Data from: Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase deficient falciparum-infected African males: two open-label, randomized, safety trials

Background: Primaquine (PQ) actively clears mature Plasmodium falciparum
gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd)
individuals can cause hemolysis. We assessed the safety of low-dose PQ in
combination with artemether-lumefantrine (AL) or
dihydroartemisinin-piperaquine (DP) in G6PDd African males with
asymptomatic P. falciparum malaria. Methods and findings: In Burkina Faso,
G6PDd adult males were randomized to treatment with AL alone (n = 10) or
with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD-normal males
received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The Gambia,
G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg
PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40
mg/kg (n = 10) PQ. The primary study endpoint was change in hemoglobin
concentration during the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6
(CYP2D6) metabolizer status, gametocyte carriage, haptoglobin, lactate
dehydrogenase levels and reticulocyte counts were also determined. In
Burkina Faso, the mean maximum absolute change in hemoglobin was -2.13
g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd individuals
randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in those
receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change
in hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd
individuals receiving 0.25 PQ mg/kg. After adjustment for baseline
concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso
were more pronounced compared to those in G6PD-normal individuals
receiving the same PQ doses (P = 0.062 and P = 0.022, respectively).
Hemoglobin levels normalized during follow-up. Abnormal haptoglobin and
lactate dehydrogenase levels provided additional evidence of mild
transient hemolysis post-PQ. Conclusions: Single low-dose PQ in
combination with AL and DP was associated with mild and transient
reductions in hemoglobin. None of the study participants developed
moderate or severe anemia; there were no severe adverse events. This
indicates that single low-dose PQ is safe in G6PDd African males when used
with artemisinin-based combination therapy.