title: Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges.
abstract: BACKGROUND
  Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population.
  
  
  METHODS
  Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P. falciparum malaria in infants and children in Africa were analysed according to body weight group.
  
  
  RESULTS
  The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively.
  
  
  CONCLUSIONS
  Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.
authors.affiliation: Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain. quique.bassat@cresib.cat
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.forename: Sónia
authors.initials: S
authors.lastname: Machevo
authors.forename: Alain
authors.initials: A
authors.lastname: Nahum
authors.forename: John
authors.initials: J
authors.lastname: Lyimo
authors.forename: Hamma
authors.initials: H
authors.lastname: Maiga
authors.forename: Andreas
authors.initials: A
authors.lastname: Mårtensson
authors.forename: Mahfudh
authors.initials: M
authors.lastname: Bashraheil
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.forename: David
authors.initials: D
authors.lastname: Ubben
authors.forename: Verena
authors.initials: V
authors.lastname: Walter
authors.forename: Obiyo
authors.initials: O
authors.lastname: Nwaiwu
authors.forename: Chemtai
authors.initials: C
authors.lastname: Kipkeu
authors.forename: Gilbert
authors.initials: G
authors.lastname: Lefèvre
authors.forename: Bernhards
authors.initials: B
authors.lastname: Ogutu
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000367:Age Factors; D000962:Antimalarials / Q000008:administration & dosage* / Q000627:therapeutic use; D000077549:Artemether; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C039060:artenimol; D000077549:Artemether; D000078102:Lumefantrine