Mefloquine

Mefloquine is an oral quinoline-methanol antimalarial used for weekly prophylaxis in travellers and, with artesunate, for treatment of uncomplicated falciparum malaria in some regions. It has a boxed warning for neuropsychiatric effects that can persist after stopping. It is not used in East African programmes.

Class. Antimalarial; quinoline-methanol.

Mechanism. Probably interferes with haem detoxification and parasite protein synthesis within the food vacuole; it acts on blood stages.

Pharmacokinetics. Absorbed well orally, increased by food. Half life about 3 weeks. Metabolised by CYP3A4 and extensively bound to plasma proteins.

Prophylaxis (adults and children). 250 mg (adult) once weekly, starting 2 to 3 weeks before travel, continuing during travel and for 4 weeks after return. Children: 5 mg/kg weekly by weight bands (under 5 kg: not advised).

Treatment of uncomplicated falciparum malaria (with artesunate). Mefloquine 25 mg/kg total, given as 15 mg/kg then 10 mg/kg 24 hours later, or as a fixed-dose combination with artesunate once daily for 3 days.

Loading dose, maintenance dose and titration. For treatment, 15 mg/kg then 10 mg/kg 24 hours later; prophylaxis starts 2 to 3 weeks before travel. Maximum: 1250 mg treatment total.

Main alternative. Atovaquone with proguanil, or doxycycline for prophylaxis.

Contraindications. Hypersensitivity; current or past psychiatric disorders (depression, anxiety, psychosis, schizophrenia); seizures; cardiac conduction defects; use of quinine, quinidine or halofantrine within 12 hours.

Serious adverse effects. Neuropsychiatric events (anxiety, depression, hallucinations, psychosis, suicidal thoughts), seizures, vestibular symptoms (vertigo, tinnitus, ataxia, which may persist), arrhythmia, and hepatotoxicity.

Common adverse effects. Nausea, vomiting, dizziness, vivid dreams, insomnia and headache.

Interactions. Quinine, chloroquine and QT-prolonging drugs: avoid; rifampicin lowers levels; ketoconazole raises them; may reduce the effect of anticonvulsants.

Common prescribing errors. Prescribing with psychiatric history, giving with quinine, and starting prophylaxis too late to detect adverse effects.

Special groups. - Pregnancy: used in the second and third trimesters when needed. - Breastfeeding: compatible. - Children: weight-based; not under 5 kg. - Older adults: caution. - Kidney impairment: no adjustment. - Liver impairment: caution.

Formulations. Tablets 250 mg; fixed-dose combination with artesunate.

Administration. After a meal with water, on the same day each week.

Baseline. Psychiatric and seizure history, ECG if cardiac history, pregnancy test, drug history.

Monitoring. Mood, sleep, balance and vision at each contact; stop at any new symptom.

Stopping thresholds. Stop for anxiety, depression, hallucinations, vertigo, tinnitus, seizures or palpitations.

Referral and escalation. Urgent psychiatric or neurological review for persisting neuropsychiatric symptoms.