(ME floe kwin)
Treatment of mild-to-moderate acute malarial infections and prevention of malaria caused by Plasmodium falciparum (including chloroquine-resistant strains) or P. vivax
Note: Due to geographical resistance and cross-resistance, consult current CDC guidelines.
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)
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.
Neuropsychiatric effects:Mefloquine may cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued.
Malaria: Oral (dose expressed as mg of mefloquine hydrochloride):
Mild-to-moderate, treatment: 1250 mg (5 tablets) as a single dose. Note: If clinical improvement is not seen within 48-72 hours, an alternative therapy should be used for re-treatment.
Uncomplicated, treatment (off-label dose): 750 mg (3 tablets) as initial dose, followed 6-12 hours later by 500 mg (2 tablets) (CDC, 2013b)
Uncomplicated, chloroquine-resistant P. vivax malaria treatment (off-label use): 750 mg (3 tablets) as initial dose, followed 6-12 hours later by 500 mg (2 tablets) with concomitant primaquine (CDC, 2013b)
Chemoprophylaxis: 250 mg weekly starting 1 week (CDC, 2014: ≥2 weeks) before arrival in endemic area, continuing weekly during travel and for 4 weeks after leaving endemic area. Note: Prophylaxis may begin 2-3 weeks prior to travel to ensure tolerance.
Refer to adult dosing.
Malaria: Children ≥6 months: Oral (dose expressed as mg of mefloquine hydrochloride):
Mild-to-moderate, treatment: 20-25 mg/kg/day in 2 divided doses, taken 6-8 hours apart (maximum total dose: 1250 mg). Note: If clinical improvement is not seen within 48-72 hours, an alternative therapy should be used for re-treatment.
Uncomplicated, treatment (off-label dose): 15 mg/kg, followed 6-12 hours later by 10 mg/kg/dose (maximum total dose: 1250 mg) (CDC, 2013b)
Uncomplicated, chloroquine-resistant P. vivax malaria treatment (off-label use): 15 mg/kg, followed 6-12 hours later by 10 mg/kg/dose (maximum total dose: 1250 mg) with concomitant primaquine (CDC, 2013b)
Chemoprophylaxis: 5 mg/kg/dose once weekly (maximum dose: 250 mg) starting 1 week (CDC, 2014: ≥2 weeks) before arrival in endemic area, continuing weekly during travel and for 4 weeks after leaving endemic area. Note: Prophylaxis may begin 2-3 weeks prior to travel to ensure tolerance.
Manufacturer 's labeling:
20-30 kg: 1/2 of 250 mg tablet (125 mg) once weekly
30-45 kg: 3/4 of 250 mg tablet (187.5 mg) once weekly
>45 kg: One tablet (250 mg) once weekly
Off-label dosing (CDC, 2014):
≤9 kg: 5 mg/kg/dose once weekly
>9-19 kg: 1/4 of 250 mg tablet (62.5 mg) once weekly
>19-30 kg: 1/2 of 250 mg tablet (125 mg) once weekly
>30-45 kg: 3/4 of 250 mg tablet (187.5 mg) once weekly
>45 kg: One tablet (250 mg) once weekly
No dosage adjustment necessary; only a small amount of mefloquine is renally eliminated.
No dosage adjustment provided in manufacturers labeling; however, half-life may be prolonged and plasma levels may be higher in patients with hepatic impairment.
Administer with food and with at least 8 oz 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 30-60 minutes after dose, an additional half-dose should be given. Tablets may be crushed and suspended in a small amount of water, milk, or another beverage for persons unable to swallow tablets.
Take with food and with at least 8 oz of water.
Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 250 mg
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification
Aminoquinolines (Antimalarial): May enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for QTc-prolongation and the risk for convulsions may be increased. Mefloquine may increase the serum concentration of Aminoquinolines (Antimalarial). Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of an aminoquinoline antimalarial when possible. Avoid combination
Amodiaquine: May enhance the adverse/toxic effect of Mefloquine. Specifically, the risk for vision problems may be increased. Monitor therapy
Anticonvulsants: Mefloquine may diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification
Antipsychotic Agents (Phenothiazines): Antimalarial Agents may increase the serum concentration of Antipsychotic Agents (Phenothiazines). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Artemether: May enhance the adverse/toxic effect of Antimalarial Agents. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Bosutinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bosutinib. Avoid combination
Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. Consider therapy modification
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. Consider therapy modification
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
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. 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: Closely monitor for signs/symptoms of hemolytic reactions with concomitant use of topical dapsone and antimalarial agents. Patients with glucose-6-phosphate dehydrogenase deficiency may be at particularly high risk for adverse hematologic effects. Consider therapy modification
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification
Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Consider therapy modification
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Halofantrine: Mefloquine may enhance the QTc-prolonging effect of Halofantrine. Avoid combination
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Lumefantrine: Antimalarial Agents may enhance the adverse/toxic effect of Lumefantrine. Management: Artemether/Lumefantrine (combination product) should not be used with other antimalarials unless there is no other treatment option. Avoid combination
MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination
P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Prucalopride: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. 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 when possible. 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. Mefloquine may increase the serum concentration of QuiNINE. Management: Avoid concurrent use, and delay administration of mefloquine until at least 12 hours after the last dose of quinine when possible. Avoid combination
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Avoid combination
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
St Johns Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring these combinations. Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination
When use is prolonged, periodic liver function tests, evaluations for neuropsychiatric effects, and ocular examinations
1% to 10%:
Central nervous system: Chills, dizziness, fatigue, headache
Dermatologic: Skin rash
Gastrointestinal: Vomiting (3%), abdominal pain, decreased appetite, diarrhea, nausea
Neuromuscular & skeletal: Myalgia
Otic: Tinnitus
Miscellaneous: Fever
<1% (Limited to important or life-threatening): Abnormal dreams, abnormal T waves on ECG, aggressive behavior, agitation, alopecia, anxiety, arthralgia, ataxia, atrioventricular block, auditory impairment, bradycardia, brain disease, cardiac arrhythmia, cardiac conduction disturbance (transient), chest pain, confusion, decreased hematocrit, depression, diaphoresis, drowsiness, dyspepsia, dyspnea, edema, emotional lability, erythema, erythema multiforme, extrasystoles, flushing, forgetfulness, hallucination, hypersensitivity pneumonitis, hypertension, hypotension, increased liver enzymes, insomnia, irregular pulse, leukocytosis, leukopenia, loss of balance, malaise, mood changes, muscle cramps, myasthenia, palpitations, panic attack, paranoia, paresthesia, prolonged Q-T interval on ECG, pruritus, psychosis, restlessness, seizure, Stevens-Johnson syndrome, suicidal ideation (causal relationship not established), suicidal tendencies (causal relationship not established), syncope, tachycardia, thrombocytopenia, tremor, urticaria, vertigo, visual disturbance, weakness
Concerns related to adverse effects:
- Agranulocytosis/aplastic anemia: Agranulocytosis and aplastic anemia have been reported with use.
- 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 ranging from mild skin reactions to anaphylaxis have occurred.
- Neuropsychiatric effects: [U.S. Boxed Warning]: 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: [U.S. Boxed Warning]: Do not prescribe for prophylaxis in patients with major psychiatric disorders including patients with active depression, generalized anxiety disorder, psychosis, or schizophrenia; use is contraindicated in these patients. Use with caution in patients with a previous history of depression.
- 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; increase risk of seizures. Prophylactic use is contraindicated in patients with seizure disorder (WHO, 2010).
Concurrent drug therapy issues:
- Chloroquine: Concurrent use with chloroquine may increase risk of seizures (WHO, 2010).
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
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 Southeast Asia due to drug resistance (CDC, 2013b).
- 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. (Retinal abnormalities have not been observed with mefloquine in humans; however, abnormalities have been reported with long-term administration to rats.)
B
Adverse events have been observed in animal reproduction studies. Mefloquine crosses the placenta; however, clinical experience with mefloquine has not shown adverse effects in pregnant women. Use with caution during pregnancy if travel to endemic areas cannot be postponed. Malaria infection in pregnant women may be more severe than in nonpregnant women and may increase the risk of adverse pregnancy outcomes. Nonpregnant women of childbearing potential are advised to use contraception and avoid pregnancy during malaria prophylaxis and for 3 months thereafter. In case of an unplanned pregnancy, treatment with mefloquine is not considered a reason for pregnancy termination. CDC treatment guidelines are available for the use of mefloquine in the treatment of malaria during pregnancy (CDC, 2013b).
Mefloquine is a quinoline-methanol compound structurally similar to quinine; mefloquines 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
Well absorbed
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
Extensively hepatic primarily by CYP3A4 to 2,8-bis-trifluoromethyl-4-quinoline carboxylic acid (inactive) and other metabolites
Primarily bile and feces; urine (9% of total dose as unchanged drug, 4% of total dose as primary metabolite)
Plasma: ~17 hours (range: 6 to 24 hours)
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)
~98%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, nausea, vomiting, abdominal pain, diarrhea, lack of appetite, or muscle pain. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), dizziness, change in balance, tinnitus, anxiety, paranoia, depression, seizures, illogical thinking, mood changes, behavioral changes, hallucination, angina, tachycardia, flu-like symptoms, vision changes, memory impairment, insomnia, or suicidal ideation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.