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

Abstract

Objective: To investigate the compatibility of oxytocin and tranexamic acid injection products when mixed for the purpose of co-administration by intravenous infusion.

Design: Compatibility testing.

Setting: Hospitals taking part in a multicentre postpartum haemorrhage treatment (E-MOTIVE) trial in Kenya, Nigeria, Tanzania and South Africa.

Sample: Oxytocin and tranexamic acid products.

Methods: The compatibility of two sentinel products of oxytocin injection and tranexamic acid injection in 200-mL infusion bags of both 0.9% w/v saline and Ringer's lactate solution was assessed. We analysed all tranexamic acid-oxytocin combinations, and each evaluation was conducted for up to 3 h. Subsequently, the compatibility of multiple tranexamic acid products with reference oxytocin products when mixed in 0.9% w/v saline over a period of 1 h was investigated.

Main outcome measures: Concentration of oxytocin over time after mixing with tranexamic acid products.

Results: We found significant interaction between certain oxytocin and tranexamic acid products after mixing them in vitro and observing for 1 h. The interaction substantially impacted oxytocin content leading to reduction in concentration (14.8%-29.0%) immediately on mixing (t = 0 min). In some combinations, the concentration continued to decline throughout the stability assessment period. Oxytocin loss was observed in 7 out of 22 (32%) of combinations tested.

Conclusions: In a clinical setting, mixing certain oxytocin and tranexamic acid products before administration 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 intravenous infusion fluids should be avoided until the exact nature of the observed interaction and its implications are understood.

Keywords: co-administration; drug interaction; intravenous infusion; oxytocin; postpartum haemorrhage; tranexamic acid.