Increased Primaquine Total Dose in Patients with Multiple Plasmodium vivax Relapses Associated with Impaired CYP2D6 Activity: Report of Three Cases

Abstract BackgroundThe relapsing nature of Plasmodium vivax infection is a major barrier to its control and elimination. Factors such as adequate dosing, adherence, drug quality, and pharmacogenetics can impact the effectiveness of radical cure of P. vivax and need to be properly evaluated. CYP2D6 pathway mediates the activation of primaquine (PQ) into an active metabolite(s) in hepatocytes, and impaired activity has been linked to higher risk of relapse. Cases presentationThree patients diagnosed with P. vivax malaria presented repeated relapses after being initially treated with chloroquine (25mg/kg) and primaquine (3.5mg/kg in 14 days) at a non-endemic travel clinic. Recurring episodes were subsequently treated with higher dose of primaquine (7mg/kg in 14 days), which prevented further relapses in two patients. However, one patient still presented 2 episodes after higher primaquine dose and was prescribed 300mg of chloroquine weekly to prevent further episodes. Impaired CYP2D6 function was observed in all of them. ConclusionLack of response to PQ was associated with impaired CYP2D6 activity in three patients presenting multiple relapses followed in a non-endemic setting. Higher PQ dosage was a safe and effectively prevented relapses in two patients and should be further investigated as an option in Latin America. It is important to investigate the factors associated with unsuccessful radical cure and alternative therapeutic options.