MEFLOQUINE HYDROCHLORIDE
Clinical safety rating
safeAnimal 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. |
| Molecular Weight | 414.8 |
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 | Mefloquine is associated with an increased risk of first-trimester spontaneous abortion and possible teratogenicity. Use only if clearly needed and no alternative. |
| 2nd trimester | Limited data suggest no major malformations, but avoid unless benefit outweighs risk. |
| 3rd trimester | No specific safety concerns reported, but use only if necessary. |
Clinical note
Beta-blockers and other QT-prolonging agents may have additive effects Can cause severe neuropsychiatric reactions and vertigo.
| Placental transfer | Mefloquine crosses the placenta; cord blood concentrations are approximately 10-30% of maternal serum concentrations. |
| Breastfeeding | Mefloquine is excreted into breast milk in small amounts. The American Academy of Pediatrics considers it compatible with breastfeeding; however, monitor infant for potential adverse effects such as vomiting or diarrhea. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to mefloquine or related compounds (e.g., quinine, quinidine)History of psychiatric disorders (including depression, anxiety, psychosis, or seizures)Severe hepatic impairment
| 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 |
| Food/Dietary | Grapefruit and grapefruit juice may increase mefloquine concentrations; avoid concurrent use. Take with food to reduce nausea and vomiting. No other significant food interactions reported. |
| Clinical Pearls | Mefloquine is contraindicated in patients with active depression, generalized anxiety disorder, psychosis, or a history of convulsions. Due to long half-life (18-22 days), neuropsychiatric effects may persist or appear weeks after discontinuation. Use with caution in patients with hepatic impairment; monitor liver function. Cardiotoxicity: avoid use with QT-prolonging drugs; ECG monitoring recommended if concomitant use inevitable. Efficacy against multidrug-resistant P. falciparum is strain-dependent; consider regional resistance patterns. For malaria prophylaxis, start 2-3 weeks before travel to assess tolerability. |
| Patient Advice | Take exactly as prescribed; do not stop early even if feeling better. · Report any psychiatric symptoms (anxiety, depression, unusual dreams, confusion) immediately. · Avoid alcohol; may increase risk of liver toxicity and CNS effects. · Take with food and a full glass of water to reduce gastrointestinal upset. · Use effective contraception during therapy and for 3 months after last dose; may cause fetal harm. · Do not drive or operate machinery if dizziness, vertigo, or visual disturbances occur. · Complete full course for malaria treatment; for prophylaxis, continue for 4 weeks after leaving endemic area. |
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