TRANEXAMIC ACID FORPARAMEDIC USE WITHTRAUMATIC INJURYCharles Lathrop, PharmDMarch 10th, 2016

BACKGROUND

Abbreviations: TXA Brand Names: Cyklokapron (Inj) Lysteda

(Oral) Pregnancy Category: B Adverse Effects of IV Route:

Hypotension Nausea/diarrhea Blurred vision Thrombus risk?

Less vascular occlusive events in CRASH 2 trial than placebo

Contraindications: Acquired defective color vision, active intravascular

clot hypersensitivity Micromedex solutions. Accessed 2/25/2016

MECHANISM OF ACTION

http://www.obgmanagement.com/home/article/a‐new‐to‐the‐us‐first‐line‐agent‐for‐heavy‐menstrual‐bleeding/89def9489e8070e03635407caabfb88f.html

PHARMACOKINETICS

Protein Binding: Plasminogen

Elimination half life: 2 hours for IV route

Metabolism: Minimal, site unknown. Dicarboxylic acid and

acetylated metabolites: inactive

Excretion: Urine ( > 95% unchanged drug)

Micromedex solutions. Accessed 2/25/2016

Group Loading Dose (mg/kg)

Infusion dose (mg/kg/hr)

Transfusions Given

Placebo 0 0 19Quarter 2.5 0.25 33

Half 5 0.5 13Whole 10 1 10

Double 20 2 9Fourfold 40 4 14.5

Anesthesiology. 1995

ECONOMICS

Pricing Estimates Tranexamic acid 1000mg/10mL vial = ~ $22

x2 = $44 1 unit PRBC’s = ~ $200

CRASH-2 UK Data: Life Years Saved

755 years per 1,000 patients

Early administration is highly cost effective

PLoS One. 2011 May 3

USE AT COVENANT HEALTHCARE

Prevention of Blood Loss During Major Orthopedic Surgery (off label) 1g given 15 minutes prior to tourniquet inflation or

incision 1g given 15 minutes prior to tourniquet deflation or

closure Decrease in need for transfusions without any

increase in VTE

Epistaxis (off label) 500mg topical soaked in pledget and inserted to

affected nostril

Arch Bone Jt Surg. 2015 Jan; 3(1):1‐2

Am J Emerg Med. 2013 Sep;31(9):1389‐92

ADDITIONAL USES

Hemorrhage prophylaxis during tooth extraction in patients with hemophilia (FDA approved)

Menorrhagia (FDA approved)

Intracranial hemorrhage and traumatic brain injury (off label)

Postpartum hemorrhage prophylaxis (off label)

Postoperative hemorrhage prophylaxis for cardiac procedures (off label)

Micromedex solutions. Accessed 2/25/2016

Paramedic Criteria Indications:

Hemorrhagic shock from traumatic cause or severe uncontrolled bleeding

Hypotension (SBP < 90 mmHg) and/or tachycardia (>110), or declining BP and sustained tachy with traumatic injury

Contraindications: Age < 18 years Spinal, cardiogenic or septic shock Hemorrhagic shock from non-traumatic cause Peripheral hemorrhage controlled through

compression

Dosage & Administration Dose #1: 1g over 10 minutes ≤ 3 hrs of injury

Draw up vial of 1000mg/10mL Add to 100mL NS bag Administer via IV over 10 minutes

660mL/hour factoring 10mL of drug

Dose #2: 1g over 8 hours, started ≤ 3 hrs of injury Administered at destination facility Must be trauma facility capable of continuing

subsequent dose Advise receiving hospital of admin time of

tranexamic acid and need for 2nd dose when giving reports

LABELING

Saline bag, drug vial, sticker

Green sticker to be labeled and placed on bag after mixing

***Alert***EMS MEDICATION ADDED Medication Name_________ Time Started_____________ Initials__________________

TIMING

Early treatment (≤ 1 hour from injury) reduced risk of death from bleeding (5.3% TXA vs 7.7% placebo)

Treatment 1 – 3 hours reduced risk of death from bleeding (4.8% TXA vs 6.1% placebo)

Treatment > 3 hours INCREASED risk of death

MUST BE STARTED ≤ 3 HOURS OF INJURY

IV COMPATIBILITIES

Compatible: D5W, Normal Saline, Heparin

Unknown: EVEVRYTHING IN EMS BOX

Incompatible: Penicillins

Start 2nd IV site or wait to administer additional meds while Tranexamic acid is infusing

Micromedex solutions. Accessed 2/25/2016

TRANEXAMIC ACID CONCLUSION

Works to prevent clot break-down Cost effective Administer to adult trauma patients with:

Hemorrhagic shock, hypotension and/or tachycardia To improve mortality from bleeding, TXA must

be started within 3 hours of injury Receiving hospital must be informed of the

timing of the 1st dose, injury time and need to start the 2nd

Unknown IV compatibilities with most medications

REFERENCES Gross PL, Murray RK, Weil P, et al. Hemostasis & Thrombosis. In: Rodwell VW, Bender

DA, Botham KM, et al. eds. Harper’s Illustrated Biochemistry, 30e. New York, NY: McGraw-Hill; 2015

Kim E Barret, Susan M Barman, Scott Boitano, Heddwen L. Brooks: Ganong’s Review o Medical Physiology, 25th Ed. www.accessmedicine.com. McGraw-Hill Education

Mohammad R Rasouli, Javad Parvizi. Tranexamic Acid in Total Joint Arthroplasty: Efficacy and Safety. Arch Bone Jt Surg. 2015 Jan;3(1):1-2

Zahed R, Moharamzadeh P, Alizadeharasi S, Ghasemi A, Saeedi M. A new and rapid method for epistaxis treatment using injectable form of tranexamic acid topically: a randomized controlled trial. Am J Emerg Med. 2013 Sep;31(9):1389-92

Tranexamic Acid. Micromedex. Truven Health Analytics, Inc. Greenwood Village, CO. Available at http://www.micromedexsolutions.com. Accessed February 25, 2016

CRASH-2 collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet. 2011 Mar 26;377(9771):1096-101, 1101.e1-2

Guerriero C, Cairns J, Perel P, et al. Cost-effectiveness analysis of administering tranexamic acid to bleeding trauma patients using evidence from the CRASH-2 trial. PLoS One. 2011 May 3;6(5)

Horrow JC, Van Riper DF, Strong MD, et al. The dose-response relationship of tranexamic acid. Anesthesiology. 1995 Feb;82(2):383-92

Fiechtner BK, Nuttall GA, Johnson ME, et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg. 2001 May;92(5):1131-6