Tranexamic Acid is an antifibrinolytic medication, available as an IV and oral formulation. It is indicated for the treatment and prevention of bleeding disorders

Tranexamic Acid Indications:

• Oral: Treatment for cyclic heavy menstrual bleeding.

• Injection or oral (Cyklokapron, Canadian product): Short-term use in patients with hemophilia to prevent or reduce hemorrhage and decrease the need for replacement therapy during and after tooth extraction.

Tranexamic acid is used off-label in adults for the following purposes:

• Prevention of bleeding associated with hip fracture surgery

• Treatment of nonmassive hemoptysis

• Long-term prophylaxis for hereditary angioedema

• Prevention of intracranial hemorrhage associated with thrombolytics (plasminogen-activator) such as alteplase, reteplase, or tenecteplase

• Reduction of perioperative blood loss in total hip arthroplasty, bilateral total knee arthroplasty, and unilateral total knee arthroplasty

• Prevention of perioperative bleeding associated with cardiac surgery

• Treatment of post-operative bleeding associated with cervical conization

• Treatment of postpartum hemorrhage

• Prevention of early aneurysmal rebleeding in subarachnoid hemorrhage

• Treatment of trauma-associated hemorrhage

• Prevention of bleeding associated with dental procedures in patients on oral anticoagulant therapy (topical mouth rinse)

• Prevention of bleeding associated with craniosynostosis surgery, extracorporeal membrane oxygenation (ECMO), orthognathic surgery, spinal surgery (such as spinal fusion), or transurethral prostatectomy

• Treatment of traumatic hyphema.

Tranexamic Acid Dose in Adult:

The following are recommended dosages and routes of administration for tranexamic acid in various medical conditions:

Cyclic heavy menstrual bleeding:

• Oral Lysteda: 1,300 mg three times daily (total of 3,900 mg per day) for up to five days during monthly menstruation.

• Cyklokapron [Canadian product]: 1,000 to 1,500 mg three to four times daily.

Off-label use in the treatment of Hemoptysis (mild):

• Inhalation for nebulization: 500 mg three times daily for up to five days (Wand 2018).

Off-label use in the long-term prophylaxis of Hereditary angioedema (HAE):

• Oral: 1,000 to 1,500 mg two to three times daily. The dose may be reduced to 500 mg per dose once or twice daily when the frequency of attacks reduces (Gompels 2005; Levy 2010).

• Another dosing regimen is 25 mg/kg/dose administered two to three times daily (Bowen 2004).

Off-label use in blood conservation for hip fracture surgery:

• IV: 15 mg/kg administered at the time of skin incision, followed by a second dose of 15 mg/kg three hours later (Zufferey 2010). However, additional data may be necessary to further define the role of tranexamic acid in this setting.

Off-label use in Intracranial hemorrhage associated with thrombolytics (plasminogen-activator) (e.g., alteplase, reteplase, or tenecteplase):

• 10 to 15 mg/kg intravenously over 20 minutes (as an alternative to cryoprecipitate). Fibrinogen levels should be checked after administration. If fibrinogen is less than 150 mg/dL, cryoprecipitate is recommended (NCS/SCCM [Frontera 2016]).

Off-label use in blood loss reduction, Orthognathic surgery:

• IV: 20 mg/kg over 15 minutes prior 1to incision (Choi 2009).

Off-label use in Blood loss reduction during the perioperative period in bilateral total knee arthroplasty:

• Intravenous (IV) administration:

  • Three-dose regimen: A slow IV infusion of 10 mg/kg is given 30 minutes before tourniquet deflation for the first operation, 30 minutes before tourniquet deflation for the second operation, and 3 hours after commencement of the second dose (Kim 2014).

  • Two-dose regimen: 10 or 15 mg/kg is administered over 10 minutes before deflation of the first tourniquet, with the second dose given 3 hours after the first dose (MacGillivray 2011).

Off label use in Blood loss reduction during perioperative period in unilateral total knee arthroplasty:

• IV administration:

  • Intra- and postoperative regimen: 10 mg/kg is given at least 10 to 30 minutes before tourniquet release (deflation), and 10 mg/kg is given at 3 hours after the first dose (Alvarez 2008; Camarasa 2006; Maniar 2012). Instead of the second dose, a postoperative infusion may be administered at 1 mg/kg/hour for 6 hours (Alvarez 2008).

  • Pre- and intraoperative regimen: 10 mg/kg is given at least 20 minutes or immediately before tourniquet inflation, and repeated at least 15 minutes prior to deflation or immediately after release of tourniquet (Lozano 2008; Maniar 2012).

  • Pre-, intra-, and postoperative regimen: 10 mg/kg is given at least 20 minutes before tourniquet inflation, repeated at least 15 minutes prior to deflation, and postoperatively at 3 hours after the second dose (Maniar 2012).

Off label use in the Prevention or reduction of post-operative bleeding associated with cervical conization:

• Intravenous administration:

  • Intra- and postoperative regimen: 1 g of IV infusion is administered during the procedure, followed by oral therapy of 1 g 3 times daily for 14 days, beginning the day after the procedure (Grunsdell 1984).

• Oral administration:

  • Postoperative regimen: 1500 mg is given every 8 hours, beginning the evening following the procedure and continuing for 12 days (Rybo 1972).

Off label use in the Treatment of postpartum hemorrhage:

• IV administration: 1,000 mg of tranexamic acid is given over 10 minutes within 3 hours of vaginal birth or cesarean section; if bleeding continues after 30 minutes or stops and restarts within 24 hours after the first dose, a second dose of 1,000 mg may be given (WOMAN Trial Collaborators 2017).

Off label use in the Prevention of bleeding during dental procedures in patients on oral anticoagulant therapy:

• Oral rinse: 4.8% solution: Patients should hold 10 mL of the solution in their mouth and rinse for 2 minutes, then spit it out. The procedure should be repeated four times daily for 2 days after the dental procedure. Note that patients should avoid eating or drinking for 1 hour after using the oral rinse (Carter 2003).

Off label use in the Prevention of perioperative bleeding associated with cardiac surgery:

• IV: A loading dose of 50 mg/kg should be administered more than 30 minutes after induction of anesthesia (Myles 2017),

• a loading dose of 30 mg/kg should be administered over 30 minutes (including a test dose administered over the first 10 minutes) prior to incision, followed by 16 mg/kg/hour until sternal closure.

• Additionally, an extra 2 mg/kg should be added to the cardiopulmonary bypass circuit (Fergusson 2008).

• Alternatively, a loading dose of 10 mg/kg over 20 minutes prior to incision followed by 2 mg/kg/hour for 2 hours after transfer to ICU can be given.

• A prime dose of 50 mg for a 2.5 L cardiopulmonary bypass circuit should also be added.

• The maintenance infusion should be adjusted for renal insufficiency (Nuttall 2008), or a loading dose of 10 to 15 mg/kg over 10 to 15 minutes followed by 1 to 1.5 mg/kg/hour can be given.

• The authors suggest adding 2 to 2.5 mg/kg to the cardiopulmonary bypass circuit; however, amounts have varied widely in clinical trials (Gravlee 2008).

Off label use in the Prevention of perioperative bleeding associated with spinal surgery (e.g., spinal fusion):

• IV: A loading dose of 2,000 mg should be administered over 20 minutes prior to incision, followed by 100 mg/hour during surgery and for 5 hours postoperatively (Elwatidy 2008).

• Alternatively, a loading dose of 10 mg/kg prior to incision followed by 1 mg/kg/hour for the remainder of the surgery should be given.

• Administration should be discontinued at the time of wound closure (Wong 2008).

Off label use in the Prevention of early aneurysmal rebleeding in subarachnoid hemorrhage (SAH):

Note that this treatment should be used when definitive treatment of the aneurysm is unavoidably delayed.

• IV: A loading dose of 1,000 mg should be given as soon as the diagnosis of SAH has been verified, followed by 1,000 mg every 6 hours until the aneurysm is occluded.

• The maximum duration of treatment should be 72 hours (AHA/ASA [Connolly 2012]; Hillman 2002).

The administration of tranexamic acid in patients with hemophilia undergoing tooth extraction requires appropriate factor replacement therapy:

• For intravenous administration, a dose of 10 mg/kg is given immediately before surgery, followed by 10 mg/kg 3 to 4 times daily for 2 to 8 days.

• Alternatively, a single dose of 10 mg/kg is given 2 hours prior to the procedure in conjunction with Factor VIII and IX.

• Oral administration of Cyklokapron is recommended as a single dose of 25 mg/kg 2 hours prior to the procedure, followed by 25 mg/kg 3 to 4 times daily for 6 to 8 days.

For total hip replacement surgery, the off-label use of tranexamic acid is recommended for blood conservation.

• Intravenous administration of 10 to 15 mg/kg (or 1,000 mg) is given over 5 to 10 minutes immediately before the operation or 15 minutes before skin incision.

• A preoperative dose may be followed by 10 mg/kg administered 3 to 12 hours after the operation.

• Postoperative doses ranged from a 10 mg/kg IV bolus (or 1,000 mg) to a 1 mg/kg/hour infusion over 10 hours. Multiple regimens have been evaluated, and the regimen listed here reflects the more commonly used dosing based on several prospective randomized controlled trials.

• Meta-analyses have also demonstrated significant reduction in blood loss perioperatively without an increased risk of thromboembolic events. The use of intra-articular tranexamic acid has also been evaluated, demonstrating effectiveness.

For off-label use in blood loss reduction during transurethral prostatectomy:

• oral administration of 2,000 mg three times daily is recommended on the operative and first postoperative day.

In trauma-associated hemorrhage:

• intravenous administration of tranexamic acid is recommended.

• A loading dose of 1,000 mg is given over 10 minutes, followed by 1,000 mg over the next 8 hours.

• Clinical trials have demonstrated effectiveness in patients with significant hemorrhage or those at risk of significant hemorrhage, with treatment beginning within 8 hours of injury.

• However, efforts should be made to administer the treatment as soon as possible, ideally within 3 hours of injury, as treatment beyond 3 hours has been shown to be significantly less effective and may be associated with harm.

off-label use in Traumatic hyphema:

• Administer orally a dose of 25 mg/kg thrice daily for upto 5 to 7 days (Rahmani 1999; Vangsted 1983; Varnek 1980).

Note: This same regimen may also be used for secondary hemorrhage after an initial traumatic hyphema event.

Tranexamic Acid Dose in Children:

Condition/Use	Patient Population	Route	Dosing Schedule	Maximum Daily Dose
Menorrhagia	Female children ≥12 years and Adolescents	Oral	1,300 mg tablet 3 times daily	3,900 mg/day for up to 5 days during monthly menstruation
Prevention of bleeding associated with tooth extraction in hemophilic patients (in combination with replacement therapy)	Infants, Children, and Adolescents	IV	10 mg/kg immediately before surgery, then 10 mg/kg/dose 3 to 4 times daily	May be used for 2 to 8 days
Prevention of bleeding associated with cardiac surgery	Infants, Children, and Adolescents ≤15 years	IV	10 mg/kg into the by-pass circuit after induction, during cardiopulmonary bypass, and after protamine reversal of heparin for a total of 3 doses	Limited data available
Prevention of perioperative bleeding associated with spinal surgery (eg, idiopathic scoliosis)	Children ≥8 years and Adolescents	IV	Loading dose: 100 mg/kg, followed by infusion at 10 mg/kg/hour until skin closure	Limited data available
Prevention of perioperative bleeding associated with craniosyntosis surgery	Infants ≥2 months and Children ≤6 years	IV	Loading dose of 50 mg/kg over 15 minutes prior to incision, followed by infusion at 5 mg/kg/hour until skin closure or 15 mg/kg over 15 minutes prior to incision, followed by infusion at 10 mg/kg/hour until skin closure	Limited data available
Hereditary angioedema (HAE), prophylaxis	Children and Adolescents	Oral	Long-term prophylaxis: 20 to 75 mg/kg/day in 2 to 3 divided doses	Maximum daily dose range: 3,000 to 6,000 mg/day or 1,000 to 2,000 mg daily (~50 mg/kg/day; depending on age and size of patient); may consider alternate-day regimen or twice-weekly regimen when frequency of attacks reduces
Short-term prophylaxis (eg, prior to surgical or diagnostic interventions in head/neck region)	Children and Adolescents	Oral	Weight-directed: 20 to 40 mg/kg/day in 2 to 3 divided doses or Fixed dosing: Patients with an adequate weight (eg, ≥50 kg): 500 mg 4 times daily	Maximum daily dose: 6,000 mg/day
Traumatic hyphema	Children and Adolescents	Oral	25 mg/kg/dose every 8 hours for 5 to 7 days	Limited data available

 

The given text provides information on dosing regimens for various conditions in children and adolescents. The conditions include Menorrhagia, prevention of bleeding associated with tooth extraction in hemophilic patients, prevention of bleeding associated with cardiac surgery, prevention of perioperative bleeding associated with spinal surgery and craniosyntosis surgery, hereditary angioedema prophylaxis, short-term prophylaxis prior to surgical or diagnostic interventions in the head/neck region, and traumatic hyphema. The table above summarizes the patient population, route, dosing schedule, and maximum daily dose for each condition. Limited data is available for some conditions, and the ideal dose-response has not been established.

Dose during Pregnancy

Tranexamic acid has the ability to cross the placenta and reach similar concentrations in the cord blood as in the maternal serum.

Reports have suggested the use of oral tranexamic acid for long-term prophylaxis of HAE in pregnant women when the preferred treatment is not available.

This consideration is in line with the recommendations of WAO/EEACI (Maurer 2017).

Intravenous tranexamic acid has been evaluated for the management of postpartum hemorrhage. The WOMAN Trial Collaborators observed a significant reduction in the risk of death due to bleeding when treatment was initiated within 3 hours of vaginal birth or cesarean section.

Therefore, tranexamic acid is recommended for the management of obstetric hemorrhage when initial therapy fails, as per the recommendations of ACOG 183 2017 and WHO 2017.

IV tranexamic acid has also been studied for the prophylaxis of postpartum hemorrhage in low-risk females before vaginal or cesarean delivery.

However, available data on prophylactic use is insufficient, and its routine use for prophylaxis against postpartum hemorrhage is not currently recommended outside the context of clinical research, as per the recommendations of ACOG 183 2017.

Dose during Breastfeeding:

Tranexamic acid is found in breast milk of lactating women, but in very small amounts (around 1% of what is in the mother's blood) according to a study done in 1985.

Breastfed infants of mothers who used tranexamic acid did not experience any harmful effects due to the drug, and a different study recommends taking the drug right after breastfeeding to minimize the infant's exposure.

However, the manufacturer of the drug does not recommend breastfeeding.

Using other drugs for the condition is preferred, but if tranexamic acid is needed for a certain condition, breastfeeding is considered okay by some experts.

Dose in Kidney Disease:
 

Indication	Serum creatinine range	Maintenance Dose
Tooth extraction	1.36 to 2.83 mg/dL	10 mg/kg/dose twice daily
	2.83 to 5.66 mg/dL	10 mg/kg/dose once daily
	>5.66 mg/dL	10 mg/kg/dose every 48 hours
		or 5 mg/kg/dose once daily
Cardiac surgery	1.6 to 3.3 mg/dL	Reduce infusion to 1.5 mg/kg/hour (25% reduction from 2 mg/kg/hour)
	3.3 to 6.6 mg/dL	Reduce infusion to 1 mg/kg/hour (50% reduction from 2mg/kg/hour)
	>6.6 mg/dL	Reduce infusion to 0.5 mg/kg/hour (75% reduction from 2mg/kg/hour)

Oral formulation:

Medicine	Serum creatinine levels (mg/dL)	Dosage
Lysteda	>1.4 to 2.8	1,300 mg twice daily (2,600 mg/day) for up to 5 days
	2.9 to 5.7	1,300 mg once daily for up to 5 days
	>5.7	650 mg once daily for up to 5 days
Cyklokapron [Canadian product]	1.4 to 2.8 (120 to 250 micromol/L)	15 mg/kg twice daily

Dose in children:

Note: Recommendations are dependent on use and route.

Oral: Menorrhagia:

Female Children ≥12 years and Adolescents:

Serum Creatinine	Dosage	Duration
>1.4 to 2.8 mg/dL	1,300 mg twice daily (2,600 mg/day)	Up to 5 days
2.9 to 5.7 mg/dL	1,300 mg once daily	Up to 5 days
>5.7 mg/dL	650 mg once daily	Up to 5 days

 

IV: Tooth extraction in patients with hemophilia:

Infants, Children, and Adolescents:

Serum Creatinine (Scr)	Maintenance Dose
1.36 to 2.83 mg/dL	10 mg/kg/dose twice daily
>2.83 to 5.66 mg/dL	10 mg/kg/dose once daily
>5.66 mg/dL	10 mg/kg/dose every 48 hours or 5 mg/kg/dose once daily

Dose liver disease:

 No dosage adjustment is necessary.

Side effects caused:

Body System	Common	Less Common
Central nervous system	Headache (oral: 50%)	Fatigue (oral: 5%)
Gastrointestinal	Abdominal pain (oral: 20%)	-
Hematologic & oncologic	-	Anemia (oral: 6%)
Neuromuscular & skeletal	Back pain (oral: 21%)	Arthralgia (oral: 7%)
	Musculoskeletal pain (oral: 11%)	Muscle cramps (oral: ≤7%)
Respiratory	Nasal signs and symptoms (oral: 25%; including sinus symptoms)	-

Tranexamic Acid Contraindication:

Tranexamic acid injection or oral use is contraindicated in patients who have hypersensitivity to tranexamic acid or any component of the formulation.

Injection is also contraindicated in patients with acquired defective color vision, active intravascular clotting, and subarachnoid hemorrhage.

However, short-term use of tranexamic acid is a reasonable treatment option in select patients with aneurysmal subarachnoid hemorrhage when definitive treatment of the aneurysm is unavoidably delayed and no other contraindications exist.

Oral use is contraindicated in patients with active thromboembolic disease, history of thrombosis or thromboembolism, including retinal vein or retinal artery occlusion, intrinsic risk of thrombosis or thromboembolism, and concurrent use of combination hormonal contraception.

Canadian labeling also contraindicates tranexamic acid injection or oral use in patients with a history or risk of thrombosis, unless concurrent anticoagulation therapy is possible, and those with hematuria.

Warnings/Precautions

Considerations related to Side Effects:

Side Effect	Description
CNS depression	May impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
Hypersensitivity reactions	Severe hypersensitivity reactions, including anaphylaxis or anaphylactoid reaction have been reported.
Ocular effects	Visual defects (eg, color vision change, visual loss) and retinal venous and arterial occlusions have been reported. Discontinue treatment if ocular changes occur; prompt ophthalmic examination should be performed by an ophthalmologist. The injection is contraindicated in patients with acquired defective color vision. Ligneous conjunctivitis has been reported with the oral formulation, but resolved upon discontinuation of therapy.
Seizure	Seizures have been reported with use, most often with intraoperative use (eg, open chamber cardiac surgery) and in older patients. The mechanism by which tranexamic acid use results in seizures may be secondary to neuronal GABA and glycine inhibition or cerebral emboli.
Thrombotic events	Venous and arterial thrombosis or thromboembolism, including central retinal artery/vein obstruction, has been reported. Use the injection with caution in patients with thromboembolic disease. The oral formulation is contraindicated in patients with a history of or active thromboembolic disease or with an intrinsic risk of thromboembolic events. Concomitant use with certain procoagulant agents may further increase the risk of thrombosis.
Ureteral obstruction	Use the injection with caution in patients with upper urinary tract bleeding, ureteral obstruction due to clot formation has been reported.

Considerations related to medical conditions:

Medical Condition	Concerns
Disseminated intravascular coagulation (DIC)	Use antifibrinolytic therapy in patients with DIC only under strict supervision of a healthcare provider experienced in treating this disorder.
Renal impairment	Administer with caution in patients with renal impairment and adjust the dosage accordingly.
Subarachnoid hemorrhage (SAH)	Use with caution in patients with SAH as it may cause cerebral edema and infarction. While the manufacturer's labeling contraindicates the use of the injection in patients with SAH, some studies have found it to be a suitable treatment option for select patients with aneurysmal SAH (ASA [Connolly 2012]).
Vascular disease	Use with caution in patients with uncorrected cardiovascular or cerebrovascular disease due to the complications of thrombosis.

Drug Interactions

Drug/Interaction	Effect	Risk	Recommendation
Tretinoin (Systemic)	May enhance the thrombogenic effect of Antifibrinolytic Agents	C	Monitor therapy
Anti-inhibitor Coagulant Complex (Human)	Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human)	X	Avoid combination
Estrogen Derivatives (Contraceptive)	May enhance the thrombogenic effect of Tranexamic Acid	X	Avoid combination
Progestins (Contraceptive)	May enhance the thrombogenic effect of Tranexamic Acid	X	Avoid combination

Monitoring Parameters

When patients receive treatment for several days or more, their eyes should be checked at the start and regularly during therapy. This includes checking how well they can see, testing their color vision, and examining the back of their eyes and their visual fields. Doctors should also watch out for any signs of allergies, seizures, blood clots, or blockages in the tubes that carry urine from the kidneys to the bladder.

Tranexamic Acid Mechanism of Action:

Tranexamic acid forms a reversible complex that displaces plasminogen from fibrin, leading to the inhibition of fibrinolysis.

Additionally, it inhibits the proteolytic activity of plasmin. By decreasing plasmin activity, tranexamic acid reduces the activation of complement and the consumption of C1 esterase inhibitor (C1-INH).

Consequently, this decreases inflammation associated with hereditary angioedema.

Distribution:

• The volume of distribution (Vd) ranges from 9 to 12 L, with cerebrospinal fluid (CSF) levels accounting for 10% of plasma levels.

Protein binding:

• Protein binding is around 3%, mainly to plasminogen.

Bioavailability:

• Bioavailability via oral administration is approximately 45%.

Half-life elimination:

• The elimination half-life ranges from 2 to 11 hours,

Time to peak:

• The time taken to reach peak concentration after oral administration is 2.5 hours, with a range of 1 to 5 hours.

Excretion:

• The drug is excreted via urine, with over 95% being eliminated unchanged.

Top of Form

Tranexamic Acid International Brands:

• Amchafibrin

• Anaxyl

• Aneptil

• Azeptil

• Bionex

• Caprilon

• Ciclokapron

• Cyclokapron

• Cyklokapron

• Duhemos

• Espercil

• Exacyl

• Fimoplas

• Gemaxam

• Gemotran

• Haemostop

• Hemisan

• Hemoblock

• Hemoclot

• Hemokapron

• Hemostan

• Hemotrex

• Hexakapron

• Kalnex

• Lunex

• Lysteda

• Medsamic

• Nexa

• Nobleed

• Pilexam

• Qualixamin

• Ranexid

• Rikaparin

• Ronex

• Sangera

• Tiren

• Tracid

• Tramic

• Tranarest

• Tranex

• Tranexam

• Tranexic

• Tranexid

• Tranlok

• Tranmix

• Transamin

• Transamina

• Transic

• Tranxa

• Traxan

• Trenaxin

• Zamic