Primaquine response

Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing has to be performed before using primaquine. Due to the limitations of G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical support and follow-up to manage hemolytic risk should be available.

Primaquine should not be prescribed for patients with severe G6PD deficiency…

In case of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. If primaquine administration is considered, baseline hematocrit and hemoglobin must be checked before treatment and close hematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage hemolytic risk should be available.

When the G6PD status is unknown and G6PD testing is not available, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine. Risk factors for G6PD deficiency or favism must be assessed. Baseline hematocrit and hemoglobin must be checked before treatment and close hematological monitoring (e.g. at day 3 and 8) is required. Adequate medical support to manage hemolytic risk should be available.

Please review the complete therapeutic recommendations that are located here: (1).

It is recommended to avoid primaquine at standard (or higher) anti-relapse dosages of 0.25–0.5 mg/kg daily for 14 days for the treatment of P. vivax or P. ovale in G6PD deficiency. For the anti-gametocyte treatment of Plasmodium falciparum malaria, the single-dose regimen of 0.25 mg/kg is considered safe and effective (low to no risk in G6PD deficiency). For the treatment of P. vivax or P. ovale malaria for radical cure of liver-stage infections, 0.75 mg/kg once weekly for 8 weeks (WHO) or 45 mg for adults once weekly for 8 weeks (CDC) is considered in the medium risk category, and patients should be monitored closely for hemolysis… No dose of primaquine is considered safe in patients who are G6PD deficient with CNSHA and thus should be avoided.

Please review the complete therapeutic recommendations that are located here: (3).

Hemolytic anemia and G6PD deficiency

Due to the risk of hemolytic anemia in G6PD deficient patients, G6PD testing has to be performed before using primaquine. […] Due to the limitations of G6PD tests, physicians need to be aware of residual risk of hemolysis and adequate medical support and follow-up to manage hemolytic risk should be available. Observe particular caution in individuals with a personal or family history of hemolytic anemia.

In case of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine; if primaquine administration is considered, the dosage regimen should be adapted accordingly (see DOSAGE AND ADMINISTRATION) and close hematological monitoring is required.

[….]

CYP2D6 genotype:

Based on non-clinical data, primaquine activity probably depends on the formation CYP2D6 metabolite(s). Therefore, CYP2D6 polymorphism may be associated with variability in clinical response to primaquine.

Limited clinical data reported more elevated treatment failure rates in patients with CYP2D6 poor or intermediate metabolizer status than in patients with normal/extensive metabolizer status (see ACTION AND CLINICAL PHARMACOLOGY).

In case of treatment failure, after checking patient’s compliance to treatment, it may be useful to reconsider potential concomitant use of CYP2D6 inhibitors (see DRUG INTERACTIONS) and to assess the patient’s CYP2D6 status if feasible. For poor CYP2D6 metabolizers, alternative treatment should be considered.

Please review the complete therapeutic recommendations that are located here: (5).