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The compatibility of oxytocin and tranexamic acid injection products when mixed for co-administration by infusion for the treatment of postpartum haemorrhage: an in vitro investigation
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  • Peter Lambert,
  • Alessandra Tomazzini,
  • Philip Wright,
  • Claire McEvoy,
  • Ioannis Gallos,
  • Anne Ammerdorffer,
  • Lester Chinery,
  • Arri Coomarasamy,
  • Ahmet Gulmezoglu
Peter Lambert
Monash University

Corresponding Author:pete.lambert@monash.edu

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Alessandra Tomazzini
Concept Foundation
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Philip Wright
Monash Institute of Pharmaceutical Sciences
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Claire McEvoy
Monash Institute of Pharmaceutical Sciences
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Ioannis Gallos
Birmingham Women's Hospital
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Anne Ammerdorffer
Concept Foundation
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Lester Chinery
Concept Foundation
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Arri Coomarasamy
Birmingham Women's Hospital
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Ahmet Gulmezoglu
Concept Foundation
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Abstract

Objective: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co-administration by intravenous infusion. Population or Sample: Oxytocin and tranexamic acid were collected from hospitals taking part in a multicentre postpartum haemorrhage treatment (E-MOTIVE) trial in Kenya, Nigeria, Tanzania, and South Africa. Methods: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200mL infusion bags of both 0.9%w/v saline and Ringer’s Lactate was assessed. We analysed all tranexamic acid -oxytocin combinations, and each evaluation was conducted for up to 6hrs. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocins products when mixed in 0.9%w/v saline over a period of 1 hour was investigated. Results: We found a significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 hour. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8% - 29.0%) immediately on mixing (t=0 minutes). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) combinations tested. Conclusions: In a clinical setting, mixing oxytocin and tranexamic acid may result in an underdosing of oxytocin, compromising care in an emergency life-threatening situation. The mixing of oxytocin and tranexamic acid injection products for co-administration with IV infusion fluids should be avoided until the exact nature of the interaction and its implications are understood.
18 Aug 2022Submitted to BJOG: An International Journal of Obstetrics and Gynaecology
24 Aug 2022Submission Checks Completed
24 Aug 2022Assigned to Editor
25 Aug 2022Reviewer(s) Assigned
17 Sep 2022Review(s) Completed, Editorial Evaluation Pending
11 Oct 2022Editorial Decision: Revise Major
02 Nov 20221st Revision Received
11 Nov 2022Submission Checks Completed
11 Nov 2022Assigned to Editor
11 Nov 2022Review(s) Completed, Editorial Evaluation Pending
14 Dec 2022Editorial Decision: Accept