Genetically Inferred CYP2D6 Impact on PQ

Samples from 8 published clinical trials were used for separate analyses on the impact of genetically inferred CYP2D6 metabolizer status on PQ safety and efficacy. For analyses of the impact of CYP2D6 inferred metabolizer status on PQ efficacy, we included samples from 5 PQ efficacy studies. Gametocyte detection was performed following treatment with a single dose of 0.1 to 0.75 mg/kg PQ in combination with either artemether-lumefantrine (AL) (Coartem as a standard 6-dose regimen over 3 days; Novartis Pharma, Switzerland) in Burkina Faso (3 (link)) and Uganda (2 (link)) or dihydroartemisinin-piperaquine (DP) (Eurartesim as a standard 3-day regimen; Sigma-Tau, Italy) in Mali (1 (link)), the Gambia (4 (link)), and Kenya (5 (link)). Analyses on the impact of CYP2D6 inferred metabolizer status on hemolysis were restricted to G6PD-deficient (G6PDd) individuals; we included two additional studies that specifically assessed PQ safety in G6PD-deficient individuals in Mali (20 (link)) and the Gambia (19 (link)), using 0.25 to 0.5 mg/kg PQ in combination with DP. In all studies, hemoglobin (Hb) concentrations in grams per deciliter were measured by a self-calibrating HemoCue photometer (Ängelholm, Sweden). Study details are summarized in Table 1.