MEFLOQUINE HYDROCHLORIDE
Clinical safety rating: safe
Animal studies have demonstrated safety
Mefloquine is a quinoline antimalarial agent that acts as a blood schizontocide. Its exact mechanism is unknown but is thought to involve forming toxic heme complexes or inhibiting heme polymerase, leading to parasite death.
| Metabolism | Primarily metabolized by the liver via cytochrome P450 enzymes, including CYP3A4. Forms one main metabolite, 4-carboxymefloquine, which is inactive. |
| Excretion | ~83% (fecal/biliary), ~9% (renal unchanged), ~2.5% (renal as metabolite). |
| Half-life | ~2-4 weeks (terminal half-life); clinical context: long half-life allows weekly dosing for prophylaxis, but accumulation can occur with repeated doses. |
| Protein binding | ~98% bound to albumin and alpha-1-acid glycoprotein (AAG). |
| Volume of Distribution | ~13-29 L/kg (large Vd, extensive tissue distribution, including RBCs). |
| Bioavailability | Oral: ~85-90% (relative to oral solution). |
| Onset of Action | Oral: ~6-12 hours (parasitemia clearance begins). |
| Duration of Action | ~3-4 weeks (antimalarial effect); clinical note: due to long half-life, single dose effective for treatment, but adverse effects may persist. |
250 mg (1 tablet) orally once weekly for prophylaxis; 1250 mg (5 tablets) as a single oral dose for treatment of uncomplicated malaria.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl >30 mL/min). For severe renal impairment (CrCl <30 mL/min) or hemodialysis, use with caution and monitor for adverse effects; consider alternative antimalarial. |
| Liver impairment | Contraindicated in patients with active hepatitis or elevated liver enzymes. For Child-Pugh class A, no adjustment; for class B or C, avoid use due to risk of hepatic toxicity. |
| Pediatric use | Prophylaxis: 5 mg/kg (max 250 mg) orally once weekly. Treatment: 20-25 mg/kg (max 1250 mg) as a single oral dose. Use only in children >5 kg. |
| Geriatric use | Use standard adult dosing but monitor closely for neuropsychiatric adverse effects (e.g., dizziness, confusion). Consider lower initial dose (e.g., 250 mg weekly) and titrate based on tolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Beta-blockers and other QT-prolonging agents may have additive effects Can cause severe neuropsychiatric reactions and vertigo.
| Breastfeeding | Mefloquine is excreted into breast milk in small amounts (M/P ratio approximately 0.33-0.47). Amount is insufficient to cause adverse effects in term infants; however, caution in preterm or ill infants. Consider alternative antimalarials if infant has G6PD deficiency. |
| Teratogenic Risk | First trimester: Avoid due to potential teratogenicity (animal data show skeletal and vascular anomalies; limited human data suggest possible increased risk of miscarriage and malformations). Second and third trimesters: Use only if benefit outweighs risk; no clear evidence of major human teratogenicity in later trimesters. |
■ FDA Black Box Warning
Mefloquine may cause neuropsychiatric adverse reactions including dizziness, vertigo, tinnitus, and more severe effects such as psychosis, seizures, and suicidal ideation. Use with caution and consider alternative prophylaxis in patients with psychiatric or seizure disorders.
| Common Effects | Dizziness |
| Serious Effects |
["History of hypersensitivity to mefloquine or related compounds (e.g., quinine, quinidine)","Active psychiatric conditions such as depression, generalized anxiety disorder, psychosis, schizophrenia, or suicidal tendencies","History of seizures or a family history of epilepsy","Use with halofantrine or other drugs that prolong QT interval"]
| Precautions | ["Neuropsychiatric effects: can occur weeks to months after discontinuation; avoid in patients with active depression, generalized anxiety disorder, psychosis, or schizophrenia","Hepatic impairment: use caution; may exacerbate liver disease","Ocular effects: rare visual disturbances including retinopathy","Cardiac effects: may cause QT prolongation; avoid with other QT-prolonging drugs","Seizures: use caution in patients with history of seizures"] |
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| Fetal Monitoring | Monitor maternal liver function tests and CBC monthly; fetal ultrasound for malformations if first-trimester exposure; neuropsychiatric assessment (mefloquine can cause dizziness, psychosis); electrocardiogram for QTc prolongation. |
| Fertility Effects | No significant adverse effects on fertility in animal studies; human data limited. May cause reversible oligospermia in males at high doses; no evidence of impaired female fertility. |