Tafenoquine and Primaquine in Colostrum and Breast Milk
Status:
Not yet recruiting
Trial end date:
2023-10-31
Target enrollment:
Participant gender:
Summary
Each year almost a million infants are born small for gestational age due to malaria
infection in pregnancy. These infants are at risk for stillbirth or neonatal death, and being
born too small predisposes the survivors to increased metabolic diseases later in life.
Plasmodium vivax (PV) is the second most common malaria species globally. Its relapsing
nature results in multiple episodes of PV in a single pregnancy, compounding growth
restriction and stillbirth risk. Women with PV in one pregnancy may harbor dormant parasites
(hypnozoites) in their liver the cause illness and poor fetal growth in a subsequent
pregnancy.
Only radical cure with 8-aminoquinolines (8AQ)- primaquine (PMQ) or tafenoquine (TQ) - can
eliminate hypnozoites, but these drugs are contraindicated in pregnancy. The postpartum
period presents a key window of opportunity for giving radical cure to women of childbearing
age with PV. Pharmacokinetic data is needed to support safe use of these drugs postpartum and
World Health Organization has identified pharmacokinetic studies of 8AQ in lactation as a
research priority.
Primaquine is excreted minimally in mature breast milk, at <1% of the weight-adjusted
relative infant dose (RID). As the main adverse event associated with both 8AQ - hemolysis
glucose-6-phosphate dehydrogenase (G6PD) deficient individuals - is dose-dependent and
negligible at low doses, this finding strongly supports its safe use in later lactation. This
study is needed to determine if primaquine can also be given safely in the early postpartum
period. There is no published data on tafenoquine excretion in breastmilk, and this study
would quantify safety throughout early and late lactation.
Drug safety studies in lactation are essential to ensure medications are not denied and
unnecessary interruption of breastfeeding is avoided. Demonstration of safety of radical cure
for breastfeeding women in the postpartum period would allow women with PV in pregnancy and
lactation to receive 8AQ after delivery, preventing illnesses in the postpartum period and
subsequent pregnancies. Improved uptake of radical cure through elimination of unnecessary
contraindications supports malaria elimination and community health.
The main purpose of this study is to characterize the transfer of tafenoquine and primaquine
in breast milk of mothers receiving radical cure doses of 8AQ throughout the different phases
of lactation - colostrum, transitional milk, and mature milk - in order to determine the
degree of infant exposure.