Development of Weight and Age-based Dosing of Daily Primaquine for Radical Cure of Vivax Malaria
2021
Background
In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and
children. International recommendations for radical cure recommend fixed target doses of 0.25 or
0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients
of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that
children have lower exposures than adults for the same weight adjusted-dose. The aim of the study
was to develop 14-day weight-based and age-based primaquine regimens against high-frequency
relapsing tropical P. vivax. Methods
The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly
efficacious against tropical P. vivax and was assumed to produce optimal drug exposure.
Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine
regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an
anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to
define weight-for-age relationships. The median age associated with each weight was used to
derive an age-based dosing regimen from the weight-based regimen. Results
The proposed weight-based regimen has 5 dosing bands: (i) 5 – 7 kg, 5 mg, resulting in 0.71 – 1.0
mg/kg/day; (ii) 8 – 16 kg, 7.5 mg, 0.47 – 0.94 mg/kg/day; (iii) 17 – 40 kg, 15 mg, 0.38 – 0.88
mg/kg/day; (iv) 41 – 80 kg, 30 mg, 0.37 – 0.73 mg/kg/day; and (v) 81 – 100 kg, 45 mg, 0.45 –
0.56 mg/kg/day.
The corresponding age-based regimen had 4 dosing bands: 6 – 11 months, 5 mg, 0.43 – 1.0
mg/kg/day; (ii) 1 – 5 years, 7.5 mg, 0.35 – 1.25 mg/kg/day; (iii) 6 – 14 years, 15 mg, 0.30 – 1.36
mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35 – 1.07 mg/kg/day. Conclusion
The proposed weight-based regimen showed less variability around the primaquine dose within
each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy
could be achieved by additional dosing bands for both regimens. The age-based regimen might not
be applicable to regions outside the GMS, which must be based on local anthropometric data.
Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.
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