Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria

Jane Quinn, Stuart McCarthy

Research output: Contribution to journalLetter

8 Citations (Scopus)

Abstract

Cytochrome P-450 2D6 (CYP2D6) screening has been used to improve the safety and efficacy of primaquine to prevent the clinical relapse of Plasmodium vivax malaria on the recommendation of the Centers for Disease Control and Prevention.1 Tafenoquine, a primaquine analogue, requires CYP2D6-mediated metabolic activation for antimalarial efficacy.2 In the trial by Llanos-Cuentas et al. (Jan. 17 issue)3 on the prevention of relapse of P. vivax malaria, we note that the reported percentages of patients in whom treatment with either primaquine or tafenoquine had failed were similar to percentages of predicted CYP2D6 reduced-function phenotypes in comparable geographic or ethnic populations.4 Although the participants in the trial by Llanos-Cuentas et al. were not all screened for CYP2D6 status, Baird et al. recently estimated that 38.8% of the population living at risk of P. vivax infection are unable to receive safe and effective primaquine therapy because of glucose-6-phosphate dehydrogenase (G6PD) deficiency and reduced CYP2D6 function.5 We therefore recommend that CYP2D6 allelotype screening be included in future clinical studies of tafenoquine to address unresolved safety and efficacy concerns before this drug is widely used for P. vivax eradication or prophylaxis in travelers worldwide.
Original languageEnglish
Pages (from-to)1875-1876
Number of pages1
JournalNew England Journal of Medicine
Volume380
DOIs
Publication statusPublished - 09 May 2019

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Primaquine
Vivax Malaria
Cytochrome P-450 Enzyme System
Recurrence
Plasmodium vivax
Glucosephosphate Dehydrogenase Deficiency
Safety
Antimalarials
Centers for Disease Control and Prevention (U.S.)
Secondary Prevention
Malaria
tafenoquine
Phenotype
Therapeutics
Pharmaceutical Preparations

Cite this

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title = "Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria",
abstract = "Cytochrome P-450 2D6 (CYP2D6) screening has been used to improve the safety and efficacy of primaquine to prevent the clinical relapse of Plasmodium vivax malaria on the recommendation of the Centers for Disease Control and Prevention.1 Tafenoquine, a primaquine analogue, requires CYP2D6-mediated metabolic activation for antimalarial efficacy.2 In the trial by Llanos-Cuentas et al. (Jan. 17 issue)3 on the prevention of relapse of P. vivax malaria, we note that the reported percentages of patients in whom treatment with either primaquine or tafenoquine had failed were similar to percentages of predicted CYP2D6 reduced-function phenotypes in comparable geographic or ethnic populations.4 Although the participants in the trial by Llanos-Cuentas et al. were not all screened for CYP2D6 status, Baird et al. recently estimated that 38.8{\%} of the population living at risk of P. vivax infection are unable to receive safe and effective primaquine therapy because of glucose-6-phosphate dehydrogenase (G6PD) deficiency and reduced CYP2D6 function.5 We therefore recommend that CYP2D6 allelotype screening be included in future clinical studies of tafenoquine to address unresolved safety and efficacy concerns before this drug is widely used for P. vivax eradication or prophylaxis in travelers worldwide.",
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Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria. / Quinn, Jane; McCarthy, Stuart.

In: New England Journal of Medicine, Vol. 380, 09.05.2019, p. 1875-1876.

Research output: Contribution to journalLetter

TY - JOUR

T1 - Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria

AU - Quinn, Jane

AU - McCarthy, Stuart

PY - 2019/5/9

Y1 - 2019/5/9

N2 - Cytochrome P-450 2D6 (CYP2D6) screening has been used to improve the safety and efficacy of primaquine to prevent the clinical relapse of Plasmodium vivax malaria on the recommendation of the Centers for Disease Control and Prevention.1 Tafenoquine, a primaquine analogue, requires CYP2D6-mediated metabolic activation for antimalarial efficacy.2 In the trial by Llanos-Cuentas et al. (Jan. 17 issue)3 on the prevention of relapse of P. vivax malaria, we note that the reported percentages of patients in whom treatment with either primaquine or tafenoquine had failed were similar to percentages of predicted CYP2D6 reduced-function phenotypes in comparable geographic or ethnic populations.4 Although the participants in the trial by Llanos-Cuentas et al. were not all screened for CYP2D6 status, Baird et al. recently estimated that 38.8% of the population living at risk of P. vivax infection are unable to receive safe and effective primaquine therapy because of glucose-6-phosphate dehydrogenase (G6PD) deficiency and reduced CYP2D6 function.5 We therefore recommend that CYP2D6 allelotype screening be included in future clinical studies of tafenoquine to address unresolved safety and efficacy concerns before this drug is widely used for P. vivax eradication or prophylaxis in travelers worldwide.

AB - Cytochrome P-450 2D6 (CYP2D6) screening has been used to improve the safety and efficacy of primaquine to prevent the clinical relapse of Plasmodium vivax malaria on the recommendation of the Centers for Disease Control and Prevention.1 Tafenoquine, a primaquine analogue, requires CYP2D6-mediated metabolic activation for antimalarial efficacy.2 In the trial by Llanos-Cuentas et al. (Jan. 17 issue)3 on the prevention of relapse of P. vivax malaria, we note that the reported percentages of patients in whom treatment with either primaquine or tafenoquine had failed were similar to percentages of predicted CYP2D6 reduced-function phenotypes in comparable geographic or ethnic populations.4 Although the participants in the trial by Llanos-Cuentas et al. were not all screened for CYP2D6 status, Baird et al. recently estimated that 38.8% of the population living at risk of P. vivax infection are unable to receive safe and effective primaquine therapy because of glucose-6-phosphate dehydrogenase (G6PD) deficiency and reduced CYP2D6 function.5 We therefore recommend that CYP2D6 allelotype screening be included in future clinical studies of tafenoquine to address unresolved safety and efficacy concerns before this drug is widely used for P. vivax eradication or prophylaxis in travelers worldwide.

KW - tafenoquine

KW - malaria

KW - Cytochrome P450

KW - efficacy

KW - safety

KW - Plasmodium vivax

U2 - 10.1056/NEJMc1902327

DO - 10.1056/NEJMc1902327

M3 - Letter

VL - 380

SP - 1875

EP - 1876

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

ER -