Tranexamic Acid (Page 3 of 3)

12.3 Pharmacokinetics

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 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 and other drugs have been conducted.

13 NONCLINICAL TOXICOLOGY

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, USP is a clear, colorless solution supplied as follows:

NDC Tranexamic Acid Injection, USP Package Factor

72611-760-10 1,000 mg/10 mL Single-Dose Vial (100 mg/mL) 10 Single-Dose Vials per carton


Storage Conditions
Store at 20º to 25°C (68º to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Discard unused portion.

Sterile, Nonpyrogenic, Preservative-free.

The container closure is not made with natural rubber latex.

17 PATIENT COUNSELING INFORMATION

Thromboembolic Risk

Inform 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)].

Seizures

Inform 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 Reactions

Inform 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 Disturbances

Inform 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 Machinery

Inform 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:

Gland Pharma Limited

D.P.Pally, Dundigal Post

Hyderabad — 500 043, India

Distributed by:

Almaject, Inc.

Morristown, NJ 07960 USA

Product of China

Revised: 02/2021

PI760-01

PSLEA-020269-02

PACKAGE LABEL — PRINCIPAL DISPLAY PANEL

NDC 72611-760 -10
Tranexamic Acid Injection, USP


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

For Intravenous Use Only

10 x 10 mL Single-Dose Vials

carton
(click image for full-size original)

TRANEXAMIC ACID tranexamic acid injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:72611-760
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
tranexamic acid (tranexamic acid) tranexamic acid 100 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
water
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:72611-760-10 10 VIAL, SINGLE-DOSE in 1 CARTON contains a VIAL, SINGLE-DOSE (72611-760-01)
1 NDC:72611-760-01 10 mL in 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (72611-760-10)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA207239 03/01/2021
Labeler — Almaject, Inc. (116626205)

Revised: 02/2021 Almaject, Inc.

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