996), cardiac conduction disorder (transient), chest pain, ECG changes (including abnormal T waves on ECG, prolonged QT interval on ECG), edema, flushing, hypertension, hypotension, palpitations, sinoatrial nodal rhythm disorder, sinus bradycardia, tachycardia
Dermatologic: Erythema multiforme, erythema of skin, hyperhidrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis (McBride 1997), urticaria
Gastrointestinal: Dyspepsia, loose stools
Hematologic & oncologic: Agranulocytosis, aplastic anemia, leukocytosis
Hepatic: Hepatic disease (including hepatic failure)
Hypersensitivity: Hypersensitivity angiitis (White 1995), hypersensitivity reaction
Nervous system: Aggressive behavior, agitation (Tran 2006), anxiety (Tran 2006), ataxia, confusion (Nevin 2017), delusion (Tran 2006), depression, drowsiness, emotional lability, encephalopathy (Nevin 2017), hallucination (Tor 2006), illusion (Borruat 2001), malaise, mania (Tor 2006), memory impairment, myasthenia, panic attack, paranoid ideation (Tran 2006), paresthesia, polyneuropathy (peripheral) (Chester 2011), psychotic reaction (Tran 2006), restlessness, seizure (Nevin 2017), sensorimotor neuropathy, suicidal ideation (Tran 2006), tremor, vertigo
Neuromuscular & skeletal: Arthralgia, muscle cramps, rhabdomyolysis (Comelli 2016)
Ophthalmic: Blurred vision (Jain 2016), cataract, diplopia (Jain 2016), optic neuropathy, retinopathy (including central serous chorioretinopathy) (Jain 2016), visual disturbance
Otic: Auditory impairment
Respiratory: Dyspnea, pneumonitis (Soentjens 2006)
Hypersensitivity to mefloquine, related compounds (eg, quinine and quinidine), or any component of the formulation; prophylactic use in patients with a history of seizures or psychiatric disorder (including active or recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorders)
Concerns related to adverse effects:
• Agranulocytosis/aplastic anemia: Agranulocytosis and aplastic anemia have been reported.
• Altered cardiac conduction: Mefloquine may cause alterations in the ECG including sinus bradycardia, sinus arrhythmia, first-degree AV block, QT-interval prolongation, and abnormal T waves. Use caution or avoid concomitant use of agents known to cause QT-interval prolongation (eg, halofantrine, quinine, quinidine).
• Hypersensitivity reactions: Hypersensitivity reactions have occurred.
• Neuropsychiatric effects: May cause neuropsychiatric adverse effects that can persist after mefloquine has been discontinued. During prophylactic use, if symptoms occur, discontinue therapy and substitute an alternative medication. Symptoms may develop early in the course of therapy. Due to the difficulty in identifying these symptoms in infants and children, monitor closely especially in pediatric patients. Psychiatric symptoms may include anxiety, paranoia, depression, hallucinations, and psychosis. Suicidal ideation and suicide have also been reported. Neurologic symptoms of dizziness or vertigo, tinnitus, and loss of balance may also occur and have been reported to be permanent in some cases. During prophylactic use, the occurrence of psychiatric symptoms such as acute anxiety, depression, restlessness, or confusion may be a prodrome to more serious neuropsychiatric adverse reactions. Use caution in activities requiring alertness and fine motor coordination (eg, driving, piloting planes, operating machinery) with neurologic symptoms.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with significant cardiac disease; ECG changes (eg, sinus bradycardia, sinus arrhythmia, first-degree AV block, QT-interval prolongation, abnormal T waves) have been reported.
• Hepatic impairment: Use with caution in patients with hepatic impairment; elimination may be prolonged.
• Neuropsychiatric disorders: Do not prescribe for prophylaxis in patients with major psychiatric disorders including patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia; use is contraindicated in these patients. Use with caution in patients with a previous history of depression.
• Ocular effects: Eye disorders (including optic neuropathy and retinal disorders) have been reported during treatment. If visual symptoms develop during treatment, prompt ophthalmologic evaluation is warranted; discontinuation of therapy may be necessary.
• Plasmodium falciparum infections: Appropriate use: In cases of life-threatening, serious, or overwhelming malaria infections due to Plasmodium falciparum, patients should be treated with intravenous antimalarial drug. Mefloquine may be given orally to complete the course.
• Plasmodium vivax infections: Appropriate use: In cases of acute Plasmodium vivax infection treated with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (eg, primaquine) to avoid relapse.
• Seizure disorder: When using for treatment, use with caution in patients with a history of seizures; may increase risk of seizures. Prophylactic use is contraindicated in patients with seizure disorder.
Special populations:
• Pediatric: Early vomiting leading to treatment failure in children has been reported in some studies; consider alternate therapy if a second dose is not tolerated.
Other warnings/precautions:
• Appropriate use: Not recommended for the treatment of malaria acquired in certain parts of Southeast Asia due to drug resistance (CDC 2020).
• Prolonged use: If mefloquine is to be used for a prolonged period, liver function tests, evaluations for neuropsychiatric effects, and ophthalmic examinations should be performed periodically.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 250 mg
Yes
Tablets (Mefloquine HCl Oral)
250 mg (per each): $10.59 - $13.55
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 250 mg
Oral: Administer with food and at least 240 mL of water. When used for malaria prophylaxis, dose should be taken once weekly on the same day each week. If vomiting occurs within 30 minutes after the dose, an additional full dose should be given; if it occurs within 30 to 60 minutes after dose, an additional half-dose should be given. If vomiting recurs, monitor closely and consider alternative treatment. Tablets may be crushed and suspended in a small amount of water, milk, or another beverage for persons unable to swallow tablets.
Oral: Administer with food and with an adequate amount of water (eg, 240 mL of water for adults). For patients unable to swallow tablets or unable to tolerate the bitter taste, crush tablets and mix with a small amount of water, milk, or other food/beverage immediately before administration. Pulverized dose of mefloquine can be enclosed in a gelatin capsule to mask bitter taste (CDC 2023; Schlagenhauf 2011; WHO 2020; manufacturer's labeling). If vomiting occurs within 30 minutes after a dose, repeat dose. If vomiting occurs within 30 to 60 minutes after a dose, an additional half-dose should be administered. If vomiting recurs, monitor closely and consider alternative treatment. When used for malaria prophylaxis, dose should be taken on the same day each week.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/019591s026s028lbl.pdf#page=13, must be dispensed with this medication.
Malaria, prophylaxis: Prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum.
Malaria, uncomplicated, treatment: Treatment of uncomplicated malaria caused by mefloquine-susceptible strains of P. falciparum (chloroquine-susceptible and -resistant strains) or by P. vivax. Note: The CDC and World Health Organization guidelines also include mefloquine as an option for treatment of uncomplicated malaria due to non-falciparum Plasmodium species (CDC 2020; WHO 2022).
Mefloquine may be confused with Malarone
Lariam [multiple international markets] may be confused with Levaquin [Argentina, Brazil, US, Venezuela]
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoquinolines (Antimalarial): May enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial. Risk X: Avoid combination
Antiseizure Agents: Mefloquine may diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Artemether and Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Artemether and Lumefantrine. Management: Artemether/lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. If combined, monitor patients for increased toxicities of both agents, including QTc interval prolongation. Risk D: Consider therapy modification
CarBAMazepine: Mefloquine may diminish the therapeutic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Mefloquine. Mefloquine may decrease the serum concentration of CarBAMazepine. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If carbamazepine is being used for another indication, monitor for decreased concentrations and efficacy of both carbamazepine and mefloquine. Risk D: Consider therapy modification
Celiprolol: Mefloquine may enhance the bradycardic effect of Celiprolol. Risk C: Monitor therapy
ChlorproMAZINE: Antimalarial Agents may increase the serum concentration of ChlorproMAZINE. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Mefloquine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Mefloquine. Risk C: Monitor therapy
Dapsone (Systemic): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Systemic). Specifically, concomitant use of antimalarial agents with dapsone may increase the risk of hemolytic reactions. Dapsone (Systemic) may enhance the adverse/toxic effect of Antimalarial Agents. Specifically, concomitant use of dapsone with antimalarial agents may increase the risk for hemolytic reactions. Management: Closely monitor patients for signs/symptoms of hemolytic reactions with concomitant use of dapsone and antimalarial agents, particularly in patients deficient in glucose-6-phosphate dehydrogenase (G6PD), methemoglobin reductase, or with hemoglobin M. Risk D: Consider therapy modification
Dapsone (Topical): Antimalarial Agents may enhance the adverse/toxic effect of Dapsone (Topical). Specifically, the risk of hemolytic reactions may be increased. Management: Consider avoidance of this combination when possible. If combined, closely monitor for signs/symptoms of hemolytic reactions. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Risk D: Consider therapy modification
Fosphenytoin-Phenytoin: Mefloquine may diminish the therapeutic effect of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Mefloquine. Mefloquine may decrease the serum concentration of Fosphenytoin-Phenytoin. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If fosphenytoin/phenytoin is being used for another indication, monitor for decreased concentrations and efficacy of both phenytoin and mefloquine. Risk D: Consider therapy modification
Halofantrine: Mefloquine may enhance the QTc-prolonging effect of Halofantrine. Risk X: Avoid combination
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Ketoconazole (Systemic): May increase the serum concentration of Mefloquine. Risk X: Avoid combination
PHENobarbital: Mefloquine may diminish the therapeutic effect of PHENobarbital. PHENobarbital may decrease the serum concentration of Mefloquine. Mefloquine may decrease the serum concentration of PHENobarbital. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If phenobarbital is being used for another indication, monitor for decreased concentrations and efficacy of both phenobarbital and mefloquine. Risk D: Consider therapy modification
Primidone: Mefloquine may diminish the therapeutic effect of Primidone. Primidone may decrease the serum concentration of Mefloquine. Mefloquine may decrease the serum concentration of Primidone. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If primidone is being used for another indication, monitor for decreased concentrations and efficacy of both primidone/phenobarbital and mefloquine. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QuiNIDine: May enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinidine. Risk X: Avoid combination
Quinidine (Non-Therapeutic): May enhance the adverse/toxic effect of Mefloquine. Risk X: Avoid combination
QuiNINE: May enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinine. Risk X: Avoid combination
Warfarin: Mefloquine may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Food increases bioavailability by ~40%. Management: Take with food and at least 8 ounces of water. Maintain adequate nutrition and hydration, unless instructed to restrict fluid intake.
Mefloquine crosses the placenta; however, clinical experience with mefloquine has not shown an increased risk of adverse effects in pregnant patients.
Malaria infection in patients who are pregnant may be more severe than in patients who are not pregnant and has a high risk of maternal and perinatal morbidity and mortality. Malaria infection during pregnancy can lead to miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal death. Therefore, patients who are pregnant and patients who are likely to become pregnant are advised to avoid travel to malaria-risk areas. When travel is unavoidable, patients who are pregnant should take precautions to avoid mosquito bites and use effective prophylactic medications (CDC 2020; CDC Yellow Book 2020).
When other treatment options are not available, mefloquine may be used for the treatment of chloroquine-resistant uncomplicated malaria in pregnancy. In patients who are pregnant with severe malaria, mefloquine may be used as interim oral therapy when the preferred IV agent is not readily available and other oral agents are not available (discontinue once IV treatment is initiated) (consult current CDC guidelines) (CDC 2020).
Mefloquine is present in breast milk.
Mefloquine concentrations in breast milk are ~3% to 4% of a 250 mg dose. The manufacturer recommends that caution be exercised when administering mefloquine to patients who are breastfeeding. Mefloquine is considered acceptable for use in patients who are breastfeeding (CDC Yellow Book 2020).
Take with food and with at least 240 mL of water.
When use is prolonged, periodic liver function tests, evaluations for neuropsychiatric effects, and ocular examinations
Mefloquine is a quinoline-methanol compound structurally similar to quinine; mefloquine's effectiveness in the treatment and prophylaxis of malaria is due to the destruction of the asexual blood forms of the malarial pathogens that affect humans, Plasmodium falciparum, P. vivax
Absorption: Well absorbed; interpatient variability with rate observed (WHO, 2010); more complete absorption when administered as a suspension compared with tablets
Distribution: Distributes into tissues, erythrocytes, blood, urine, CSF
Vd: Children 4 to 10 years: Mean: ~18 to 19 L/kg (Price 1999); Adults: ~20 L/kg
Protein binding: ~98%
Metabolism: Extensively hepatic primarily by CYP3A4 to 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid (inactive) and other metabolites
Bioavailability: Increased by food
Half-life elimination: Children 4 to 10 years: Mean range: 11.6 to 13.6 days (range: 6.5 to 33 days) (Price 1999); Adults: ~3 weeks (range: 2 to 4 weeks); may be decreased during infection (2 weeks) (WHO 2010)
Time to peak, plasma: ~17 hours (range: 6 to 24 hours)
Excretion: Primarily bile and feces; urine (9% of total dose as unchanged drug, 4% of total dose as primary metabolite)
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