Antimalarial (quinoline methanol)
Mefloquine is an antimalarial medicine used to prevent and treat malaria in areas with chloroquine resistance. It can cause neuropsychiatric effects (dizziness, insomnia, anxiety, nightmares) — in rare cases, more serious ones.
Also known as: Lariam
Carbamazepine lowers Mefloquine levels (CYP3A4 inducer) and both lower the seizure threshold — risk of therapeutic failure and seizures.
Mefloquine is metabolised by CYP3A4; carbamazepine, a potent inducer, can reduce its concentrations below the effective threshold, compromising malaria prophylaxis or treatment. In epileptic patients, mefloquine is also to be avoided because of the seizure risk. Prefer another antimalarial (e.g. atovaquone+proguanil, doxycycline) in patients on carbamazepine.
Carbamazepine + mefloquine: carbamazepine lowers mefloquine levels (CYP3A4 induction), with risk of prophylactic/therapeutic failure. Avoid the combination.
CYP3A4 induction (which metabolises Mefloquine) + additive effects on the seizure threshold.
Clinical response and neurological status.
Seizures, confusion, lack of response to prophylaxis/treatment.
Consider an alternative antimalarial and neurological surveillance.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2
Additive QT effect; Clarithromycin may also raise Mefloquine levels.
Mefloquine is partly metabolised by CYP3A4 and prolongs the QT interval; clarithromycin inhibits CYP3A4 (raising mefloquine levels) and also prolongs the QT, so the ventricular arrhythmia risk is additive. In patients receiving mefloquine, prefer another antibiotic and another antimalarial when possible; if the combination is unavoidable, monitor the ECG and electrolytes.
Mefloquine + clarithromycin: additive QT prolongation and raised mefloquine levels (CYP3A4 inhibition). Avoid the combination.
Additive QT prolongation + inhibition of Mefloquine metabolism (CYP3A4).
ECG (QTc) and electrolytes.
Palpitations, dizziness, seizures.
Caution; monitor ECG and signs of toxicity.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Clarithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d836ae7e-fdbf-4dcb-a90d-ede1dcbc3e67
Two QT-prolonging antimalarials combined — higher arrhythmic risk with no therapeutic benefit.
Both chloroquine and mefloquine prolong the QT interval and can cause ventricular arrhythmias; the chloroquine label warns about the increased risk during concomitant administration with QT-prolonging drugs, and the mefloquine label has a dedicated section on QTc prolongation and interactions (advising against, for example, halofantrine and ketoconazole because of the risk of potentially fatal prolongation). The chloroquine+mefloquine combination should be avoided (they are not used together in antimalarial practice); if unavoidable, monitor the ECG and electrolytes and correct hypokalaemia/hypomagnesaemia.
Chloroquine + mefloquine: additive risk of QT prolongation. Avoid the combination; monitor the ECG if unavoidable.
Additive QT prolongation; additive CNS effects.
ECG and neurological surveillance.
Palpitations, seizures, behavioural changes.
Avoid; use a single antimalarial regimen.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Increased risk of QT prolongation and neuropsychiatric effects when combined.
Both drugs are antimalarials associated with QT prolongation: the artemether-lumefantrine label states that "some antimalarials (e.g. quinine, quinidine), including artemether-lumefantrine, have been associated with prolongation of the QT interval on the ECG" and recommends using other QT-prolonging drugs with caution; the mefloquine label documents QTc prolongation and advises against drugs that alter cardiac conduction (quinine and quinidine are contraindicated, and halofantrine and ketoconazole because of the potentially fatal QT risk). Combining these antimalarials is not used in practice (they are alternatives to each other), but overlap can occur in patients with therapeutic failure. If combined, monitor the ECG, electrolytes (correct hypokalaemia/hypomagnesaemia) and signs of arrhythmia.
Artemether-lumefantrine + mefloquine: additive QT (antimalarials). Avoid the combination; ECG and electrolytes if unavoidable.
Additive QT prolongation; Mefloquine also adds CNS effects.
ECG and neurological status; watch for neuropsychiatric symptoms.
Anxiety, insomnia, psychosis, seizures, palpitations.
Avoid the association; choose a single antimalarial regimen.
DailyMed/FDA (NIH/NLM) — approved Artemether + Lumefantrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7866ec19-dfac-47d4-a53f-511a12643cbf ; approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Increased risk of QT prolongation and ventricular arrhythmias.
Mefloquine prolongs the QT interval and is associated with ventricular arrhythmias and conduction blocks; with amiodarone the effect is additive. Both also affect AV conduction. In patients on chronic amiodarone needing malaria prophylaxis or treatment, prefer atovaquone+proguanil or doxycycline. If the combination is unavoidable, monitor the ECG and electrolytes and watch for proarrhythmia signs.
Mefloquine + amiodarone: additive QT prolongation with risk of ventricular arrhythmias. Avoid the combination.
Additive prolongation of cardiac repolarisation.
ECG (QTc) and electrolytes.
Palpitations, syncope.
Avoid; if unavoidable, monitor the ECG.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d
Additive QT prolongation — low-to-moderate risk, higher in at-risk patients.
Mefloquine, used for malaria prophylaxis and treatment, prolongs the QT interval and can cause arrhythmias; ciprofloxacin adds the fluoroquinolone class effect. The combination adds up the risk of torsade de pointes, especially in patients with long QT, hypokalaemia, bradycardia or taking other QT-prolonging drugs. Whenever possible, avoid the combination or choose an alternative antibiotic; if unavoidable, monitor the ECG and electrolytes and use the shortest treatment duration possible.
Ciprofloxacin + mefloquine: additive risk of QT prolongation. Avoid or monitor the ECG in at-risk patients.
Additive effect on cardiac repolarisation.
ECG if risk factors.
Palpitations, syncope.
Caution in at-risk patients; ECG if symptoms.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd ; approved Ciprofloxacin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=14c3bc33-201d-492e-9aee-a4d84c813a3d
Both prolong QT — combining adds no benefit and increases arrhythmic risk.
Piperaquine (the dihydroartemisinin-piperaquine component, Eurartesim) prolongs the QT interval in a dose-dependent way and the EMA EPAR contraindicates co-administration with other QT-prolonging drugs; the mefloquine label, in turn, documents QTc prolongation and advises against drugs that alter cardiac conduction. Combining these antimalarials is not used in practice (they are alternatives to each other), but overlap can occur in patients with therapeutic failure or severe malaria, especially with hypokalaemia, hypomagnesaemia, bradycardia or cardiac disease. Avoid; if unavoidable, monitor the ECG and electrolytes before and during therapy and correct hypokalaemia/hypomagnesaemia.
Dihydroartemisinin-piperaquine + mefloquine: additive QT. Avoid the combination (EMA contraindicates QT-prolonging drugs); ECG if unavoidable.
Additive QT prolongation.
ECG and neurological surveillance.
Palpitations, dizziness, seizures.
Avoid; use a single antimalarial regimen.
EMA — EPAR Eurartesim (dihydroartemisinin + piperaquine): https://www.ema.europa.eu/en/medicines/human/EPAR/eurartesim ; DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Fluconazole plus Mefloquine carries a risk of QT prolongation and arrhythmias.
Mefloquine can prolong the QTc interval, especially when combined with other drugs that alter cardiac conduction or prolong the QT — the label explicitly contraindicates halofantrine and ketoconazole (risk of potentially fatal QT prolongation) and advises against quinine/quinidine; the patient guide recommends not taking it with QT-prolonging drugs. Fluconazole also prolongs the QT (torsade de pointes in post-marketing experience) and, as a CYP3A4 inhibitor, may also raise mefloquine levels. The combination should be avoided (in practice, antimalarial prophylaxis and antifungal treatment rarely overlap, but they can occur in patients with invasive fungal infections); if unavoidable, monitor the ECG, electrolytes and correct hypokalaemia/hypomagnesaemia.
Fluconazole + mefloquine: additive risk of QT prolongation. Avoid the combination; monitor the ECG if unavoidable.
Additive effect on cardiac repolarization (both prolong the QT).
ECG (QT interval), electrolytes (K+, Mg2+).
Syncope, palpitations, torsades de pointes.
Use with caution; monitor ECG (QT) and electrolytes; consider an alternative antimalarial.
DailyMed/FDA (NIH/NLM) — approved Fluconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7961c029-746c-48c3-888b-8f8344102873 ; approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Alcohol may increase the risk of seizures and of the neuropsychiatric effects (dizziness, anxiety, nightmares) associated with mefloquine.
Avoid or strongly limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Taking mefloquine with food and plenty of water reduces the nausea and vomiting common early in treatment.
Take with food and a glass of water; with persistent vomiting, contact the doctor (the dose may need to be repeated).
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Mefloquine causes severe neuropsychiatric effects (anxiety, depression, psychosis, suicidal ideation); it is contraindicated in active psychiatric disease or a history of psychosis.
Contraindicated in active depression or psychosis; stop with neuropsychiatric symptoms.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Mefloquine can lower the seizure threshold; it is contraindicated in patients with epilepsy or a history of seizures.
Contraindicated in epilepsy or a history of seizures; choose an alternative antimalarial.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Mefloquine may be used in pregnancy in the 2nd and 3rd trimesters (prophylaxis and treatment); in the 1st trimester, use only if the benefit justifies it.
Avoid in the 1st trimester; in the others, use under supervision.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Mefloquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09716a24-d7da-42b2-af29-c03a1b6670bd
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Blood schizonticide antimalarial. Oral bioavailability above 85% (tablet vs solution); food enhances the rate and extent of absorption by about 40%. Peak plasma concentrations 6 to 24 hours (median about 17 hours) after a single dose. Protein binding of about 98% and apparent volume of distribution of approximately 20 L/kg, indicating extensive tissue distribution.
Blood schizonticide; the exact mechanism is not known. Active against the erythrocytic stages of Plasmodium species, with no effect on the exoerythrocytic (hepatic) stages; effective against chloroquine-resistant parasites and may accumulate in parasitised erythrocytes.
Oral bioavailability above 85%; food enhances the rate and extent of absorption by about 40%. Peak plasma concentrations 6 to 24 hours after dosing; with 250 mg weekly, steady state is reached after 7 to 10 weeks, with peak concentrations of 1000 to 2000 mcg/L.
Extensively metabolised in the liver by the cytochrome P450 system, mainly CYP3A4. The main metabolite, a carboxylic acid (2,8-bis-trifluoromethyl-4-quinoline), is inactive; its AUC is 3 to 5 times larger than that of the parent drug. Excretion is mainly biliary and faecal; only about 9% of the dose appears unchanged in the urine.
Mean elimination half-life of about 3 weeks (2 to 4 weeks); total clearance essentially hepatic, in the order of 30 mL/min. Due to the long half-life, adverse reactions may occur or persist for several weeks after discontinuation.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
