Table 1 Key studies with pharmacokinetic data on mefloquine use in children and other important clinical data on prophylaxis and therapy in children
From: Use of mefloquine in children - a review of dosage, pharmacokinetics and tolerability data
Reference | Children Total (n) | Age (in years) | Children (n) using Mefloquine | Main findings |
|---|---|---|---|---|
CHEMOPROPHYLAXIS DATA | ||||
Research Report Salako, Nigeria, 1989 Data on file of F. Hoffmann-La Roche | 280 | 6-10 y | 140 (with body weight range 14-40 kg including 62 children weighing ≤ 20 kg) | Weekly 62.5 mg mefloquine or 125 mg mefloquine every two weeks (in the form of Fansimef®) was effective and well tolerated even in the children weighing < 20 kg. The 62.5 mg weekly dose used here is equivalent to the currently recommended quarter tablet for malaria chemoprophylaxis in this weight category |
Weiss W. R. et al. [5] Daily Primaquine Is Effective for Prophylaxis against Falciparum Malaria in Kenya: Comparison with Mefloquine, Doxycycline, and Chloroquine plus Proguanil. The Journal of Infectious Diseases, 171, 1569-1575, 1995 | 165 | 9-14 y | 30 (weighing 20-54 kg) | Kenyan school children aged 9-14 had lower than expected trough levels of mefloquine after standard doses (5 mg/kg/week) (mean 406 ng/mL after 6 weeks of chemoprophylaxis). This lower trough level is explained by increased mefloquine clearence in older children. |
TREATMENT DATA | ||||
Luxemburger C. et al. [18] Mefloquine in infants and young children. Annals of Tropical Paediatrics 16, 281-5, 1996 | >500 and | <5 y | 417 (with 102 children weighing 8-12 kg with mean body weight 8 kg) | No serious toxicity or adverse events. High dose of mefloquine (25 mg/kg) was associated with vomiting. Mefloquine was administered to very young children aged 3-30 months. Young age was associated with a higher risk of vomiting. Split treatment dose is recommended: 15 mg/kg initially, followed by 10 mg/kg > 12 hours later. Apart from vomiting, mefloquine was very well tolerated by young children. |
Fryauff DJ, et al. [23] Mefloquine treatment for uncomplicated Falciparum malaria in young children 6-24 months of age in northern Ghana Am J Trop Med Hyg, 76(2); 224-231, 2007 | 186 | 0.5-2 y | 186 (with mean body weight 8 kg) | Mefloquine single dose 20 mg/kg was evaluated in Ghanaian infants. Drug levels among infants that tolerated MQ well were not associated with age, weight or pre-existing symptoms of vomiting or diarrhea. |
Bourahla A. et al. [10] Stereoselective pharmacokinetics of mefloquine in young children. European Journal of Clinical Pharmacology 50, 241-244, 1996. | 12 | 0.5-2 y | 12 (with mean body weight of 9.5 kg) | Stereoselective pharmacokinetics in children aged 6 to 24 months are similar to those observed in adults |
Hellgren U. et al. [24] Standard and reduced doses of mefloquine for treatment of Plasmodium falciparum in Tanzania: whole blood concentrations in relation to adverse reactions, in vivo response, and in vitro tolerability. Am J Trop Med Hyg 45, 254-262, 1991 | 53 | 7-10 y | 53 | The dose of 6 mg/kg and higher doses eliminated P. falciparum parasites in children whereas a 2.5 mg/kg dose was not as effective. This supports the currently recommended 5 mg/kg dosage. |
Nosten F. et al. [25] Mefloquine pharmacokinetics and resistance in children with acute falciparum malaria. Brit J Clin Pharmacol 31, 556-559, 1991 | 12 | 5-10 y | 12 | A single dose of 15 mg/kg led to whole blood Cmax of 2031 ug/L, tmax mean of 8 hours (6-24) and a mean oral clearance of 0.031 L/h/kg. Comparable to adults. |
Singhasivanon V. et al. [8] Pharmacokinetics of mefloquine in children aged 6 to 24 months. European Journal of Drug Metabolism and Pharmacokinetics 17, 275-279, 1992 | 12 | 0.5-2 y | 12 | A single dose of mefloquine 25 mg/kg led to a Cmax of 3320 ug/L, tmax 12.8 hours, elimination half-life (10.3 days), volume of distribution (12 L/kg) and AUC (35.6 mg/L/day) in children aged 6 months to 2 years. Comparable to adults. |
Singhasivanon V. et al. [9] Pharmacokinetics of mefloquine in Thai children aged 5-12 years suffering from uncomplicated falciparum malaria treated with MSP or MSP plus primaquine. Eur J Drug Metab Pharmacokin 19, No 1, 27-32, 1994 | 18 | 5-12 y | 18 | Pharmacokinetic values in older children similar to children aged 6 months to 2 years except that clearance per body weight (0.049 L/h/kg) was higher in older children. |