LARIAM
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 378.31 |
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 | Avoid use in first trimester due to potential teratogenic effects (animal studies show embryotoxicity and teratogenicity). Use only if benefit outweighs risk for severe malaria. |
| 2nd trimester | Use only if clearly needed; no well-controlled studies in pregnant women. Animal studies suggest risk, but human data limited. |
| 3rd trimester | Use with caution; may increase the risk of congenital malformations if used in first trimester, but second and third trimester use is generally considered safer for treatment of malaria if indicated. |
Clinical note
Comprehensive clinical and safety monograph for LARIAM (LARIAM).
| Placental transfer | Mefloquine crosses the placenta; cord blood levels are approximately 30% of maternal serum levels. |
| Breastfeeding | Mefloquine is excreted into human milk in small amounts. The American Academy of Pediatrics considers it compatible with breastfeeding. Monitor infant for adverse effects (e.g., vomiting, diarrhea, rash) and consider risk of malaria transmission if mother is infected. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Known hypersensitivity to mefloquine or related compounds (e.g., quinine, quinidine)History of convulsions (e.g., epilepsy, recent head injury)History of psychiatric disorders (including depression, anxiety, psychosis)Concurrent use with halofantrine (risk of QT prolongation)Severe hepatic impairment
| 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. |
| Food/Dietary | Grapefruit juice may increase mefloquine concentrations and risk of side effects; avoid concurrent use. Take with food or milk to reduce gastrointestinal upset. No other significant food interactions. |
| Clinical Pearls | Lariam (mefloquine) is used for malaria prophylaxis and treatment. Neuropsychiatric effects (anxiety, depression, hallucinations) can occur even weeks after discontinuation. Caution in patients with history of seizures or psychiatric disorders. Use with caution in patients with cardiac conduction abnormalities due to potential QT prolongation. Administer with food to reduce gastrointestinal side effects. Not recommended for patients with severe hepatic impairment. |
| Patient Advice | Take exactly as prescribed, usually once weekly for prophylaxis starting 2 weeks before travel and continuing for 4 weeks after leaving area. · Report any symptoms of anxiety, depression, confusion, or unusual dreams immediately. · May cause dizziness or balance problems; avoid driving or operating machinery until reaction is known. · Use effective contraception during treatment and for 3 months after last dose as it may cause fetal harm. · Avoid grapefruit juice as it may increase side effects. |
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