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tranexamic acid (Cyklokapron, Lysteda)

Indications: 1) prevention of bleeding with dental procedures in patients with hemophilia 2) reduction of bleeding in trauma patients* [3] - reduces all-cause & bleeding-related mortality in all trauma patients except those with lowest risk [7] 3) reduction in menorrhagia [4,5] 4) systemic fibrinolysis 5) amniotic fluid embolism 6) dental procedures 7) postpartum hemorrhage* [8] 8) nebulized tranexamic acid of benefit in patients with hemoptysis <200 mL [10] 9) used routinely to reduce bleeding during cardiac surgery & orthopedic surgery [14] * effectiveness decreases 10% for every 15-minute delay & is negligible at 3 hours [9] Contraindications: - history of thrombosis - high risk of hypercoagulable disorder - valvular heart disease - atrial fibrillation - acute gastrointestinal hemorrhage (ineffective) - prehospital of tranexamic acid administration may increase mortality in patients with isolated severe traumatic brain injury [12] - prehospital administration of tranexamic acid after injury does not lower 30 day mortality, but may be safe & associated with survival benefit in specific subgroups of patients [13] - hemodynamically significant anemia; RBC transfusion indicated [15] Benefit/risk: - number needed to treat when given within 8 hours of trauma* - 67 to save 1 life [3] * effectiveness decreases 10% for every 15-minute delay & is negligible at 3 hours [9] Dosage: - trauma: 1 g IV over 10 min then 1 g IV over 8 h [3] - menorrhagia: 1300 mg PO TID for maximum of 5 days , Tabs: 650 mg Dosage adjustment in renal failure: - dosages for menorrhagia serum creatinine dosage < 1.4 mg/dL 1300 mg TID 1.4-2.7 mg/dL 1300 mg BID 2.8-5.6 mg/dL 1300 mg QD >= 5.7 mg/dL 650 mg QD Adverse effects: - nausea/vomiting - diarrhea - musculoskeletal pain, including back pain - disturbances in color vision - venous thromboembolism, retinal vein occlusion - arterial thromboembolism, retinal artery occlusion - allergic reaction may occur at any time during treatment - no relevant adverse cardiovascular events if used during noncardiac surgery* [14] * non inferiority to placebo not shown [14] Drug interactions: - use of the drug while taking hormonal contraceptives may increase the risk for thrombi, stroke, & myocardial infarction - concurrent use of facotr IX complex concentrates may increase risk of thrombosis [4] Mechanism of action: 1) inhibitor of fibrinolysis 2) a derivative of the amino acid lysine 3) blocks lysine-binding sites on plasminogen, thus blocking fibrinolysis 4) effectiveness decreases 10% for every 15-minute delay is negligible at 3 hours [9]

General

fibrinolytic agent (thrombolytic agent)

Properties

MISC-INFO: pregnancy-category B safety in lactation -

Database Correlations

PUBCHEM cid=5526

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
  2. FDA NEWS RELEASE, Nov. 13, 2009 FDA Approves Lysteda to Treat Heavy Menstrual Bleeding http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm190551.htm
  3. The NNT: Tranexamic Acid for Severe Trauma. http://www.thennt.com/nnt/tranexamic-acid-for-severe-trauma/ - CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): A randomised, placebo-controlled trial. Lancet 2010 Jun 15; [e-pub ahead of print]. PMID: 20554319 http://dx.doi.org/10.1016/S0140-6736(10)60835-5 - Levy JH. Antifibrinolytic therapy: New data and new concepts. Lancet 2010 Jun 15; [e-pub ahead of print]. PMID: 20554318 http://dx.doi.org/10.1016/S0140-6736(10)60939-7
  4. Prescriber's Letter 17(8): 2010 COMMENTARY: New Drug: Lysteda (Tranexamic Acid) COMMENTARY: Stop the Bleeding: Tranexamic Acid in Trauma Patients Detail-Document#: 260827 (subscription needed) http://www.prescribersletter.com
  5. Lukes AS et al. Tranexamic acid treatment for heavy menstrual bleeding: A randomized controlled trial. Obstet Gynecol 2010 Oct; 116:865 PMID: 20859150
  6. McNeil DG A Cheap Drug Is Found to Save Bleeding Victims New York Times, March 20, 2012 http://www.nytimes.com/2012/03/21/health/tranexamic-acid-cheap-drug-is-found-to-staunch-bleeding.html
  7. Roberts I et al Effect of tranexamic acid on mortality in patients with traumatic bleeding: prespecified analysis of data from randomised controlled trial BMJ 2012;345:e5839 PMID: 22968527 http://www.bmj.com/content/345/bmj.e5839
  8. WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): An international, randomised, double-blind, placebo-controlled trial. Lancet 2017 Apr 26 PMID: 28456509 Free Article http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30638-4/fulltext
  9. Gayet-Ageron A, Prieto-Merino D et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: A meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 2017 Nov 7; [e-pub]. PMID: 29126600 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32455-8/fulltext - Dries DJ. Tranexamic acid: Is it about time? Lancet 2017 Nov 7 PMID: 29126598 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32806-4/fulltext
  10. Wand O, Guber E, Guber A et al. Inhaled tranexamic acid for hemoptysis treatment. Chest 2018 Dec; 154:1379 PMID: 30321510 https://journal.chestnet.org/article/S0012-3692(18)32572-8/fulltext
  11. HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): An international randomised, double-blind, placebo-controlled trial. Lancet 2020 Jun 20; 395:1927 PMID: 32563378 Free PMC article https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)30848-5.pdf
  12. Bossers SM, Loer SA, Bloemers, FW et al Association Between Prehospital Tranexamic Acid Administration and Outcomes of Severe Traumatic Brain Injury. JAMA Neurol. Published online December 7, 2020 PMID: 33284310 https://jamanetwork.com/journals/jamaneurology/article-abstract/2773529
  13. Guyette FX, Brown JB, Zenati MS et al Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury. A Double-blind, Placebo-Controlled, Randomized Clinical Trial. JAMA Surg. 2021;156(1):11-20 PMID: 33016996 PMCID: PMC7536625 https://jamanetwork.com/journals/jamasurgery/fullarticle/2771225
  14. Devereaux PJ et al. Tranexamic acid in patients undergoing noncardiac surgery. N Engl J Med 2022 Apr 2; [e-pub]. PMID: 35363452 https://www.nejm.org/doi/10.1056/NEJMoa2201171
  15. NEJM Knowledge+ Hematology