Can Tranexamic Acid (TXA) be administered intramuscularly (IM) and does the dose change?

Intramuscular Administration of Tranexamic Acid (TXA)

Tranexamic acid (TXA) can be administered intramuscularly (IM) with a bioavailability of approximately 97-105%, but current guidelines only explicitly recommend intravenous (IV) administration, and the IM dose should be increased to 30 mg/kg to achieve comparable serum concentrations to IV administration.

Current Guideline Recommendations for TXA Administration

• Current guidelines from the World Health Organization (WHO) and European guidelines on management of major bleeding specifically recommend intravenous administration of TXA at a loading dose of 1 g infused over 10 minutes, followed by an IV infusion of 1 g over 8 hours 1
• TXA should be administered as soon as possible after injury or onset of bleeding, and within 3 hours, as effectiveness decreases by 10% for every 15-minute delay 1
• Guidelines explicitly state that their recommendations apply to giving the drug intravenously only, as the benefits and potential harms of other routes are considered a research priority 1

Evidence for Intramuscular TXA Administration

• Pharmacokinetic studies in healthy volunteers show that IM TXA has a bioavailability of approximately 105%, suggesting complete absorption 2
• In swine models of hemorrhagic shock, IM TXA achieved similar pharmacokinetics to IV TXA with no significant differences in the concentration-time areas under the curve 3, 4
• IM TXA successfully corrected in vitro hyperfibrinolysis in animal studies, similar to IV administration 3
• The half-life of TXA was similar across IV, IO, and IM routes in animal models of hemorrhagic shock 4

Dosage Considerations for IM Administration

• When administering TXA intramuscularly, research suggests that the dose should be increased from the standard 15 mg/kg to 30 mg/kg to achieve serum concentrations comparable to IV administration 5
• Distributing the IM dose between two injection sites did not affect drug uptake or serum concentrations 5
• Peak concentration (Cmax) is significantly higher with IV and IO routes compared to IM administration, but the overall drug exposure over time is similar 4

Clinical Implications and Limitations

• IM administration may be particularly valuable in austere environments, military settings, or situations where IV access is difficult to establish 3, 5
• There is a slight delay in achieving therapeutic concentrations with IM compared to IV administration, which should be considered in time-sensitive scenarios 5
• Current clinical guidelines do not yet include specific recommendations for IM dosing of TXA, as human clinical trials comparing outcomes between IV and IM administration are lacking 1
• Similar to IM administration, intraosseous (IO) administration of TXA appears to result in similar total drug exposure compared to IV administration in preliminary human data 6

Practical Recommendations

• In settings where IV access is readily available, IV administration remains the recommended route for TXA at 1 g over 10 minutes, followed by 1 g over 8 hours 1
• When IV access is difficult or impossible to establish, IM administration at a dose of 30 mg/kg (approximately 2 g for a 70 kg adult) may be a practical alternative 5
• IM administration should still adhere to the 3-hour window from time of injury or onset of bleeding 1
• The decision to use IM administration should consider the slight delay in achieving peak concentrations compared to IV administration 3, 5