Abstract
BackgroundUse of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data.MethodsData 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.ResultsChemoprophylaxis 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.ConclusionCurrently 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.
Highlights
Use of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data
A first study on mefloquine in a prophylactic setting includes a simulated plasma profile using maintenance doses of 62.5 mg weekly mefloquine (n = 70) equivalent to 1⁄4 of a tablet, the currently recommended chemoprophylactic dose in small children weighing 10-20 kg (Figure 1). This dosage leads to a blood concentration of mefloquine of approximately 620 ng/mL which is considered effective against P. falciparum malaria [6,7]
The main age related difference in pharmacokinetics is that clearance per body weight is higher in older children aged 5-12 years compared to younger children aged 6 to 24 months [8,9]
Summary
Use of anti-malarial medication in children is hampered by a paucity of dosage, pharmacokinetic and tolerability data. Plasmodium falciparum malaria in a young child is a life threatening disease. The majority of European countries, the United States of America (USA), Australia, Japan and other industrialised countries are classified as malaria non-endemic but need guidelines and effective prevention for travellers. At highest risk are children of immigrant families visiting friends and relatives (VFR), those travelling to sub-Saharan Africa, because they tend to visit high-risk destinations for prolonged periods, they lack immunity and often do not use chemoprophylaxis or preventive measures [3] and travel medicine needs to target this group of travellers [4]. The high cost of some anti-malarial medication is a prohibitive factor for many VFR families. Malaria is a real threat to tourist and child expatriates visiting or living in malaria endemic areas
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