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

{ "type": "p", "children": [], "text": "Tranexamic acid injection is indicated in patients with hemophilia for short-term use (2 to 8 days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction." }

The recommended dose of Tranexamic acid is 10 mg/kg actual body weight intravenously administered as a single dose, immediately before tooth extractions. Infuse no more than 1 mL/minute to avoid hypotension [see Warnings and Precautions (5.1)]. Following tooth extraction, Tranexamic acid may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight 3 to 4 times daily, intravenously. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. For intravenous infusion, Tranexamic acid Injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to Tranexamic acid Injection. Tranexamic acid Injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin. Discard any unused portion. The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.

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

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

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="top"><span class="Bold">Serum Creatinine (mg/dL)</span> <br/> </td><td align="center" class="Rrule" valign="top"><span class="Bold">Tranexamic acid Intravenous</span><span class="Bold">Dosage</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">1.36 to 2.83<br/> (120 to 250 micromol/L)<br/> </td><td align="center" class="Rrule" valign="top">10 mg/kg twice daily<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="top">2.83 to 5.66 (250 to 500 micromol/L)<br/> </td><td align="center" class="Rrule" valign="top">10 mg/kg daily<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="top">&gt;5.66 (&gt;500 micromol/L)<br/> </td><td align="center" class="Rrule" valign="top">10 mg/kg every 48 hours<br/> or<br/> 5 mg/kg every 24 hours<br/> </td> </tr> </tbody> </table></div>

* Dose reduction is recommended for all doses, both before and after tooth extraction.

Injection: 1000 mg tranexamic acid (100 mg/mL) clear and colorless solution in 10 mL single-dose vials

{ "type": "p", "children": [], "text": "Injection: 1000 mg tranexamic acid (100 mg/mL) clear and colorless solution in 10 mL single-dose vials" }

Tranexamic acid Injection is contraindicated: • In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by Tranexamic acid in such patients. •  In patients with active intravascular clotting [see Warnings and Precautions (5.1)]. •  In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Tranexamic acid Injection is contraindicated: • In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by Tranexamic acid in such patients. •  In patients with active intravascular clotting [see Warnings and Precautions (5.1)].\n •  In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.4)].\n" }

Tranexamic acid 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. Avoid concomitant use of Tranexamic acid 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)].

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

Confirm the correct route of administration for Tranexamic acid injection and avoid confusion with other injectable solutions that might be administered at the same time as Tranexamic acid injection. Syringes containing Tranexamic acid injection should be clearly labeled with the intravenous route of administration.

Tranexamic acid may cause seizures, including focal and generalized seizures. The most common setting for tranexamic acid-induced seizures has been during cardiovascular surgery (a setting in which Tranexamic acid is not FDA-approved and which uses doses of up to 10-fold higher than the recommended human dose and in patients inadvertently given tranexamic acid into the neuraxial system). Tranexamic acid 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 if seizures occur.

Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with Tranexamic acid if serious reaction occurs, provide appropriate medical management, and do not restart treatment. Tranexamic acid is contraindicated in patients with a history of hypersensitivity to tranexamic acid.

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 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals. Discontinue Tranexamic acid if changes in ophthalmological examination occurs.

Tranexamic acid 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 affects them.

The following adverse reactions have been identified during postapproval use of tranexamic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur and may resolve with dose-reduction. Allergic dermatitis and giddiness have been reported. Hypotension has been reported when intravenous injection is too rapid.

Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery, vein obstruction and cases associated with concomitant use of combination hormonal contraceptives) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, cromatopsia, and visual impairment have also been reported.

Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

Avoid concomitant use of Tranexamic acid with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid [see Warnings and Precautions (5.1), Use in Specific Populations (8.3)].

Risk Summary Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration (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 3 times (mouse), 6 times (rat), and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat, and rabbit, respectively (see Data). The estimated background risk for major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2-4% and 15-20%, respectively. It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of Tranexamic acid during pregnancy, the potential risk of Tranexamic acid administration on the fetus should always be considered along with the mother’s clinical need for Tranexamic acid; an accurate risk-benefit evaluation should drive the treating physician’s decision. Data Human Data Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood. There were 13 clinical studies that described fetal and/or neonatal functional issues such as low Apgar score, neonatal sepsis, cephalohematoma and 9 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22-36 weeks of gestation in fetuses and infants exposed to tranexamic acid in-utero. Animal Data In embryo-fetal development studies, tranexamic acid was administered to pregnant mice from Gestation day (GD) 6 through GD 12 and rats from GD 9 through GD 14 at daily doses of 0.3 or 1.5 g/kg. There was no evidence of adverse developmental outcomes in mice and rats at multiple of 3 and 6 times the maximum recommended human dose based on body surface area in the mouse and rat, respectively. In rabbits, tranexamic acid was administered intravenously at doses of 50, 100, or 200 mg/kg/day or orally at doses of 100, 200, or 400 mg/kg/day from GD 6 through GD 18. There was no evidence of adverse developmental outcomes at dose multiples of 2 or 3 times, respectively, the maximum recommended human dose based on body surface area. Intravenous doses of 200 mg/kg/day showed slightly retarded weight gain in  pregnant rabbits.

Risk Summary Published 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 mother’s clinical need for Tranexamic acid and any potential adverse effects on the breastfed child from Tranexamic acid or from the underlying maternal condition.

Contraception Concomitant use of Tranexamic acid, 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)].

There are limited data concerning the use of Tranexamic acid 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.

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.

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)].

Reduce the dosage of Tranexamic acid in patients with renal impairment, based on the patient’s serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Cases of overdosage of Tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash.

{ "type": "p", "children": [], "text": "Cases of overdosage of Tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic, e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash." }

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is

{ "type": "p", "children": [], "text": "Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is" }

  Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid and Water for Injection to 1 mL. The aqueous solution for injection has a pH of 6.5 to 8.0.

{ "type": "p", "children": [], "text": "  Each mL of the sterile solution for intravenous injection contains 100 mg tranexamic acid and Water for Injection to 1 mL. The aqueous solution for injection has a pH of 6.5 to 8.0." }

Tranexamic acid is a 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 fibrin’s matrix structure. The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/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.

Tranexamic acid, in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. An antifibrinolytic concentration of tranexamic acid remains in different tissues for about 17 hours, and in the serum, up to 7 or 8 hours. Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

Distribution The initial volume of distribution is about 9 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. Elimination After an intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase. Excretion 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/kg body weight. Specific Populations Patients with Renal Impairment The blood levels of tranexamic acid are increased in patients with renal insufficiency. Urinary excretion following a single intravenous injection of tranexamic acid declines as renal function decreases. Following a 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 a 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 Studies No studies of interactions between Tranexamic acid and other drugs have been conducted.

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 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 a 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 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

Nonclinical studies have shown a 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 a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

Tranexamic Acid Injection USP, 100 mg/mL is supplied as a sterile, clear, colorless, preservative-free aqueous solution in single use 10 mL vials, packed in boxes of 10. (NDC 65145-106-10, 10 x 10 mL single-dose vials).

{ "type": "p", "children": [], "text": "Tranexamic Acid Injection USP, 100 mg/mL is supplied as a sterile, clear, colorless, preservative-free aqueous solution in single use 10 mL vials, packed in boxes of 10.\n(NDC 65145-106-10, 10 x 10 mL single-dose vials)." }

Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]." }

Thromboembolic Risk Inform patients that Tranexamic acid 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 may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with Tranexamic acid [see Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.3)]. Seizures Inform patients that Tranexamic acid may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.3)]. Hypersensitivity Reactions Inform patients that Tranexamic acid 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 Disturbances Inform patients that Tranexamic acid 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 a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.5)]. Risk of Driving and Operating Machinery Inform patients that Tranexamic acid may cause dizziness, and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking Tranexamic acid [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "\nThromboembolic Risk\n\nInform patients that Tranexamic acid 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.\nAdvise patients using hormonal contraception that combined use with Tranexamic acid may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with Tranexamic acid [see Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.3)].\n\nSeizures\n\nInform patients that Tranexamic acid may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.3)].\n\nHypersensitivity Reactions\n\nInform patients that Tranexamic acid may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.4)].\n\nVisual Disturbances\n\nInform patients that Tranexamic acid 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 a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.5)].\n\nRisk of Driving and Operating Machinery\n\nInform patients that Tranexamic acid may cause dizziness, and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking Tranexamic acid [see Warnings and Precautions (5.6)]." }

Made in India

{ "type": "p", "children": [], "text": " Made in India" }

Distributed by: Caplin Steriles USA Inc, Hamilton, NJ 08619. Code: TN/Drugs/TN00003457

{ "type": "p", "children": [], "text": "\nDistributed by:\n Caplin Steriles USA Inc, Hamilton, NJ 08619. Code: TN/Drugs/TN00003457" }

June, 2024 22200912

{ "type": "p", "children": [], "text": "June, 2024 22200912" }

Vial Label

{ "type": "p", "children": [], "text": "\nVial Label\n" }

Rx only NDC 65145-106-01 Tranexamic Acid Injection, USP 1000 mg/10 mL (100 mg/mL) Solution for Intravenous Injection 10 mL Vial Single - Dose Only Discard any remaining portion

{ "type": "p", "children": [], "text": "\nRx only NDC 65145-106-01 Tranexamic Acid Injection, USP 1000 mg/10 mL\n (100 mg/mL)\nSolution for Intravenous Injection 10 mL Vial\n Single - Dose Only Discard any remaining portion" }

Box Label Rx only NDC 65145-106-10 Tranexamic Acid Injection, USP 1000 mg/10 mL (100 mg/mL) Solution for Intravenous Injection 10 x 10 mL Vials Single-Dose Only

{ "type": "p", "children": [], "text": "\nBox Label\n\nRx only NDC 65145-106-10 Tranexamic Acid Injection, USP 1000 mg/10 mL\n (100 mg/mL)\nSolution for Intravenous Injection\n\n10 x 10 mL Vials Single-Dose Only\n" }

Tranexamic acid tablets are indicated for the treatment of cyclic heavy menstrual bleeding in females of reproductive potential [see Clinical Studies ( 14)].

{ "type": "p", "children": [], "text": "Tranexamic acid tablets are indicated for the treatment of cyclic heavy menstrual bleeding in females of reproductive potential [see Clinical Studies ( 14)]. \n" }

Prior to prescribing tranexamic acid tablets, exclude endometrial pathology that can be associated with heavy menstrual bleeding.

The recommended dosage of tranexamic acid tablets for patients with normal renal function is 1300 mg orally three times daily (3900 mg/day) for a maximum of 5 days during monthly menstruation. Tranexamic acid tablets may be administered with or without food. Swallow tablets whole; do not chew or break apart.

The recommended dosage (for a maximum of 5 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 Tablets in Patients with Renal Impairment

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="17%"/> <col width="20%"/> <col width="11%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Toprule" valign="top"> <p class="First"> <span class="Bold">Serum Creatinine </span> <br/> <span class="Bold"> (mg/dL) </span> </p> </td><td align="center" class="Botrule Lrule Toprule" valign="top"> <p class="First"> <span class="Bold">Recommended Dosage</span> <br/> <span class="Bold"> (maximum of 5 days </span> <br/> <span class="Bold"> during menstruation) </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Total Daily </span> <br/> <span class="Bold"> Dose </span> </p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First">Above 1.4 and ≤ 2.8</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1300 mg two times a day</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2600 mg</p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First">Above 2.8 and ≤ 5.7</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">1300 mg once a day</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">1300 mg</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule" valign="top"> <p class="First">Above 5.7</p> </td><td align="center" class="Botrule Lrule" valign="top"> <p class="First">650 mg once a day</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">650 mg</p> </td> </tr> </tbody> </table></div>

Tablets:  650 mg white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side.

{ "type": "p", "children": [], "text": "Tablets:  650 mg white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side." }

Tranexamic acid tablets are contraindicated in females of reproductive potential who are [see Warnings and Precautions ( 5.1)]:

Tranexamic acid 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)].

Venous and arterial thrombosis or thromboembolism, as well as cases of retinal artery and retinal vein occlusions, have been reported with tranexamic acid tablets.

Retinal venous and arterial occlusion have been reported in patients using tranexamic acid tablets. 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 tablets immediately and should be referred to an ophthalmologist for a complete ophthalmic evaluation, including dilated retinal examination, to exclude the possibility of retinal venous or arterial occlusion.

Concomitant Use of Hormonal Contraceptives Combined 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 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 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 tablets, and there are no clinical trial data on the risk of thrombotic events with the concomitant use of tranexamic acid 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 tablets concomitantly with combined hormonal contraceptives.  For this reason, concomitant use of tranexamic acid tablets 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 Concentrates Tranexamic acid 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 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) ].

A case of severe allergic reaction to tranexamic acid tablets was reported in the clinical trials, involving a subject who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment.  A case of anaphylactic shock has also been reported in the literature, involving a patient who received an intravenous bolus of tranexamic acid. Tranexamic acid tablets are contraindicated in females of reproductive potential with known hypersensitivity to tranexamic acid.

Cerebral edema and cerebral infarction may be caused by use of tranexamic acid tablets in patients with subarachnoid hemorrhage.

Ligneous conjunctivitis has been reported in patients taking tranexamic acid tablets. The conjunctivitis resolved following cessation of tranexamic acid tablets.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 Studies The safety of tranexamic acid 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) ].

Across the studies, the combined exposure to 3900 mg/day tranexamic acid 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 a mean age of approximately 40 years, had cyclic menses every 21-35 days, and a body mass index (BMI) of approximately 32 kg/m 2.  On average, subjects had a 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.

A list of adverse reactions occurring in ≥ 5% of subjects and more frequently in tranexamic acid 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 1 and 2)

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="21%"/> <col width="15%"/> <col width="12%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Toprule" valign="top"></td><td align="center" class="Botrule Lrule Toprule" valign="top"> <p class="First"> <span class="Bold">Tranexamic Acid </span> <br/> <span class="Bold"> Tablets </span> <br/> <span class="Bold"> 3900 mg/day </span> <br/> <span class="Bold"> n (%) </span> <br/> <span class="Bold"> (N=232) </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo </span> <br/> <span class="Bold"> n(%) </span> <br/> <span class="Bold"> (N=139) </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> Number of Subjects with at Least One Adverse Reaction</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">208 (89.7%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">122 (87.8%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Headache <span class="Sup">a</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">117 (50.4%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">65 (46.8%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Nasal &amp; sinus symptoms <span class="Sup">b</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">59 (25.4%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">24 (17.3%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Back pain</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">48 (20.7%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">21 (15.1%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Abdominal pain <span class="Sup">c</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">46 (19.8%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">25 (18.0%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Musculoskeletal pain <span class="Sup">d</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">26 (11.2%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4 (2.9%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Arthralgia <span class="Sup">e</span> </p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">16 (6.9%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7 (5.0%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Muscle cramps &amp; spasms</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">15 (6.5%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8 (5.8%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Migraine</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">14 (6.0%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8 (5.8%)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Anemia</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">13 (5.6%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5 (3.6%)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">   Fatigue</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12 (5.2%)</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">6 (4.3%)</p> </td> </tr> </tbody> </table></div>

*Adverse reactions that were reported by ≥ 5% of tranexamic acid tablets -treated subjects and more frequently in tranexamic acid tablets -treated subjects compared to placebo-treated subjects aIncludes headache and tension headache bNasal 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 cAbdominal pain includes abdominal tenderness and discomfort dMusculoskeletal pain includes musculoskeletal discomfort and myalgia eArthralgia includes joint stiffness and swelling

Adverse Reactions in Long-term Studies Long-term safety of tranexamic acid 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 5 days during each menstrual period for up to 27 menstrual cycles. A total of 781 subjects were enrolled and 239 completed the study through 27 menstrual cycles.  A 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 tablets was 10,213 cycles. The average duration of tranexamic acid 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 5 days during each menstrual period for up to 9 menstrual cycles.  A total of 288 subjects were enrolled and 196 subjects completed the study through 9 menstrual cycles. A total of 2.1% of the subjects withdrew due to adverse reactions. The total exposure to 3900 mg/day tranexamic acid tablets in this study was 1,956 cycles. The average duration of tranexamic acid 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 tablets was reported in the extension trial, involving a subject on her fourth cycle of treatment, who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment.

The following adverse reactions have been identified from postmarketing experience with tranexamic acid tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Because tranexamic acid tablets are antifibrinolytic, concomitant use of combined hormonal contraception and tranexamic acid tablets may increase the thrombotic risk associated with combined hormonal contraceptives. For this reason, concomitant use of tranexamic acid tablets with combined hormonal contraceptives is contraindicated [see Contraindications ( 4) and Warnings and Precautions ( 5.1)].

Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both tranexamic acid tablets and tissue plasminogen activators.  Discontinue tranexamic acid tablets if a patient requires tissue plasminogen activators.

Tranexamic acid 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)

Tranexamic acid 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)].

Risk Summary

Tranexamic acid tablets are not indicated for use in pregnant women .There are no available data on tranexamic acid tablets use in pregnant women to evaluate for a 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 4 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.

Data

Animal Data

In a 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 6 through 17) at twice daily doses of 0, 150, 375, and 750 mg/kg (1, 2 and 4 times the recommended human oral dosage of 3900 mg/day based on body surface area (mg/m 2).

In a perinatal-postnatal developmental toxicity study in rats administered tranexamic acid from gestation day 6 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 F 0and F 1generations, which is equivalent to 4 times the recommended human oral dose of 3900 mg/day based on body surface area (mg/m 2).

Risk Summary

Tranexamic acid is present in the mother’s milk at a concentration of about one hundredth of the corresponding serum concentration (see Data). The amount of tranexamic acid a 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 mother’s clinical need for tranexamic acid tablets and any potential adverse effects on the breast-fed child from tranexamic acid tablets or from the underlying maternal condition.

Data

HumanData

One hour after the last dose following a 2-day treatment course in lactating women, the milk concentration of the tranexamic acid was 1% of the peak serum concentration.

The safety and effectiveness of tranexamic acid 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 tablets are not indicated before menarche.

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

The effect of renal impairment on the pharmacokinetics of tranexamic acid 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) ].

The effect of hepatic impairment on the pharmacokinetics of tranexamic acid tablets has not been studied.  Because only a 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) ].

There are no known cases of intentional overdose with tranexamic acid tablets and no subjects in the clinical program took more than 2 times the prescribed amount of tranexamic acid tablets in a 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 tablets. In the event of overdose, employ the usual supportive measures (e.g., clinical monitoring and supportive therapy) as dictated by the patient's clinical status.

{ "type": "p", "children": [], "text": "There are no known cases of intentional overdose with tranexamic acid tablets and no subjects in the clinical program took more than 2 times the prescribed amount of tranexamic acid tablets in a 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 tablets. In the event of overdose, employ the usual supportive measures (e.g., clinical monitoring and supportive therapy) as dictated by the patient's clinical status. " }

Tranexamic acid tablets, USP are an antifibrinolytic drug administered orally.  The chemical name is trans-4-aminomethyl-cyclohexanecarboxylic acid.  The structural formula is:

{ "type": "p", "children": [], "text": "Tranexamic acid tablets, USP are an antifibrinolytic drug administered orally.  The chemical name is trans-4-aminomethyl-cyclohexanecarboxylic acid.  The structural formula is:" }

Tranexamic acid is a 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 C 8H 15NO 2 and the molecular weight is 157.2.

{ "type": "p", "children": [], "text": "Tranexamic acid is a 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 C 8H 15NO 2 and the molecular weight is 157.2. " }

Tranexamic acid tablets are provided as white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side.” The active ingredient in each tablet is 650 mg tranexamic acid. The inactive ingredients contained in each tablet are: colloidal silicon dioxide, croscarmellose sodium, ethyl cellulose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and povidone.

{ "type": "p", "children": [], "text": "Tranexamic acid tablets are provided as white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side.” The active ingredient in each tablet is 650 mg tranexamic acid. The inactive ingredients contained in each tablet are: colloidal silicon dioxide, croscarmellose sodium, ethyl cellulose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and povidone." }

FDA approved dissolution test specifications differ from USP.

{ "type": "p", "children": [], "text": "FDA approved dissolution test specifications differ from USP." }

Tranexamic acid is a 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 fibrin’s matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (K d= 750 µmol/L) and 1 with high affinity (K d= 1.1 µmol/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.

Tranexamic acid, at in vitroconcentrations of 25 - 100 µM, 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 tablets total oral doses of 2-3 g/day for 5 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 1 and 10 mg/mL prolongs the thrombin time.

Cardiac Electrophysiology The effect of tranexamic acid tablets on QT interval was evaluated in a randomized, single-dose, 4-way crossover study in 48 healthy females aged 18 to 49 years. Subjects received (1) tranexamic acid tablets 1300 mg (2) tranexamic acid 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 tablets. Moxifloxacin, the active control, was associated with a maximum 14.1 msec mean increase in corrected QT interval (moxifloxacin – placebo) at 3 hours after administration.

Absorption

After a single oral administration of 1300 mg of tranexamic acid tablets, the peak plasma concentration (C max) occurred at approximately 3 hours (T max). The absolute bioavailability of tranexamic acid tablets in women aged 18-49 is approximately 45%. Following multiple oral doses (1300 mg tablets three times daily) administration of tranexamic acid tablets for 5 days, the mean C maxincreased by approximately 19% and the mean area under the plasma concentration-time curve (AUC) remained unchanged, compared to a single oral dose administration (1300 mg).  Plasma concentrations reached steady state at the 5 th dose of tranexamic acid tablets on Day 2.

The mean plasma pharmacokinetic parameters of tranexamic acid determined in 19 healthy women following a single (1300 mg) and multiple (1300 mg tablets three times daily for 5 days) oral dose of tranexamic acid tablets are shown in Table 3.

Table 3. Mean (CV%) Pharmacokinetic Parameters Following a Single (1300 mg) and Multiple Dose (1300 mg three times daily for 5 days) Oral Administration of Tranexamic Acid Tablets in 19 Healthy Women under Fasting Conditions

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="18%"/> <col width="14%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" rowspan="2" valign="top"> <p class="First"> <span class="Bold">Parameter</span> </p> </td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Arithmetic Mean (CV%)</span> </p> </td> </tr> <tr> <td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Single dose</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First"> <span class="Bold">Multiple dose</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">C <span class="Sub">max</span>(mcg/mL) </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">13.83 (32.14)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">16.41 (26.19)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC <span class="Sub">tldc</span>(mcg∙h/mL) </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">77.96 (31.14)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">77.67 <span class="Sup">a</span>(29.39) </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">AUC <span class="Sub">inf</span>(mcg∙h/mL) </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">80.19 (30.43)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">-</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">T <span class="Sub">max</span>(h) <span class="Sup">b</span> </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.5 (1 – 5)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">2.5 (2 – 3.5)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">t <span class="Sub">1/2</span>(h) </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">11.08 (16.94)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">-</p> </td> </tr> </tbody> </table></div>

C max= maximum concentration AUC tldc= area under the drug concentration curve from time 0 to time of last determinable concentration AUC inf= area under the drug concentration curve from time 0 to infinity T max= time to maximum concentration t 1/2= terminal elimination half-life aAUC 0-tau(mcg·h/mL) = area under the drug concentration curve from time 0 to 8 hours bData presented as median (range)

Effect of food: Tranexamic acid tablets may be administered with or without food. A single dose administration (1300 mg) of tranexamic acid tablets with food increased both C maxand AUC by 7% and 16%, respectively.

Distribution Tranexamic 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 a concentration of approximately one tenth of plasma concentrations.

Elimination Most elimination post intravenous administration occurred during the first 10 hours, giving an apparent elimination half-life of approximately 2 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 Populations

Pediatric Patients Tranexamic acid tablets are indicated for females of reproductive age (not approved for use in premenarcheal girls). In a 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 C maxand AUC values after a single oral dose of 650 mg in the adolescent females were 32 – 36% less than those after a single oral dose of 1,300 mg in the adolescent females. The C maxand AUC values after a 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 a separate study. [See Use in Specific Populations ( 8.4)]

Patients with Renal Impairment The effect of renal impairment on the disposition of Tranexamic acid tablets has not been evaluated.  Urinary excretion following a single intravenous injection of tranexamic acid declines as renal function decreases.  Following a 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 a direct relationship to the degree of renal impairment. Therefore, a lower dosage is needed in patients with renal impairment [see Dosage and Administration ( 2.2) ].

Patients with Hepatic Impairment The effect of hepatic impairment on the disposition of tranexamic acid tablets has not been evaluated. One percent and 0.5 percent of an oral dose are excreted as a dicarboxylic acid and acetylated metabolite, respectively.  Because only a 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 Studies No drug-drug interaction studies were conducted with tranexamic acid tablets.

All-Trans Retinoic Acid (Oral Tretinoin) In a 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 4 patients who were given all-trans retinoic acid plus tranexamic acid died, with 3 of the 4 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 tablets are not recommended in patients with acute promyelocytic leukemia taking all-trans retinoic acid [see Warnings and Precautions ( 5.1) and Drug Interactions ( 7.4) ].

Carcinogenesis

Carcinogenicity studies with tranexamic acid in male mice at doses as high as 6 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 a 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.

Mutagenesis

Tranexamic acid was neither mutagenic nor clastogenic in the in vitroBacterial Reverse Mutation Assay (Ames test), in vitrochromosome aberration test in Chinese hamster cells, and in in vivochromosome aberration tests in mice and rats.

Impairment of Fertility

Reproductive 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.

Ocular Effects

In a 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 6 times, respectively, the recommended human oral dose of 3900 mg/day based on AUC. At 6 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 5 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 2(actual animal doses between 250-1600 mg/kg/day).

The efficacy of tranexamic acid 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 a mean age of approximately 40 years, had cyclic menses every 21-35 days, and a BMI of approximately 32 kg/m 2.  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 a key secondary outcome measure.

Study 1 compared the effects of two doses of tranexamic acid tablets (1950 mg and 3900 mg per day for up to 5 days during each menstrual period) versus placebo on MBL over a 3-cycle treatment duration. Of the 294 evaluable subjects, 115 subjects received tranexamic acid tablets 1950 mg/day, 112 subjects received tranexamic acid 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 tablets compared to placebo. Study success also required achieving a reduction in MBL that was determined to be clinically meaningful to the subjects. The 1950 mg/day tranexamic acid tablets dose did not meet the criteria for success.

Table 4. Mean Reduction from Baseline in Menstrual Blood Loss in Women with Heavy Menstrual Bleeding (Study 1)

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="15%"/> <col width="7%"/> <col width="11%"/> <col width="13%"/> <col width="15%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment Arm</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Baseline Mean MBL (mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Least Squares Mean Reduction in MBL (mL)</span> <br/> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Percent Reduction in MBL</span> <br/> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tranexamic acid tablets 3900 mg/day</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">112</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">169</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">65*</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">39%</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tranexamic acid tablets 1950 mg/day</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">115</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">178</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">44</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">25%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">67</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">154</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">5%</p> </td> </tr> </tbody> </table></div>

* p<0.001 versus placebo

Tranexamic acid 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.

Table 5: Secondary Outcomes in 3-Cycle Study in Women with Heavy Menstrual Bleeding (Study 1)

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="24%"/> <col width="7%"/> <col width="12%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Outcome Measure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Baseline </span> <br/> <span class="Bold">Mean<span class="Sup">a</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Least Squares Mean </span> <br/> <span class="Bold">Reduction <span class="Sup">b</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Social and Leisure Activities</span> </p> <p>   3900 mg/day</p> <p>   Tranexamic acid tablets</p> <p>   Placebo</p> <p> <span class="Bold">Physical Activities</span> </p> <p>   3900 mg/day</p> <p>   Tranexamic acid tablets</p> <p>   Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">112</p> <p>66</p> <p>112</p> <p>66</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">3.00</p> <p>2.85</p> <p>3.07</p> <p>2.96</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.98 <span class="Sup">c</span> </p> <p>0.39</p> <p>0.94 <span class="Sup">c</span> </p> <p>0.34</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Responders <span class="Sup">d</span></span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Reduction in Large Stains</span> </p> <p>   3900 mg/day </p> <p>   Tranexamic acid tablets</p> <p>   Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">111</p> <p>67</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">64% <span class="Sup">e</span> </p> <p>52%</p> </td> </tr> </tbody> </table></div>

aResponse categories: 1= not at all limited; 2= slightly limited; 3= moderately limited; 4= quite a bit limited; 5= extremely limited bPositive means reflect an improvement from baseline. cp-value <0.05 versus placebo dResponders are defined as subjects who experienced a reduction from baseline in frequency of large stains. eNon-significant difference versus placebo

Study 2 compared the effects of tranexamic acid tablets 3900 mg/day given daily for up to 5 days during each menstrual period versus placebo on menstrual blood loss (MBL) over a 6-cycle treatment duration.  Of the 187 evaluable subjects, 115 subjects received tranexamic acid 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 tablets compared to placebo.  Study success also required achieving a 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)

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="20%"/> <col width="6%"/> <col width="18%"/> <col width="27%"/> <col width="26%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Treatment Arm</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Baseline Mean MBL </span> <br/> <span class="Bold"> (mL) </span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Least Squares Mean </span> <br/> <span class="Bold">Reduction in MBL (mL)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Percent Reduction in </span> <br/> <span class="Bold">MBL</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Tranexamic acid tablets <br/> 3900 mg/day </p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">115</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">172</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">66*</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">38%</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">Placebo</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">72</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">153</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">18</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">12%</p> </td> </tr> </tbody> </table></div>

* p<0.001 versus placebo

Limitations on social, leisure, and physical activities were also statistically significantly reduced in the tranexamic acid 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)

<div class="scrollingtable"><table cellpadding="0.5pt" cellspacing="6pt" width="40%"> <col width="24%"/> <col width="7%"/> <col width="12%"/> <col width="25%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Outcome Measure</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Baseline </span> <br/> <span class="Bold">Mean<span class="Sup">a</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Least Squares Mean </span> <br/> <span class="Bold">Reduction <span class="Sup">b</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Social and Leisure Activities</span> </p> <p>   3900 mg/day Tranexamic acid tablets</p> <p>   Placebo</p> <p> <span class="Bold">Physical Activities</span> </p> <p>   3900 mg/day Tranexamic acid tablets</p> <p>   Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">115</p> <p>72</p> <p>115</p> <p>72</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">2.92</p> <p>2.74</p> <p>3.05</p> <p>2.90</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.85 <span class="Sup">c</span> </p> <p>0.44</p> <p>0.87 <span class="Sup">c</span> </p> <p>0.40</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">N</span> </p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Responders <span class="Sup">d</span></span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Reduction in Large Stains</span> </p> <p>   3900 mg/day </p> <p>   Tranexamic acid tablets</p> <p>   Placebo</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">115</p> <p>72</p> </td><td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">57% <span class="Sup">e</span> </p> <p>51%</p> </td> </tr> </tbody> </table></div>

aResponse categories: 1= not at all limited; 2= slightly limited; 3= moderately limited; 4= quite a bit limited; 5= extremely limited bPositive means reflect an improvement from baseline cp-value <0.05 versus placebo dResponders are defined as subjects who experienced a reduction from baseline in frequency of large stains eNon-significant difference versus placebo

The efficacy of tranexamic acid tablets 3900 mg/day over 3 menstrual cycles and over 6 menstrual cycles was demonstrated versus placebo in Studies 1 and 2 (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 1 and 2)

Tranexamic acid tablets, USP are provided as white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side and are supplied as:

{ "type": "p", "children": [], "text": "Tranexamic acid tablets, USP are provided as white to off white oval-shaped tablets debossed with A64 on one side and “˄” on the other side and are supplied as:" }

<div class="scrollingtable"><table cellpadding="0pt" cellspacing="0pt" width="40%"> <col width="16%"/> <col width="15%"/> <col width="15%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Quantity</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Package Type</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">NDC Number</span> </p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">15 tablets</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">Bottle</p> </td><td class="Botrule Lrule Rrule" valign="top"> <p class="First">82804-208-15</p> </td> </tr> </tbody> </table></div>

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Storage

{ "type": "p", "children": [], "text": "\nStorage\n" }

Store at room temperature 25° C (77° F); excursions permitted to 15-30° C (59-86° F). [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at room temperature 25° C (77° F); excursions permitted to 15-30° C (59-86° F). [See USP Controlled Room Temperature]." }

Advise the patient to read the FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Patient Information)." }

Thromboembolic Risk Inform patients that tranexamic acid 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)].

{ "type": "p", "children": [], "text": "\nThromboembolic Risk\n Inform patients that tranexamic acid 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)]. \n" }

Advise patients to discontinue use of tranexamic acid 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 tablets [see Warnings and Precautions ( 5.1)] .

{ "type": "p", "children": [], "text": "Advise patients to discontinue use of tranexamic acid 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 tablets [see Warnings and Precautions ( 5.1)] . " }

Severe Allergic Reactions Inform patients that they should stop tranexamic acid tablets and seek immediate medical attention if they notice symptoms of a severe allergic reaction (e.g., shortness of breath or throat tightening) [see Warnings and Precautions ( 5.2)] .

{ "type": "p", "children": [], "text": "\nSevere Allergic Reactions\n Inform patients that they should stop tranexamic acid tablets and seek immediate medical attention if they notice symptoms of a severe allergic reaction (e.g., shortness of breath or throat tightening) [see Warnings and Precautions ( 5.2)] . " }

Administration Instructions Instruct patients to take tranexamic acid tablets only during menstruation and for a maximum of 5 days each month [see Recommended Dosage ( 2.1)] .

{ "type": "p", "children": [], "text": "\nAdministration Instructions\n Instruct patients to take tranexamic acid tablets only during menstruation and for a maximum of 5 days each month [see Recommended Dosage ( 2.1)] . " }

Manufactured by:

{ "type": "p", "children": [], "text": "\nManufactured by:\n" }

Rubicon Research Pvt Ltd., Thane 421506 India.

{ "type": "p", "children": [], "text": "Rubicon Research Pvt Ltd., Thane 421506 India. " }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:\n" }

Advagen Pharma Ltd., East Windsor, NJ 08520, USA

{ "type": "p", "children": [], "text": "Advagen Pharma Ltd., East Windsor, NJ 08520, USA " }

Repackaged and Relabeled by:

{ "type": "p", "children": [], "text": "\nRepackaged and Relabeled by:\n" }

Proficient Rx LP Thousand Oaks, CA 91320

{ "type": "p", "children": [], "text": "Proficient Rx LP Thousand Oaks, CA 91320 " }

Revision: 05/2024

{ "type": "p", "children": [], "text": "Revision: 05/2024" }

PATIENT INFORMATION                                                                                                                                                                                                     Tranexamic Acid Tablets, for oral use

{ "type": "p", "children": [], "text": "\nPATIENT INFORMATION \n\n                                                                                                                                                                                                     Tranexamic Acid Tablets, for oral use \n" }

Read the Patient Information that comes with tranexamic acid tablets before you start using the drug and each time you get a 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.

{ "type": "p", "children": [], "text": "Read the Patient Information that comes with tranexamic acid tablets before you start using the drug and each time you get a 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 are tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nWhat are tranexamic acid tablets?\n" }

Tranexamic acid tablets are a 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 tablets do not contain any hormones. On average, tranexamic acid tablets have 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.

{ "type": "p", "children": [], "text": "Tranexamic acid tablets are a 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 tablets do not contain any hormones. On average, tranexamic acid tablets have 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 tablets are taken only during your period and is not meant to treat pre-menstrual symptoms (symptoms that occur before your bleeding starts).  Tranexamic acid tablets do not affect your fertility and cannot be used as birth control. Tranexamic acid tablets do not protect you against diseases that you may get if you have unprotected sex.

{ "type": "p", "children": [], "text": "Tranexamic acid tablets are taken only during your period and is not meant to treat pre-menstrual symptoms (symptoms that occur before your bleeding starts).  Tranexamic acid tablets do not affect your fertility and cannot be used as birth control. Tranexamic acid tablets do not protect you against diseases that you may get if you have unprotected sex." }

Tranexamic acid tablets have not been studied in adolescents younger than 18 years of age.

{ "type": "p", "children": [], "text": "Tranexamic acid tablets have not been studied in adolescents younger than 18 years of age." }

Tranexamic acid tablets are not for women who have already gone through menopause (post-menopausal).

{ "type": "p", "children": [], "text": "Tranexamic acid tablets are not for women who have already gone through menopause (post-menopausal)." }

Who should not take Tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nWho should not take Tranexamic acid tablets?\n" }

Do not take Tranexamic acid tablets if you:

{ "type": "p", "children": [], "text": "Do not take Tranexamic acid tablets if you:" }

{ "type": "", "children": [], "text": "" }

What should I tell my healthcare provider before taking tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nWhat should I tell my healthcare provider before taking tranexamic acid tablets?\n" }

Before taking tranexamic acid tablets, tell your healthcare provider about all of your medical conditions, including whether:

{ "type": "p", "children": [], "text": "Before taking tranexamic acid tablets, tell your healthcare provider about all of your medical conditions, including whether:" }

{ "type": "", "children": [], "text": "" }

Tellyour healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tranexamic acid tablets and other medicines can affect each other, causing side effects.  Tranexamic acid tablets can affect the way other medicines work and other medicines can affect how tranexamic acid tablets works.

{ "type": "p", "children": [], "text": "\nTellyour healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tranexamic acid tablets and other medicines can affect each other, causing side effects.  Tranexamic acid tablets can affect the way other medicines work and other medicines can affect how tranexamic acid tablets works. " }

Especially tell your healthcare provider if you take:

{ "type": "p", "children": [], "text": "\nEspecially tell your healthcare provider if you take:\n" }

{ "type": "", "children": [], "text": "" }

Ask your healthcare provider if you are not sure if your medicine is one that is described above.

{ "type": "p", "children": [], "text": "Ask your healthcare provider if you are not sure if your medicine is one that is described above." }

How should I take Tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nHow should I take Tranexamic acid tablets?\n" }

{ "type": "", "children": [], "text": "" }

What are the possible side effects of tranexamic acid tablets? Tranexamic acid tablets can cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of tranexamic acid tablets? \n\n Tranexamic acid tablets can cause serious side effects, including: \n" }

{ "type": "", "children": [], "text": "" }

The most common side effects of tranexamic acid tablets include:

{ "type": "p", "children": [], "text": "The most common side effects of tranexamic acid tablets include:" }

{ "type": "", "children": [], "text": "" }

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

{ "type": "p", "children": [], "text": "Tell 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 tablets. For more information, ask your healthcare provider or pharmacist.

{ "type": "p", "children": [], "text": "These are not all of the possible side effects of tranexamic acid tablets. For more information, ask your healthcare provider or pharmacist." }

If you notice a change in your usual bleeding pattern that worries you, or your heavy bleeding continues, contact your healthcare provider right away.  This may be a   sign of a more serious condition.

{ "type": "p", "children": [], "text": "\nIf you notice a change in your usual bleeding pattern that worries you, or your heavy bleeding continues, contact your healthcare provider right away.  This may be a   sign of a more serious condition.\n" }

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 Advagen Pharma Ltd. at 866-488-0312.

{ "type": "p", "children": [], "text": "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 Advagen Pharma Ltd. at 866-488-0312." }

How should I store tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nHow should I store tranexamic acid tablets?\n" }

Store tranexamic acid tablets at room temperature between 59°F to 86°F (15°C to 30°C).

{ "type": "p", "children": [], "text": "Store tranexamic acid tablets at room temperature between 59°F to 86°F (15°C to 30°C)." }

Keep tranexamic acid tablets and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep tranexamic acid tablets and all medicines out of the reach of children.\n" }

General information about tranexamic acid tablets Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information Leaflets.  Do not use tranexamic acid tablets for a condition for which it was not prescribed. Do not give tranexamic acid tablets to other people, even if they have the same symptoms that you have.  It may harm them.

{ "type": "p", "children": [], "text": "\nGeneral information about tranexamic acid tablets\n Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information Leaflets.  Do not use tranexamic acid tablets for a condition for which it was not prescribed. Do not give tranexamic acid 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 tablets. If you would like more information about tranexamic acid tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about tranexamic acid tablets that is written for healthcare professionals.  For more information, call 866-488-0312.

{ "type": "p", "children": [], "text": "This patient information leaflet summarizes the most important information about tranexamic acid tablets. If you would like more information about tranexamic acid tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about tranexamic acid tablets that is written for healthcare professionals.  For more information, call 866-488-0312." }

What are the ingredients of tranexamic acid tablets?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients of tranexamic acid tablets?\n" }

Active ingredient: tranexamic acid

{ "type": "p", "children": [], "text": "Active ingredient: tranexamic acid" }

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, ethyl cellulose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and povidone.

{ "type": "p", "children": [], "text": "Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, ethyl cellulose, magnesium stearate, microcrystalline cellulose, pregelatinized starch and povidone." }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration." }

Manufactured by:

{ "type": "p", "children": [], "text": "\nManufactured by:\n" }

Rubicon Research Pvt Ltd., Thane 421506 India.

{ "type": "p", "children": [], "text": "Rubicon Research Pvt Ltd., Thane 421506 India. " }

Distributed by:

{ "type": "p", "children": [], "text": "\nDistributed by:\n" }

Advagen Pharma Ltd., East Windsor, NJ 08520, USA

{ "type": "p", "children": [], "text": "Advagen Pharma Ltd., East Windsor, NJ 08520, USA " }

Repackaged and Relabeled by:

{ "type": "p", "children": [], "text": "\nRepackaged and Relabeled by:\n" }

Proficient Rx LP Thousand Oaks, CA 91320 Revision: 05/2024

{ "type": "p", "children": [], "text": "Proficient Rx LP Thousand Oaks, CA 91320\n Revision: 05/2024 " }

Tranexamic Acid Tablets, USP 650 mg - NDC-82804-208-15 15's - Bottle Label

{ "type": "p", "children": [], "text": "\nTranexamic Acid Tablets, USP 650 mg - NDC-82804-208-15 15's - Bottle Label\n" }

Tranexamic acid in 0.7% sodium chloride injection is indicated in patients with hemophilia for short-term use (two to eight days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction.

{ "type": "p", "children": [], "text": "Tranexamic acid in 0.7% sodium chloride injection is indicated in patients with hemophilia for short-term use (two to eight days) to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction." }

The recommended dose of tranexamic acid in 0.7% sodium chloride injection is 10 mg/kg actual body weight intravenously administered as a single-dose, immediately before tooth extractions. Infuse no more than 10 mL/minute to avoid hypotension [see Warnings and Precautions (5.1)]. Following tooth extraction, tranexamic acid in 0.7% sodium chloride injection may be administered for 2 to 8 days at a dose of 10 mg/kg actual body weight three to four times daily, intravenously.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use tranexamic acid in 0.7% sodium chloride injection if particulate matter or coloration is seen.

Tranexamic acid in 0.7% sodium chloride injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.

The premix non-PVC bag contains no preservative; discard any unused portion.

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

Table 1: Recommended Dosage in Patients with Varying Degrees of Renal Impairment

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Serum Creatinine (mg/dL)</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Tranexamic Acid in 0.7% Sodium Chloride Injection Intravenous Dosage</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">1.36 to 2.83</p> <p>(120 to 250 micromol/L)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10 mg/kg twice daily</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">2.83 to 5.66</p> <p>(250 to 500 micromol/L)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10 mg/kg daily</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"> <p class="First">&gt; 5.66</p> <p>(&gt; 500 micromol/L)</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">10 mg/kg every 48 hours or 5 mg/kg every 24 hours</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" colspan="2"> <p class="First"> <span class="Sup">*</span>Dose reduction is recommended for all doses, both before and after tooth extraction.</p> </td> </tr> </tbody> </table></div>

Injection: 1,000 mg of tranexamic acid in 100 mL (10 mg per mL), sterile, clear, colorless solution in a single-dose bag for intravenous use.

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Tranexamic acid in 0.7% sodium chloride injection is contraindicated:

{ "type": "p", "children": [], "text": "Tranexamic acid in 0.7% sodium chloride injection is contraindicated: " }

{ "type": "ul", "children": [ "In patients with subarachnoid hemorrhage. Anecdotal experience indicates that cerebral edema and cerebral infarction may be caused by tranexamic acid in such patients. ", "In patients with active intravascular clotting [see Warnings and Precautions (5.1)].", "In patients with hypersensitivity to tranexamic acid or any of the ingredients [see Warnings and Precautions (5.3)]. " ], "text": "" }

Tranexamic acid in 0.7% sodium chloride 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. Avoid concomitant use of tranexamic acid in 0.7% sodium chloride 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)].

Tranexamic acid 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 in 0.7% sodium chloride injection is not FDA approved and which uses doses of up to ten-fold higher than the recommended human dose and in patients inadvertently given tranexamic acid into the neuraxial system). Tranexamic acid in 0.7% sodium chloride 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 in 0.7% sodium chloride injection if seizures occur.

Cases of hypersensitivity reactions, including anaphylactic reactions, have occurred with use of intravenous tranexamic acid. Discontinue treatment with tranexamic acid in 0.7% sodium chloride injection if serious reaction occurs, provide appropriate medical management and do not restart treatment. Tranexamic acid in 0.7% sodium chloride injection is contraindicated in patients with a history of hypersensitivity to tranexamic acid.

Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1,600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals. Discontinue tranexamic acid in 0.7% sodium chloride injection if changes in ophthalmological examination occurs.

Tranexamic acid 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 in 0.7% sodium chloride injection affects them.

The following adverse reactions have been identified during post-approval use of tranexamic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal disturbances (nausea, vomiting, diarrhea) may occur and may resolve with dose-reduction. Allergic dermatitis and giddiness have been reported. Hypotension has been reported when intravenous injection is too rapid.

Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis and central retinal artery, vein obstruction and cases associated with concomitant use of combination hormonal contraceptives) have been rarely reported in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. Convulsion, cromatopsia and visual impairment have also been reported.

Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

Avoid concomitant use of tranexamic acid in 0.7% sodium chloride injection with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid [see Warnings and Precautions (5.1), Use in Specific Populations (8.3)].

Risk Summary

Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration (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 3 times (mouse), 6 times (rat) and 3 times (rabbit) the maximum human dose based on body surface area in the mouse, rat and rabbit, respectively (see Data).

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

It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of tranexamic acid in 0.7% sodium chloride injection during pregnancy, the potential risk of tranexamic acid in 0.7% sodium chloride injection administration on the fetus should always be considered along with the mother’s clinical need for tranexamic acid in 0.7% sodium chloride injection; an accurate risk-benefit evaluation should drive the treating physician’s decision.

Data

Human Data

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

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

Animal Data

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

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

Risk Summary

Published 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 mother’s clinical need for tranexamic acid in 0.7% sodium chloride injection and any potential adverse effects on the breastfed child from tranexamic acid in 0.7% sodium chloride injection or from the underlying maternal condition.

Contraception

Concomitant use of tranexamic acid in 0.7% sodium chloride 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 (5.5), Drug Interactions (7.1)].

There are limited data concerning the use of tranexamic acid in pediatric patients with hemophilia who are undergoing tooth extraction. The limited data suggest that there are no significant pharmacokinetic differences between adult and pediatric patients.

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.

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 [Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Reduce the dosage of tranexamic acid in 0.7% sodium chloride injection in patients with renal impairment, based on the patient’s serum creatinine [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Cases of overdosage of tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic; e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash. Tranexamic acid is not dialyzable.

{ "type": "p", "children": [], "text": "Cases of overdosage of tranexamic acid have been reported. Based on these reports, symptoms of overdosage may be gastrointestinal, e.g., nausea, vomiting, diarrhea; hypotensive, e.g., orthostatic symptoms; thromboembolic; e.g., arterial, venous, embolic; neurologic, e.g., visual impairment, convulsions, headache, mental status changes; myoclonus; and rash. Tranexamic acid is not dialyzable." }

Tranexamic acid, USP is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid, USP is a white, crystalline powder. The structural formula is

{ "type": "p", "children": [], "text": "Tranexamic acid, USP is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid, USP is a white, crystalline powder. The structural formula is" }

Molecular Formula: C8H15NO2                                             Molecular Weight: 157.21 g/mol

{ "type": "p", "children": [], "text": "Molecular Formula: C8H15NO2                                             Molecular Weight: 157.21 g/mol " }

Tranexamic Acid in 0.7% Sodium Chloride Injection, 1,000 mg per 100 mL (10 mg per mL) is a sterile, clear, colorless, nonpyrogenic injectable solution for intravenous administration. Each IV bag contains: 1,000 mg of tranexamic acid, USP; 700 mg of sodium chloride, USP and water for injection, USP. The aqueous solution has a pH of 6.5 to 8.0.

{ "type": "p", "children": [], "text": "Tranexamic Acid in 0.7% Sodium Chloride Injection, 1,000 mg per 100 mL (10 mg per mL) is a sterile, clear, colorless, nonpyrogenic injectable solution for intravenous administration. Each IV bag contains: 1,000 mg of tranexamic acid, USP; 700 mg of sodium chloride, USP and water for injection, USP. The aqueous solution has a pH of 6.5 to 8.0." }

Tranexamic acid is a 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 fibrin’s matrix structure.

The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (Kd = 750 μmol/L) and 1 with high affinity (Kd = 1.1 μmol/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.

Tranexamic acid in concentrations of 1 mg/mL and 10 mg/mL prolongs the thrombin time. 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 in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood from healthy subjects.

Distribution

The initial volume of distribution is about 9 liters 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.

Elimination

After an intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase.

Excretion

Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 mL/min 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 Impairment

The blood levels of tranexamic acid are increased in patients with renal insufficiency. Urinary excretion following a single intravenous injection of tranexamic acid declines as renal function decreases. Following a single 10 mg/kg intravenous injection of tranexamic acid, the 24-hour urinary fractions of tranexamic acid with serum creatinine concentrations 1.4 to 2.8, 2.8 to 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 a 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 Studies

No studies of interactions between tranexamic acid in 0.7% sodium chloride injection and other drugs have been conducted.

Tranexamic acid was not carcinogenic in a 2-year study in rats and mice at oral doses up to 3 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 a 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 4 or 5 times the maximum recommended human dose based on body surface area, respectively.

Nonclinical studies have shown a 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 a transient retinal ischemia at high exposures, linked to the known sympathomimetic effect of high plasma exposures of tranexamic acid.

Tranexamic Acid in 0.7% Sodium Chloride Injection, 1,000 mg per 100 mL (10 mg per mL) is supplied as a sterile, unpreserved, clear, colorless solution in a single-dose polymeric bag containing 1,000 mg tranexamic acid in 100 mL of solution sealed with a Twist-off port and oversealed in an aluminum pouch.

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It is available as follows:

{ "type": "p", "children": [], "text": "It is available as follows:" }

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0" width="100%"> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Strength</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Each</span> </p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First"> <span class="Bold">Unit of Sale</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First"> <span class="Bold"><span class="Underline">1,000 mg per 100 mL</span></span> </p> <p>(10 mg per mL)</p> </td><td class="Botrule Lrule Rrule Toprule" rowspan="2"> <p class="First">NDC 80830-2329-1</p> <p>1 Single-dose Infusion Bag in an Overwrap</p> </td><td class="Botrule Lrule Rrule Toprule"> <p class="First">NDC 80830-2329-2</p> <p>Unit of 10</p> </td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">  <p class="First">NDC 80830-2329-3</p> Unit of 12</td> </tr> </tbody> </table></div>

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Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Discard any unused portion.

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Thromboembolic Risk

{ "type": "p", "children": [], "text": "\nThromboembolic Risk \n" }

{ "type": "ul", "children": [ "Inform patients that tranexamic acid in 0.7% sodium chloride 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. \n", "Advise patients using hormonal contraception that combined use with tranexamic acid in 0.7% sodium chloride injection may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with tranexamic acid in 0.7% sodium chloride injection [see Warnings and Precautions (5.1), Drug Interactions (7.1), Use in Specific Populations (8.3)]. " ], "text": "" }

Seizures

{ "type": "p", "children": [], "text": "\nSeizures \n" }

Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions (5.2)]. \n" }

Hypersensitivity Reactions

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions \n" }

Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions (5.3)].\n" }

Visual Disturbances

{ "type": "p", "children": [], "text": "\nVisual Disturbances \n" }

Inform patients that tranexamic acid in 0.7% sodium chloride 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 a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "Inform patients that tranexamic acid in 0.7% sodium chloride 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 a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions (5.4)]. " }

Risk of Driving and Operating Machinery

{ "type": "p", "children": [], "text": "\nRisk of Driving and Operating Machinery \n" }

Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause dizziness and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking tranexamic acid in 0.7% sodium chloride injection [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Inform patients that tranexamic acid in 0.7% sodium chloride injection may cause dizziness and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking tranexamic acid in 0.7% sodium chloride injection [see Warnings and Precautions (5.5)]." }

Manufactured by:

{ "type": "p", "children": [], "text": "Manufactured by:" }

Amneal Pharmaceuticals Pvt. Ltd.

{ "type": "p", "children": [], "text": "\nAmneal Pharmaceuticals Pvt. Ltd.\n" }

Parenteral Unit

{ "type": "p", "children": [], "text": "\nParenteral Unit\n" }

Ahmedabad 382110, INDIA

{ "type": "p", "children": [], "text": "Ahmedabad 382110, INDIA" }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by: " }

Amneal Pharmaceuticals LLC

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Bridgewater, NJ 08807

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Rev. 11-2023-02

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NDC 80830-2329-1

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Tranexamic Acid in 0.7% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nTranexamic Acid in 0.7% Sodium Chloride Injection\n" }

1,000 mg/100 mL (10 mg/mL)

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Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

Intravenous Bag Label

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Amneal Pharmaceuticals LLC

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NDC 80830-2329-1

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Tranexamic Acid in 0.7% Sodium Chloride Injection

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1,000 mg/100 mL (10 mg/mL)

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Rx only

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Pouch Label

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Amneal Pharmaceuticals LLC

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Pouch label

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NDC 80830-2329-2

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Tranexamic Acid in 0.7% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nTranexamic Acid in 0.7% Sodium Chloride Injection\n" }

1,000 mg/100 mL (10 mg/mL)

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Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

10 x 100 mL Carton Label

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Amneal Pharmaceuticals LLC

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Shipper label (10 x 100 mL)

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NDC 80830-2329-3

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Tranexamic Acid in 0.7% Sodium Chloride Injection

{ "type": "p", "children": [], "text": "\nTranexamic Acid in 0.7% Sodium Chloride Injection\n" }

1,000 mg/100 mL (10 mg/mL)

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Rx only

{ "type": "p", "children": [], "text": "\nRx only\n" }

12 x 100 mL Carton Label

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Amneal Pharmaceuticals LLC

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Shipper label (12 x 100 mL)

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