Amodiaquine dosage and tolerability for intermittent preventive treatment to prevent malaria in children.
Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.
Cairns
M
M
Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom. matthew.cairns@lshtm.ac.uk
Cisse
B
B
Sokhna
C
C
Cames
C
C
Simondon
K
K
Ba
E H
EH
Trape
J-F
JF
Gaye
O
O
Greenwood
B M
BM
Milligan
P J M
PJ
D000367:Age Factors; D000655:Amodiaquine / Q000008:administration & dosage* / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D007223:Infant; D008288:Malaria / Q000517:prevention & control*; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects; D012621:Seasons; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000962:Antimalarials; D004338:Drug Combinations; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine