ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. Most common adverse reactions in clinical trials (>= 5%, and more frequent in tranexamic acid USP tablets-treated subjects compared to placebo-treated subjects) are headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, joint pain, muscle cramps, migraine, anemia and fatigue. 6.1) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Adverse Reactions in Short-term StudiesThe safety of tranexamic acid USP tablets in the treatment of heavy menstrual bleeding in females of reproductive potential was studied in two randomized, double-blind, placebo-controlled studies [see Clinical Studies (14)]. Study compared the effects of two doses of tranexamic acid USP tablets (1950 mg and 3900 mg per day for up to days during each menstrual period) versus placebo over 3-cycle treatment duration. total of 304 women were randomized to this study, with 115 receiving at least one dose of 3900 mg/day of tranexamic acid USP tablets.Study compared the effects of tranexamic acid USP tablets (3900 mg/day) versus placebo over 6-cycle treatment duration. total of 196 women were randomized to this study, with 117 receiving at least one dose of tranexamic acid USP tablets.Across the studies, the combined exposure to 3900 mg/day tranexamic acid USP tablets was 947 cycles and the average duration of use was 3.4 days per cycle. In both studies, subjects were generally healthy women who had menstrual blood loss of >= 80 mL. In these studies, subjects were 18 to 49 years of age with mean age of approximately 40 years, had cyclic menses every 21-35 days, and body mass index (BMI) of approximately 32 kg/m 2. On average, subjects had history of heavy menstrual bleeding for approximately 10 years and 40% had fibroids as determined by transvaginal ultrasound. Approximately 70% were Caucasian, 25% were Black, and 5% were Asian, Native American, Pacific Islander, or Other. Seven percent (7%) of all subjects were of Hispanic origin. Women using hormonal contraception were excluded from the trials. list of adverse reactions occurring in >= 5% of subjects and more frequently in tranexamic acid USP tablets-treated subjects receiving 3900 mg/day compared to placebo-treated subjects is provided in Table 2.Table 2. Adverse Reactions Reported in Women with Heavy Menstrual Bleeding (Studies and 2) Tranexamic acid USP tablets 3900 mg/day (%) (N=232) Placebo (%) (N=139) Adverse reactions that were reported by >= 5% of tranexamic acid USP tablets-treated subjects and more frequently in tranexamic acid USP tablets -treated subjects compared to placebo-treated subjects Includes headache and tension headache Nasal and sinus symptoms include nasal, respiratory tract and sinus congestion, sinusitis, acute sinusitis, sinus headache, allergic sinusitis and sinus pain, and multiple allergies and seasonal allergies Abdominal pain includes abdominal tenderness and discomfort Musculoskeletal pain includes musculoskeletal discomfort and myalgia Arthralgia includes joint stiffness and swelling Number of Subjects with at Least One Adverse Reaction208 (89.7%)122 (87.8%) Headache 117 (50.4%)65 (46.8%) Nasal sinus symptoms 59 (25.4%)24 (17.3%) Back pain48 (20.7%)21 (15.1%) Abdominal pain 46 (19.8%)25 (18.0%) Musculoskeletal pain 26 (11.2%)4 (2.9%) Arthralgia 16 (6.9%)7 (5.0%) Muscle cramps spasms15 (6.5%)8 (5.8%) Migraine14 (6.0%)8 (5.8%) Anemia13 (5.6%)5 (3.6%) Fatigue12 (5.2%)6 (4.3%)Adverse Reactions in Long-term StudiesLong-term safety of tranexamic acid USP tablets was studied in two open-label studies. In one study, subjects with physician-diagnosed heavy menstrual bleeding (not using the alkaline hematin methodology) were treated with 3900 mg/day for up to days during each menstrual period for up to 27 menstrual cycles. total of 781 subjects were enrolled and 239 completed the study through 27 menstrual cycles. total of 12.4% of the subjects withdrew due to adverse reactions. Women using hormonal contraception were excluded from the study. The total exposure in this study to 3900 mg/day tranexamic acid USP tablets was 10,213 cycles. The average duration of tranexamic acid USP tablets use was 2.9 days per cycle.A long-term open-label extension study of subjects from the two short-term efficacy studies was also conducted in which subjects were treated with 3900 mg/day for up to days during each menstrual period for up to menstrual cycles. total of 288 subjects were enrolled and 196 subjects completed the study through menstrual cycles. total of 2.1% of the subjects withdrew due to adverse reactions. The total exposure to 3900 mg/day tranexamic acid USP tablets in this study was 1,956 cycles. The average duration of tranexamic acid USP tablets use was 3.5 days per cycle.The types and severity of adverse reactions in these two long-term open-label trials were similar to those observed in the double-blind, placebo-controlled studies although the percentage of subjects reporting them was greater in the 27-month study, most likely because of the longer study duration.A case of severe allergic reaction to tranexamic acid USP tablets was reported in the extension trial, involving subject on her fourth cycle of treatment, who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment.. Study compared the effects of two doses of tranexamic acid USP tablets (1950 mg and 3900 mg per day for up to days during each menstrual period) versus placebo over 3-cycle treatment duration. total of 304 women were randomized to this study, with 115 receiving at least one dose of 3900 mg/day of tranexamic acid USP tablets.. Study compared the effects of tranexamic acid USP tablets (3900 mg/day) versus placebo over 6-cycle treatment duration. total of 196 women were randomized to this study, with 117 receiving at least one dose of tranexamic acid USP tablets.. 6.2 Postmarketing Experience. The following adverse reactions have been identified from postmarketing experience with tranexamic acid USP tablets. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Eye disorders: Impaired color vision and other visual disturbances Gastrointestinal disorders: Nausea, vomiting, and diarrhea Immune system disorders: Anaphylactic shock and anaphylactoid reactions Nervous system disorders: Dizziness Skin and subcutaneous tissue disorders: Allergic skin reactions Vascular disorders: Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction); cases have been associated with concomitant use of combined hormonal contraceptives Eye disorders: Impaired color vision and other visual disturbances Gastrointestinal disorders: Nausea, vomiting, and diarrhea Immune system disorders: Anaphylactic shock and anaphylactoid reactions Nervous system disorders: Dizziness Skin and subcutaneous tissue disorders: Allergic skin reactions Vascular disorders: Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction); cases have been associated with concomitant use of combined hormonal contraceptives.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION.

13.2 Animal Toxicology and/or Pharmacology. Ocular EffectsIn 9-month toxicology study, dogs were administered tranexamic acid in food at doses of 0, 200, 600, or 1200 mg/kg/day. These doses are approximately 2, 5, and times, respectively, the recommended human oral dose of 3900 mg/day based on AUC. At times the human dose, some dogs developed reversible reddening and gelatinous discharge from the eyes. Ophthalmologic examination revealed reversible changes in the nictitating membrane/conjunctiva. In some female dogs, the presence of inflammatory exudate over the bulbar conjunctival mucosa was observed. Histopathological examinations did not reveal any retinal alteration. No adverse effects were observed at times the human dose.In other studies, focal areas of retinal degeneration were observed in cats, dogs and rats following oral or intravenous tranexamic acid doses at 6-40 times the recommended usual human dose based on mg/m (actual animal doses between 250-1600 mg/kg/day).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisCarcinogenicity studies with tranexamic acid in male mice at doses as high as times the recommended human dose of 3900 mg/day showed an increased incidence of leukemia which may have been related to treatment. Female mice were not included in this experiment.The dose multiple referenced above is based on body surface area (mg/m 2). Actual daily dose in mice was up to 5000 mg/kg/day in food. 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.MutagenesisTranexamic acid was neither mutagenic nor clastogenic in the in vitro Bacterial Reverse Mutation Assay (Ames test), in vitro chromosome aberration test in Chinese hamster cells, and in in vivo chromosome aberration tests in mice and rats. Impairment of FertilityReproductive 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.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Tranexamic acid is synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrins matrix structure.The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains to lysine binding sites with low affinity for tranexamic acid (K = 750 umol/L) and with high affinity (K = 1.1 umol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited. 12.2 Pharmacodynamics. Tranexamic acid, at in vitro concentrations of 25 100 uM, reduces by 20 60% the maximal rate of plasmin lysis of fibrin catalyzed by tissue plasminogen activator (tPA). Elevated concentrations of endometrial, uterine, and menstrual blood tPA are observed in women with heavy menstrual bleeding (HMB) compared to women with normal menstrual blood loss. The effect of tranexamic acid on lowering endometrial tPA activity and menstrual fluid fibrinolysis is observed in women with HMB receiving tranexamic acid total oral doses of 2-3 g/day for days.In healthy subjects, tranexamic acid at blood concentrations less than 10 mg/mL has no effect on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood. Tranexamic acid, however, at blood concentrations of and 10 mg/mL prolongs the thrombin time.Cardiac ElectrophysiologyThe effect of tranexamic acid USP tablets on QT interval was evaluated in randomized, single-dose, 4-way crossover study in 48 healthy females aged 18 to 49 years. Subjects received (1) tranexamic acid USP tablets 1300 mg (2) tranexamic acid USP tablets 3900 mg (three times the maximum recommended single dose), (3) moxifloxacin 400 mg, and (4) placebo. There was no significant increase in the corrected QT interval at any time up to 24 hours after the administration of either dose of tranexamic acid USP tablets. Moxifloxacin, the active control, was associated with maximum 14.1 msec mean increase in corrected QT interval (moxifloxacin placebo) at hours after administration.. 12.3 Pharmacokinetics. AbsorptionAfter single oral administration of 1300 mg of tranexamic acid USP tablets, the peak plasma concentration (C max) occurred at approximately hours (T max). The absolute bioavailability of tranexamic acid USP tablets in women aged 18-49 is approximately 45%. Following multiple oral doses (1300 mg tablets three times daily) administration of tranexamic acid USP tablets for days, the mean max increased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to single oral dose administration (1300 mg ). Plasma concentrations reached steady state at the th dose of tranexamic acid USP tablets on Day 2. The mean plasma pharmacokinetic parameters of tranexamic acid determined in 19 healthy women following single (1300 mg and multiple (1300 mg tablets three times daily for days) oral dose of tranexamic acid USP tablets are shown in Table 3.Table 3. Mean (CV%) Pharmacokinetic Parameters Following Single (1300 mg) and Multiple Dose (1300 mg three times daily for days) Oral Administration of tranexamic acid USP tablets in 19 Healthy Women under Fasting ConditionsParameterArithmetic Mean (CV%)Single doseMultiple doseC max maximum concentration AUC tldc area under the drug concentration curve from time to time of last determinable concentration AUC inf area under the drug concentration curve from time to infinity max time to maximum concentration 1/2 terminal elimination half-life aAUC 0-tau(mcg.h/mL) area under the drug concentration curve from time to hours bData presented as median (range) max (mcg/mL) 13.83 (32.14)16.41 (26.19)AUC tldc (mcgh/mL) 77.96 (31.14)77.67 a(29.39) AUC inf (mcgh/mL) 80.19 (30.43)-T max (h) 2.5 (1 5)2.5 (2 3.5)t 1/2 (h) 11.08 (16.94)-Effect of food: Tranexamic acid USP tablets may be administered with or without food. single dose administration (1300 mg of tranexamic acid USP tablets with food increased both max and AUC by 7% and 16%, respectively. DistributionTranexamic acid is 3% bound to plasma proteins with no apparent binding to albumin. Tranexamic acid is distributed with an initial volume of distribution of 0.18 L/kg and steady-state apparent volume of distribution of 0.39 L/kg.Tranexamic acid crosses 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.Tranexamic acid concentration in cerebrospinal fluid is about one tenth of the plasma concentration.The drug passes into the aqueous humor of the eye achieving concentration of approximately one tenth of plasma concentrations.EliminationMost elimination post intravenous administration occurred during the first 10 hours, giving an apparent elimination half-life of approximately hours. The mean terminal half-life of tranexamic acid is approximately 11 hours. Plasma clearance of tranexamic acid is 110-116 mL/min.MetabolismA small fraction of the tranexamic acid is metabolized.ExcretionTranexamic acid is eliminated by urinary excretion primarily via glomerular filtration with more than 95% of the dose excreted unchanged. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg. Specific PopulationsPediatric Patients Tranexamic acid USP tablets are indicated for females of reproductive age (not approved for use in premenarcheal girls). In randomized, single dose, two-way crossover study of two dose levels (650 mg and 1,300 mg), pharmacokinetics of tranexamic acid was evaluated in 20 female adolescents (12 to 16 years of age) with heavy menstrual bleeding. The max and AUC values after single oral dose of 650 mg in the adolescent females were 32 36% less than those after single oral dose of 1,300 mg in the adolescent females. The max and AUC values after single oral dose of 1300 mg in the adolescent females were 20 25% less than those in the adult females given the same dose in separate study. [See Use in Specific Populations (8.4) Patients with Renal ImpairmentThe effect of renal impairment on the disposition of tranexamic acid USP tablets has not been evaluated. Urinary excretion following single intravenous injection of tranexamic acid declines as renal function decreases. Following single 10 mg/kg intravenous injection of tranexamic acid in 28 patients, 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, lower dosage is needed in patients with renal impairment [see Dosage and Administration (2.2)]. Patients with Hepatic ImpairmentThe effect of hepatic impairment on the disposition of tranexamic acid USP tablets has not been evaluated. One percent and 0.5 percent of an oral dose are excreted as dicarboxylic acid and acetylated metabolite, respectively. Because only small fraction of the drug is metabolized, the recommended dosage in patients with hepatic impairment is the same as in patients with normal hepatic impairment.Drug Interactions StudiesNo drug-drug interaction studies were conducted with tranexamic acid USP tablets.All-Trans Retinoic Acid (Oral Tretinoin)In study involving 28 patients with acute promyelocytic leukemia who were given either orally administered (1) all-trans retinoic acid plus intravenously administered tranexamic acid, (2) all-trans retinoic acid plus chemotherapy, or (3) all-trans retinoic acid plus tranexamic acid plus chemotherapy, all patients who were given all-trans retinoic acid plus tranexamic acid died, with of the deaths due to thrombotic complications. The procoagulant effect of all-trans retinoic acid may have been exacerbated by concomitant use of tranexamic acid. Therefore, tranexamic acid USP tablets is not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid [see Warnings and Precautions (5.1) and Drug Interactions (7.4)].

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Overview of the Clinical Studies. The efficacy of tranexamic acid USP tablets in the treatment of heavy menstrual bleeding (HMB) in women of reproductive potential was demonstrated in two randomized, double-blind, placebo-controlled studies: one 3-cycle treatment study (Study 1) and one 6-cycle treatment study (Study 2) [see Adverse Reactions (6.1)]. In these studies, HMB was defined as an average menstrual blood loss of >= 80 mL as assessed by alkaline hematin analysis of collected sanitary products over two baseline menstrual cycles. Subjects were 18 to 49 years of age with mean age of approximately 40 years, had cyclic menses every 21-35 days, and BMI of approximately 32 kg/m2. On average, subjects had an HMB history of approximately 10 years and 40% had fibroids as determined by transvaginal ultrasound. Approximately 70% were Caucasian, 25% were Black, and 5% were Asian, Native American, Pacific Islander, or Other. Seven percent (7%) of all subjects were of Hispanic origin. In these studies, the primary outcome measure was menstrual blood loss (MBL), measured using the alkaline hematin method. The endpoint was change from baseline in MBL, calculated by subtracting the mean MBL during treatment from the mean pretreatment MBL. The key secondary outcome measures were based on specific questions concerning limitations in social or leisure activities (LSLA) and limitations in physical activities (LPA). Large stains (soiling beyond the undergarment) were also included as key secondary outcome measure.. 14.2 Heavy Menstrual Bleeding in the Three-Cycle Treatment Study. Study compared the effects of two doses of tranexamic acid USP tablets (1950 mg and 3900 mg per day for up to days during each menstrual period) versus placebo on MBL over 3-cycle treatment duration. Of the 294 evaluable subjects, 115 subjects received tranexamic acid USP tablets 1950 mg/day, 112 subjects received tranexamic acid USP tablets 3900 mg/day and 67 subjects received placebo (subjects took at least one dose of study drug and had post-treatment data available).Results are shown in Table 4. Menstrual blood loss (MBL) was statistically significantly reduced in patients treated with 3900 mg/day tranexamic acid USP tablets compared to placebo. Study success also required achieving reduction in MBL that was determined to be clinically meaningful to the subjects. The 1950 mg/day tranexamic acid USP tablets dose did not meet the criteria for success.Tranexamic acid USP tablets also statistically significantly reduced limitations on social, leisure, and physical activities in the 3900 mg/day dose group compared to the placebo group (see Table 5). No statistically significant treatment difference was observed in response rates on the number of large stains.. 4. 5. 14.3 Heavy Menstrual Bleeding in the Six-Cycle Treatment Study. Study compared the effects of tranexamic acid USP tablets 3900 mg/day given daily for up to days during each menstrual period versus placebo on menstrual blood loss (MBL) over 6-cycle treatment duration. Of the 187 evaluable subjects, 115 subjects received tranexamic acid USP tablets and 72 subjects received placebo (subjects took at least one dose of study drug and had post-treatment data available).Results are shown in Table 6. MBL was statistically significantly reduced in patients treated with 3900 mg/day tranexamic acid USP tablets compared to placebo. Study success also required achieving reduction in MBL that was determined to be clinically meaningful to the subjects.Table 6. Mean Reduction from Baseline in Menstrual Blood Loss in Women with Heavy Menstrual Bleeding (Study 2)Treatment ArmNBaseline Mean MBL (mL) Least Squares Mean Reduction in MBL (mL) Percent Reduction in MBL Tranexamic acid USP tablets 3900 mg/day11517266 p<0.001 versus placebo 38% Placebo721531812%Limitations on social, leisure, and physical activities were also statistically significantly reduced in the tranexamic acid USP tablets group compared to placebo (see Table 7). No statistically significant treatment difference was observed in response rates on the number of large stains.Table 7. Secondary Outcomes in 6-Cycle Study in Women with Heavy Menstrual Bleeding (Study 2) Outcome MeasureNBaseline Mean Least Squares Mean Reduction a Response categories: 1=not at all limited; 2=slightly limited; 3=moderately limited; 4=quite bit limited; 5=extremely limited Positive means reflect an improvement from baseline p-value <0.05 versus placebo Responders are defined as subjects who experienced reduction from baseline in frequency of large stains Non-significant difference versus placebo Social and Leisure Activities 3900 mg/day tranexamic acid USP tablets1152.920.85 Placebo722.740.44Physical Activities 3900 mg/day tranexamic acid USP tablets1153.050.87 Placebo722.900.40NRespondersdReduction in Large Stains 3900 mg/day tranexamic acid USP tablets11557% Placebo7251%. 14.4 Heavy Menstrual Bleeding Results over Time. The efficacy of tranexamic acid USP tablets 3900 mg/day over menstrual cycles and over menstrual cycles was demonstrated versus placebo in Studies and (see Figure 1). The change in menstrual bleeding loss from baseline was similar across all post-baseline treatment cycles. Figure 1: Menstrual Bleeding Loss Levels over Duration of Therapy in Women with Heavy Menstrual Bleeding (Studies and 2). Figure 1.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. Concomitant use of combined hormonal contraceptives 4.1) Active thromboembolic disease or history or intrinsic risk of thrombosis or thromboembolism, including retinal vein or artery occlusion 4.1) Hypersensitivity to tranexamic acid 4.2) Concomitant use of combined hormonal contraceptives 4.1) Active thromboembolic disease or history or intrinsic risk of thrombosis or thromboembolism, including retinal vein or artery occlusion 4.1) Hypersensitivity to tranexamic acid 4.2) 4.1 Thromboembolic Risk. Tranexamic acid USP tablets are contraindicated in females of reproductive potential who are [see Warnings and Precautions (5.1)]: Using combined hormonal contraception Known to have any of the following conditions: Active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, or cerebral thrombosis)A history of thrombosis or thromboembolism, including retinal vein or artery occlusionAn intrinsic risk of thrombosis or thromboembolism (e.g., thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy) Using combined hormonal contraception Known to have any of the following conditions: Active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, or cerebral thrombosis)A history of thrombosis or thromboembolism, including retinal vein or artery occlusionAn intrinsic risk of thrombosis or thromboembolism (e.g., thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy) Active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, or cerebral thrombosis). history of thrombosis or thromboembolism, including retinal vein or artery occlusion. An intrinsic risk of thrombosis or thromboembolism (e.g., thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy). 4.2 Hypersensitivity to Tranexamic Acid. Tranexamic acid USP tablets are contraindicated in females with reproductive potential with known hypersensitivity to tranexamic acid [see Warnings and Precautions (5.2) and Adverse Reactions (6.1)].

DESCRIPTION SECTION.

11 DESCRIPTION. Tranexamic acid USP tablets is an antifibrinolytic drug administered orally. The chemical name is trans-4-aminomethyl-cyclohexanecarboxylic acid. The structural formula is:Tranexamic acid is white crystalline powder. It is freely soluble in water and in glacial acetic acid and is very slightly soluble in ethanol and practically insoluble in ether. The molecular formula is 8H 15N0 and the molecular weight is 157.2. Tranexamic acid USP tablets are provided as white oval-shaped tablets and are not scored. Each tablet is debossed with the marking FP650. The active ingredient in each tablet is 650 mg tranexamic acid. The inactive ingredients contained in each tablet are: microcrystalline cellulose, colloidal silicon dioxide, pregelatinized corn starch, povidone, hypromellose, stearic acid, and magnesium stearate.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. 1,300 mg three times day (3,900 mg/day) for maximum of days during monthly menstruation 2.1) Renal impairment: Lower dosage is needed (for maximum of days during menstruation) if serum creatinine concentration (Cr) is higher than 1.4 mg/dL 2.2) Cr above 1.4 mg/dL and <= 2.8 mg/dL: 1,300 mg two times day (2,600 mg/day)Cr above 2.8 mg/dL and <= 5.7 mg/dL: 1,300 mg once day (1,300 mg/day)Cr above 5.7 mg/dL: 650 mg once day (650 mg/day). 1,300 mg three times day (3,900 mg/day) for maximum of days during monthly menstruation 2.1) Renal impairment: Lower dosage is needed (for maximum of days during menstruation) if serum creatinine concentration (Cr) is higher than 1.4 mg/dL 2.2) Cr above 1.4 mg/dL and <= 2.8 mg/dL: 1,300 mg two times day (2,600 mg/day)Cr above 2.8 mg/dL and <= 5.7 mg/dL: 1,300 mg once day (1,300 mg/day)Cr above 5.7 mg/dL: 650 mg once day (650 mg/day). Cr above 1.4 mg/dL and <= 2.8 mg/dL: 1,300 mg two times day (2,600 mg/day). Cr above 2.8 mg/dL and <= 5.7 mg/dL: 1,300 mg once day (1,300 mg/day). Cr above 5.7 mg/dL: 650 mg once day (650 mg/day). 2.1 Recommended Testing Prior to Tranexamic Acid USP Tablets Administration. Prior to prescribing tranexamic acid USP tablets, exclude endometrial pathology that can be associated with heavy menstrual bleeding.. 2.2 Recommended Dosage. The recommended dosage of tranexamic acid USP tablets for patients with normal renal function is 1300 mg orally three times daily (3900 mg/day) for maximum of days during monthly menstruation. Tranexamic acid USP tablets may be administered with or without food. Swallow tablets whole; do not chew or break apart.. 2.3 Dosage Recommendations in Patients with Renal Impairment. The recommended dosage (for maximum of days during monthly menstruation) in patients with renal impairment with serum creatinine concentration higher than 1.4 mg/dL is described in Table 1.Table 1. Recommended Dosage of Tranexamic Acid USP Tablets in Patients with Renal ImpairmentSerum Creatinine (mg/dL)Recommended Dosage (maximum of days during menstruation) Total Daily Dose Above 1.4 and <= 2.81300 mg two times day2600 mgAbove 2.8 and <= 5.71300 mg once day1300 mgAbove 5.7650 mg once day650 mg.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Tablets: 650 mg white oval-shaped debossed with the marking FP650. Tablets: 650 mg 3).

DRUG INTERACTIONS SECTION.

7 DRUG INTERACTIONS. No drug-drug interaction studies were conducted with tranexamic acid USP tablets.. Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both tranexamic acid USP tablets and tissue plasminogen activators. 7.2) 7.1 Combined Hormonal Contraceptives. Because tranexamic acid USP tablets are antifibrinolytic, concomitant use of combined hormonal contraception and tranexamic acid USP tablets may increase the thrombotic risk associated with combined hormonal contraceptives. For this reason, concomitant use of tranexamic acid USP tablets with combined hormonal contraceptives is contraindicated [see Contraindications (4) and Warnings and Precautions (5.1) ]. 7.2 Tissue Plasminogen Activators. Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both tranexamic acid USP tablets and tissue plasminogen activators. Discontinue tranexamic acid USP tablets if patient requires tissue plasminogen activators.. 7.3 Factor IX Complex Concentrates or Anti-Inhibitor Coagulant Concentrates. Tranexamic acid USP tablets are not recommended in patients taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased [see Warnings and Precautions (5.1)]. 7.4 All-Trans Retinoic Acid (Oral Tretinoin). Tranexamic acid USP tablets are not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid [see Warnings and Precautions (5.1)].

GERIATRIC USE SECTION.

8.5 Geriatric Use. Tranexamic acid USP tablets are indicated for females of reproductive potential and is not intended for use by postmenopausal women.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Tranexamic acid USP tablets are provided as white oval-shaped 650 mg tablets. Each tablet is debossed with the marking FP650and are supplied as:NDC 50268-772-13 (10 tablets per card, cards per carton).. Dispensed in Unit Dose Package. For Institutional Use Only.StorageStore at room temperature 25 (77 F); excursions permitted to 15-30 (59-86 F). [See USP Controlled Room Temperature].

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Tranexamic acid USP tablets are indicated for the treatment of cyclic heavy menstrual bleeding in females of reproductive potential [see Clinical Studies (14)]. Tranexamic acid USP tablets is an antifibrinolytic indicated for the treatment of cyclic heavy menstrual bleeding in females of reproductive potential. 1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling Patient Information). Thromboembolic RiskInform patients that tranexamic acid USP tablets 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 [see Warnings and Precautions (5.1)]. Advise patients to discontinue use of tranexamic acid USP tablets and promptly report visual and ocular symptoms to their health care provider as retinal venous and arterial occlusion have been reported in patients using tranexamic acid USP tablets [see Warnings and Precautions (5.1)]. Severe Allergic ReactionsInform patients that they should stop tranexamic acid USP tablets and seek immediate medical attention if they notice symptoms of severe allergic reaction (e.g., shortness of breath or throat tightening) [see Warnings and Precautions (5.2)]. Administration InstructionsInstruct patients to take tranexamic acid USP tablets only during menstruation and for maximum of days each month [see Recommended Dosage (2.1)]. Manufactured for: AvKARE Pulaski, TN 38478 Mfg. Rev. 12/20 AV 09/22 (W) AvPAK.

LACTATION SECTION.

8.2 Lactation. Risk SummaryTranexamic acid is present in the mothers milk at concentration of about one hundredth of the corresponding serum concentration (see Data). The amount of tranexamic acid nursing infant would absorb is unknown. There are no adequate data on the effects of tranexamic acid on the breastfed infant or the effects of tranexamic acid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for tranexamic acid USP tablets and any potential adverse effects on the breast-fed child from tranexamic acid USP tablets or from the underlying maternal condition. DataHuman DataOne hour after the last dose following 2-day treatment course in lactating women, the milk concentration of the tranexamic acid was 1% of the peak serum concentration.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Tranexamic acid is synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrins matrix structure.The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains to lysine binding sites with low affinity for tranexamic acid (K = 750 umol/L) and with high affinity (K = 1.1 umol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisCarcinogenicity studies with tranexamic acid in male mice at doses as high as times the recommended human dose of 3900 mg/day showed an increased incidence of leukemia which may have been related to treatment. Female mice were not included in this experiment.The dose multiple referenced above is based on body surface area (mg/m 2). Actual daily dose in mice was up to 5000 mg/kg/day in food. 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.MutagenesisTranexamic acid was neither mutagenic nor clastogenic in the in vitro Bacterial Reverse Mutation Assay (Ames test), in vitro chromosome aberration test in Chinese hamster cells, and in in vivo chromosome aberration tests in mice and rats. Impairment of FertilityReproductive 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.. 13.2 Animal Toxicology and/or Pharmacology. Ocular EffectsIn 9-month toxicology study, dogs were administered tranexamic acid in food at doses of 0, 200, 600, or 1200 mg/kg/day. These doses are approximately 2, 5, and times, respectively, the recommended human oral dose of 3900 mg/day based on AUC. At times the human dose, some dogs developed reversible reddening and gelatinous discharge from the eyes. Ophthalmologic examination revealed reversible changes in the nictitating membrane/conjunctiva. In some female dogs, the presence of inflammatory exudate over the bulbar conjunctival mucosa was observed. Histopathological examinations did not reveal any retinal alteration. No adverse effects were observed at times the human dose.In other studies, focal areas of retinal degeneration were observed in cats, dogs and rats following oral or intravenous tranexamic acid doses at 6-40 times the recommended usual human dose based on mg/m (actual animal doses between 250-1600 mg/kg/day).

OVERDOSAGE SECTION.

10 OVERDOSAGE. There are no known cases of intentional overdose with tranexamic acid USP tablets and no subjects in the clinical program took more than times the prescribed amount of tranexamic acid USP tablets in 24-hour period (>7800 mg/day). However, cases of overdose of tranexamic acid have been reported. Based on these reports, symptoms of overdose may include gastrointestinal (nausea, vomiting, diarrhea); hypotensive (e.g., orthostatic symptoms); thromboembolic (arterial, venous, embolic); visual impairment; mental status changes; myoclonus; or rash. No specific information is available on the treatment of overdose with tranexamic acid USP tablets. In the event of overdose, employ the usual supportive measures (e.g., clinical monitoring and supportive therapy) as dictated by the patients clinical status.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 30 Tablets Bottle Label. 30.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and effectiveness of tranexamic acid USP tablets have been established in females of reproductive potential. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for those 17 years and older. Tranexamic acid USP tablets are not indicated before menarche.

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Tranexamic acid, at in vitro concentrations of 25 100 uM, reduces by 20 60% the maximal rate of plasmin lysis of fibrin catalyzed by tissue plasminogen activator (tPA). Elevated concentrations of endometrial, uterine, and menstrual blood tPA are observed in women with heavy menstrual bleeding (HMB) compared to women with normal menstrual blood loss. The effect of tranexamic acid on lowering endometrial tPA activity and menstrual fluid fibrinolysis is observed in women with HMB receiving tranexamic acid total oral doses of 2-3 g/day for days.In healthy subjects, tranexamic acid at blood concentrations less than 10 mg/mL has no effect on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood. Tranexamic acid, however, at blood concentrations of and 10 mg/mL prolongs the thrombin time.Cardiac ElectrophysiologyThe effect of tranexamic acid USP tablets on QT interval was evaluated in randomized, single-dose, 4-way crossover study in 48 healthy females aged 18 to 49 years. Subjects received (1) tranexamic acid USP tablets 1300 mg (2) tranexamic acid USP tablets 3900 mg (three times the maximum recommended single dose), (3) moxifloxacin 400 mg, and (4) placebo. There was no significant increase in the corrected QT interval at any time up to 24 hours after the administration of either dose of tranexamic acid USP tablets. Moxifloxacin, the active control, was associated with maximum 14.1 msec mean increase in corrected QT interval (moxifloxacin placebo) at hours after administration.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionAfter single oral administration of 1300 mg of tranexamic acid USP tablets, the peak plasma concentration (C max) occurred at approximately hours (T max). The absolute bioavailability of tranexamic acid USP tablets in women aged 18-49 is approximately 45%. Following multiple oral doses (1300 mg tablets three times daily) administration of tranexamic acid USP tablets for days, the mean max increased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to single oral dose administration (1300 mg ). Plasma concentrations reached steady state at the th dose of tranexamic acid USP tablets on Day 2. The mean plasma pharmacokinetic parameters of tranexamic acid determined in 19 healthy women following single (1300 mg and multiple (1300 mg tablets three times daily for days) oral dose of tranexamic acid USP tablets are shown in Table 3.Table 3. Mean (CV%) Pharmacokinetic Parameters Following Single (1300 mg) and Multiple Dose (1300 mg three times daily for days) Oral Administration of tranexamic acid USP tablets in 19 Healthy Women under Fasting ConditionsParameterArithmetic Mean (CV%)Single doseMultiple doseC max maximum concentration AUC tldc area under the drug concentration curve from time to time of last determinable concentration AUC inf area under the drug concentration curve from time to infinity max time to maximum concentration 1/2 terminal elimination half-life aAUC 0-tau(mcg.h/mL) area under the drug concentration curve from time to hours bData presented as median (range) max (mcg/mL) 13.83 (32.14)16.41 (26.19)AUC tldc (mcgh/mL) 77.96 (31.14)77.67 a(29.39) AUC inf (mcgh/mL) 80.19 (30.43)-T max (h) 2.5 (1 5)2.5 (2 3.5)t 1/2 (h) 11.08 (16.94)-Effect of food: Tranexamic acid USP tablets may be administered with or without food. single dose administration (1300 mg of tranexamic acid USP tablets with food increased both max and AUC by 7% and 16%, respectively. DistributionTranexamic acid is 3% bound to plasma proteins with no apparent binding to albumin. Tranexamic acid is distributed with an initial volume of distribution of 0.18 L/kg and steady-state apparent volume of distribution of 0.39 L/kg.Tranexamic acid crosses 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.Tranexamic acid concentration in cerebrospinal fluid is about one tenth of the plasma concentration.The drug passes into the aqueous humor of the eye achieving concentration of approximately one tenth of plasma concentrations.EliminationMost elimination post intravenous administration occurred during the first 10 hours, giving an apparent elimination half-life of approximately hours. The mean terminal half-life of tranexamic acid is approximately 11 hours. Plasma clearance of tranexamic acid is 110-116 mL/min.MetabolismA small fraction of the tranexamic acid is metabolized.ExcretionTranexamic acid is eliminated by urinary excretion primarily via glomerular filtration with more than 95% of the dose excreted unchanged. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg. Specific PopulationsPediatric Patients Tranexamic acid USP tablets are indicated for females of reproductive age (not approved for use in premenarcheal girls). In randomized, single dose, two-way crossover study of two dose levels (650 mg and 1,300 mg), pharmacokinetics of tranexamic acid was evaluated in 20 female adolescents (12 to 16 years of age) with heavy menstrual bleeding. The max and AUC values after single oral dose of 650 mg in the adolescent females were 32 36% less than those after single oral dose of 1,300 mg in the adolescent females. The max and AUC values after single oral dose of 1300 mg in the adolescent females were 20 25% less than those in the adult females given the same dose in separate study. [See Use in Specific Populations (8.4) Patients with Renal ImpairmentThe effect of renal impairment on the disposition of tranexamic acid USP tablets has not been evaluated. Urinary excretion following single intravenous injection of tranexamic acid declines as renal function decreases. Following single 10 mg/kg intravenous injection of tranexamic acid in 28 patients, 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, lower dosage is needed in patients with renal impairment [see Dosage and Administration (2.2)]. Patients with Hepatic ImpairmentThe effect of hepatic impairment on the disposition of tranexamic acid USP tablets has not been evaluated. One percent and 0.5 percent of an oral dose are excreted as dicarboxylic acid and acetylated metabolite, respectively. Because only small fraction of the drug is metabolized, the recommended dosage in patients with hepatic impairment is the same as in patients with normal hepatic impairment.Drug Interactions StudiesNo drug-drug interaction studies were conducted with tranexamic acid USP tablets.All-Trans Retinoic Acid (Oral Tretinoin)In study involving 28 patients with acute promyelocytic leukemia who were given either orally administered (1) all-trans retinoic acid plus intravenously administered tranexamic acid, (2) all-trans retinoic acid plus chemotherapy, or (3) all-trans retinoic acid plus tranexamic acid plus chemotherapy, all patients who were given all-trans retinoic acid plus tranexamic acid died, with of the deaths due to thrombotic complications. The procoagulant effect of all-trans retinoic acid may have been exacerbated by concomitant use of tranexamic acid. Therefore, tranexamic acid USP tablets is not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid [see Warnings and Precautions (5.1) and Drug Interactions (7.4)].

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryTranexamic acid USP tablets are not indicated for use in pregnant women. There is no available data on tranexamic acid USP tablets use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Tranexamic acid crosses the placenta. Animal reproduction studies have not identified adverse developmental outcomes with oral administration of tranexamic acid to pregnant rats at doses up to times the recommended human dose see Data). In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal DataIn rat embryo-fetal developmental toxicity study, tranexamic acid had no adverse effects on embryo-fetal development when administered during the period of organogenesis (from gestation days through 17) at twice daily doses of 0, 150, 375, and 750 mg/kg (1, and times the recommended human oral dosage of 3900 mg/day based on body surface area (mg/m 2)). In perinatal-postnatal developmental toxicity study in rats administered tranexamic acid from gestation day through postnatal day 20 at twice daily doses of 0, 150, 375, and 750 mg/kg, no significant adverse effects on maternal behavior or body weight were observed, and no significant effects on pup viability, body weight, developmental milestones or adult fertility were observed. It was concluded that the no-observed-effect-level (NOEL) for this study was 1500 mg/kg/day in both 0 and 1 generations, which is equivalent to times the recommended human oral dose of 3900 mg/day based on body surface area (mg/m 2).

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATION. TRANEXAMIC ACID (TRAN-ex-AM-ik AS-id), USP TABLETS, for oral useRead the Patient Information that comes with tranexamic acid USP tablets before you start using the drug and each time you get refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.What is tranexamic acid USP tabletsTranexamic acid USP tablets is prescription medicine used to treat your heavy monthly period (menstruation) when your bleeding gets in the way of social, leisure and physical activities. Tranexamic acid USP tablets does not contain any hormones. On average, tranexamic acid USP tablets has been shown to lower the amount of blood lost during your monthly period by about one-third, but it is not meant to stop your period.Tranexamic acid USP tablets is taken only during your period and is not meant to treat pre-menstrual symptoms (symptoms that occur before your bleeding starts). Tranexamic acid USP tablets does not affect your fertility and cannot be used as birth control. Tranexamic acid USP tablets does not protect you against diseases that you may get if you have unprotected sex.Tranexamic acid USP tablets has not been studied in adolescents younger than 18 years of age.Tranexamic acid is not for women who have already gone through menopause (post-menopausal).Who should not take tranexamic acid USP tabletsDo not take tranexamic acid USP tablets if you:Are using form of birth control that contains estrogen and progestin (like birth control pill, patch, or vaginal ring). Ask your healthcare provider before taking tranexamic acid USP tablets if you are not sure if your birth control method contains estrogen and progestin.Currently have blood clotHave ever had blood clotHave been told that you are at risk of having blood clotAre allergic to tranexamic acidWhat should tell my healthcare provider before taking tranexamic acid USP tabletsBefore taking tranexamic acid USP tablets, tell your healthcare provider about all of your medical conditions, including whether:You have ever had blood clot or been told that you are at risk of having blood clotYou are using form of birth control that contains estrogen and progestin (like birth control pill, patch, or vaginal ring). Using hormonal birth control along with tranexamic acid USP tablets may increase your chance of having serious blood clot, stroke, or heart attack. For this reason, do not use tranexamic acid USP tablets if you use form of birth control that contains estrogen and progestin. You are pregnant or think you may be pregnantYou are breastfeeding or plan to breast-feed. Tranexamic acid USP tablets can pass into your milk. Talk to your healthcare provider about the best way to feed your baby if you take tranexamic acid USP tablets.The time between the start of your periods is less than 21 days or more than 35 daysYou have any other medical conditionsTell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tranexamic acid USP tablets and other medicines can affect each other, causing side effects. Tranexamic acid USP tablets can affect the way other medicines work and other medicines can affect how tranexamic acid USP tablets works. Especially tell your healthcare provider if you take:Birth control pills or other hormonal birth controlMedicines used to help your blood form clotsMedicines used to break up blood clotsAny medicines to treat leukemiaAsk your healthcare provider if you are not sure if your medicine is one that is described above.How should take tranexamic acid USP tabletsTake tranexamic acid USP tablets exactly as your healthcare provider tells you.Do not take tranexamic acid USP tablets until your period has started.Do not take tranexamic acid USP tablets for more than days in row.Do not take tranexamic acid USP tablets when you do not have your period.Once your period has started, take tablets of tranexamic acid USP tablets three times per day (e.g., in the morning, afternoon, and evening).Tranexamic acid USP tablets should be swallowed whole and not chewed or broken apart.Tranexamic acid USP tablets may be taken with or without food.Do not take more than tablets of tranexamic acid USP tablets in day. If you take more than tablets, call your healthcare provider.If you miss dose, take it when you remember, and then take your next dose at least six hours later. Do not take more than two tablets at time to make up for missed doses.If tranexamic acid USP tablets does not help to lessen bleeding with your periods after cycles or seems to stop working, talk to your healthcare provider.What are the possible side effects of tranexamic acid USP tabletsTranexamic acid USP tablets can cause serious side effects, including:Blood clots. You may have higher risk of having serious blood clots if you take tranexamic acid USP tablets with: medicines used to help your blood form clotssome medicines used to treat leukemia Eye changes. Stop taking tranexamic acid USP tablets and promptly report any eye problems you have while taking tranexamic acid USP tablets. Your doctor will refer you to an eye doctor who will examine your eyes.Allergic reaction. If you have severe shortness of breath and your throat feels tight, stop taking tranexamic acid USP tablets and get medical care right away.The most common side effects of tranexamic acid USP tablets include:HeadachesSinus and nasal problemsBack painPain in your abdomenPain in your muscles or jointsAnemiaFatigueTell your healthcare provider if you have any side effect that bothers you or does not go away.These are not all of the possible side effects of tranexamic acid USP tablets. For more information, ask your healthcare provider or pharmacist.If you notice change in your usual bleeding pattern that worries you, or your heavy bleeding continues, contact your healthcare provider right away. This may be sign of more serious condition.Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Amring Pharmaceuticals Inc. at 1-844-Amring1 (1-844-267-4641).How should store tranexamic acid USP tabletsStore tranexamic acid USP tablets at room temperature between 59F to 86F (15C to 30C).Keep tranexamic acid USP tablets and all medicines out of the reach of children.General information about tranexamic acid USP tabletsMedicines are sometimes prescribed for conditions that are not mentioned in Patient Information Leaflets. Do not use tranexamic acid USP tablets for condition for which it was not prescribed. Do not give tranexamic acid USP tablets to other people, even if they have the same symptoms that you have. It may harm them.This patient information leaflet summarizes the most important information about tranexamic acid USP tablets. If you would like more information about tranexamic acid USP tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about tranexamic acid USP tablets that is written for healthcare professionals. For more information, call AvKARE at 1-855-361-3993.What are the ingredients of tranexamic acid USP tabletsActive ingredient: tranexamic acidInactive ingredients: microcrystalline cellulose, colloidal silicon dioxide, pregelatinized corn starch, povidone, hypromellose, stearic acid, and magnesium stearate.This Patient Information has been approved by the U.S. Food and Drug Administration.Manufactured for: AvKARE Pulaski, TN 38478 Mfg. Rev. 12/20 AV 09/22 (W) AvPAK Are using form of birth control that contains estrogen and progestin (like birth control pill, patch, or vaginal ring). Ask your healthcare provider before taking tranexamic acid USP tablets if you are not sure if your birth control method contains estrogen and progestin.. Currently have blood clot. Have ever had blood clot. Have been told that you are at risk of having blood clot. Are allergic to tranexamic acid. You have ever had blood clot or been told that you are at risk of having blood clot. You are using form of birth control that contains estrogen and progestin (like birth control pill, patch, or vaginal ring). Using hormonal birth control along with tranexamic acid USP tablets may increase your chance of having serious blood clot, stroke, or heart attack. For this reason, do not use tranexamic acid USP tablets if you use form of birth control that contains estrogen and progestin. You are pregnant or think you may be pregnant. You are breastfeeding or plan to breast-feed. Tranexamic acid USP tablets can pass into your milk. Talk to your healthcare provider about the best way to feed your baby if you take tranexamic acid USP tablets.. The time between the start of your periods is less than 21 days or more than 35 days. You have any other medical conditions. Birth control pills or other hormonal birth control. Medicines used to help your blood form clots. Medicines used to break up blood clots. Any medicines to treat leukemia. Take tranexamic acid USP tablets exactly as your healthcare provider tells you.. Do not take tranexamic acid USP tablets until your period has started.. Do not take tranexamic acid USP tablets for more than days in row.. Do not take tranexamic acid USP tablets when you do not have your period.. Once your period has started, take tablets of tranexamic acid USP tablets three times per day (e.g., in the morning, afternoon, and evening).. Tranexamic acid USP tablets should be swallowed whole and not chewed or broken apart.. Tranexamic acid USP tablets may be taken with or without food.. Do not take more than tablets of tranexamic acid USP tablets in day. If you take more than tablets, call your healthcare provider.. If you miss dose, take it when you remember, and then take your next dose at least six hours later. Do not take more than two tablets at time to make up for missed doses.. If tranexamic acid USP tablets does not help to lessen bleeding with your periods after cycles or seems to stop working, talk to your healthcare provider.. Blood clots. You may have higher risk of having serious blood clots if you take tranexamic acid USP tablets with: medicines used to help your blood form clotssome medicines used to treat leukemia medicines used to help your blood form clots. some medicines used to treat leukemia. Eye changes. Stop taking tranexamic acid USP tablets and promptly report any eye problems you have while taking tranexamic acid USP tablets. Your doctor will refer you to an eye doctor who will examine your eyes.. Allergic reaction. If you have severe shortness of breath and your throat feels tight, stop taking tranexamic acid USP tablets and get medical care right away.. Headaches. Sinus and nasal problems. Back pain. Pain in your abdomen. Pain in your muscles or joints. Anemia. Fatigue.

SPL UNCLASSIFIED SECTION.

2.1 Recommended Testing Prior to Tranexamic Acid USP Tablets Administration. Prior to prescribing tranexamic acid USP tablets, exclude endometrial pathology that can be associated with heavy menstrual bleeding.

STORAGE AND HANDLING SECTION.

Dispensed in Unit Dose Package. For Institutional Use Only.StorageStore at room temperature 25 (77 F); excursions permitted to 15-30 (59-86 F). [See USP Controlled Room Temperature].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Geriatric use: Tranexamic acid USP tablets is not indicated for use in postmenopausal women 8.5) Renal impairment: lower dosage is needed. 2.2, 8.6) Hepatic impairment: No dosage adjustment is needed. 8.7) Geriatric use: Tranexamic acid USP tablets is not indicated for use in postmenopausal women 8.5) Renal impairment: lower dosage is needed. 2.2, 8.6) Hepatic impairment: No dosage adjustment is needed. 8.7) 8.1 Pregnancy. Risk SummaryTranexamic acid USP tablets are not indicated for use in pregnant women. There is no available data on tranexamic acid USP tablets use in pregnant women to evaluate for drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Tranexamic acid crosses the placenta. Animal reproduction studies have not identified adverse developmental outcomes with oral administration of tranexamic acid to pregnant rats at doses up to times the recommended human dose see Data). In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.DataAnimal DataIn rat embryo-fetal developmental toxicity study, tranexamic acid had no adverse effects on embryo-fetal development when administered during the period of organogenesis (from gestation days through 17) at twice daily doses of 0, 150, 375, and 750 mg/kg (1, and times the recommended human oral dosage of 3900 mg/day based on body surface area (mg/m 2)). In perinatal-postnatal developmental toxicity study in rats administered tranexamic acid from gestation day through postnatal day 20 at twice daily doses of 0, 150, 375, and 750 mg/kg, no significant adverse effects on maternal behavior or body weight were observed, and no significant effects on pup viability, body weight, developmental milestones or adult fertility were observed. It was concluded that the no-observed-effect-level (NOEL) for this study was 1500 mg/kg/day in both 0 and 1 generations, which is equivalent to times the recommended human oral dose of 3900 mg/day based on body surface area (mg/m 2). 8.2 Lactation. Risk SummaryTranexamic acid is present in the mothers milk at concentration of about one hundredth of the corresponding serum concentration (see Data). The amount of tranexamic acid nursing infant would absorb is unknown. There are no adequate data on the effects of tranexamic acid on the breastfed infant or the effects of tranexamic acid on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for tranexamic acid USP tablets and any potential adverse effects on the breast-fed child from tranexamic acid USP tablets or from the underlying maternal condition. DataHuman DataOne hour after the last dose following 2-day treatment course in lactating women, the milk concentration of the tranexamic acid was 1% of the peak serum concentration.. 8.4 Pediatric Use. The safety and effectiveness of tranexamic acid USP tablets have been established in females of reproductive potential. Efficacy is expected to be the same for post-menarchal females under the age of 17 as for those 17 years and older. Tranexamic acid USP tablets are not indicated before menarche.. 8.5 Geriatric Use. Tranexamic acid USP tablets are indicated for females of reproductive potential and is not intended for use by postmenopausal women.. 8.6 Renal Impairment. The effect of renal impairment on the pharmacokinetics of tranexamic acid USP tablets has not been studied. Because tranexamic acid is primarily eliminated via the kidneys by glomerular filtration with more than 95% excreted as unchanged in urine, the recommended dosage in patient with renal impairment is lower than the recommended dosage in patients with normal renal function [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment. The effect of hepatic impairment on the pharmacokinetics of tranexamic acid USP tablets has not been studied. Because only small fraction of the drug is metabolized, the recommended dosage in patients with hepatic impairment is the same as in patients with normal hepatic function [see Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Thromboembolism, including retinal occlusion, has been reported with tranexamic acid USP tablets use. Concomitant use of tranexamic acid USP tablets with combined hormonal contraceptives, Factor IX complex concentrates, anti-inhibitor coagulant concentrates or all-trans retinoic acid (oral tretinoin) may increase the risk of thrombosis. 5.1) Visual or ocular adverse reactions may occur with tranexamic acid USP tablets. Immediately discontinue use if visual or ocular symptoms occur. 5.1) In case of severe allergic reaction, discontinue tranexamic acid USP tablets and seek immediate medical attention. 5.2) Cerebral edema and cerebral infarction may be caused by use of tranexamic acid USP tablets in patients with subarachnoid hemorrhage. 5.3) Ligneous conjunctivitis has been reported in patients taking tranexamic acid. 5.4) Thromboembolism, including retinal occlusion, has been reported with tranexamic acid USP tablets use. Concomitant use of tranexamic acid USP tablets with combined hormonal contraceptives, Factor IX complex concentrates, anti-inhibitor coagulant concentrates or all-trans retinoic acid (oral tretinoin) may increase the risk of thrombosis. 5.1) Visual or ocular adverse reactions may occur with tranexamic acid USP tablets. Immediately discontinue use if visual or ocular symptoms occur. 5.1) In case of severe allergic reaction, discontinue tranexamic acid USP tablets and seek immediate medical attention. 5.2) Cerebral edema and cerebral infarction may be caused by use of tranexamic acid USP tablets in patients with subarachnoid hemorrhage. 5.3) Ligneous conjunctivitis has been reported in patients taking tranexamic acid. 5.4) 5.1 Thromboembolic Risk. Venous and arterial thrombosis or thromboembolism, as well as cases of retinal artery and retinal vein occlusions, have been reported with tranexamic acid USP tablets. Retinal venous and arterial occlusion have been reported in patients using tranexamic acid. Patients should be instructed to report visual and ocular symptoms promptly. In the event of such symptoms, patients should be instructed to discontinue tranexamic acid USP tablets immediately and should be referred to an ophthalmologist for complete ophthalmic evaluation, including dilated retinal examination, to exclude the possibility of retinal venous or arterial occlusion. Concomitant Use of Hormonal ContraceptivesCombined hormonal contraceptives are known to increase the risk of venous thromboembolism, as well as arterial thromboses such as stroke and myocardial infarction. Because tranexamic acid USP tablets are antifibrinolytic, the risk of venous thromboembolism, as well as arterial thromboses such as stroke, may increase further when combined hormonal contraceptives are administered with tranexamic acid USP tablets. This is of particular concern in women who are obese or smoke cigarettes, especially smokers over 35 years of age. Women using combined hormonal contraception were excluded from the clinical trials supporting the safety and efficacy of tranexamic acid USP tablets, and there are no clinical trial data on the risk of thrombotic events with the concomitant use of tranexamic acid USP tablets with combined hormonal contraceptives. However, there have been US postmarketing reports of venous and arterial thrombotic events in women who have used tranexamic acid USP tablets concomitantly with combined hormonal contraceptives. For this reason, concomitant use of tranexamic acid with combined hormonal contraceptives is contraindicated [see Contraindications (4.1) and Drug Interactions (7.1) ]. Concomitant Use with Factor IX Complex Concentrates or Anti-Inhibitor Coagulant ConcentratesTranexamic acid USP tablets are not recommended in patients taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased [see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ]. Patients with Acute Promyelocytic Leukemia Taking Concomitant All-Trans Retinoic Acid (Oral Tretinoin)Tranexamic acid USP tablets are not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid [see Drug Interactions (7.4) and Clinical Pharmacology (12.3) ]. 5.2 Severe Allergic Reactions. case of severe allergic reaction to tranexamic acid USP tablets was reported in the clinical trials, involving subject who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment. case of anaphylactic shock has also been reported in the literature, involving patient who received an intravenous bolus of tranexamic acid. Tranexamic acid USP tablets are contraindicated in females of reproductive potential with known hypersensitivity to tranexamic acid.. 5.3 Subarachnoid Hemorrhage. Cerebral edema and cerebral infarction may be caused by use of tranexamic acid USP tablets in patients with subarachnoid hemorrhage.. 5.4 Ligneous Conjunctivitis. Ligneous conjunctivitis has been reported in patients taking tranexamic acid. The conjunctivitis resolved following cessation of tranexamic acid USP tablets.