Tafenoquine and Primaquine in Colostrum and Breast Milk

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.

Conditions

• Healthy Lactating Women

Interventions

DRUG

Primaquine

Primaquine GPO® (Government Pharmaceutical Organization (GPO), Thailand) 0.5 mg/kg will be given once daily with food for 14 days. This is the dose recommended for radical cure of P. vivax in tropical areas with high rates of relapse, such as the study design setting. Doses will be directly supervised (DOT).

DRUG

Tafenoquine

Tafenoquine (Kodatef, Biocelect Pty Ltd.) 300 mg will be given as a directly observed single dose with food. This is the standard dose recommended globally for radical cure of P. vivax.

Sponsors & Collaborators

• Mahidol Oxford Tropical Medicine Research Unit

  collaborator OTHER

• University of Oxford

  lead OTHER

Principal Investigators

• Rose McGready, Ph.D · Shoklo Malaria Research Unit (SMRU), PO Box 46, 68/30 Ban Toong Road, Mae Sot, Tak 63110

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

16 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-07-01

Primary Completion

2025-06-30

Completion

2025-06-30

Countries

• Thailand

Study Locations