Practical info

• In patients known to be G6PD deficient, primaquine may be considered at a dose of 0.75 mg base/kg bw once a week for 8 weeks. The decision to give or withhold primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
• Some heterozygote females who test as normal or not deficient in qualitative G6PD screening tests have intermediate G6PD activity and can still haemolyse substantially. Intermediate deficiency (30–80% of normal) and normal enzyme activity (> 80% of normal) can be differentiated only with a quantitative test. In the absence of quantitative testing, all females should be considered as potentially having intermediate G6PD activity and given the 14-day regimen of primaquine, with counselling on how to recognize symptoms and signs of haemolytic anaemia. They should be advised to stop primaquine and be told where to seek care should these signs develop.
• If G6PD testing is not available, a decision to prescribe or withhold primaquine should be based on the balance of the probability and benefits of preventing relapse against the risks of primaquine-induced haemolytic anaemia. This depends on the population prevalence of G6PD deficiency, the severity of the prevalent genotypes and on the capacity of health services to identify and manage primaquine-induced haemolytic reactions.

Other considerations In the absence of evidence to recommend alternatives, the guideline development group considers 0.75 mg/kg bw primaquine given once weekly for 8 weeks to be the safest regimen for people with mild-to-moderate G6PD deficiency. Primaquine and glucose-6-phosphate dehydrogenase deficiency Any person (male or female) with red cell G6PD activity < 30% of the normal mean has G6PD deficiency and will experience haemolysis after primaquine. Heterozygote females with higher mean red cell activities may still show substantial haemolysis. G6PD deficiency is an inherited sex-linked genetic disorder, which is associated with some protection against P. falciparum and P. vivax malaria but increased susceptibility to oxidant haemolysis. The prevalence of G6PD deficiency varies, but in tropical areas it is typically 3–35%; high frequencies are found only in areas where malaria is or has been endemic. There are many (> 180) different G6PD deficiency genetic variants; nearly all of which make the red cells susceptible to oxidant haemolysis, but the severity of haemolysis may vary. Primaquine generates reactive intermediate metabolites that are oxidant and cause variable haemolysis in G6PDdeficient individuals. It also causes methemoglobinaemia. The severity of haemolytic anaemia depends on the dose of primaquine and on the variant of the G6PD enzyme. Fortunately, primaquine is eliminated rapidly so haemolysis is selflimiting once the drug is stopped. In the absence of exposure to primaquine or another oxidant agent, G6PD deficiency rarely causes clinical manifestations so, many patients are unaware of their G6PD status. Screening for G6PD deficiency is not widely available outside hospitals, but rapid screening tests that can be used at points of care have recently become commercially available. Remarks Primaquine is contraindicated in pregnancy and lactation, unless the infant has been tested for G6PD deficiency. It could be given to women once they have delivered and ceased breastfeeding.