Tranexamic acid - Drug Monograph

Introduction

Tranexamic acid is a synthetic lysine analogue antifibrinolytic agent that inhibits fibrinolysis by blocking the lysine binding sites on plasminogen. First introduced in the 1960s, it has become an essential medication in various clinical settings where excessive bleeding poses a significant risk. Its well-established safety profile and efficacy have led to both FDA-approved uses and numerous off-label applications across multiple medical specialties.

Mechanism of Action

Tranexamic acid competitively inhibits the activation of plasminogen to plasmin by binding to the lysine binding sites on plasminogen. This prevents plasmin from binding to fibrin, thereby stabilizing fibrin clots and reducing fibrinolysis. At higher concentrations, it noncompetitively inhibits plasmin. The drug does not affect platelet count, aggregation, or coagulation parameters, making it a targeted approach to bleeding control without altering the overall coagulation cascade.

Indications

• Short-term use in hemophilia patients to reduce or prevent hemorrhage during and following tooth extraction
• Treatment of cyclic heavy menstrual bleeding
• Prophylaxis and treatment of bleeding in patients with hereditary angioedema

• Trauma-induced hemorrhage (CRASH-2 trial established efficacy)
• Surgical bleeding prophylaxis (cardiac, orthopedic, obstetric surgeries)
• Post-partum hemorrhage
• Gastrointestinal bleeding
• Epistaxis management
• Reducing transfusion requirements in various surgical procedures

Dosage and Administration

• Cyclic heavy menstrual bleeding: 1300 mg three times daily for up to 5 days during menstruation
• Dental procedures in hemophiliacs: 25 mg/kg three to four times daily starting 1 day pre-procedure

• Surgical prophylaxis: 10 mg/kg before incision, followed by maintenance infusion
• Trauma: 1 g infused over 10 minutes, then 1 g over 8 hours
• Post-partum hemorrhage: 1 g IV, may repeat after 30 minutes if bleeding continues

• Renal impairment: Dose adjustment required for CrCl <50 mL/min
• Hepatic impairment: No specific recommendation; use with caution
• Elderly: Consider reduced dosing due to potential decreased renal function
• Pediatrics: Limited data; use based on body weight with close monitoring

Pharmacokinetics

Contraindications

• Hypersensitivity to tranexamic acid or any component of the formulation
• Active intravascular clotting
• History of venous or arterial thrombosis
• Subarachnoid hemorrhage (increased risk of cerebral edema and infarction)
• Color vision disturbances (relative contraindication)

Warnings and Precautions

• Thrombotic risk: Use with extreme caution in patients with history of thrombosis or thrombophilic disorders
• Renal impairment: Requires dose reduction and careful monitoring
• Seizures: Reported with high doses during cardiac surgery
• Visual disturbances: Discontinue if visual symptoms occur
• Dizziness: May impair mental/physical abilities required for hazardous tasks
• Rapid IV administration: May cause hypotension; infuse slowly

Drug Interactions

• Combined hormonal contraceptives: Increased thrombotic risk (additive effect)
• Factor IX complex concentrates, anti-inhibitor coagulant concentrates: Increased thrombotic risk
• Tissue plasminogen activators (tPA): Antagonizes fibrinolytic effects
• Medications affecting renal function: May alter tranexamic acid clearance

Adverse Effects

• Gastrointestinal: Nausea, vomiting, diarrhea
• Neurological: Headache, dizziness
• Ophthalmological: Visual disturbances
• Dermatological: Rash

• Thrombotic events: DVT, PE, arterial thrombosis
• Seizures (particularly with high doses in cardiac surgery)
• Anaphylactic reactions
• Acute renal cortical necrosis
• Visual field defects

Monitoring Parameters

• Renal function (serum creatinine, CrCl)
• Coagulation parameters
• Thrombotic risk assessment
• Visual acuity and color vision

• Signs/symptoms of thrombosis
• Neurological status (especially in cardiac surgery patients)
• Renal function in patients with pre-existing impairment
• Bleeding control efficacy
• Visual changes

• Thrombotic events within 30 days
• Resolution of bleeding
• Visual function follow-up if symptoms occurred

Patient Education

• Take exactly as prescribed; do not exceed recommended dosage
• Report any signs of blood clots (leg pain/swelling, chest pain, shortness of breath)
• Seek immediate medical attention for visual changes, severe headache, or speech problems
• Inform all healthcare providers about tranexamic acid use before any procedure
• Be aware of potential dizziness and avoid hazardous activities if affected
• Store at room temperature away from moisture
• Oral solution: Use measuring device provided; do not use household spoon
• Missed dose: Take as soon as remembered unless close to next dose

References

1. McCormack PL. Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis. Drugs. 2012;72(5):585-617. 2. 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;376(9734):23-32. 3. FDA Prescribing Information: Lysteda® (tranexamic acid) tablets. 4. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999;57(6):1005-1032. 5. Ker K, Edwards P, Perel P, et al. Effect of tranexamic acid on surgical bleeding: systematic review and cumulative meta-analysis. BMJ. 2012;344:e3054. 6. 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;389(10084):2105-2116. 7. Fergusson DA, Hébert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008;358(22):2319-2331.