OC 51.5 - Individual patient data meta-analysis of tranexamic acid pharmacokinetic data for postpartum hemorrhage

Tuesday, June 25, 2024

10:30 – 10:45 ICT

Room: Ballroom B1

Co-Author(s)

MF

Mina Felfeli

MD, Research Coordinator
Department of Obstetrics and Gynecology, The George Washington University School of Medicine and Health Sciences, Washington D.C., USA
Washington, District of Columbia, United States
AD

Allison Dunn

Research Assistant Professor, PhD
University of Maryland School of Pharmacy Center for Translational Medicine
Baltimore, Maryland, United States
SS

Sebastian M. Seifert

Associate Division Chief, Division of Obstetric Anesthesia
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Harvard Medical School
Boston, Massachusetts, United States
SG

Sixtine Gilliot

Professor
Univ. Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France
Lille, Ile-de-France, France
AD

Anne-Sophie Ducloy-Bouthors

Professor
Univ. Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France
Lille, Ile-de-France, France
HS

Haleema Shakur-Still

Professor of Global Health Clinical Trials
Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
London, England, United Kingdom
AG

Amber Geer

Clinical Trials Data Manager
Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
London, England, United Kingdom
NL

Naomi L. Luban

Medical Director, Office for Protection of Human Subjects Vice Chair, Faculty Affairs
Department of Pediatrics George Washington University, Division of Pediatric Hematology, Children's National Hospital, Washington, DC, USA
Washington, District of Columbia, United States
JN

Johannes N. van den Anker

Division Chief of Clinical Pharmacology Vice Chair of Experimental Therapeutics Evan and Cindy Jones
Division of Clinical Pharmacology, Children's National Hospital, Washington, District of Columbia, USA
Washington, District of Columbia, United States
JV

Jogarao V.S. Gobburu

Professor of Practice, Sciences, and Health Outcomes Research Director, Center for Translational Me
Center for Translational Medicine, University of Maryland School of Pharmacy, 20 North Pine Street, Baltimore, MD, 21201, USA
Baltimore, Maryland, United States
IR

Ian Roberts

Professor of Epidemiology and Public Health
Clinical Trials Unit, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK
London, England, United Kingdom

Presenting Author(s)

Homa K. Ahmadzia, MD, MPH

Associate Professor Division of Maternal-Fetal Medicine, Deputy Director Perinatal Research Unit
Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Inova Health System, 3300 Gallows Rd, Falls Church, VA, USA
Falls Church, Virginia, United States

Background: Tranexamic acid (TXA) decreases blood loss when given to women with postpartum hemorrhage (PPH), particularly in low resource settings. The risk of PPH increases with increasing body mass index but the implications of body mass for optimal dosing are uncertain.

Aims: 1)To describe the pharmacokinetics (PK) of tranexamic acid in a large, heterogeneous population of pregnant women and 2) to assess whether weight based dosing is needed.

Methods: We conducted an individual patient data meta-analysis of four pharmacokinetic studies (NCT: 04274335, 03287336, 00872469, 02797119) in pregnant women receiving either intravenous, oral, or intramuscular TXA. We conducted a population PK analysis using nonlinear mixed-effects modeling in Pumas (version 2.4, Pumas AI, Baltimore, MD, https://pumas.ai/) to fit the collected TXA concentration-time data for the studies. We used a stepwise approach to select the structural model and identify covariates that explain the observed variability in TXA PK. We assessed age, body weight, height, and study location as covariates. We used the final model to asses dosing strategies.

Results: A total of 211 pregnant women who received between 0.35 and 4 grams(g) of TXA provided 1,303 TXA plasma concentrations for model development. A two-compartment model with first-order elimination and first-order absorption most adequately described the TXA concentration-time profile (Table 1). Body weight was the only statistically significant covariate identified and was incorporated using a power function centered around 80 kg into the final model. Final model simulations using a virtual population (n=1000) revealed that weight-based and fixed dosing regimens gave similar TXA exposures (Figure 1).

Conclusion(s): Weight-based dosing did not significantly change TXA exposure compared to a fixed dose. Therefore, a 1g intravenous dose of TXA should maintain the plasma level above a minimum threshold of 10 ug/mL for most pregnant women for at least 2 hours regardless of weight.