Tranexamic Acid

Tranexamic acid injection, USP is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

•   Before Extraction: Administer 10 mg/kg actual body weight of tranexamic acid injection intravenously with replacement therapy. (
  2.1 Recommended Dosage

  The recommended dose of tranexamic acid injection is 10 mg/kg actual body weight intravenously administered as a single dose, immediately before tooth extractions. Infuse no more than 1 mL/minute to avoid hypotension

  [see Warnings and Precautions ].

  Following tooth extraction, tranexamic acid injection may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight 3 to 4 times daily, intravenously.

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  For intravenous infusion, tranexamic acid injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to tranexamic acid injection. Tranexamic acid injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.

  Discard any unused portion.

  The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.
  )
•   After Extraction: Administer 10 mg/kg actual body weight 3 to 4 times daily for 2 to 8 days. Infuse no more than 1 mL/minute to avoid hypotension. (
  2.1 Recommended Dosage

  The recommended dose of tranexamic acid injection is 10 mg/kg actual body weight intravenously administered as a single dose, immediately before tooth extractions. Infuse no more than 1 mL/minute to avoid hypotension

  [see Warnings and Precautions ].

  Following tooth extraction, tranexamic acid injection may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight 3 to 4 times daily, intravenously.

  Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  For intravenous infusion, tranexamic acid injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to tranexamic acid injection. Tranexamic acid injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.

  Discard any unused portion.

  The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.
  ).
•   Reduce the dosage for patients with renal impairment. (
  2.2 Recommended Dosage for Patients With Varying Degrees of Renal Impairment*

  For patients with moderate to severe impaired renal function, the following dosages are recommended:

  Table 1. Recommended Dosage in Patients With Varying Degrees of Renal Impairment*

  * Dose reduction is recommended for all doses, both before and after tooth extraction.
  Serum Creatinine (mg/dL)	Tranexamic Acid Intravenous Dosage
  1.36 to 2.83 (120 to 250 micromol/L)	10 mg/kg twice daily
  2.83 to 5.66 (250 to 500 micromol/L)	10 mg/kg daily
  >5.66 (>500 micromol/L)	10 mg/kg every 48 hours or 5 mg/kg every 24 hours
  ,
  8.6 Renal Impairment

  Reduce the dosage of tranexamic acid injection in patients with renal impairment, based on the patient's serum creatinine

  [see Dosage and Administration , Clinical Pharmacology ]

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  )

Injection: 1,000 mg tranexamic acid (100 mg/mL) clear and colorless solution in 10 mL single-dose vials

Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration

Reproduction studies performed in mice, rats, and rabbits have not revealed any adverse effects on the fetus due to tranexamic acid administered during organogenesis. Doses examined were multiples of up to 3 times (mouse), 6 times (rat), and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively

The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of tranexamic acid injection during pregnancy, the potential risk of tranexamic acid injection administration on the fetus should always be considered along with the mother's clinical need for tranexamic acid injection; an accurate risk-benefit evaluation should drive the treating physician's decision.

Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood.

There were 13 clinical studies that described fetal and/or neonatal functional issues such as low Apgar score, neonatal sepsis, cephalohematoma and 9 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22 to 36 weeks of gestation in fetuses and infants exposed to tranexamic acid in-utero.

In embryo-fetal development studies, tranexamic acid was administered to pregnant mice from Gestation day (GD) 6 through GD 12 and rats from GD 9 through GD 14 at daily doses of 0.3 or 1.5 g/kg. There was no evidence of adverse developmental outcomes in mice and rats at multiple of 3 and 6 times the maximum recommended human dose based on body surface area in the mouse and rat, respectively.

In rabbits, tranexamic acid was administered intravenously at doses of 50, 100, or 200 mg/kg/day or orally at doses of 100, 200, or 400 mg/kg/day from GD 6 through GD 18. There was no evidence of adverse developmental outcomes at dose multiples of 2 or 3 times, respectively, the maximum recommended human dose based on body surface area. Intravenous doses of 200 mg/kg/day showed slightly retarded weight gain in pregnant rabbits.

•   Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (
  5.1 Thromboembolic Risk

  Tranexamic acid injection is contraindicated in patients with active intravascular clotting.

  Tranexamic acid is an antifibrinolytic and may increase the risk of thromboembolic events. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid injection. Avoid concomitant use of tranexamic acid injection and medical products that are pro-thrombotic, as the risk of thrombosis may be increased. These medications include but are not limited to, Factor IX Complex concentrates, Anti-inhibitor Coagulant concentrates, and hormonal contraceptives

  [see Drug Interactions , Use in Specific Populations ]

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  )
•   Risk of Medication Errors Due to Incorrect Route of Administration: FOR INTRAVENOUS USE ONLY. (
  5.2 Risk of Medication Errors Due to Incorrect Route of Administration

  Tranexamic acid injection is for intravenous use only. Serious adverse reactions including seizures and cardiac arrythmias have occurred when tranexamic acid injection was inadvertently administered intrathecally instead of intravenously.

  Confirm the correct route of administration for tranexamic acid injection and avoid confusion with other injectable solutions that might be administered at the same time as tranexamic acid injection. Syringes containing tranexamic acid injection should be clearly labeled with the intravenous route of administration.
  )
•   Seizures: Inadvertent injection into neuraxial system may result in seizures. (
  5.3 Seizures

  Tranexamic acid injection may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery (a setting in which tranexamic acid is not FDA-approved and which uses doses of up to 10-fold higher than the recommended human dose and in patients inadvertently given tranexamic acid into the neuraxial system). Tranexamic acid injection is not approved and not recommended for neuraxial administration. Consider dose reduction during surgery and dose adjustments for patients with clinical conditions such as renal dysfunction. Closely monitor the patient during surgery. Consider electroencephalogram (EEG) monitoring for patients with history of seizures or who experience myoclonic movements, twitching, or show evidence of focal seizures. Discontinue tranexamic acid injection if seizures occur.
  )
•   Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (
  5.4 Hypersensitivity Reactions

  Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with tranexamic acid injection if serious reaction occurs, provide appropriate medical management, and do not restart treatment. Tranexamic acid injection is contraindicated in patients with a history of hypersensitivity to tranexamic acid.
  )
•   Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (
  5.5 Visual Disturbances

  Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1,600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals.

  Discontinue tranexamic acid injection if changes in ophthalmological examination occurs.
  )
•   Dizziness: Advise patients not to drive if dizziness occurs (
  5.6 Dizziness

  Tranexamic acid injection may cause dizziness. Concomitant use of other drugs that may also cause dizziness may worsen this effect. Advise patients to avoid driving or using machines until they know how tranexamic acid injection affects them.
  ).