Lariam

Antimalarials

For storage information, see specific product information within the How Supplied section.
 
NOTE: A medication guide from the manufacturer should be made available to patients upon medication dispensing.

Oral Administration

Mefloquine should not be taken on an empty stomach; administer with at least 8 ounces (240 ml) of water. Because food increases the rate and extent of absorption of mefloquine, it is recommended that mefloquine be administered with food. For very young patients, the dose may be crushed, mixed with water or sugar water and administered via an oral syringe.

Severe

erythema multiforme / Delayed / 0-1.0
Stevens-Johnson syndrome / Delayed / 0-1.0
hearing loss / Delayed / 0-1.0
visual impairment / Early / 0-1.0
seizures / Delayed / 0-1.0
suicidal ideation / Delayed / 0-1.0
bradycardia / Rapid / 0-1.0
AV block / Early / 0-1.0
hepatic failure / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

Moderate

sinus tachycardia / Rapid / 0-1.0
chest pain (unspecified) / Early / 0-1.0
palpitations / Early / 0-1.0
hypertension / Early / 0-1.0
hypotension / Rapid / 0-1.0
pneumonitis / Delayed / 0-1.0
dyspnea / Early / 0-1.0
edema / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
memory impairment / Delayed / Incidence not known
depression / Delayed / Incidence not known
hallucinations / Early / Incidence not known
confusion / Early / Incidence not known
encephalopathy / Delayed / Incidence not known
psychosis / Early / Incidence not known
ataxia / Delayed / Incidence not known
PR prolongation / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
thrombocytopenia / Delayed / Incidence not known

Mild

vomiting / Early / 3.0-3.0
dyspepsia / Early / 0-1.0
pruritus / Rapid / 0-1.0
alopecia / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
tinnitus / Delayed / 0-1.0
syncope / Early / 0-1.0
emotional lability / Early / 0-1.0
asthenia / Delayed / 0-1.0
muscle cramps / Delayed / 0-1.0
fatigue / Early / 0-1.0
arthralgia / Delayed / 0-1.0
hyperhidrosis / Delayed / 0-1.0
chills / Rapid / 0-1.0
flushing / Rapid / 0-1.0
myalgia / Early / 0-1.0
weakness / Early / 0-1.0
malaise / Early / 0-1.0
fever / Early / 0-1.0
diarrhea / Early / Incidence not known
abdominal pain / Early / Incidence not known
nausea / Early / Incidence not known
rash / Early / Incidence not known
tremor / Early / Incidence not known
anxiety / Delayed / Incidence not known
insomnia / Early / Incidence not known
drowsiness / Early / Incidence not known
dizziness / Early / Incidence not known
agitation / Early / Incidence not known
paresthesias / Delayed / Incidence not known
vertigo / Early / Incidence not known
paranoia / Early / Incidence not known
headache / Early / Incidence not known
restlessness / Early / Incidence not known
leukocytosis / Delayed / Incidence not known

Anxiety, behavioral changes, depression, psychiatric event, psychosis, schizophrenia, suicidal ideation

Mefloquine is contraindicated for use as a prophylactic therapy in patients with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorder. Use of the drug can cause a psychiatric event in both adults and children. These events or disturbances may occur early in the course of therapy, and, in some patients, were reported to continue for months or years after discontinuation. Rare cases of suicidal ideation and suicide have been reported, though relationship to mefloquine therapy has not been confirmed. Instruct patients and caregivers to closely monitor for behavioral changes which can the development of psychiatric symptoms; extra vigilance is required for nonverbal children in whom symptoms can be difficult to identify. During prophylactic use, if signs of unexplained anxiety, depression, restlessness or confusion are noticed, these may be considered prodromal to a more serious event. In these cases, the drug must be discontinued and an alternative therapy should be substituted.

Lariam

Rx

Oral antimalarial agent used for malaria prophylaxis or treatment. Prophylactic dosing should begin 1 week before entering endemic area and continue for 4 weeks after leaving. Alternative antimalarial in areas where chloroquine- and proguanil-resistant strains of malaria exist (i.e., European countries). Treatment of choice for malaria in the United States.

For the treatment of malaria. For the treatment of uncomplicated malaria due to P. falciparum, P. vivax, P. ovale†, P. malariae†, or P. knowlesi†. Oral dosage Adults

750 mg PO as initial dose, then 500 mg PO at 6 to 12 hours after initial dose. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. For P. vivax or P. ovale infections, add primaquine phosphate. The FDA-approved dosage is 1,250 mg PO as a single dose.

Infants, Children, and Adolescents 6 months to 17 years

15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose, then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. For P. vivax or P. ovale infections, add primaquine phosphate. The FDA-approved dosage is 20 to 25 mg/kg/dose (Max: 1,250 mg/dose) PO as a single dose. Administering as divided doses may reduce the occurrence or severity of adverse effects.

Infants 1 to 5 months†

15 mg/kg/dose PO as initial dose, then 10 mg/kg/dose PO at 6 to 12 hours after initial dose. Guidelines recommend for chloroquine-resistant infections and for infections of unknown resistance; may also use for chloroquine-sensitive infections if necessary. For P. vivax or P. ovale infections, add primaquine phosphate.

For the treatment of severe malaria† prior to the availability of IV artesunate. Oral dosage Adults

750 mg PO as initial dose, then 500 mg PO at 6 to 12 hours after initial dose. Only use if other options are not available. Discontinue when IV artesunate therapy is started.

Infants, Children, and Adolescents

15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose, then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose. Only use if other options are not available. Discontinue when IV artesunate therapy is started.

For the treatment of severe malaria† after IV artesunate is completed. Oral dosage Adults

750 mg PO as initial dose, then 500 mg PO at 6 to 12 hours after initial dose. Only use if other options are not available.

Infants, Children, and Adolescents

15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose, then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose. Only use if other options are not available.

For malaria prophylaxis for travel to areas where mefloquine-resistance has not been reported. Oral dosage Adults

250 mg PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area. The FDA-approved labeling recommends starting 1 week prior to entry into endemic area; however, in certain cases (e.g., when a traveler is taking other medications), it may be desirable to start prophylaxis 2 to 3 weeks prior to departure to ensure tolerated.

Children and Adolescents weighing more than 45 kg

250 mg PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area. The FDA-approved labeling recommends starting 1 week prior to entry into endemic area; however, in certain cases (e.g., when a traveler is taking other medications), it may be desirable to start prophylaxis 2 to 3 weeks prior to departure to ensure tolerated.

Children and Adolescents weighing 31 to 45 kg

Three-quarters tablet (187.5 mg) PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area. The FDA-approved labeling recommends starting 1 week prior to entry into endemic area; however, in certain cases (e.g., when a traveler is taking other medications), it may be desirable to start prophylaxis 2 to 3 weeks prior to departure to ensure tolerated.

Children weighing 20 to 30 kg

One-half tablet (125 mg) PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area. The FDA-approved labeling recommends starting 1 week prior to entry into endemic area; however, in certain cases (e.g., when a traveler is taking other medications), it may be desirable to start prophylaxis 2 to 3 weeks prior to departure to ensure tolerated.

Infants† and Children† weighing 10 to 19 kg

One-quarter tablet (62.5 mg) PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area.

Infants† and Children† weighing 9 kg or less

5 mg/kg/dose PO once weekly, starting at least 2 weeks prior to entry into endemic area and continuing for 4 weeks after leaving the area.

Hepatic Impairment

Mefloquine should be used with caution in patients with hepatic disease. The elimination of mefloquine may be prolonged, leading to higher plasma drug concentrations; however, no quantitative recommendations for dose adjustment are available.

Renal Impairment

No dosage adjustment needed.

Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously with other drugs that are associated with QT prolongation, such as mefloquine.
Abrocitinib: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of abrocitinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Acebutolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Adagrasib: (Major) Avoid concomitant use of adagrasib and mefloquine due to the potential for increased mefloquine exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for mefloquine-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Mefloquine is a CYP3A and P-gp substrate, adagrasib is a strong CYP3A and P-gp inhibitor, and both medications have been associated with QT interval prolongation. Coadministration with another strong CYP3A inhibitor increased the exposure of mefloquine by 79%.
Afatinib: (Moderate) If the concomitant use of mefloquine and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of mefloquine. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Alfuzosin: (Moderate) Mefloquine should be used with caution in patients receiving alfuzosin as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner.
Amiodarone: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Inhibitors of these enzymes that also prolong the QT interval, such as amiodarone, may decrease the clearance of mefloquine and increase mefloquine systemic exposure further increasing the risk for QT prolongation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with mefloquine. Amisulpride causes dose- and concentration- dependent QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Amobarbital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Amoxicillin; Clarithromycin; Omeprazole: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as clarithromycin. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Clarithromycin is an inhibitor of these enzymes and may decrease the clearance of mefloquine and further increasing the risk for QT prolongation.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include mefloquine.
Antacids: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, Cmax was increased 42.4% and 20.5%, respectively. The AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Anticonvulsants: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors. Some, but not all anticonvulsants, induce CYP3A4 and may increase the metabolism of mefloquine. Use of enzyme-inducing anticonvulsants can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
Apalutamide: (Moderate) Monitor for decreased efficacy of mefloquine if coadministration with apalutamide is necessary. Mefloquine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased mefloquine exposure by 68%.
Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with mefloquine due to the potential for additive QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Moderate) Use caution if mefloquine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in mefloquine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Mefloquine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of mefloquine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include mefloquine. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Artemether; Lumefantrine: (Major) Mefloquine use immediately prior to lumefantrine treatment may decrease lumefantrine exposure resulting in suboptimal lumefantrine concentrations. Mefloquine causes a reduction in bile production, which is necessary for adequate lumefantrine absorption (see Pharmacokinetics). Sequential oral administration of mefloquine 12 hours prior to initiating the artemether; lumefantrine 6-dose regimen had no statistically significant effects of artemether or on the artemether/dihydroartemisinin (DHA, metabolite of artemether) ratio in 14 healthy volunteers; however, there was a 30% reduction in the Cmax and 40% reduction in the AUC of lumefantrine. Additionally, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as mefloquine, coadministration of such drugs may result in additive QT prolongation and should be avoided.
Asciminib: (Moderate) Use mefloquine with caution if coadministration with asciminib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and asciminib is a weak CYP3A inhibitor.
Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should be avoided in combination with other agents also known to have this effect (e.g., mefloquine). There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Antacids may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
Atazanavir: (Moderate) Mefloquine is metabolized by CYP3A4. Atazanavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Atazanavir; Cobicistat: (Moderate) Mefloquine is metabolized by CYP3A4. Atazanavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure. (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Atenolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Atenolol; Chlorthalidone: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Avacopan: (Moderate) Use mefloquine with caution if coadministration with avacopan is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and avacopan is a weak CYP3A inhibitor.
Azithromycin: (Major) Avoid coadministration of azithromycin with mefloquine due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Barbiturates: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with mefloquine. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. There is evidence that the use of halofantrine after mefloquine also causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Belumosudil: (Moderate) Use mefloquine with caution if coadministration with belumosudil is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and belumosudil is a weak CYP3A inhibitor.
Belzutifan: (Moderate) Use mefloquine with caution if coadministration with belzutifan is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and belzutifan is a weak CYP3A inducer.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking mefloquine. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Additionally, monitor for increased toxicity of mefloquine as concurrent use may also increase the exposure of mefloquine. Berotralstat is a P-gp substrate and P-gp and moderate CYP3A4 inhibitor; mefloquine is a CYP3A4 and P-gp substrate and P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Beta-adrenergic blockers: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Betaxolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving mefloquine. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving mefloquine. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; mefloquine inhibits P-gp.
Bicalutamide: (Moderate) Use mefloquine with caution if coadministration with bicalutamide is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and bicalutamide is a weak CYP3A4 inhibitor.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bisoprolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Bosentan: (Moderate) Mefloquine is metabolized by CYP3A4. Bosentan is an inducer of CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
Brigatinib: (Moderate) Use mefloquine with caution if coadministration with brigatinib is necessary as concurrent use may affect mefloquine exposure which may reduce efficacy or increase mefloquine-related adverse reactions. Mefloquine is a CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Brigatinib is a weak CYP3A4 inducer and a P-gp inhibitor.
Brimonidine; Timolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Butabarbital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Butalbital; Acetaminophen: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Butalbital; Acetaminophen; Caffeine: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Cabotegravir; Rilpivirine: (Moderate) Mefloquine should be used with caution in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Cabozantinib: (Minor) Monitor for an increase in mefloquine-related adverse reactions if coadministration with cabozantinib is necessary; a dose adjustment of mefloquine may be necessary. Mefloquine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Calcium Carbonate: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Calcium Carbonate; Simethicone: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Calcium; Vitamin D: (Moderate) Antacids, H2-blockers, and proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO bid. In both healthy subjects and peptic ulcer patients, mefloquine Cmax was increased 42.4% and 20.5%, respectively, and AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially in patients with a neurological or psychiatric history.
Cannabidiol: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of cannabidiol is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in mefloquine-related adverse reactions if coadministration with capmatinib is necessary. Mefloquine is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor.
Carbamazepine: (Moderate) Carbamazepine induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected carbamazepine anticonvulsant concentrations and loss of seizure control. Monitoring of the carbamazepine serum concentration is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Carbonic anhydrase inhibitors: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Carteolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Carvedilol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Cenobamate: (Moderate) Use mefloquine with caution if coadministration with cenobamate is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and cenobamate is a moderate CYP3A4 inducer.
Ceritinib: (Major) Avoid coadministration of ceritinib with mefloquine if possible due to the risk of QT prolongation; plasma concentrations of mefloquine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Mefloquine is a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been reported to cause concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased mefloquine exposure by 79%.
Chloramphenicol: (Moderate) Mefloquine is metabolized by CYP3A4. Chloramphenicol is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Chloroquine: (Major) Avoid coadministration of chloroquine with mefloquine due to the increased risk of QT prolongation and seizures. These drugs are both analogs of quinine. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Also, both drugs may lower the seizure threshold.
Chlorpromazine: (Major) Concurrent use of chlorpromazine and mefloquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine is associated with QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. However, use of mefloquine alone has not been reported to cause QT prolongation.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data and the potential for torsade de pointes (TdP), use of cisapride with mefloquine is contraindicated.
Citalopram: (Major) Concurrent use of citalopram and mefloquine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. There is evidence that the use of halofantrine after mefloquine also causes significant lengthening of the QTc interval. However, use of mefloquine alone has not been reported to cause QT prolongation.
Clarithromycin: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as clarithromycin. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Clarithromycin is an inhibitor of these enzymes and may decrease the clearance of mefloquine and further increasing the risk for QT prolongation.
Clofazimine: (Moderate) Concomitant use of clofazimine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clonazepam: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Clozapine: (Moderate) Mefloquine should be used with caution in patients receiving clozapine as concurrent use may increase the risk of QT prolongation. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Cobicistat: (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Cobimetinib: (Minor) If concurrent use of cobimetinib and mefloquine is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects. Cobimetinib is a P-glycoprotein (P-gp) substrate, and mefloquine is a P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib (960 mg twice daily), did not result in clinically relevant pharmacokinetic drug interactions.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Colchicine: (Major) Avoid concomitant use of colchicine and mefloquine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and mefloquine is a P-gp inhibitor.
Conivaptan: (Moderate) Use mefloquine with caution if coadministration with conivaptan is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and P-gp and conivaptan is a moderate CYP3A and P-gp inhibitor.
Crizotinib: (Major) Avoid coadministration of crizotinib with mefloquine due to the risk of QT prolongation; exposure to mefloquine may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; also monitor for an increase in mefloquine-related adverse reactions. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib is a moderate CYP3A inhibitor that has been associated with concentration-dependent QT prolongation. Mefloquine is a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Cyclosporine: (Moderate) Mefloquine is metabolized by CYP3A4. Cyclosporine is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Dabigatran: (Moderate) Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with mefloquine, a P-gp inhibitor. Patients should be monitored for increased adverse effects of dabigatran. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE), or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with P-gp inhibitors like mefloquine in patients with CrCl less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCl less than 30 mL/minute), avoid coadministration with mefloquine, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran.
Daclatasvir: (Moderate) Systemic exposure of mefloquine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of mefloquine; monitor patients for potential adverse effects.
Danazol: (Moderate) Mefloquine is metabolized by CYP3A4. Danazol is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Darunavir: (Moderate) Mefloquine is metabolized by CYP3A4. Darunavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Darunavir; Cobicistat: (Moderate) Mefloquine is metabolized by CYP3A4. Darunavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure. (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Mefloquine is metabolized by CYP3A4. Darunavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure. (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Dasatinib: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering dasatinib with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval).
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Delavirdine: (Moderate) Mefloquine is metabolized by CYP3A4. Delavirdine is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mefloquine. Halogenated anesthetics can prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Deutetrabenazine: (Minor) Use mefloquine with caution in patients receiving deutetrabenazine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexamethasone: (Moderate) Use mefloquine with caution if coadministration with dexamethasone is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and dexamethasone is a weak CYP3A inducer.
Dexmedetomidine: (Minor) QT/QTc prolongation can occur with concomitant use of dexmedetomidine and mefloquine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Contraindicated) The use of mefloquine is contraindicated in patients receiving quinidine or quinidine containing drugs, including dextromethorphan; quinidine. Quinidine is a Class IA antiarrhythmic agent and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP); using these drugs together could increase the risk of TdP.
Diazepam: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Diltiazem: (Moderate) Mefloquine is metabolized by CYP3A4. Diltiazem is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Disopyramide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering disopyramide with mefloquine. Disopyramide administration is associated with QT prolongation and TdP. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Dofetilide: (Major) Coadministration of dofetilide and mefloquine is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with mefloquine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Mefloquine should be used with caution in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with mefloquine as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with mefloquine as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Dorzolamide; Timolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Dronedarone: (Contraindicated) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data and the potential for torsade de pointes (TdP), concurrent use of mefloquine and dronedarone is contraindicated. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include mefloquine.
Edoxaban: (Moderate) Coadministration of edoxaban and mefloquine may result in increased concentrations of edoxaban. Edoxaban is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use of mefloquine; monitor for increased adverse effects of edoxaban. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with mefloquine. QTc prolongation has been observed with the use of efavirenz. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. In addition, efavirenz may induce the CYP3A4 metabolism of mefloquine; potentially reducing the efficacy of mefloquine. Concomitant administration may increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Consider alternatives to efavirenz when coadministering with mefloquine. QTc prolongation has been observed with the use of efavirenz. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. In addition, efavirenz may induce the CYP3A4 metabolism of mefloquine; potentially reducing the efficacy of mefloquine. Concomitant administration may increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Consider alternatives to efavirenz when coadministering with mefloquine. QTc prolongation has been observed with the use of efavirenz. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. In addition, efavirenz may induce the CYP3A4 metabolism of mefloquine; potentially reducing the efficacy of mefloquine. Concomitant administration may increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Elacestrant: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of elacestrant is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elbasvir; Grazoprevir: (Moderate) Administering mefloquine with elbasvir; grazoprevir may result in elevated mefloquine plasma concentrations. Mefloquine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Major) Coadminister mefloquine and eliglustat cautiously with close monitoring; there may be an increased risk of QT prolongation and/or mefloquine-associated adverse effects. Although mefloquine alone has not been reported to cause QT prolongation, there is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Due to the lack of clinical data and the potential for torsade de pointes (TdP), mefloquine should be used with caution in patients receiving other drugs that prolong the QT interval, such as eliglustat. In addition, coadministration of mefloquine, a P-glycoprotein (P-gp) substrate, and eliglustat, a P-gp inhibitor, may result in increased concentrations of mefloquine, further increasing the risk of adverse effects (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or neurophsychiatric effects, is recommended during coadministration. Cobicistat is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Mefloquine should be used with caution in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions. (Moderate) Mefloquine should be used with caution in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrent

ly with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Encorafenib: (Major) Avoid coadministration of encorafenib and mefloquine due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Entrectinib: (Major) Avoid coadministration of entrectinib with mefloquine due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Enzalutamide: (Moderate) Monitor for decreased efficacy of mefloquine if coadministration with enzalutamide is necessary. Mefloquine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased mefloquine exposure by 68%.
Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as mefloquine, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with mefloquine. Erythromycin is associated with prolongation of the QT interval and TdP. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp) and erythromycin is a CYP3A4 and P-gp inhibitor. Coadministration may decrease the clearance of mefloquine and increase mefloquine systemic exposure further increasing the risk for QT prolongation.
Escitalopram: (Moderate) Concomitant use of escitalopram and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Esmolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Ethosuximide: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor. Mefloquine is a CYP3A4 substrate and PGP substrate/inhibitor. Caution is warranted if these drugs are coadministered.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with mefloquine is necessary; also, monitor for mefloquine-related adverse events. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and a weak CYP3A4 inhibitor. Mefloquine is a P-gp inhibitor and a CYP3A4 substrate. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations. Concurrent use with CYP3A4 inhibitors may increase mefloquine exposure.
Felbamate: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Patients may also experience additive sedation or dizziness, or changes in moods and behaviors.
Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with mefloquine as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Flecainide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering flecainide with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or TdP; flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Causality for TdP has not been established for flecainide.
Fluconazole: (Contraindicated) Due to the risk of life-threatening arrhythmias such as torsade de pointes (TdP), coadministration of fluconazole with drugs that both prolong the QT interval and are CYP3A4 substrates, like mefloquine, is contraindicated. Fluconazole has been associated with QT prolongation and rare cases of TdP. Additonally, fluconazole is an inhibitor of CYP3A4. Coadministration may result in elevated plasma concentrations of mefloquine, causing an increased risk for adverse events such as QT prolongation.
Fluoxetine: (Moderate) Use fluoxetine with caution in combination with mefloquine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Additionally, fluoxetine may increase the systemic exposure of mefloquine due to CYP3A4 inhibition and increase the potential for mefloquine-related adverse reactions. QT prolongation and TdP have been reported in patients treated with fluoxetine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Fluphenazine: (Minor) Mefloquine should be used with caution in patients receiving fluphenazine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluvoxamine: (Moderate) Mefloquine should be used with caution in patients receiving fluvoxamine as concurrent use may increase the risk of QT prolongation. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Fosamprenavir: (Moderate) Use mefloquine with caution if coadministration with fosamprenavir is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and fosamprenavir is a moderate CYP3A inhibitor.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as mefloquine. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fostamatinib: (Moderate) Monitor for mefloquine toxicities that may require mefloquine dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a P-gp substrate may increase the concentration of the P-gp substrate. Fostamatinib is a P-gp inhibitor; mefloquine is a substrate for P-gp. Coadministration of fostamatinib with another P-gp substrate increased the P-gp substrate AUC by 37% and Cmax by 70%.
Fostemsavir: (Moderate) Mefloquine should be used with caution in patients receiving fostemsavir due to the potential for QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Futibatinib: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of futibatinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and futibatinib is a P-gp inhibitor.
Gabapentin: (Moderate) It is not clear if mefloquine will alter the activity of gabapentin, as gabapentin is not appreciably metabolized nor does it typically interfere with the metabolism of other medications. Coadministration of mefloquine and certain anticonvulsants has been reported to result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Gabapentin concentrations are not usually monitored. Mefloquine may additionally cause CNS side effects that may cause seizures or alter moods or behaviors.
Gemifloxacin: (Moderate) Mefloquine should be used with caution in patients receiving gemifloxacin as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and mefloquine together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Gilteritinib: (Moderate) Monitor for additive QT prolongation if concurrent use of gilteritinib and mefloquine is necessary. Gilteritinib has been associated with QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Monitor for an increase in mefloquine-related adverse effects if concomitant use of gilteritinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Glasdegib: (Major) Avoid coadministration of glasdegib with mefloquine due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and mefloquine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Glecaprevir and mefloquine are both substrates and inhibitors of P-glycoprotein (P-gp). (Moderate) Caution is advised with the coadministration of pibrentasvir and mefloquine as coadministration may increase serum concentrations of both drugs and increase the risk of adverse effects. Pibrentasvir and mefloquine are both substrates and inhibitors of P-glycoprotein (P-gp).
Glycerol Phenylbutyrate: (Moderate) Use mefloquine with caution if coadministration with glycerol phenylbutyrate is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and glycerol phenylbutyrate is a weak CYP3A inducer.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Granisetron: (Moderate) Mefloquine should be used with caution in patients receiving granisetron due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Grapefruit juice: (Moderate) Mefloquine is metabolized by CYP3A4. Inhibitors of this enzyme (e.g., grapefruit juice) may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
H2-blockers: (Moderate) H2-blockers may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history. In a small study involving 6 healthy subjects and 6 peptic ulcer patients, cimetidine increased the Cmax and AUC of mefloquine. In the study, the pharmacokinetics of mefloquine were determined after receiving a single oral mefloquine 500 mg dose alone and after 3-days of cimetidine 400 mg PO twice daily. In both healthy subjects and peptic ulcer patients, Cmax was increased 42.4% and 20.5%, respectively. The AUC was increased by 37.5% in both groups. Elimination half-life, total clearance, and volume of distribution were not significantly affected. An increase in adverse reactions was not noted.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mefloquine. Halogenated anesthetics can prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Haloperidol: (Moderate) Mefloquine should be used with caution in patients receiving haloperidol as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Hydantoins: (Moderate) The hydantoin anticonvulsants induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and hydantoin anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the hydantoin (e.g., phenytoin) anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine with mefloquine due to an increased risk of QT prolongation and seizures. These drugs are both analogs of quinine. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Hydroxychloroquine prolongs the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Also, both drugs may lower the seizure threshold.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP should be used cautiously with mefloquine. Ibutilide administration can cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with mefloquine, a CYP3A substrate, as mefloquine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as mefloquine.
Imatinib: (Moderate) Mefloquine is metabolized by CYP3A4. Imatinib is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Indinavir: (Moderate) Mefloquine is metabolized by CYP3A4. Indinavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with mefloquine due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with mefloquine may result in increased serum concentrations of mefloquine. Mefloquine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Clinical monitoring for adverse effects, such as GI or neuropsychiatric effects, is recommended during coadministration.
Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mefloquine. Halogenated anesthetics can prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Isoniazid, INH: (Moderate) Mefloquine is metabolized by CYP3A4. Isoniazid is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Mefloquine is metabolized by CYP3A4. Isoniazid is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure. (Moderate) Mefloquine is metabolized by CYP3A4. Rifampin, an inducer of CYP3A4, has been reported to increase the metabolism of mefloquine and reduce mefloquine plasma concentrations in healthy volunteers (decreased mean Cmax by 19% and mean AUC by 68%). Rifampin induces both hepatic and gut wall CYP3A4 and increases the formation of the carboxylic acid mefloquine metabolite. Concomitant administration of rifampin and mefloquine can reduce the clinical efficacy of mefloquine and increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Isoniazid, INH; Rifampin: (Moderate) Mefloquine is metabolized by CYP3A4. Isoniazid is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure. (Moderate) Mefloquine is metabolized by CYP3A4. Rifampin, an inducer of CYP3A4, has been reported to increase the metabolism of mefloquine and reduce mefloquine plasma concentrations in healthy volunteers (decreased mean Cmax by 19% and mean AUC by 68%). Rifampin induces both hepatic and gut wall CYP3A4 and increases the formation of the carboxylic acid mefloquine metabolite. Concomitant administration of rifampin and mefloquine can reduce the clinical efficacy of mefloquine and increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Itraconazole: (Major) Caution is advised when administering itraconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as mefloquine. Both mefloquine and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with mefloquine (a CYP3A4 substrate) may result in elevated mefloquine plasma concentrations and an increased risk for adverse events, including QT prolongation. If itraconazole therapy is stopped, it may be prudent to continue close monitoring for up to 2 weeks after discontinuing itraconazole. Once discontinued, the plasma concentration of itraconazole decreases to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with mefloquine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and mefloquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ketoconazole should not be administered within 15 weeks of the last dose of mefloquine. Concomitant use may also increase the exposure of mefloquine, further increasing the risk for adverse effects. Mefloquine is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of mefloquine by 79%.
Labetalol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as clarithromycin. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Clarithromycin is an inhibitor of these enzymes and may decrease the clearance of mefloquine and further increasing the risk for QT prolongation.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation and torsade de pointes (TdP) when coadministering lapatinib with mefloquine. Also, monitor for treatment-related adverse reactions. Lapatinib is a P-glycoprotein (P-gp) substrate/inhibitor as well as a weak CYP3A4 inhibitor, that has been associated with concentration-dependent QT prolongation. Ventricular arrhythmias and TdP have been reported in postmarketing experience with lapatinib. Mefloquine is also a P-gp substrate/inhibitor, as well as a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
Lasmiditan: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of lasmiditan is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of adverse reactions is advised with concomitant administration of mefloquine and ledipasvir; sofosbuvir. Both ledipasvir and mefloquine are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp); sofosbuvir is a P-gp substrate. Taking these drugs together may increase plasma concentrations of all three drugs. According to the manufacturer, no dosage adjustments are required when ledipasvir; sofosbuvir is administered concurrently with P-gp inhibitors.
Lefamulin: (Major) Avoid coadministration of lefamulin with mefloquine as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG during treatment; additionally, monitor for lefamulin-related adverse effects if oral lefamulin is administered. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Mefloquine is a P-gp inhibitor. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Lenacapavir: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of lenacapavir is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a CYP3A and P-gp substrate and lenacapavir is a moderate CYP3A and P-gp inhibitor.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with mefloquine due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Letermovir: (Moderate) An increase in the plasma concentration of mefloquine may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Mefloquine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. In a drug interaction study, concurrent administration of mefloquine with a strong CYP3A4 inhibitor resulted in an increase in the mean maximum plasma concentration and exposure of mefloquine by 64% and 79%, respectively; in addition, the mean elimination half-life increased from 322 hours to 448 hours.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Levobunolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and mefloquine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Ketoconazole should not be administered within 15 weeks of the last dose of mefloquine. Concomitant use may also increase the exposure of mefloquine, further increasing the risk for adverse effects. Mefloquine is a CYP3A4 substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of mefloquine by 79%.
Lithium: (Moderate) Concomitant use of lithium and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with mefloquine due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Lonafarnib: (Moderate) Use mefloquine with caution if coadministration with lonafarnib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse reactions. Mefloquine is a substrate of CYP3A4 and P-gp and lonafarnib is a P-gp inhibitor and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of mefloquine by 79%.
Loperamide: (Moderate) Concomitant use of loperamide and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with mefloquine due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Lopinavir is associated with QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as GI or neuropsychiatric effects, is recommended during coadministration. Ritonavir is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Lorazepam: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Lorlatinib: (Moderate) Use mefloquine with caution if coadministration with lorlatinib is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and lorlatinib is a moderate CYP3A4 inducer.
Lumacaftor; Ivacaftor: (Moderate) Lumacaftor; ivacaftor may reduce the efficacy of mefloquine by decreasing its systemic exposure; caution and close monitoring are advised if these drugs are used together. Mefloquine is a substrate of CYP3A (in vivo) and P-glycoprotein (P-gp) (in vitro). Lumacaftor is a strong CYP3A inducer; in vitro data also suggest lumacaftor; ivacaftor may induce and/or inhibit P-gp. Although induction of mefloquine through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Coadministration of mefloquine and rifampin , another strong CYP3A inducer, resulted in a 19% and 68% decrease in mean Cmax and AUC, respectively; mefloquine half-life decreased from 305 hours to 113 hours.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as mefloquine. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Maprotiline: (Moderate) Mefloquine should be used with caution in patients receiving maprotiline as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Maraviroc: (Moderate) Use caution and closely monitor for increased adverse effects with the coadministration of maraviroc and mefloquine as increased maraviroc concentrations may occur. Maraviroc is a substrate of P-glycoprotein (P-gp); mefloquine is an inhibitor of P-gp. The effects of P-gp on the concentrations of maraviroc are unknown, although an increase in concentrations and thus, toxicity, are possible.
Maribavir: (Moderate) Use mefloquine with caution if coadministration with maribavir is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and P-gp; maribavir is a P-gp and weak CYP3A inhibitor.
Mavacamten: (Moderate) Use mefloquine with caution if coadministration with mavacamten is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Methadone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering methadone with mefloquine. The need to coadminister these drugs should be done with extreme caution and a careful assessment of treatment risks versus benefits. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). In addition, methadone is a substrate for P-glycoprotein (P-gp), while mefloquine is a P-gp substrate/inhibitor. Coadministration may result in increased serum concentrations of methadone.
Methohexital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Methsuximide: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Metoprolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Metronidazole: (Moderate) Concomitant use of metronidazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) The concomitant use of midostaurin and mefloquine may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Mifepristone: (Major) Concurrent use may increase the serum concentrations of mefloquine, further increasing the risk for mefloquine-related adverse effects, including dizziness, changes in moods or behaviors, vision changes, and QT prolongation. Mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Mifepristone is a potent and prolonged inhibitor of CYP3A4 and P-gp. In addition, mifepristone may cause QT prolongation. Based on the long terminal half-life of mifepristone after reaching steady state, at least 2 weeks should elapse after cessation of mifepristone, when used for chronic conditions, before initiating or increasing the dose of any interacting concomitant medication. Discontinuation or dose reduction of mefloquine may be necessary if mifepristone must be used.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mitapivat: (Moderate) Use mefloquine with caution and monitor for mefloquine-related adverse effects if coadministration with mitapivat is necessary as concurrent use may decrease mefloquine exposure and efficacy or increase mefloquine exposure and risk for adverse reactions. Mefloquine is a CYP3A and P-gp substrate and mitapivat is a weak CYP3A inducer and P-gp inhibitor.
Mitotane: (Major) Use caution if mitotane and mefloquine are used concomitantly, and monitor for decreased efficacy of mefloquine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and mefloquine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of mefloquine. Another strong CYP3A inducer, rifampin, has been reported to increase the metabolism of mefloquine and reduce mefloquine plasma concentrations in healthy volunteers (decreased mean Cmax by 19% and mean AUC by 68%).
Mobocertinib: (Major) Concomitant use of mobocertinib and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also decrease mefloquine exposure resulting in decreased efficacy. Mefloquine is a CYP3A substrate and mobocertinib is a weak CYP3A inducer.
Moxifloxacin: (Major) Concurrent use of mefloquine and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Nadolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with mefloquine. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a P-gp substrate; mefloquine is a moderate P-gp inhibitor in vitro.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and mefloquine. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and mefloquine is a P-gp inhibitor.
Nebivolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Nebivolol; Valsartan: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Nefazodone: (Moderate) Mefloquine is metabolized by CYP3A4. Nefazodone is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Nelfinavir: (Moderate) Mefloquine is metabolized by CYP3A4. Nelfinavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Neratinib: (Moderate) Use mefloquine with caution if coadministration with neratinib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Nevirapine: (Moderate) Use mefloquine with caution if coadministration with nevirapine is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and nevirapine is a weak CYP3A inducer.
Nicardipine: (Moderate) Mefloquine is metabolized by CYP3A4. Nicardipine is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with mefloquine due to an increased risk for QT prolongation. Systemic exposure of mefloquine may also be increased resulting in increase in treatment-related adverse reactions. Nilotinib is a moderate CYP3A4 inhibitor; sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Mefloquine is a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Nirmatrelvir; Ritonavir: (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as GI or neuropsychiatric effects, is recommended during coadministration. Ritonavir is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Odevixibat: (Moderate) Use mefloquine with caution if coadministration with odevixibat is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and odevixibat is a weak CYP3A inducer.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Mefloquine should be used with caution in patients receiving olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Olanzapine; Fluoxetine: (Moderate) Mefloquine should be used with caution in patients receiving olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. (Moderate) Use fluoxetine with caution in combination with mefloquine. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Additionally, fluoxetine may increase the systemic exposure of mefloquine due to CYP3A4 inhibition and increase the potential for mefloquine-related adverse reactions. QT prolongation and TdP have been reported in patients treated with fluoxetine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Olanzapine; Samidorphan: (Moderate) Mefloquine should be used with caution in patients receiving olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. There is also evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Olutasidenib: (Moderate) Use mefloquine with caution if coadministration with olutasidenib is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and olutasidenib is a weak CYP3A inducer.
Omaveloxolone: (Moderate) Use mefloquine with caution if coadministration with omaveloxolone is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and omaveloxolone is a weak CYP3A inducer.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Mefloquine is metabolized by CYP3A4. Rifabutin is an inducer of CYP3A4, and may increase the metabolism of mefloquine and reduce mefloquine plasma concentrations if coadministered.
Omeprazole; Sodium Bicarbonate: (Moderate) Antacids may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
Ondansetron: (Major) Concomitant use of ondansetron and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Oritavancin: (Moderate) Mefloquine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of mefloquine may be reduced if these drugs are administered concurrently.
Osilodrostat: (Moderate) Use mefloquine with caution if coadministration with osilodrostat is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and osilodrostat is a weak CYP3A4 inhibitor.
Osimertinib: (Major) Avoid coadministration of mefloquine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for increased mefloquine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Additionally, mefloquine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of mefloquine with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Oxcarbazepine: (Moderate) Oxcarbazepine induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected oxcarbazepine anticonvulsant concentrations and loss of seizure control. Monitoring of the oxcarbazepine serum concentration is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking mefloquine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Mefloquine exposure may also increase, increasing the risk of adverse reactions. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Mefloquine is a CYP3A4 and P-gp substrate; pacritinib is a weak CYP3A4 inhibitor and a P-gp inhibitor.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients who require drugs that prolong the QT interval. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT p rolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include mefloquine.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with mefloquine as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Pazopanib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering pazopanib with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as pazopanib. In addition, mefloquine is metabolized by CYP3A4 and is a P-gp inhibitor. Pazopanib inhibits CYP3A4 and is a substrate for P-gp. Concurrent use may increase the serum concentrations of mefloquine and/or pazopanib, further increasing the risk for QT prolongation.
Penicillamine: (Major) Do not use penicillamine concurrently with antimalarials due to an increased risk of severe hematologic and renal adverse reactions.
Pentamidine: (Major) Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as pentamidine. Intravenous pentamidine has been associated with QT prolongation and this risk may be increased with other drugs that might prolong the QT interval.
Pentobarbital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Perphenazine: (Minor) Mefloquine should be used with caution in patients receiving perphenazine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Mefloquine should be used with caution in patients receiving perphenazine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Pexidartinib: (Moderate) Use mefloquine with caution if coadministration with pexidartinib is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and pexidartinib is a moderate CYP3A4 inducer.
Phenobarbital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Phentermine; Topiramate: (Moderate) Topiramate induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Use may reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of drug concentrations (if therapeutic monitoring is advised for the anticonvulsant) is recommended. When topiramate is used for other conditions, monitor for clinical efficacy. Mefloquine may additionally cause CNS side effects that may cause seizures or alter moods or behaviors.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of mefloquine with pimozide is contraindicated.
Pindolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Pirtobrutinib: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of pirtobrutinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a CYP3A and P-gp substrate and pirtobrutinib is a P-gp and weak CYP3A inhibitor.
Pitolisant: (Minor) Coadministration of pitolisant and mefloquine may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval; however, mefloquine alone has not been reported to cause QT prolongation.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking mefloquine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Posaconazole: (Contraindicated) The concurrent use of posaconazole and mefloquine is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of mefloquine, Further, both posaconazole and mefloquine are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This complex interaction may ultimately result in altered plasma concentrations of both posaconazole and mefloquine. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as mefloquine.
Pralsetinib: (Major) Avoid concomitant use of mefloquine with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Pretomanid: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of pretomanid is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and pretomanid is a P-gp inhibitor.
Primaquine: (Moderate) Mefloquine should be used with caution in patients receiving primaquine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Primaquine is associated with QT prolongation.
Primidone: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and mefloquine due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and mefloquine is a P-gp inhibitor.
Procainamide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering procainamide with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) Mefloquine should be used with caution in patients receiving prochlorperazine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with mefloquine. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as propafenone. In addition, mefloquine is metabolized by P-glycoprotein (P-gp) and propafenone is a P-gp inhibitor. Coadministration may increase mefloquine systemic exposure and further increasing the risk for QT prolongation.
Propranolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Proton pump inhibitors: (Moderate) Proton pump inhibitors (PPIs) may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
Quetiapine: (Major) Concomitant use of quetiapine and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Contraindicated) The use of mefloquine is contraindicated in patients receiving quinidine or quinidine containing drugs, including dextromethorphan; quinidine. Quinidine is a Class IA antiarrhythmic agent and is associated with a well-established risk of QT prolongation and torsade de pointes (TdP); using these drugs together could increase the risk of TdP.
Quinine: (Contraindicated) Due to the risk for QT prolongation and seizures, do not administer mefloquine until at least 12 hours after quinine discontinuation have passed. Both drugs have been associated with QT prolongation. In addition, quinine is an inhibitor of CYP3A4, and mefloquine is a CYP3A4 substrate. Coadministration has resulted in a 22% increase in mefloquine systemic exposure, causing an increased risk for adverse events, such as QT prolongation and seizures.
Quizartinib: (Major) Concomitant use of quizartinib and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Rabies Vaccine: (Major) If administered concurrently, antimalarials can impair the immunologic response to the rabies vaccine, thereby, decreasing its protective effect. If possible, administration of antimalarials should be avoided during use of the rabies vaccine for postexposure prophylaxis. When antimalarials must be administered to persons also receiving the rabies vaccine for postexposure prophylaxis, a serum rabies antibody titer should be obtained on day 14 (day of the 4th vaccination) to ensure an acceptable antibody response has been induced.
Ranolazine: (Moderate) Mefloquine should be used with caution in patients receiving ranolazine; exposure to both drugs may also be increased. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp) and is a P-gp inhibitor. Ranolazine is an inhibitor of CYP3A4 and P-gp and is a substrate for P-gp. Concurrent use may increase the serum concentrations of mefloquine and/or ranolazine, further increasing the risk for QT prolongation.
Relugolix: (Major) Avoid concomitant use of relugolix and oral mefloquine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer mefloquine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor in vitro, although the clinical relevance of P-gp interactions is unknown. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral mefloquine. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer mefloquine at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor in vitro, although the clinical relevance of P-gp interactions is unknown. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Ribociclib: (Major) Avoid coadministration of ribociclib with mefloquine due to an increased risk for QT prolongation. Systemic exposure of mefloquine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Mefloquine is a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with mefloquine due to an increased risk for QT prolongation. Systemic exposure of mefloquine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Mefloquine is a CYP3A4 substrate. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Rifabutin: (Moderate) Mefloquine is metabolized by CYP3A4. Rifabutin is an inducer of CYP3A4, and may increase the metabolism of mefloquine and reduce mefloquine plasma concentrations if coadministered.
Rifampin: (Moderate) Mefloquine is metabolized by CYP3A4. Rifampin, an inducer of CYP3A4, has been reported to increase the metabolism of mefloquine and reduce mefloquine plasma concentrations in healthy volunteers (decreased mean Cmax by 19% and mean AUC by 68%). Rifampin induces both hepatic and gut wall CYP3A4 and increases the formation of the carboxylic acid mefloquine metabolite. Concomitant administration of rifampin and mefloquine can reduce the clinical efficacy of mefloquine and increase the risk of Plasmodium falciparum resistance during treatment of malaria.
Rifapentine: (Moderate) Use mefloquine with caution if coadministration with rifapentine is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased mefloquine exposure by 68%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mefloquine is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and mefloquine is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Moderate) Mefloquine should be used with caution in patients receiving rilpivirine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with mefloquine; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and mefloquine is a P-gp inhibitor.
Risperidone: (Moderate) Use risperidone and mefloquine together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Ritlecitinib: (Moderate) Use mefloquine with caution if coadministration with ritlecitinib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Moderate) The plasma concentrations of mefloquine may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as GI or neuropsychiatric effects, is recommended during coadministration. Ritonavir is a strong inhibitor of CYP3A4 and P-glycoprotein (P-gp) inhibitor, while mefloquine is a CYP3A4 and P-gp substrate.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and mefloquine may result in increases in rivaroxaban exposure and may increase bleeding risk. Mefloquine is an inhibitor of P-gp, and rivaroxaban is a substrate of P-gp. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with mefloquine as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Rucaparib: (Moderate) Use mefloquine with caution if coadministration with rucaparib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and rucaparib is a weak CYP3A4 inhibitor.
Saquinavir: (Contraindicated) Concurrent use of saquinavir boosted with ritonavir and mefloquine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of mefloquine. Further, both saquinavir and mefloquine are substrates and inhibitors of the drug efflux protein, P-glycoprotein. This complex interaction may ultimately result in altered plasma concentrations of both mefloquine and saquinavir. Additionally, saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; avoid use with other drugs that may prolong the QT or PR interval, such as mefloquine.
Secobarbital: (Moderate) The barbiturates induce CYP3A4 and may increase the metabolism of mefloquine if coadministered. Concomitant administration can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and barbiturates that are used as anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with mefloquine is necessary due to the risk of additive QT prolongation; mefloquine exposure may also be increased. Mefloquine is a CYP3A4 and P-gp substrate. Selpercatinib is a P-gp inhibitor and a weak CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Sertraline: (Moderate) Concomitant use of sertraline and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with mefloquine. Halogenated anesthetics can prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving mefloquine due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of mefloquine. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and mefloquine is a P-gp inhibitor.
Sodium Bicarbonate: (Moderate) Antacids may increase plasma concentrations of mefloquine. Patients on chronic mefloquine therapy might be at increased risk of adverse reactions, especially patients with a neurological or psychiatric history.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for decreased efficacy and/or increased mefloquine-related adverse effects if concomitant use of taurursodiol is necessary. Concomitant use may alter mefloquine exposure. Mefloquine is a P-gp and CYP3A substrate and taurursodiol is a weak CYP3A inducer and P-gp inhibitor. The net effect on mefloquine exposure is unknown.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with mefloquine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of mefloquine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. (Moderate) Use caution when administering velpatasvir with mefloquine. Taking these medications together may increase the plasma concentrations of both drugs, potentially resulting in adverse events. Both drugs are substrates and inhibitors of the drug transporter P-glycoprotein (P-gp).
Solifenacin: (Moderate) Mefloquine should be used with caution in patients receiving solifenacin as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with mefloquine due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Sorafenib is associated with QTc prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Sotalol: (Moderate) Concomitant use of sotalol and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sotorasib: (Moderate) Monitor for an increase in mefloquine-related adverse effects or decrease in efficacy if concomitant use of sotorasib is necessary. Concomitant use may alter mefloquine exposure. Mefloquine is a CYP3A4 and P-gp substrate; sotorasib is a moderate CYP3A4 inducer and P-gp inhibitor.
Sparsentan: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of sparsentan is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and sparsentan is a P-gp inhibitor.
Spironolactone: (Moderate) Use mefloquine with caution if coadministration with spironolactone is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and spironolactone is a weak CYP3A4 inhibitor.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Use mefloquine with caution if coadministration with spironolactone is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and spironolactone is a weak CYP3A4 inhibitor.
St. John's Wort, Hypericum perforatum: (Moderate) Mefloquine is metabolized by CYP3A4. St. John's Wort is an inducer of CYP3A4, and may increase the metabolism of mefloquine and reduce mefloquine plasma concentrations if coadministered.
Succinimides: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with mefloquine as concurrent use may increase the risk of QT prolongation. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with mefloquine is necessary. Talazoparib is a P-gp substrate and mefloquine is a P-gp inhibitor.
Tazemetostat: (Moderate) Use mefloquine with caution if coadministration with tazemetostat is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and tazemetostat is a weak CYP3A4 inducer.
Telavancin: (Moderate) Mefloquine should be used with caution in patients receiving telavancin as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. There is also evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Telotristat Ethyl: (Moderate) Use mefloquine with caution if coadministration with telotristat is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A4 substrate and telotristat is a weak CYP3A4 inducer.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus- and mefloquine-related adverse reactions if coadministration is necessary. Both drugs are P-glycoprotein (P-gp) substrates inhibitors. Concomitant use is likely to lead to increased concentrations of temsirolimus and mefloquine.
Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering tenofovir, PMPA, a P-glycoprotein (P-gp) substrate, concurrently with inhibitors of P-gp, such as mefloquine. Coadministration may result in increased absorption of tenofovir. Monitor for tenofovir-associated adverse reactions.
Tepotinib: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of tepotinib is necessary. Concomitant use may increase mefloquine exposure. Mefloquine is a P-gp substrate and tepotinib is a P-gp inhibitor.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval. Caution is advisable during concurrent use of other agents associated with a possible risk for QT prolongation and TdP including mefloquine. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with mefloquine which, when combined with thioridazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension.
Ticagrelor: (Moderate) Coadministration of ticagrelor and mefloquine may result in increased exposure to ticagrelor which may increase the bleeding risk. Ticagrelor is a P-glycoprotein (P-gp) substrate and mefloquine is a P-gp inhibitor. Based on drug information data with cyclosporine, no dose adjustment is recommended by the manufacturer of ticagrelor. Use combination with caution and monitor for evidence of bleeding.
Timolol: (Major) Concurrent use of mefloquine and beta blockers can result in ECG abnormalities or cardiac arrest.
Tipranavir: (Moderate) Mefloquine is metabolized by CYP3A4. Tipranavir is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Tolterodine: (Moderate) Mefloquine should be used with caution in patients receiving tolterodine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Topiramate: (Moderate) Topiramate induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Use may reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of drug concentrations (if therapeutic monitoring is advised for the anticonvulsant) is recommended. When topiramate is used for other conditions, monitor for clinical efficacy. Mefloquine may additionally cause CNS side effects that may cause seizures or alter moods or behaviors.
Topotecan: (Major) Avoid coadministration of mefloquine with oral topotecan due to increased topotecan exposure; mefloquine may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and mefloquine is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Avoid coadministration of mefloquine with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Trandolapril; Verapamil: (Moderate) Mefloquine is metabolized by CYP3A4. Verapamil is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Trazodone: (Major) Concomitant use of trazodone and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Mefloquine should be used with caution in patients receiving trifluoperazine as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving mefloquine as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation.
Trofinetide: (Moderate) Use mefloquine with caution if coadministration with trofinetide is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and trofinetide is a weak CYP3A inhibitor.
Tucatinib: (Moderate) Use mefloquine with caution if coadministration with tucatinib is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse reactions. Mefloquine is a substrate of CYP3A4 and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of mefloquine by 79%.
Typhoid Vaccine: (Moderate) When antimalarial medications are administered concurrently with oral live typhoid vaccine, attenuation of immunization cannot be excluded. Therefore, the manufacturer of mefloquine recommends waiting at least 3 days after use of the vaccine before administering the first dose of mefloquine. However, in a study to determine the effects of antimalarials on the immune response to the vaccine, 30 individuals were administered mefloquine (250 mg weekly) concurrently with the oral typhoid vaccine. Concomitant administration did not significantly reduce the immune response. Based on these findings, the manufacturer of the vaccine allows for simulaneous administration; however, caution is advised whenever these medications are administered concurrently.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with mefloquine. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; mefloquine is a P-gp inhibitor.
Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of mefloquine and valrproic acid or related anticonvulsants (valproate, divalproex) may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the valproic acid serum concentration is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors.
Vandetanib: (Major) Avoid coadministration of vandetanib with mefloquine due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
Vardenafil: (Moderate) Concomitant use of vardenafil and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering vemurafenib with mefloquine. If these drugs must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. There is evidence that the use of halofantrine after mefloquine causes significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as vemurafenib. Also, mefloquine is a CYP3A4 substrate and P-glycoprotein (P-gp) substrate/inhibitor, while vemurafenib is a CYP3A4 substrate/inducer and a P-gp substrate/inhibitor. Concomitant use may increase vemurafenib concentrations and may alter mefloquine concentrations. Monitor patients for toxicity and efficacy.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with mefloquine due to the potential for increased venetoclax exposure. Additionally, mefloquine exposure may be increased. Resume the original venetoclax dose 2 to 3 days after discontinuation of mefloquine. Both venetoclax and mefloquine are P-glycoprotein (P-gp) substrates and inhibitors. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Verapamil: (Moderate) Mefloquine is metabolized by CYP3A4. Verapamil is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Viloxazine: (Moderate) Use mefloquine with caution if coadministration with viloxazine is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and viloxazine is a weak CYP3A4 inhibitor.
Vincristine Liposomal: (Major) Mefloquine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Vincristine: (Major) Mefloquine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Voclosporin: (Moderate) Monitor for an increase in mefloquine-related adverse effects if concomitant use of voclosporin is necessary. Concomitant use may increase mefloquine exposure and the risk of additive QT prolongation. Consider interventions to minimize the risk of progression to torsades de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Mefloquine is a P-gp substrate; voclosporin is a P-gp inhibitor that has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin: (Moderate) Use mefloquine with caution if coadministration with vonoprazan is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and vonoprazan is a weak CYP3A inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval, such as clarithromycin. In addition, mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Clarithromycin is an inhibitor of these enzymes and may decrease the clearance of mefloquine and further increasing the risk for QT prolongation. (Moderate) Use mefloquine with caution if coadministration with vonoprazan is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and vonoprazan is a weak CYP3A inhibitor.
Voriconazole: (Moderate) Caution is advised when administering voriconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as mefloquine. Both drugs have been associated with QT prolongation; coadministration may increase this risk. Voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. In addition, coadministration of voriconazole (a strong CYP3A4 inhibitor) with mefloquine (a CYP3A4 substrate) may result in elevated mefloquine plasma concentrations and could increase the risk for adverse events, including QT prolongation. If these drugs are given together, closely monitor for prolongation of the QT interval.
Vorinostat: (Moderate) Mefloquine should be used with caution in patients receiving vorinostat as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation.
Voxelotor: (Moderate) Use mefloquine with caution if coadministration with voxelotor is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A and voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Mefloquine has been reported to increase the effects of warfarin in patients stabilized on warfarin therapy. For patients who are stabilized on warfarin therapy and require mefloquine malaria prophylaxis, it is recommended that steady state mefloquine concentrations be achieved prior to leaving for malarial areas. This allows for prothrombin time monitoring and warfarin dosage adjustments.
Zafirlukast: (Moderate) Mefloquine is metabolized by CYP3A4. Zafirlukast is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and mefloquine is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Mefloquine alone has not been reported to cause QT prolongation; however, there is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval.

Lariam/Mefloquine Hydrochloride Oral Tab: 250mg

Adults

1,250 mg PO once for treatment or 250 mg PO once/week for prophylaxis.

Geriatric

1,250 mg PO once for treatment or 250 mg PO once/week for prophylaxis.

Adolescents

more than 45 kg: 20 to 25 mg/kg PO (Max: 1,250 mg) once for treatment or 250 mg PO once/week for prophylaxis.
30 to 45 kg: 20 to 25 mg/kg PO once for treatment or 187.5 mg (3/4 tablet) PO once/week for prophylaxis.

Children

more than 45 kg: 20 to 25 mg/kg PO (Max: 1,250 mg) once for treatment or 250 mg PO once/week for prophylaxis.
30 to 45 kg: 20 to 25 mg/kg PO once for treatment or 187.5 mg (3/4 tablet) PO once/week for prophylaxis.
20 to 29 kg: 20 to 25 mg/kg PO once for treatment or 125 mg (1/2 tablet) PO once/week for prophylaxis.
less than 20 kg: Safety and efficacy have not been established; however, 20 to 25 mg/kg PO once for treatment or 62.5 mg (1/4 tablet) PO once/week for prophylaxis has been recommended.

Infants

6 to 11 months and weighing 5 kg or more: Safety and efficacy have not been established; however, 20 to 25 mg/kg PO once for treatment or 5 mg/kg/dose PO once/week for prophylaxis has been used.
1 to 5 months or weighing less than 5 kg: Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism of Action: The exact mechanism of action is unknown. Mefloquine has been shown to act as a blood schizonticide. It inhibits replication of asexual erythrocytic parasites, but has no effect on the gametocytes of Plasmodium falciparum. Mefloquine may bind weakly to DNA, resulting in inhibition of nucleic acid synthesis and protein synthesis. It may also act as a weak base, raising the intravesicular pH of acid vesicles of the parasite an thus inhibiting parasitic growth. Additionally, the drug may have non-weak base effects on vesicular pH by means of a specific interaction between mefloquine and parasitic acid vesicles, resulting in swelling of secondary lysosomes (food vacuoles) of the parasite. Mefloquine does not eliminate the exoerythrocytic (intrahepatic) stages of P. vivax or P. ovale infection. Strains of mefloquine-resistant P. falciparum have been reported. Mefloquine also is a myocardial depressant, however, its effects are much less pronounced than those associated with quinidine or quinine.

Mefloquine is administered orally. It is distributed to blood, urine, cerebrospinal fluid (CSF), and tissues and concentrated in erythrocytes. It is also distributed to breast milk in low concentrations (about 3% to 4% of the ingested dose). Protein binding is about 98% to 99%. Mefloquine is partially metabolized by the liver, primarily to the carboxylic acid metabolite. Mefloquine is eliminated very slowly mainly via bile into the feces; subtherapeutic concentrations may persist in the blood for up to several months or more. Approximately 5% of an oral dose is excreted unchanged in the urine. The elimination half-life ranges 13 to 33 days (median 20 days) and may be shorter in seriously ill patients such as patients with acute malaria.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-glycoprotein (P-gp)
Mefloquine is a substrate for cytochrome P450 (CYP) isoenzyme 3A4 and P-gp. Drugs that inhibit or induce these enzymes may have a significant effect on the clearance of mefloquine. Mefloquine also inhibits P-gp and may increase the plasma concentrations of drugs that are P-gp substrates.

Oral Route

Mefloquine is well absorbed from the GI tract with a bioavailability greater than 85%. The absolute bioavailability can not be determined because an intravenous formulation is not available. Rate of absorption is usually relatively rapid, but may be prolonged in some patients. Absorption may be incomplete in seriously ill patients, such as patients with cerebral malaria.

Pregnancy

Published data on mefloquine use during pregnancy showed that pregnant women who took mefloquine at various doses for both prevention and treatment of malaria did not have an increased risk of teratogenic effects or adverse pregnancy outcomes. These data include more than 700 exposures in the first trimester and over 2,000 exposures in the second and third trimesters. Animal data suggest that mefloquine may have teratogenic and embryotoxic effects. Because the studies in humans cannot rule out the possibility of harm, use mefloquine during pregnancy only if clearly needed.[28301] Guidelines support mefloquine use for treatment of chloroquine-resistant P. falciparum malaria during all pregnancy trimesters.[64059] Mefloquine is the only medication recommended for malaria chemoprophylaxis for travel to areas where chloroquine resistance is present during pregnancy.

Use caution when administering mefloquine to breast-feeding women. Mefloquine is excreted in human milk. Based on a study in a few subjects, low concentrations (3% to 4%) were excreted in human milk after a dose equivalent to 250 mg of the free base. Guidelines suggest that because mefloquine may be safely prescribed to infants that it is also safe for infants to be exposed to the small amounts excreted in breast milk. Because the quantity of antimalarial drugs transferred in breast milk is insufficient to provide adequate protection against malaria, an infant who requires chemoprophylaxis must receive the recommended dosages of antimalarial drugs.