Tranexamic Acid (tranexamic acid)

No dosing information is available for this tab.

Tranexamic acid is administered orally or by slow IV injection or IV infusion. The drug also has been administered topically+ (as a solution via irrigation, mouthwash, or gauze pad) for local application such as during dental procedures; however, a topical preparation is not commercially available in the US.

The manufacturers state that no drug interaction studies have been conducted with tranexamic acid.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Antifibrinolytics/Factor Ix; Anti-Inhibitor Coagulant Conc

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Concurrent use may result in additive or synergistic effects on the coagulation pathways.(1-3)

CLINICAL EFFECTS: Concurrent use may result in thrombosis.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of aminocaproic acid states that aminocaproic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates.(1) The US manufacturer of tranexamic acid states that concomitant use with Factor IX Complex concentrates or with Anti-inhibitor Coagulant concentrates should be avoided.(2,3) The Japanese manufacturer of tranexamic acid recommends caution when coadministered with drugs such as coagulation factor agents as coagulation may be further activated at sites with enhanced local fibrinolysis.(4) Concurrent use may be warranted in select patients with hemophilia A or hemophilia B or in select major trauma scenarios. Monitor patients closely for signs of thrombosis, disseminated intravascular coagulation, and hypercoagulability if concurrent use is deemed necessary.(5-13)

DISCUSSION: There is very limited data on the risk of thrombosis with combination therapy. In a study, eight hemophilia B patients undergoing dental extraction procedures received combination therapy with aminocaproic acid or tranexamic acid and monoclonal antibody purified factor IX for bleeding prophylaxis. All patients achieved hemostasis without clinical evidence of thrombosis as well as no changes were seen in hemoglobin, hematocrit, or in markers of hemostatic system activation.(5) In a study, seven hemophilia A patients with inhibitors and one with acquired hemophilia patient received activated prothrombin complex concentrate (APCC) and tranexamic acid for management of bleeding episodes and prevention of hemorrhage during surgery. Hemostatic outcomes were rated excellent or good in 10 out of 11 (91%) treatment episodes. No episodes of thrombosis or disseminated intravascular coagulation occurred during treatment.(6) A study in six hemophilia A patients and five healthy volunteers evaluated the use of tranexamic acid as an adjunct to APCC to control bleeding. Patients who received tranexamic acid had a significant increase in maximum clot firmness compared to healthy controls. No clinical or laboratory signs of thromboembolic events, disseminated intravascular coagulation, or hypercoagulability were observed.(7) In a retrospective cohort of 76 patients who received PCC for bleeding not caused by anticoagulation, some patients received additional hemostatic agents (protamine (59%), desmopressin (43%), and tranexamic acid (42%). Eight patients (11%) suffered thromboembolic complications but this was not stratified by the hemostatic agent.(8) In a prospective case crossover study, five healthy volunteers and six hemophilia patients with inhibitors received tranexamic acid with single-dose activated PCC or with recombinant activated factor VII. There were no thromboembolic events during the study.(9) In a double-blind, randomized, placebo-controlled superiority trial to investigate the efficacy and safety of 4-factor prothrombin complex concentrate (4F-PCC) administration in trauma patients at risk of massive transfusion, a significantly higher risk of thromboembolic events occurred in the 4F-PCC group compared to the placebo group (35% vs 24%; relative risk 1.48 [95% CI, 1.04-2.10]). This was observed despite more frequent use of tranexamic acid in the placebo group (86% vs 76%).(10) Case reports reviewed the use of recombinant factor VIIa and FEIBA in 4 patients with severe hemophilia with inhibitors who underwent major surgery. The patients were also treated with tranexamic acid. Non-surgical bleeding was encountered in 4 of 8 surgical procedures. The overall outcome was good for all procedures.(11) In a retrospective cohort of 112 ambulatory tooth extractions in 23 hemophilia patients using a coagulation factor replacement therapy in combination with tranexamic acid, only one episode of mild postoperative bleeding occurred after seven days in a patient who did not have good treatment compliance.(12) In a prospective study evaluating the use of initial hemoglobin levels as a guideline for the initial treatment of clotting disorders in multiple trauma patients, 25 patients received a combination of hemostatic agents (fibrinogen (100%), PCC (96%), desmopressin (56%), tranexamic acid (52%), and factor VIIa (44%). Of the 25 patients treated, 16 (64%) survived. Two patients (8%) suffered thromboembolic complications but this was not stratified by the hemostatic agent. One patient survived after developing a grade II pulmonary embolism caused by deep leg vein trombosis and one patient died from multi-organ failure after developing multiple small vessel thrombosis.(13)

Tranexamic Acid (INJECTABLE)/Estrogenic Agents

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Tranexamic acid is an antifibrinolytic and estrogen-containing hormonal contraceptives are known to increase the risk of venous thromboembolism and arterial thromboses, including stroke and myocardial infarction. Concurrent use may increase the risk of these events.(1,2)

CLINICAL EFFECTS: Concurrent use of tranexamic acid in patients taking estrogen-containing agents or hormonal contraceptives may increase the risk of embolisms.(1,2)

PREDISPOSING FACTORS: The risk of thrombosis may be even greater in women who are obese or smoke, especially smokers over age 35.(1)

PATIENT MANAGEMENT: The concurrent use of injectable tranexamic and and estrogen-containing hormonal contraception or estrogen replacement therapy should be approached with caution.(1)

DISCUSSION: There are no clinical trial data on the risk of concurrent therapy with tranexamic acid and hormonal contraceptives. There have been postmarketing reports of venous and arterial thrombotic events in women receiving combination therapy with oral tranexamic acid.(2) Women taking hormonal contraception were excluded from safety and efficacy trials of oral tranexamic acid.(2)

Tranexamic Acid; Aminocaproic Acid;Aprotinin/Tretinoin, Oral

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Tranexamic acid, aminocaproic acid, or aprotinin may increase the procoagulant effect of all-trans retinoic acid (tretinoin).(1)

CLINICAL EFFECTS: Concurrent use of tranexamic acid, aminocaproic acid, or aprotinin in patients taking tretinoin may increase the risk of embolisms.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Tranexamic acid, aminocaproic acid, and aprotinin should be used with caution in patients taking oral tretinoin for acute promyelocytic leukemia.(1)

DISCUSSION: In a small study of 28 patients with acute promyelocytic leukemia, patients were administered oral tretinoin with intravenous tranexamic acid, oral tretinoin with chemotherapy, or oral tretinoin with intravenous tranexamic acid and chemotherapy. All four patients who received oral tretinoin with tranexamic acid died. Three of these deaths involved thrombotic complications.(1) There is a case report of fatal thromboembolism in a patient with acute promyelocytic leukemia who was administered oral tretinoin and tranexamic acid concurrently.(2) There are two case reports of thrombosis in patients with acute promyelocytic leukemia who were administered oral tretinoin and aprotinin concurrently.(2-4) Ones of the cases resulted in fatal thromboembolism.(4)

There are no moderate interactions for this drug.

*Neuraxial (i.e., intrathecal, epidural) injection.

*Patients with subarachnoid hemorrhage; tranexamic acid may cause cerebral edema and cerebral infarction in such patients.

*Patients with active thromboembolic disease (e.g., deep-vein thrombosis, pulmonary embolism, cerebral thrombosis, active intravascular clotting) or a history or risk of thromboembolism, including retinal vein or artery occlusion; intrinsic risks include thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy.

*Concomitant use of oral tranexamic tablets with combination hormonal contraceptives.

*Hypersensitivity reactions to tranexamic acid or any other ingredients in the preparation.

• Subarachnoid intracranial hemorrhage

• Acute myocardial infarction
• Acute pulmonary thromboembolism
• Cerebral thrombosis
• Cerebrovascular accident
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Deep venous thrombosis
• Retinal thrombosis
• Thromboembolic disorder
• Thrombophilia
• Thrombotic disorder
• Valvular heart disease

• Kidney disease with likely reduction in glomerular filtration rate (GFr)
• Ligneous conjunctivitis
• Seizure disorder

The manufacturer states that the most common adverse effects of IV tranexamic acid include nausea, vomiting, diarrhea, allergic dermatitis, giddiness, hypotension, and thromboembolic events.

The manufacturer states that the most common adverse effects of oral tranexamic acid include headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, joint pain, muscle cramps, migraine, anemia, and fatigue.

More Frequent

• Hypotension
• Thromboembolic disorder

Rare or Very Rare

• Anaphylaxis
• Hypersensitivity drug reaction
• Renal infarction
• Retinal vascular occlusion
• Seizure disorder
• Thrombotic disorder
• Visual changes

More Frequent

• Diarrhea
• Dizziness
• Nausea
• Vomiting

Less Frequent

• Allergic dermatitis

Rare or Very Rare

• Acquired chromatopsia

No enhanced messaging available.

There are limited data on the use of tranexamic acid in pediatric patients with hemophilia undergoing tooth extraction.

The manufacturer of tranexamic acid tablets states that the drug is indicated for use in females of reproductive age and is not intended for premenarchal girls.

The available information suggests that there are no significant pharmacokinetic differences between adults and pediatric patients.

It is not known whether tranexamic acid use is associated with a risk of adverse maternal or fetal outcomes; however, the drug is known to cross the placenta and appears in cord blood in concentrations similar to maternal concentrations. The potential risks to the fetus should be considered along with potential benefits of the drug and the mother's clinical need for tranexamic acid.

There are no adequate and well-controlled studies of tranexamic acid in pregnant women. Fatal structural abnormalities have been reported in 2 cases when tranexamic acid was used during conception or the first trimester of pregnancy; however, it is not clear whether these effects were related to the drug or other factors. Animal reproduction studies have not revealed any evidence of adverse fetal or developmental effects from in utero exposure to tranexamic acid.

Tranexamic acid is distributed into human milk. It is not known whether the drug has any effects on the breastfed infant or on milk production. The known benefits of breast-feeding should be considered along with the mother's clinical need for tranexamic acid and the potential adverse effects on the infant from the drug or underlying maternal condition.

Care should be taken in dosage selection in geriatric patients because they are more likely to have decreased renal function.

Clinical studies of tranexamic acid injection did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between geriatric and younger patients.

Tranexamic acid is substantially excreted by the kidneys; because geriatric patients are more likely to have decreased renal function, dosage should be selected carefully and renal function monitoring should be considered in such patients.

The manufacturer of tranexamic acid tablets states that the drug is indicated for use in women of reproductive age and is not intended for use by postmenopausal women.