NDC 72485-107 Tranexamic Acid

Tranexamic Acid

NDC Product Code 72485-107

NDC CODE: 72485-107

Proprietary Name: Tranexamic Acid What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Tranexamic Acid What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat heavy bleeding during your menstrual period. Tranexamic acid works by slowing the breakdown of blood clots, which helps to prevent prolonged bleeding. It belongs to a class of drugs known as antifibrinolytics. Tranexamic acid is not a hormone. It does not treat other menstrual or pre-menstrual symptoms. It does not stop your period. It is not a form of birth control and does not protect against sexually transmitted diseases.

NDC Code Structure

NDC 72485-107-01

Package Description: 1 VIAL, GLASS in 1 CARTON > 10 mL in 1 VIAL, GLASS

NDC 72485-107-10

Package Description: 10 VIAL, GLASS in 1 CARTON > 10 mL in 1 VIAL, GLASS

NDC Product Information

Tranexamic Acid with NDC 72485-107 is a a human prescription drug product labeled by Armas Pharmaceuticals Inc.. The generic name of Tranexamic Acid is tranexamic acid. The product's dosage form is injection and is administered via intravenous form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 238720.

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Tranexamic Acid Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Antifibrinolytic Agent - [EPC] (Established Pharmacologic Class)
  • Decreased Fibrinolysis - [PE] (Physiologic Effect)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Armas Pharmaceuticals Inc.
Labeler Code: 72485
FDA Application Number: ANDA206713 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-11-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Tranexamic Acid Product Label Images

Tranexamic Acid Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

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.

2.1 Recommended Dosage

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


[see


Warnings and Precautions (5.1)].


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


Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.For intravenous infusion, tranexamic acid Injection may be mixed with most solutions for infusion such as electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solutions. Heparin may be added to tranexamic acid Injection. Tranexamic acid Injection should NOT be mixed with blood. The drug is a synthetic amino acid and should NOT be mixed with solutions containing penicillin.Discard any unused portion.The diluted mixture may be stored for up to 4 hours at room temperature prior to patient administration.

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 ImpairmentSerum Creatinine (mg/dL)Tranexamic Acid Intravenous Dosage1.36 to 2.83 (120 to 250 micromol/L)10 mg/kg twice daily2.83 to 5.66 (250 to 500 micromol/L)10 mg/kg daily>5.66 (>500 micromol/L)10 mg/kg every 48 hours or 5 mg/kg every 24 hours* Dose reduction is recommended for all doses, both before and after tooth extraction.

3 Dosage Forms And Strengths

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

4 Contraindications

  • 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 injection 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 )] .

5.1 Thromboembolic Risk

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


[see


Drug Interactions (7.1),


Use in Specific Populations (8.3)]


.

5.2 Risk Of Medication Errors Due To Incorrect Route Of Administration

Tranexamic acid injection is for intravenous use only. Serious adverse reactions including seizures and cardiac 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.

5.3 Seizures

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

5.4 Hypersensitivity Reactions

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

5.5 Visual Disturbances

Although not seen in humans, focal areas of retinal degeneration have been observed in cats and dogs following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (1.6 to 22 times the recommended usual human dose based on body surface area) from 6 days to 1 year. No retinal changes have been observed in eye examinations of patients treated with tranexamic acid for up to 8 years. Patients expected to be treated for greater than 3 months may consider ophthalmic monitoring including visual acuity and optical coherence tomography at regular intervals.Discontinue tranexamic acid injection if changes in ophthalmological examination occurs.

5.6 Dizziness

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

6 Adverse Reactions

  • The following clinically significant adverse reactions are described elsewhere in the labeling:Thromboembolic Risk[see Warnings and Precautions(5.1)] Seizures[see Warnings and Precautions(5.3)] Hypersensitivity Reactions[see Warnings and Precautions(5.4)] Visual Disturbances[see Warnings and Precautions(5.5)] Dizziness[see Warnings and Precautions(5.6)]

6.2 Postmarketing Experience

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, chromatopsia, and visual impairment have also been reported.Anaphylaxis or anaphylactoid reactions have been reported that are suggestive of a causal relationship.

7.1 Prothrombotic Medical Products

Avoid concomitant use of tranexamic acid 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)]


.

8.1 Pregnancy

Risk SummaryAvailable data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is 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 injection during pregnancy, the potential risk of tranexamic acid injection administration on the fetus should always be considered along with the mother’s clinical need for tranexamic acid injection; an accurate risk-benefit evaluation should drive the treating physician’s decision.DataHuman DataTranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood.There were 13 clinical studies that described fetal and/or neonatal functional issues such as low Apgar score, neonatal sepsis, cephalohematoma and 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 DataIn 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.

8.2 Lactation

Risk SummaryPublished literature reports the presence of tranexamic acid in human milk. There are no data on the effects of tranexamic acid on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tranexamic acid injection and any potential adverse effects on the breastfed child from tranexamic acid injection or from the underlying maternal condition.

8.3 Females And Males Of Reproductive Potential

ContraceptionConcomitant use of tranexamic acid injection, which is an antifibrinolytic, with hormonal contraceptives may increase the risk for thromboembolic adverse reactions. Advise patients to use an effective alternative (nonhormonal) contraceptive method [see Warnings and Precautions(5.1), Drug Interactions(7.1)] .

8.4 Pediatric Use

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

8.5 Geriatric Use

Clinical studies of tranexamic acid injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration(2.2), Clinical Pharmacology(12.3)].

8.6 Renal Impairment

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

10 Overdosage

Cases of overdosage of tranexamic acid injection 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.

11 Description

Tranexamic acid is trans-4-(aminomethyl)cyclohexanecarboxylic acid, an antifibrinolytic agent. Tranexamic acid is a white crystalline powder. The structural formula is Molecular Formula: C8H15NO2           Molecular Weight: 157.2Each 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.

12.1 Mechanism Of Action

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.

12.2 Pharmacodynamics

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.

12.3 Pharmacokinetics

DistributionThe 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.EliminationAfter an intravenous dose of 1 g, the plasma concentration time curve shows a tri exponential decay with a half-life of about 2 hours for the terminal elimination phase.ExcretionUrinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min), and more than 95% of the dose is excreted in the urine as unchanged drug. Excretion of tranexamic acid is about 90% at 24 hours after intravenous administration of 10 mg/kg body weight.Specific PopulationsPatients with Renal ImpairmentThe 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 StudiesNo studies of interactions between tranexamic acid injection and other drugs have been conducted.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

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.

13.2 Animal Toxicology And/Or Pharmacology

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.

16 How Supplied/Storage And Handling

Tranexamic Acid Injection 100 mg/mL is a clear, colorless solution and is available as follows.Mono Carton of 10 mL glass vials (10 mL fill in 10 mL glass vials)             NDC  72485-107-01Outer Carton of 10 x 10 mL                                                                   NDC  72485-107-10Store 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].

17 Patient Counseling Information

Thromboembolic RiskInform patients that tranexamic acid injection may increase the risk of venous and arterial thrombosis or thromboembolism and to contact their healthcare provider for any signs or symptoms suggestive of thromboembolism.Advise patients using hormonal contraception that combined use with tranexamic acid injection may increase the risk for thromboembolic adverse reactions and to use effective alternative (nonhormonal) contraception during therapy with tranexamic acid injection [see Warnings and Precautions(5.1), Drug Interactions(7.1), Use in Specific Populations(8.3)] .SeizuresInform patients that tranexamic acid injection may cause seizures and to contact their healthcare provider for any signs or symptoms suggestive of seizures [see Warnings and Precautions(5.3)] .Hypersensitivity ReactionsInform patients that tranexamic acid injection may cause hypersensitivity reactions and to contact their healthcare provider for any signs or symptoms of hypersensitivity reactions [see Warnings and Precautions(5.4)] .Visual DisturbancesInform patients that tranexamic acid injection can cause visual disturbance and that they should report any eye symptoms or change in their vision to their healthcare provider and to follow-up with an ophthalmologist for a complete ophthalmologic evaluation, including dilated retinal examination of the retina [see Warnings and Precautions(5.5)] .Risk of Driving and Operating MachineryInform patients that tranexamic acid injection may cause dizziness, and that the patient should be cautioned about driving, operating machinery, or performing hazardous tasks while taking tranexamic acid injection [see Warnings and Precautions(5.6)] .Manufactured by:Micro Labs LimitedBangalore- 560 099, INDIA.Distributed by:Armas Pharmaceuticals, Inc.Manalapan, NJ 07726 (USA)Revised: February 2021

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