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Tranexamic acid: Drug information

Tranexamic acid: Drug information
(For additional information see "Tranexamic acid: Patient drug information" and see "Tranexamic acid: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Cyklokapron;
  • Lysteda
Brand Names: Canada
  • Cyklokapron;
  • Erfa-Tranexamic;
  • GD-Tranexamic Acid;
  • MAR-Tranexamic Acid
Pharmacologic Category
  • Antifibrinolytic Agent;
  • Antihemophilic Agent;
  • Hemostatic Agent;
  • Lysine Analog
Dosing: Adult

The adult dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editor: Edith A Nutescu, PharmD, MS, FCCP.

Note: Safety: Higher total IV doses (eg, ≥50 mg/kg), such as those given perioperatively, may be associated with an increased risk of seizures; lower doses (eg, 1 or 2 g given in the first 8 hours of trauma) do not appear to increase the risk of seizure or venous thromboembolism (CRASH-3 Trial Collaborators 2019; Fillingham 2018a; Lecker 2016; Myles 2017; Sigaut 2014).

Dental procedures in patients on oral anticoagulant therapy

Dental procedures in patients on oral anticoagulant therapy (off-label use):

Oral rinse: 5% solution (extemporaneously prepared): Administer 5 to 10 minutes prior to the procedure; hold 5 to 10 mL in mouth and rinse for 2 minutes; drain gently, being careful not to forcibly spit and dislodge clots; do not eat or drink for 1 hour after using oral rinse. Repeat 3 to 4 times daily for 1 to 2 days after the procedure (ACCP [Douketis 2012]; Borea 1993; Gaspar 1997; Lam 2011; Patatanian 2006).

Hemoptysis, treatment

Hemoptysis (nonmassive), treatment (off-label use):

Inhalation for nebulization: 500 mg (using injectable solution) 3 times daily for up to 5 days (Segrelles 2016; Wand 2018).

Hereditary angioedema, long-term prophylaxis

Hereditary angioedema, long-term prophylaxis (alternative agent) (off-label use):

Note: May be used when other agents (eg, C1 inhibitor, human monoclonal antibody) are not available or contraindicated (US HAEA [Busse 2021]).

Oral: Initial: 500 to 650 mg two to three times daily; titrate gradually based on response and tolerability; usual daily dose: 3 g/day (US HAEA [Busse 2021]; Zuraw 2022).

Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites

Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites (alternative agent) (off-label use):

Note: May be used in carefully selected patients in whom local therapy and other management options are insufficient.

Oral: Initial: 1.5 g twice daily or 1 g three times daily for 4 to 10 days; adjust dose as needed based on response and tolerability to a usual daily dose of 2 to 4.5 g in 2 or 3 divided doses (Gaillard 2014; Geisthoff 2014; Pabinger 2017).

Intracranial hemorrhage associated with thrombolytic treatment

Intracranial hemorrhage associated with thrombolytic treatment (alternative therapy) (off-label use):

Note: Consider for use in addition to cryoprecipitate or when cryoprecipitate is contraindicated in patients who have a symptomatic intracranial hemorrhage after receiving thrombolytic within the past 24 hours (NCS/SCCM [Frontera 2016]).

IV: 1 g (or 10 to 15 mg/kg) once; administer at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes) (AHA/ASA [Powers 2018]; NCS/SCCM [Frontera 2016]).

Menstrual bleeding, heavy

Menstrual bleeding, heavy (alternative agent):

Note: Consider for use in women who decline or should not use hormonal therapy. Start once heavy menstrual bleeding has begun.

Oral:

Lysteda: 1.3 g three times daily for up to 5 days during monthly menstruation.

Cyklokapron [Canadian product]: 1 to 1.5 g three to four times daily for several days during menstruation.

Perioperative prevention of blood loss and transfusion

Perioperative prevention of blood loss and transfusion (eg, cardiac surgery, other surgeries with significant blood loss):

Note: There is wide variety in doses and routes of administration (IV, oral, and/or topical). Dosing and timing of administration are procedure and institution specific. Recommendations provided below are examples of IV regimens for use in selected surgeries; refer to institutional protocols.

Usual dose and range: IV: 1 g (or 10 to 30 mg/kg) prior to procedure; administer at a rate not to exceed 100 mg/minute (generally over 10 to 30 minutes). Depending upon type of procedure, a continuous infusion may be given intraoperatively after the initial bolus dose, or the bolus dose may be repeated at the end of procedure and/or during the postoperative period.

Cardiac surgery (off-label use):

Note: Optimal regimen is uncertain; refer to institutional protocol.

IV: Loading dose: 10 to 30 mg/kg administered at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 16 mg/kg/hour (Fergusson 2008; Nuttall 2008; Sigaut 2014). Alternatively, some centers administer a single loading dose of 50 mg/kg (Myles 2017).

Orthopedic surgery (hip or knee arthroplasty) (off-label use):

Note: Optimal regimen is uncertain; refer to institutional protocol. Use in patients without a baseline high risk of thromboembolism. For patients with risk factors for thromboembolism, consider risk of thromboembolism vs benefit of reduced blood loss (Amundson 2022).

IV: 1 g (or 10 to 15 mg/kg) administered before skin incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes); repeat dose at skin closure or up to 12 hours later; some experts recommend a third dose during the postoperative period if needed (AAHKS/ASRA/AAOS [Fillingham 2018b]; Erens 2019; Kim 2014; MacGillivray 2011; Maniar 2012; Martin 2020; Xiao 2019; Zufferey 2010). Note: Some experts use intra-articular tranexamic acid (ie, 1 g per 50 mL of NS applied topically into the wound at the end of the procedure) (AAHKS/ASRA/AAOS [Fillingham 2018b]; Alshryda 2013a; Alshryda 2013b).

Spinal surgery (eg, spinal fusion) (off-label use):

Note: Optimal regimen is uncertain; refer to institutional protocol.

IV: 10 to 15 mg/kg administered prior to incision at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), followed by 1 to 2 mg/kg/hour as a continuous infusion for the remainder of the surgery; discontinue at the end of the procedure (Brown 2021; Lu 2018; Wong 2008).

Postpartum hemorrhage, prevention

Postpartum hemorrhage, prevention (adjunctive therapy) (off-label use):

Note: For use in women in high–bleeding risk situations in conjunction with standard prophylactic uterotonics (eg, oxytocin) (Berghella 2021; Muñoz 2019).

IV: 1 g (or 10 to 15 mg/kg) over 10 to 20 minutes (Berghella 2021; Saccone 2019); some experts administer before skin incision for cesarean deliveries and after cord clamping for vaginal deliveries (Berghella 2021).

Postpartum hemorrhage, treatment

Postpartum hemorrhage, treatment (off-label use):

Note: For continued bleeding despite oxytocin; used in conjunction with other therapies/procedures.

IV: 1 g over 10 to 20 minutes given within 3 hours of vaginal birth or cesarean delivery. If bleeding continues after 30 minutes, may repeat the dose in conjunction with thorough re-evaluation for cause of continued or recurrent bleeding (WOMAN Trial Collaborators 2017).

Tooth extraction in patients with hemostatic defects

Tooth extraction in patients with hemostatic defects (eg, hemophilia, von Willebrand disease, other factor deficiencies associated with bleeding) (adjunctive therapy):

Note: Generally used in conjunction with (and not as a substitute for) replacement of the appropriate clotting factor, especially in individuals with hemophilia. Do not give simultaneously with an activated prothrombin complex concentrate, as this can increase the risk of thromboembolism; if used concurrently, they should be separated by ≥12 hours (WFH [Srivastava 2013]). Consultation with a hemophilia treatment center is advised.

IV: 10 mg/kg using actual body weight (usual dose range: 500 mg to 1 g) administered ~2 hours before procedure at a rate not to exceed 100 mg/minute (generally over 10 to 20 minutes), then 10 mg/kg 3 to 4 times daily for 2 to 8 days. Alternatively, 10 mg/kg as a single dose ~2 hours prior to procedure; following procedure, transition to oral tranexamic acid depending on individual patient characteristics, type of procedure, other therapies, and degree of bleeding (Bérubé 2021; Cyklokapron Canadian product monograph; van Galen 2019).

Oral: 25 mg/kg (usual dose range: 1 to 1.5 g) given 2 hours prior to procedure, then 25 mg/kg (usual dose range: 1 to 1.5 g) 3 to 4 times daily for up to 7 to 10 days (Bérubé 2021; Cyklokapron Canadian product monograph; Hoots 2021; van Galen 2019).

Trauma-associated hemorrhage or traumatic brain injury

Trauma-associated hemorrhage or traumatic brain injury (off-label use):

Note: Consider for use in patients with significant hemorrhage, at risk of significant hemorrhage, or in moderate traumatic brain injury (TBI) (Glasgow Coma Scale [GCS] score >8 and <13); patients with severe TBI (GCS score 3 to 8) may not demonstrate benefit (CRASH-2 Trial Collaborators 2010; CRASH-3 Trial Collaborators 2019; Rajajee 2020).

IV: Loading dose: 1 g over 10 minutes started within 3 hours of injury, followed by 1 g over the next 8 hours as a continuous infusion. Note: Some experts suggest using thromboelastogram or rotational thromboelastometry to guide therapy (Callum 2019; Colwell 2021; CRASH-2 Trial Collaborators 2010; CRASH-2 Trial Collaborators 2011; CRASH-3 Trial Collaborators 2019; Galvagno 2019).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Tranexamic acid is >95% eliminated by the kidney. Dosing recommendations may vary by institution; also consult institutional protocols. No dosage adjustment necessary for indications requiring only 1 to 2 doses (expert opinion). Tranexamic acid oral rinses have limited absorption (Sindet-Pedersen 1987); therefore, the need for renal dose adjustment is unlikely when used for a limited period of time (expert opinion). There are no data on bioavailability of tranexamic acid administered via nebulization; renal dose adjustment recommendations cannot be provided; use with caution (expert opinion).

Altered kidney function:

IV:

Intermittent injection (Andersson 1978; manufacturer's labeling; expert opinion): Note: The following adjustments are based on a usual recommended dose of 10 mg/kg or 1 g 3 to 4 times daily.

Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.

Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 micromol/L to <250 micromol/L): Administer usual dose twice daily.

Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.

Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours or 50% of the usual dose once daily.

Continuous infusion:

General recommendations (Jerath 2018; Yang 2015): Note: Developed using the principal that % to be administered is (actual GFR divided by normal GFR) × 100%, with normal GFR = 90 mL/minute/1.73 m2. Recommendations should only be considered for cardiac or spinal indications; not applicable to trauma patients (expert opinion).

Maintenance infusion following loading dose:

eGFR ≥90 mL/minute/1.73 m2: Administer 100% of the usual maintenance rate.

eGFR 60 to <90 mL/minute/1.73 m2: Administer 66% to 100% of the usual maintenance rate.

eGFR ≥30 to <60 mL/minute/1.73 m2: Administer 33% to 66% of the usual maintenance rate.

eGFR <30 mL/minute/1.73 m2: Administer 17% to 33% of the usual maintenance rate.

Cardiac surgery regimen-specific examples: Note: These are examples of published regimens utilizing a continuous infusion; optimal regimen is uncertain; also refer to institutional protocol.

eGFR-based regimen (BART regimen) (Jerath 2018):

eGFR ≥90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 16 mg/kg/hour.

eGFR 60 to <90 mL/minute/1.73 m2: Loading dose: 30 mg/kg followed by 11 to 16 mg/kg/hour.

eGFR >30 to <60 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 5 to 10 mg/kg/hour.

eGFR ≤30 mL/minute/1.73 m2: Loading dose: 25 to 30 mg/kg followed by 3 to 5 mg/kg/hour.

Serum creatinine-based regimen (Nuttall 2008):

Serum creatinine 1.6 to 3.3 mg/dL: Reduce maintenance infusion to 1.5 mg/kg/hour (based on a 25% reduction from 2 mg/kg/hour).

Serum creatinine 3.3 to 6.6 mg/dL: Reduce maintenance infusion to 1 mg/kg/hour (based on a 50% reduction from 2 mg/kg/hour).

Serum creatinine >6.6 mg/dL: Reduce maintenance infusion to 0.5 mg/kg/hour (based on a 75% reduction from 2 mg/kg/hour).

Oral (Andersson 1978; expert opinion): Note: The following adjustments are based on a usual recommended dose of 10 to 15 mg/kg or 1 to 1.5 g 3 to 4 times daily.

Serum creatinine <1.4 mg/dL (<120 micromol/L): No dosage adjustment necessary.

Serum creatinine ≥1.4 to <2.8 mg/dL (≥120 to <250 micromol/L): Administer usual dose twice daily.

Serum creatinine ≥2.8 to <5.7 mg/dL (≥250 to <500 micromol/L): Administer usual dose once daily.

Serum creatinine ≥5.7 mg/dL (≥500 micromol/L): Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours.

Hemodialysis, intermittent (thrice weekly): Likely to be dialyzable (low protein binding, low Vd [expert opinion]): Note: Because tranexamic acid is dialyzable, schedule intermittent doses after hemodialysis when possible.

IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Pavord 2011; expert opinion).

IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (Jerath 2018; expert opinion).

Peritoneal dialysis: Likely to be dialyzable (low protein binding, low Vd [expert opinion]).

IV (intermittent injection), Oral: Administer usual dose every 48 hours, or 50% of the usual dose every 24 hours (Pavord 2011; expert opinion).

IV (continuous infusion): Dose as for eGFR <30 mL/minute/1.73 m2 (expert opinion).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.

IV (intermittent injection), Oral: Administer usual dose twice daily (expert opinion).

IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (expert opinion).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, seizures, thrombotic events) due to drug accumulation is important.

IV (intermittent injection), Oral: Administer usual dose twice daily (expert opinion).

IV (continuous infusion): Dose as for eGFR 30 to 60 mL/minute/1.73 m2 (expert opinion).

Dosing: Hepatic Impairment: Adult

No dosage adjustment is necessary.

Dosing: Pediatric

(For additional information see "Tranexamic acid: Pediatric drug information")

Diffuse alveolar hemorrhage (intractable), treatment: Very limited data available (Bafaqih 2015), ideal dose-response not established:

Children ≤25 kg: Inhaled: 250 mg every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.

Children >25 kg and Adolescents: Inhaled: 500 mg inhaled every 6 hours for 3 to 4 doses (18 to 24 hours); if response occurs, continue treatment for another 2 to 3 doses after bleeding completely stops; if no or minimal response or bleeding worsens, add inhaled recombinant factor VIIa; maximum duration of inhaled therapy: 3 days.

Dosing based on a prospective pilot study of 18 children (median age: 24 months [interquartile range: 11.3 to 58.5 months]) with intractable diffuse alveolar hemorrhage (DAH) who received inhaled tranexamic acid; DAH responded to inhaled tranexamic treatment alone in 10 children (56%); the 8 nonresponders had inhaled recombinant factor VIIa added; 75% (n=6) of these patients had complete cessation of DAH; none of the patients who responded to treatment had recurrence or complications reported (Bafaqih 2015). Two retrospective studies have reported doses of 250 to 500 mg every 6 to 12 hours until resolution of bleeding for pulmonary hemorrhages (Bernardo 2019; O'Neil 2020).

Hereditary angioedema (HAE), prophylaxis: Limited data available:

Long-term prophylaxis: Note: Not the preferred treatment option; reserve use for when C1-inhibitor concentrate is unavailable (WOA/EAACI [Maurer 2018]).

Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; doses up to 75 mg/kg/day have been reported; maximum daily dose range: 3,000 to 6,000 mg/day (Bowen 2010; Farkas 2007; Gompels 2005; Hereditary Angioedema International Working Group [Farkas 2017]; WOA/EAACI [Maurer 2018]; Zuraw 2013); may consider alternate-day regimen or twice-weekly regimen when frequency of attacks reduces (Gompels 2005).

Short-term prophylaxis (eg, prior to surgical or diagnostic interventions in head/neck region): Note: Not the preferred treatment option; some experts do not recommend use for short-term prophylaxis (Hereditary Angioedema International Working Group [Farkas 2017]; WOA/EAACI [Maurer 2018]).

Weight directed: Children and Adolescents: Oral: 20 to 50 mg/kg/day in 2 to 3 divided doses; maximum daily dose range: 3,000 to 6,000 mg/day; initiate therapy at least 5 days before and continue for 2 days postprocedure (Hereditary Angioedema International Working Group [Farkas 2017]).

Fixed dosing: Children and Adolescents: Patients with an adequate weight (eg, ≥50 kg): Oral: 500 mg 4 times daily (Gompels 2005); therapy usually initiated 2 to 5 days before dental work and continue for 2 days after the procedure (Bowen 2004; Gompels 2005).

Menstrual bleeding, heavy: Postmenarche female: Tablet (Lysteda): Oral: 1,300 mg 3 times daily for up to 5 days during monthly menstruation; maximum daily dose: 3,900 mg/day.

Prevention of bleeding associated with tooth extraction in hemophilic patients: Note: Use 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 for 2 to 8 days.

Prevention of perioperative bleeding: Limited data available; reported regimens variable and ideal dose-response not established:

General dosing (non-cardiac): Infants, Children, and Adolescents: IV: Loading dose: 10 to 30 mg/kg followed by a continuous IV infusion at 5 to 10 mg/kg/hour; dosing based on a pharmacokinetic model to achieve a target serum concentration of 20 mcg/mL and 70 mcg/mL, respectively (Goobie 2019).

Cardiac surgery with cardiopulmonary bypass: Infants, Children, and Adolescents:

Low dose: IV: Loading dose: 10 mg/kg followed by a continuous IV infusion at 5 mg/kg/hour; dosing based on a pharmacokinetic model to achieve a target serum concentration of 20 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 20 mcg/mL (Goobie 2019). A pharmacokinetic analysis (n=43; mean age: 123 days [range: 6 to 348 days]; mean weight: 4.95 kg [range: 2.3 to 9.5 kg]) targeting a serum concentration of 20 mcg/mL proposed the following regimen: Loading dose: 10 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until initiation of cardiopulmonary bypass, then IV priming bolus: 4 mg/kg into the bypass prime volume, followed by a continuous IV infusion at 4 mg/kg/hour (Gertler 2017). Another regimen studied in 2 trials (n=80; age range: 2 months to 15 years) is 10 mg/kg into the bypass circuit after induction, during cardiopulmonary bypass, and after protamine reversal of heparin for a total of 3 doses (Chauhan 2004a; Chauhan 2004b). A pharmacokinetic analysis has proposed the following regimen to achieve a target serum concentration range of 20 to 30 mcg/mL in children 1 to 12 years and weighing 5 to 40 kg: IV: Loading dose: 6.4 mg/kg over 5 minutes followed by a weight-adjusted continuous IV infusion in the range of 2 to 3.1 mg/kg/hour; the pharmacokinetic data showed that patients weighing less should receive an initial continuous IV infusion rate at the higher end of the range (ie, if patient weight=5 kg then initial continuous IV infusion rate: 3.1 mg/kg/hour; if patient weight=40 kg then initial continuous IV infusion rate: 2 mg/kg/hour) (Grassin-Delyle 2013).

Intermediate dose: IV: Loading dose: 30 mg/kg followed by a continuous IV infusion at 10 mg/kg/hour; dosing based on a pharmacokinetic model to achieve a target serum concentration of 70 mcg/mL; tranexamic acid must also be added to cardiopulmonary bypass solution at a concentration of 70 mcg/mL (Goobie 2019).

High dose: IV: Loading dose: 50 mg/kg, followed by a continuous IV infusion at 15 mg/kg/hour and 50 mg/kg priming dose into the circuit when bypass initiated (Goobie 2019; Shimizu 2011); dosing based on a pharmacokinetic model to achieve a target serum concentration of 150 mcg/mL (Goobie 2019).

Spinal surgery (eg, idiopathic scoliosis): Children ≥8 years and Adolescents: IV: Loading dose: 100 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Sethna 2005; Shapiro 2007). Other reported regimens with positive results: Loading dose: 20 mg/kg, followed by a continuous IV infusion at 10 mg/kg/hour (Grant 2009); loading dose: 10 mg/kg, followed by a continuous IV infusion at 1 mg/kg/hour (Grant 2009; Neilipovitz 2001); loading dose: 50 mg/kg, followed by a continuous IV infusion at 5 mg/kg/hour (Johnson 2017).

Craniosyntosis surgery: Infants ≥2 months and Children ≤6 years: IV: Loading dose: 50 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 5 mg/kg/hour until skin closure (Goobie 2011; Martin 2016) or loading dose: 15 mg/kg over 15 minutes prior to incision, followed by a continuous IV infusion at 10 mg/kg/hour until skin closure (Dadure 2011). Other reported regimens with positive results: Loading dose: 10 mg/kg at start of surgery, followed by a continuous IV infusion at 5 mg/kg/hour for 24 hours postoperatively (Kurnik 2017).

Trauma, hemorrhagic (acute traumatic coagulopathy): Limited data available: Note: Reported regimens are variable and ideal dose-response is not established:

Children <12 years: IV: Loading dose: 15 mg/kg over 10 minutes given within 3 hours of injury (maximum dose: 1,000 mg/dose), followed by continuous IV infusion at 2 mg/kg/hour for ≥8 hours or until bleeding stops (Beno 2014; Royal College of Pediatrics and Child Health 2012).

Children ≥12 years and Adolescents: IV: Loading dose: 1,000 mg over 10 minutes given within 3 hours of injury, followed by 1,000 mg infused over 8 hours (Beno 2014; Royal College of Pediatrics and Child Health 2012).

Traumatic hyphema: Limited data available: Children and Adolescents: Oral: 25 mg/kg/dose every 8 hours for 5 to 7 days (Gharaibeh 2019; Rahmani 1999; Vangsted 1983). Note: This same regimen may also be used for secondary hemorrhage after an initial traumatic hyphema event.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Note: Recommendations are dependent on use and route.

Oral:

Menorrhagia: Female Children ≥12 years and Adolescents:

Scr >1.4 to ≤2.8 mg/dL: 1,300 mg twice daily for up to 5 days during monthly menstruation.

Scr >2.8 to ≤5.7 mg/dL: 1,300 mg once daily for up to 5 days during monthly menstruation.

Scr >5.7 mg/dL: 650 mg once daily for up to 5 days during monthly menstruation.

Prophylaxis of hereditary angioedema: Children and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Hereditary Angioedema International Working Group [Farkas 2017]).

IV:

Tooth extraction in patients with hemophilia: Infants, Children, and Adolescents:

Scr 1.36 to ≤2.83 mg/dL: Maintenance dose of 10 mg/kg/dose twice daily.

Scr >2.83 to ≤5.66 mg/dL: Maintenance dose of 10 mg/kg/dose once daily.

Scr >5.66 mg/dL: Maintenance dose of 10 mg/kg/dose every 48 hours or 5 mg/kg/dose every 24 hours.

Prophylaxis or treatment of mild to major bleeding secondary to trauma or surgery : Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, due to risk of accumulation with kidney impairment, dosage adjustments are recommended (Goobie 2019).

Dosing: Hepatic Impairment: Pediatric

Infants, Children, and Adolescents: No adjustment is necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 1000 mg/10 mL (10 mL)

Solution, Intravenous [preservative free]:

Cyklokapron: 1000 mg/10 mL (10 mL)

Generic: 1000 mg/10 mL (10 mL); 1000 mg/100 mL in NaCl 0.7% (100 mL)

Tablet, Oral:

Lysteda: 650 mg

Generic: 650 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Cyklokapron: 100 mg/mL (5 mL, 10 mL)

Generic: 100 mg/mL (5 mL, 10 mL, 50 mL); 1000 mg/10 mL (10 mL)

Tablet, Oral:

Cyklokapron: 500 mg

Generic: 500 mg

Administration: Adult

Inhalation via nebulization (off-label use/route): Administer over 15 minutes via jet nebulizer (Segrelles 2016; Wand 2018).

Injection: For indications requiring a loading dose (eg, trauma-associated hemorrhage, perioperative prevention of blood loss and transfusion), may administer undiluted by IV injection at a maximum rate of 100 mg/minute (Crash-trial collaborators 2010; Elwatidy 2008; WOMAN Trial Collaborators 2017); faster rates may cause hypotension. For continuous IV infusions, dilute with compatible solutions and administer at a rate not to exceed 100 mg/minute.

Oral: Administer without regard to meals. Swallow tablet whole; do not break, chew, or crush.

Administration: Pediatric

Oral: Administer without regard to meals; tablets should be swallowed whole; do not break, split, chew, or crush.

Parenteral:

Intermittent IV dose: May be administered undiluted by direct IV injection at a maximum rate of 100 mg/minute; faster rates may cause hypotension.

Continuous IV infusion:

Loading dose: May be administered either undiluted or diluted in a compatible diluent; infuse over 5 to 15 minutes (Beno 2014; Dadure 2011; Goobie 2011; Neilipovitz 2001; Reid 1997; Royal College of Pediatrics and Child Health 2012; Sethna 2005). Neonatal patients received loading doses over 60 minutes (Keijzer 2012).

IV infusion: Following dilution, administer by continuous IV infusion at a rate not to exceed 100 mg/minute.

Inhalation: Administer undiluted (100 mg/mL) by jet nebulization (Bafaqih 2015); time for nebulization average 15 minutes in adults (Segrelles 2016).

Use: Labeled Indications

Menstrual bleeding, heavy (oral): Treatment of cyclic heavy menstrual bleeding in females of reproductive potential.

Tooth extraction in patients with hemostatic defects (injection, oral [Cyklokapron; Canadian product]): Short-term use in hemophilia patients to reduce or prevent hemorrhage and reduce need for replacement therapy during and following tooth extraction.

Use: Off-Label: Adult

Dental procedures in patients on oral anticoagulant therapy; Hemoptysis (nonmassive), treatment; Hereditary angioedema, long-term prophylaxis; Hereditary hemorrhagic telangiectasia, epistaxis or other bleeding sites; Intracranial hemorrhage associated with thrombolytic treatment; Perioperative prevention of blood loss and transfusion, cardiac surgery; Perioperative prevention of blood loss and transfusion, orthopedic surgery (hip or knee arthroplasty); Perioperative prevention of blood loss and transfusion, spinal surgery; Postpartum hemorrhage, prevention; Postpartum hemorrhage, treatment; Trauma-associated hemorrhage or traumatic brain injury

Medication Safety Issues
Sound-alike/look-alike issues:

Cyklokapron may be confused with cycloSPORINE

TXA (occasional abbreviation for tranexamic acid) is an error-prone abbreviation (mistaken as TNK an error-prone abbreviation for tenecteplase and tPA an error-prone abbreviation for alteplase)

Administration issues:

Inadvertent administration of tranexamic acid by the epidural or spinal route during neuraxial (eg, epidural, spinal) anesthesia has led to potentially fatal neurotoxic adverse reactions. Care should be taken when evaluating storage procedures within the surgical suite, including separating tranexamic acid from local anesthetics; additional prevention measures, including purchasing, dispensing, and administration, should be considered (ISMP [Smetzer] 2019; NAN Alert 2020; Patel 2019).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with oral formulation unless otherwise noted.

>10%:

Gastrointestinal: Abdominal pain (20%)

Nervous system: Headache (50%)

Neuromuscular & skeletal: Back pain (21%), musculoskeletal pain (11%)

Respiratory: Nasal signs and symptoms (25%; including sinus symptoms)

1% to 10%:

Hematologic & oncologic: Anemia (6%)

Nervous system: Fatigue (5%)

Neuromuscular & skeletal: Arthralgia (7%), muscle cramps ( ≤7%), muscle spasm (≤7%)

Postmarketing (all formulations):

Cardiovascular: Arterial thromboembolism, arterial thrombosis, cerebral thrombosis, deep vein thrombosis, hypotension (with rapid IV injection), pulmonary embolism, venous thromboembolism, venous thrombosis

Dermatologic: Allergic dermatitis, allergic skin reaction

Gastrointestinal: Diarrhea, nausea, vomiting

Hypersensitivity: Anaphylactic shock, anaphylaxis, hypersensitivity reaction, nonimmune anaphylaxis, severe hypersensitivity reaction

Nervous system: Dizziness, seizure (Lecker 2016)

Ophthalmic: Chromatopsia, conjunctivitis (ligneous), retinal artery occlusion, retinal vein occlusion, vision color changes, visual disturbance, visual impairment

Renal: Renal cortical necrosis

Contraindications

Hypersensitivity to tranexamic acid or any component of the formulation.

Injection: Active intravascular clotting; subarachnoid hemorrhage.

Oral: Active thromboembolic disease (eg, cerebral thrombosis, DVT, or pulmonary embolism); history of thrombosis or thromboembolism, including retinal vein or retinal artery occlusion; intrinsic risk of thrombosis or thromboembolism (eg, hypercoagulopathy, thrombogenic cardiac rhythm disease, thrombogenic valvular disease); concurrent use of combination hormonal contraception; patients who may become pregnant.

Canadian labeling: Additional contraindications (not in the US labeling): Injection, oral: History or risk of thrombosis (unless concurrent anticoagulation therapy is possible); hematuria; epidural administration; intrathecal administration.

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: May cause dizziness, which 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. Discontinue use if serious reactions occur; do not reinitiate treatment.

• 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, including dilated retinal examination, should be performed by an ophthalmologist. Ligneous conjunctivitis has been reported with the oral formulation but resolved upon discontinuation of therapy. Consider ophthalmic monitoring at regular intervals in patients on long-term therapy (>3 months).

• Seizure: Seizures have been reported with use; most often with intraoperative use (eg, open chamber cardiac surgery and in patients inadvertently administered into the neuraxial system) and in older patients (Murkin 2010). The mechanism by which tranexamic acid use results in seizures may be secondary to neuronal GABA and glycine inhibition or cerebral emboli (Levy 2018). Consider EEG monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or evidence of focal seizures. Discontinue use if seizures occur.

• 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; oral formulation is contraindicated in patients with a history of or active thromboembolic disease or with an intrinsic risk of thromboembolic events (eg, thrombogenic valvular disease, thrombogenic cardiac rhythm disease, hypercoagulopathy). Concomitant use with certain procoagulant agents (eg, anti-inhibitor coagulant complex/factor IX complex concentrates, oral tretinoin, hormonal contraceptives) may further increase the risk of thrombosis; concurrent use with either the oral or injectable formulation may be contraindicated, not recommended, or to be used with caution.

Disease-related concerns:

• Disseminated intravascular coagulation: Use with extreme caution in patients with disseminated intravascular coagulation requiring antifibrinolytic therapy; patients should be under strict supervision of a health care provider experienced in treating this disorder.

• Renal impairment: Use with caution in patients with renal impairment; dosage modification necessary.

• Subarachnoid hemorrhage: Use with caution in patients with subarachnoid hemorrhage; cerebral edema and infarction may occur.

• Vascular disease: Use with caution in patients with uncorrected cardiovascular or cerebrovascular disease due to the complications of thrombosis.

Metabolism/Transport Effects

None known.

Drug Interactions

Anti-inhibitor Coagulant Complex (Human): Antifibrinolytic Agents may enhance the thrombogenic effect of Anti-inhibitor Coagulant Complex (Human). Risk X: Avoid combination

Estrogen Derivatives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

Factor IX Complex (Human) [(Factors II, IX, X)]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Factor IX Complex (Human) [(Factors II, IX, X)]. Specifically, the risk for thrombosis may be increased. Risk X: Avoid combination

Hormonal Contraceptives: May enhance the thrombogenic effect of Tranexamic Acid. Risk X: Avoid combination

Prothrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]: Antifibrinolytic Agents may enhance the adverse/toxic effect of Prothrombin Complex Concentrate (Human) [(Factors II, VII, IX, X), Protein C, and Protein S]. Specifically, the risk for thrombosis may be increased. Risk X: Avoid combination

Thrombolytic Agents: Tranexamic Acid may diminish the therapeutic effect of Thrombolytic Agents. Thrombolytic Agents may diminish the therapeutic effect of Tranexamic Acid. Risk X: Avoid combination

Tretinoin (Systemic): May enhance the thrombogenic effect of Antifibrinolytic Agents. Management: Concomitant use of antifibrinolytics and tretinoin is not recommended. If combined, monitor patients closely for any signs of thrombotic complications. Risk D: Consider therapy modification

Reproductive Considerations

Tranexamic acid is an alternative agent for the treatment of heavy menstrual bleeding and one option for females who desire future fertility (ACOG 785 2019). The manufacturer recommends non-hormonal contraception during treatment, as hormonal contraceptives may increase the risk of thromboembolic events (use of hormonal contraception is contraindicated by some manufacturers). However, tranexamic acid in combination with oral contraceptives may be considered for the treatment of heavy menstrual bleeding when monotherapy is ineffective and other treatment options have failed (ACOG 557 2013; ACOG 785 2019).

Pregnancy Considerations

Tranexamic acid crosses the placenta; concentrations within cord blood are similar to maternal serum.

Oral tranexamic acid is used off label for the long-term prophylaxis of hereditary angioedema (HAE) and use for this indication in pregnant females has been reported (González-Quevedo 2016; Machado 2017; Milingos 2009). Tranexamic acid may be considered for long-term prophylaxis of HAE during pregnancy when preferred treatment is not available (WAO/EEACI [Maurer 2018]).

IV tranexamic acid is used off label for the treatment of postpartum hemorrhage (Ducloy-Bouthors 2011; WOMAN Trial Collaborators 2017). A significant reduction in risk of death due to bleeding was observed when treatment was started within 3 hours of vaginal birth or cesarean section (WOMAN Trial Collaborators 2017). Tranexamic acid is recommended for the treatment of obstetric hemorrhage when initial therapy fails (ACOG 183 2017; WHO 2017).

IV tranexamic acid has also been studied for prophylaxis of postpartum hemorrhage in females prior to vaginal or cesarean delivery (Novikova 2015; Saccone 2019; Sentilhes 2018; Simonazzi 2016; Xia 2020). Tranexamic acid may be considered as adjunctive therapy in women at high risk for postpartum hemorrhage. However, available data related to prophylactic use is insufficient and use for routine prophylaxis against postpartum hemorrhage is not currently recommended outside of the context of clinical research (ACOG 183 2017; Muñoz 2019).

Breastfeeding Considerations

Tranexamic acid is present in breast milk.

Breast milk concentrations of tranexamic acid in lactating women were ~1% of the maximum maternal serum concentration when measured 1 hour after the last dose following 2 days of treatment (maternal dose and actual milk concentrations not provided) (Verstraete 1985).

Thromboembolic disorders were not observed in breastfed infants following maternal use of tranexamic acid for the treatment of postpartum hemorrhage (WOMAN Trial Collaborators 2017). An increased risk of adverse events was not observed in 21 breastfed infants exposed to tranexamic acid following maternal use for coagulation disorders (maternal dose range: 1.5 to 4 g/day). Authors of this study suggest taking the maternal dose immediately after breastfeeding to minimize infant exposure and monitor the infant for adverse events (Gilad 2014). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Although other agents are preferred, breastfeeding is considered acceptable during use of tranexamic acid for prophylaxis of hereditary angioedema (WAO/EEACI [Maurer 2018]).

Monitoring Parameters

Ophthalmic examination (visual acuity, optical coherence tomography) at regular intervals if on long-term therapy (>3 months); signs/symptoms of hypersensitivity reactions, seizures, and thrombotic events; in patients with trauma-associated hemorrhage, thromboelastography (TEG), or rotational thromboelastometry (ROTEM) where available (Colwell 2021).

Mechanism of Action

Forms a reversible complex that displaces plasminogen from fibrin resulting in inhibition of fibrinolysis; it also inhibits the proteolytic activity of plasmin

With reduction in plasmin activity, tranexamic acid also reduces activation of complement and consumption of C1 esterase inhibitor (C1-INH), thereby decreasing inflammation associated with hereditary angioedema.

Pharmacokinetics

Distribution: Vd: IV: 9 to 12 L; cerebrospinal fluid and aqueous humor of eye concentrations are 10% of plasma.

Protein binding: ~3%, primarily to plasminogen.

Bioavailability: Oral: ~45%.

Half-life elimination: IV: ~2 hours; Oral: ~11 hours.

Time to peak: Oral:

Single dose: Mean: 2.5 hours (range: 1 to 5 hours).

Multiple dose: Mean: 2.5 hours (range: 2 to 3.5 hours).

Excretion: Urine (>95% as unchanged drug).

Pharmacokinetics: Additional Considerations

Renal function impairment: Following administration of a single IV injection, urinary excretion declines as renal function decreases.

Pediatric: The Cmax and AUC values after a single oral dose of 1,300 mg in adolescent females were 20% to 25% less than those in adult females given the same dose.

In vitro data suggests that neonates require a lower serum tranexamic acid concentration than adults (6.54 mcg/mL vs 17.5 mcg/mL) to completely prevent fibrinolysis (Yee 2013). In pediatric patients weighing 5 to 40 kg undergoing cardiac surgery with by-pass, a target serum concentration range of 20 to 30 mcg/mL has been used in pharmacokinetic analysis (Dowd 2002; Grassin-Delyle 2013).

Pricing: US

Solution (Cyklokapron Intravenous)

1000 mg/10 mL (per mL): $3.65

Solution (Tranexamic Acid Intravenous)

1000 mg/10 mL (per mL): $0.46 - $8.68

Solution (Tranexamic Acid-NaCl Intravenous)

1000MG/100ML 0.7% (per mL): $0.25

Tablets (Lysteda Oral)

650 mg (per each): $6.52

Tablets (Tranexamic Acid Oral)

650 mg (per each): $5.21 - $5.22

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Amchafibrin (ES);
  • Anaxyl (BD);
  • Aneptil (LK);
  • Azeptil (TR);
  • Bionex (BD);
  • Caprilon (FI);
  • Ciclokapron (VE);
  • Cyclokapron (BE, CL, IS, LU, MT);
  • Cyklokapron (AE, AT, AU, BB, BH, CH, CY, DE, DK, EE, ET, FI, GB, IE, IQ, IR, JO, KW, LB, LY, NL, NO, NZ, OM, QA, SA, SE, SG, SY, YE, ZA, ZW);
  • Duhemos (VN);
  • Espercil (CL);
  • Exacyl (AE, BE, CZ, FR, HN, LB, LU, PL);
  • Fimoplas (PH);
  • Gemaxam (UA);
  • Gemotran (UA);
  • Hemanex (PH);
  • Hemoblock (EC);
  • Hemoclot (PH);
  • Hemokapron (EG);
  • Hemostan (PH);
  • Hemotrex (PH);
  • Hexakapron (IL);
  • Kalnex (ID);
  • Lunex (ID);
  • Lysteda (CR, DO, GT, HN, NI, PA, SV);
  • Medsamic (VN);
  • Morwak (ZA);
  • Nexa (ID);
  • Nobleed (LK);
  • Oilexam (DK);
  • Pilexam (NO);
  • Qualixamin (HK);
  • Ranexid (PH);
  • Rikaparin (TW);
  • Ronex (ID);
  • Sangera (UA);
  • Tiren (MY);
  • Tosano (HK);
  • Tracid (BD);
  • Tramic (TH);
  • Tranarest (IN);
  • Tranex (BD, EG, IT);
  • Tranexam (RU, TW);
  • Tranexic (TW);
  • Tranexid (ID);
  • Tranic (ZA);
  • Tranlok (LK);
  • Tranmix (VN);
  • Transamin (BR, CN, HK, JP, KR, MY, PK, TH, TW, VN);
  • Transamina (UY);
  • Transic (TH);
  • Tranxa (ID);
  • Traxan (PH);
  • Trenaxin (PH);
  • Trenolk (HR);
  • Trexacont (BR);
  • Zamic (AU)


For country abbreviations used in Lexicomp (show table)

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