PRECAUTIONS SECTION.

PRECAUTIONS:. General. The dose of tranexamic acid injection should be reduced in patients with renal insufficiency because of the risk of accumulation (see DOSAGE AND ADMINISTRATION). Ureteral obstruction due to clot formation in patients with upper urinary tract bleeding has been reported in patients treated with tranexamic acid.Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. In addition, cases of central retinal artery and central retinal vein obstruction have been reported.Patients with previous history of thromboembolic disease may be at increased risk for venous or arterial thrombosis. Tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.Patients with disseminated intravascular coagulation (DIC), who require treatment with tranexamic acid, must be under strict supervision of physician experienced in treating this disorder.Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.. Drug Interactions. No studies of interactions between tranexamic acid injection and other drugs have been conducted.. Carcinogenesis, Mutagenesis, Impairment of Fertility. An increased incidence of leukemia in male mice receiving tranexamic acid in food at concentration of 4.8% (equivalent to doses as high as g/kg/day) may have been related to treatment. Female mice were not included in this experiment. Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver. No mutagenic activity has been demonstrated in several in vitro and in vivo test systems.There are no clinical data to assess the effects of tranexamic acid on fertility.. Pregnancy. Reproduction studies performed in mice, rats, and rabbits have not revealed any evidence of impaired fertility or adverse effects on the fetus due to tranexamic acid.There are no adequate and well-controlled studies in pregnant women. However, tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.. Labor and Delivery. See above under Pregnancy.. Nursing Mothers. Tranexamic acid is present in the mothers milk at concentration of about hundredth of the corresponding serum levels. Caution should be exercised when tranexamic acid is administered to nursing woman.. Pediatric Use. The drug has had limited use in pediatric patients, principally in connection with tooth extraction. The limited data suggest that dosing instructions for adults can be used for pediatric patients needing tranexamic acid therapy.. Geriatric Use. Clinical studies of tranexamic acid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS:. Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur but disappear when the dosage is reduced. Allergic dermatitis, giddiness, and hypotension have been reported occasionally. Hypotension has been observed when intravenous injection is too rapid. To avoid this response, the solution should not be injected more rapidly than mL per minute.. Worldwide Postmarketing Reports. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, chromatopsia, and visual impairment have also been reported. However, due to the spontaneous nature of the reporting of medical events and the lack of controls, the actual incidence and causal relationship of drug and event cannot be determined.Anaphylaxis or anaphylactoid reaction have been reported that are suggestive of causal relationship (see WARNINGS).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. An increased incidence of leukemia in male mice receiving tranexamic acid in food at concentration of 4.8% (equivalent to doses as high as g/kg/day) may have been related to treatment. Female mice were not included in this experiment. Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver. No mutagenic activity has been demonstrated in several in vitro and in vivo test systems.There are no clinical data to assess the effects of tranexamic acid on fertility.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY:. Tranexamic acid is competitive inhibitor of plasminogen activation, and at much higher concentrations, noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid. Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in ratio corresponding to the difference in potency between the compounds. Tranexamic acid in concentration of mg per mL does not aggregate platelets in vitro. Tranexamic acid, in concentrations as low as mg per mL, can prolong the thrombin time. However, tranexamic acid in concentrations up to 10 mg per mL in blood showed no influence on the platelet count, the coagulation time, or other coagulation factors in whole blood or citrated blood from normal subjects. The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin. After an intravenous dose of g, the plasma concentration time curve shows triexponential decay with half-life of about hours for the terminal elimination phase. The initial volume of distribution is about to 12 liters. Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min), and more than 95% of the dose is excreted in the urine as unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg per kg body weight. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to seven or eight hours. Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg per kg to pregnant women is about 30 mg per liter, as high as in the maternal blood. Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. In the joint fluid, the same concentration is obtained as in the serum. The biological half-life of tranexamic acid in the joint fluid is about three hours. The concentration of tranexamic acid in number of other tissues is lower than in blood. In breast milk, the concentration is about one hundredth of the serum peak concentration. Tranexamic acid concentration in cerebrospinal fluid is about one tenth of that of the plasma. The drug passes into the aqueous humor, the concentration being about one tenth of the plasma concentration. Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION:. Immediately before tooth extraction in patients with hemophilia, administer 10 mg per kg body weight of tranexamic acid intravenously together with replacement therapy (see PRECAUTIONS). Following tooth extraction, intravenous therapy, at dose of 10 mg per kg body weight three to four times daily, may be used for to days. Note: For patients with moderate to severe impaired renal function, the following dosages are recommended: Serum Creatinine (umol/L)Tranexamic Acid Intravenous Dosage120 to 250 (1.36 to 2.83 mg/dL) 10 mg/kg twice daily 250 to 500 (2.83 to 5.66 mg/dL) 10 mg/kg daily >500 (>5.66 mg/dL) 10 mg/kg every 48 hours or mg/kg every 24 hours 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 synthetic amino acid, and should NOT be mixed with solutions containing penicillin. Single-dose vial: Discard tranexamic acid vial and any remaining portion in the vial after single use. The diluted mixture may be stored for up to hours at room temperature prior to patient administration.

GENERAL PRECAUTIONS SECTION.

General. The dose of tranexamic acid injection should be reduced in patients with renal insufficiency because of the risk of accumulation (see DOSAGE AND ADMINISTRATION). Ureteral obstruction due to clot formation in patients with upper urinary tract bleeding has been reported in patients treated with tranexamic acid.Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. In addition, cases of central retinal artery and central retinal vein obstruction have been reported.Patients with previous history of thromboembolic disease may be at increased risk for venous or arterial thrombosis. Tranexamic acid should not be administered concomitantly with Factor IX Complex concentrates or Anti-inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.Patients with disseminated intravascular coagulation (DIC), who require treatment with tranexamic acid, must be under strict supervision of physician experienced in treating this disorder.Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.

WARNINGS SECTION.

WARNINGS:. Focal areas of retinal degeneration have developed in cats, dogs, and rats following oral or intravenous tranexamic acid at doses between 250 to 1,600 mg/kg/day (6 to 40 times the recommended usual human dose) from days to year. The incidence of such lesions has varied from 25% to 100% of animals treated and was dose-related. At lower doses, some lesions have appeared to be reversible. Limited data in cats and rabbits showed retinal changes in some animals with doses as low as 126 mg/kg/day (only about times the recommended human dose) administered for several days to two weeks. No retinal changes have been reported or noted in eye examinations in patients treated with tranexamic acid for weeks to months in clinical trials. However, visual abnormalities, often poorly characterized, represent the most frequently reported postmarketing adverse reaction in Sweden. For patients who are to be treated continually for longer than several days, an ophthalmological examination, including visual acuity, color vision, eye-ground and visual fields, is advised, before commencing and at regular intervals during the course of treatment. Tranexamic acid should be discontinued if changes in examination results are found. Convulsions have been reported in association with tranexamic acid treatment, particularly in patients receiving tranexamic acid during cardiovascular surgery and in patients inadvertently given tranexamic acid into the neuraxial system. Cases of allergic reaction with use of intravenous tranexamic acid, including anaphylaxis or anaphylactoid reaction have been reported that are suggestive of causal relationship.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION.

13.2 Animal Toxicology and/or Pharmacology. Nonclinical studies have shown retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Thromboembolic RiskInform patients that Tranexamic acid injection may increase the risk of venous and arterial thrombosis or thromboembolism and to contact their healthcare provider for any signs or symptoms suggestive of thromboembolism.Advise patients using hormonal contraception that combined use with Tranexamic acid injection may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with Tranexamic acid injection [see Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.3)].. SeizuresInform patients that Tranexamic acid injection may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.3)].. Hypersensitivity ReactionsInform patients that Tranexamic acid injection may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.4)].. Visual DisturbancesInform patients that Tranexamic acid injection can cause visual disturbance and that they should report any eye symptoms or change in their vision to their healthcare provider and to follow-up with an ophthalmologist for complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.5)].. Risk of Driving and Operating MachineryInform patients that Tranexamic acid injection may cause dizziness, and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking Tranexamic acid injection [see Warnings and Precautions (5.6)].Lake Zurich, IL 60047www.fresenius-kabi.com/us451453C. Fresenius Kabi Logo.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Tranexamic acid was not carcinogenic in 2-year study in rats and mice at oral doses up to and 5.3 g/kg/day, which are approximately 12 and 11 times the maximum recommended human dose based on body surface area, respectively.Tranexamic acid was not genotoxic in the reverse mutation bacterial (Ames) test, and in vitro and in vivo cytogenetic test.In fertility and early embryonic development study, tranexamic acid was administered to male rats as 0.3% and 1% of drug in diet (average doses of 222 and 856 mg/kg/day) or to female rats at dose levels of 0.3% and 1.2% of drug in diet. Tranexamic acid had no effect on fertility or reproductive function of male or female rats at dose multiples of or times the maximum recommended human dose based on body surface area, respectively.. 13.2 Animal Toxicology and/or Pharmacology. Nonclinical studies have shown retinal toxicity associated with tranexamic acid. Toxicity is characterized by retinal atrophy commencing with changes to the retinal pigmented epithelium and progressing to retinal detachment in cats. The toxicity appears to be dose related, and changes are partially reversible at lower doses. Effects were observed in dogs at oral doses of 800 mg/kg/day and higher (multiple of 11 times the maximum human dose based on body surface area), and in cats at 250 mg/kg/day for 14 days (multiple of 1.6 times the maximum human dose based on body surface area). Some fully reversible changes in pigmentation were observed in cats at doses of 125 mg/kg/day (multiple of 0.8 times the maximum human dose based on body surface area). Studies suggest that the underlying mechanism may be related to transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. DistributionThe initial volume of distribution is about to 12 liters. The plasma protein binding of tranexamic acid is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen. Tranexamic acid does not bind to serum albumin.. EliminationAfter an intravenous dose of g, the plasma concentration time curve shows triexponential decay with half-life of about hours for the terminal elimination phase.. ExcretionUrinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min), and more than 95% of the dose is excreted in the urine as unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg body weight.. Specific Populations. Patients with Renal ImpairmentThe blood levels of tranexamic acid are increased in patients with renal insufficiency. Urinary excretion following single intravenous injection of tranexamic acid declines as renal function decreases. Following single 10 mg/kg intravenous injection of tranexamic acid, the 24-hour urinary fractions of tranexamic acid with serum creatinine concentrations 1.4 2.8, 2.8 5.7, and greater than 5.7 mg/dL were 51, 39, and 19%, respectively. The 24-hour tranexamic acid plasma concentrations for these patients demonstrated direct relationship to the degree of renal impairment. Therefore, dose adjustment is needed in patients with renal impairment [see Dosage and Administration (2.2), Use in Specific Populations (8.6)].. Drug Interaction StudiesNo studies of interactions between Tranexamic acid injection and other drugs have been conducted.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryAvailable 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 drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are (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 (see Data).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 times (mouse), times (rat), and times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively (see Data).The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have 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 2-4% and 15-20%, respectively.It is not known whether tranexamic acid use in pregnant women may cause 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 mothers clinical need for Tranexamic acid injection; an accurate risk-benefit evaluation should drive the treating physicians decision.. Data. Human DataTranexamic 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 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22-36 weeks of gestation in fetuses and infants exposed to tranexamic acid in-utero.. Animal DataIn embryo-fetal development studies, tranexamic acid was administered to pregnant mice from Gestation day (GD) through GD 12 and rats from GD 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 and 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 through GD 18. There was no evidence of adverse developmental outcomes at dose multiples of or 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.. 8.2 Lactation. Risk SummaryPublished literature reports the presence of tranexamic acid in human milk. There are no data on the effects of tranexamic acid on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for Tranexamic acid injection and any potential adverse effects on the breastfed child from Tranexamic acid injection or from the underlying maternal condition.. 8.3 Females and Males of Reproductive Potential. ContraceptionConcomitant use of Tranexamic acid injection, which is an antifibrinolytic, with hormonal contraceptives may increase the risk for thromboembolic adverse reactions. Advise patients to use an effective alternative (nonhormonal) contraceptive method [see Warnings and Precautions (5.1), Drug Interactions (7.1)].. 8.4 Pediatric Use. There are limited data concerning the use of Tranexamic acid injection in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adults and pediatric patients.. 8.5 Geriatric Use. Clinical studies of Tranexamic acid injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].. 8.6 Renal Impairment. Reduce the dosage of Tranexamic acid injection in patients with renal impairment, based on the patients serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.1)Risk of Medication Errors Due to Incorrect Route of Administration: FOR INTRAVENOUS USE ONLY. (5.2)Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3)Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4)Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5)Dizziness: Advise patients not to drive if dizziness occurs. (5.6). Risk of Thrombosis with Concomitant Use of Factor IX: Avoid concomitant use. (5.1). Risk of Medication Errors Due to Incorrect Route of Administration: FOR INTRAVENOUS USE ONLY. (5.2). Seizures: Inadvertent injection into neuraxial system may result in seizures. (5.3). Hypersensitivity Reactions: In case of severe reaction, discontinue use and seek immediate medical attention. (5.4). Visual Disturbances: Visual or ocular adverse effects may occur. Discontinue use if visual or ocular symptoms occur. (5.5). Dizziness: Advise patients not to drive if dizziness occurs. (5.6). 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 (7.1), Use in Specific Populations (8.3)].. 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 arrhythmias 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.. 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 injection 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.. 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 history of hypersensitivity to tranexamic acid.. 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 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from days to year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to years. Patients expected to be treated for greater than 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.. 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.