LARIAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LARIAM (LARIAM).
Mefloquine is a 4-quinolinemethanol antimalarial agent that acts as a blood schizontocide. Its exact mechanism is unknown, but it is thought to inhibit heme polymerase, leading to toxic accumulation of free heme in the parasite.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 3A4 to inactive metabolites. It also undergoes enterohepatic recirculation. |
| Excretion | Hepatic metabolism (primarily CYP3A4) followed by biliary/fecal elimination; ~40% unchanged in feces, ~9% as metabolites in urine, minimal renal excretion of parent drug (<5%). |
| Half-life | Terminal elimination half-life: approximately 3 weeks (range 13–33 days); prolonged due to extensive tissue distribution and slow release from erythrocytes. |
| Protein binding | Approximately 98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 15–30 L/kg; extensive distribution into tissues, including erythrocytes (high concentration), liver, lungs, and spleen. |
| Bioavailability | Oral: ~85% (well absorbed); not available parenterally in the US. |
| Onset of Action | Oral: Clinical antimalarial effect noted within 24–48 hours; peak plasma concentrations at 6–24 hours. |
| Duration of Action | Chemoprophylaxis: Weekly dosing provides continuous protection due to long half-life; treatment: single dose provides cure for uncomplicated malaria. |
For malaria prophylaxis: 250 mg (base) orally once weekly starting 1-2 weeks before travel, continuing weekly during stay and for 4 weeks after leaving endemic area. For malaria treatment: 1250 mg (base) orally as a single dose, divided if needed (750 mg followed by 500 mg after 6-12 hours). Route: oral. Frequency: weekly for prophylaxis; single dose for treatment.
| Dosage form | TABLET |
| Renal impairment | No specific dosing adjustment required for renal impairment, but caution in GFR <30 mL/min due to limited data; monitor for adverse effects. |
| Liver impairment | Contraindicated in patients with significant hepatic impairment (Child-Pugh class B or C). For mild impairment (Child-Pugh class A), no adjustment needed but use with caution. |
| Pediatric use | Prophylaxis and treatment: 15-25 mg base/kg orally; maximum 1250 mg. For children weighing ≤45 kg: 5 mg base/kg weekly for prophylaxis; for treatment, same mg/kg as adults. Dosing based on mefloquine base. Not recommended for children <5 kg or <3 months. |
| Geriatric use | No specific dose adjustment, but monitor for neuropsychiatric and cardiac effects (QT prolongation, bradycardia). Use caution due to age-related decline in hepatic and renal function, and potential drug interactions. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LARIAM (LARIAM).
| Breastfeeding | Mefloquine is excreted in human breast milk in small amounts. The milk-to-plasma ratio (M/P) is approximately 0.1-0.2. Studies indicate that the amount ingested by a nursing infant is about 3-4% of the maternal weight-adjusted dose, which is below the therapeutic pediatric dose. The American Academy of Pediatrics considers mefloquine compatible with breastfeeding. Monitor infant for potential adverse effects (e.g., gastrointestinal disturbance, sleep disturbance). |
| Teratogenic Risk | Pregnancy Category C. In animal studies, mefloquine (LARIAM) has been shown to be teratogenic in mice (cleft palate, anophthalmia) and rats (hydrocephalus, anophthalmia) at doses similar to human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed. Because malaria infection in pregnancy carries significant maternal and fetal risk, treatment of confirmed malaria with mefloquine is not contraindicated. Prophylaxis should be avoided in pregnancy unless travel to a high-risk area is unavoidable. First trimester: known fetal risks; second and third trimesters: limited data suggest no increased malformations, but caution advised. |
■ FDA Black Box Warning
WARNING: Mefloquine can cause serious psychiatric and neurological adverse reactions, including suicide, hallucinations, anxiety, depression, paranoia, confusion, dizziness, and seizures. Use caution in patients with recent history of depression, generalized anxiety disorder, psychosis, or schizophrenia. Discontinue immediately if psychiatric or neurological symptoms occur. Not recommended for prophylaxis in patients with active or recent depression, generalized anxiety disorder, psychosis, or schizophrenia.
| Serious Effects |
History of hypersensitivity to mefloquine or related compounds (e.g., quinine); active or recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, or other major psychiatric disorders; history of convulsions or epilepsy; concurrent use with halofantrine or other drugs that prolong QT interval.
| Precautions | Psychiatric effects: suicidal ideation, hallucinations, anxiety, depression; Neurologic effects: dizziness, vertigo, seizures; QT prolongation (caution with drugs that prolong QT); use in pregnancy only if benefit outweighs risk; avoid in patients with cardiac conduction disorders; may cause visual disturbances; use caution with activities requiring alertness. |
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| Fetal Monitoring | Monitor maternal liver function tests (especially transaminases) at baseline and periodically during therapy due to potential hepatotoxicity. Assess for neuropsychiatric symptoms (anxiety, depression, confusion, seizures) before and during therapy. In pregnancy, monitor fetal growth via ultrasound due to potential for low birth weight; assess for adverse fetal outcomes. Monitor complete blood count (CBC) for rare thrombocytopenia or agranulocytosis. |
| Fertility Effects | Animal studies have not shown significant impairment of fertility at therapeutic doses. No adequate human studies on fertility; however, no specific adverse effects on female or male fertility have been reported in clinical use. Mefloquine may cause menstrual irregularities in some women, but impact on fertility is not established. |