Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data

Abstract

Background: Use of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data.

Methods: Data on the use of mefloquine in children, particularly in young children weighing less than 20 kg, were reviewed using PubMed literature and reports on file.

Results: Chemoprophylaxis data: Two studies with a total of 170 children were found. A simulated mefloquine plasma profile showed that doses to achieve protective chemoprophylaxis blood concentration of mefloquine of approximately 620 ng/mL (or 1.67 μmol/L) in children should be at least 5 mg/kg. This simulated plasma profile in children corresponds to that seen in adult travellers using a weekly prophylaxis dose of 250 mg. This reinforces current practice of using weight-based dosage for children. Clearance per body weight is higher in older children. For children who travel to malaria risk areas tablets can be broken and crushed as required. It is necessary to disguise the bitter taste of the drug. Treatment data: Mefloquine treatment (alone or in combination) data are available for more than 6000 children of all age and weight categories. The stereoselectivity and pharmacokinetic profile of mefloquine in children is similar to that observed in adults. There is higher clearance in older children (aged 5-12 years) compared to younger children (aged 6-24 months). Mefloquine treatment is well tolerated in infants (5-12 kg) but vomiting is a problem at high doses. This led to the use of a "split dose" regimen with 15 mg/kg initially, followed 12 hours later by 10 mg/kg. Mefloquine 125 mg has been used as intermittent preventive treatment (IPT) and was found to be efficacious in reducing episodes of malaria in a moderate-transmission setting but vomiting was a problem in 8% of children aged 2-11 months. Mefloquine is also used as a component of artemisinin combination therapy (ACT) in small children. The combination artesunate plus mefloquine is a WHO approved first-line treatment for uncomplicated malaria in Africa.

Conclusion: Currently available data provide a scientific basis for the use of mefloquine in small children in the chemoprophylaxis setting and as a part of treatment regimens for children living in endemic areas.

Figure 1

Plasma levels during chemoprophylaxis in children. The Figure shows the simulated plasma levels of mefloquine expected to be achieved in a child weighting 13 kg who received an initial dose of 125 mg of mefloquine and then 16 weekly prophylaxis doses of 62.5 mg mefloquine (equivalent to the currently recommended ¼ tablet for this weight category of child). Mefloquine concentrations of 620 ng/mL (= 1.67 μmol/L) are considered to be effective against Plasmodium falciparum in the bloodstream.

Figure 2

Plasma levels achieved during chemoprophylaxis in adult travellers. Data [52] showing plasma levels achieved during weekly prophylaxis in adult travellers, prior to travel in Africa and post travel. *Protective levels of mefloquine (620 ng/mL or 1.67 μmol/L) are achieved after two weeks of chemoprophylaxis dosing. The plasma profile in adults is similar to that in the simulated profile in children (Figure 1). MQ: mefloquine, MQ+, MQ-: mefloquine enantiomers, MMQ: carboxylic acid metabolite of mefloquine