Transamin

Tranexamic acid.

Each capsule also contains sodium bisulfite, sodium lauryl sulfate and Yellow No. 5 as inactive ingredients.
Capsule Size: No. 2, total length of 17.6 mm and weighs about 350 mg.
Tablet Size: Major axis 17.8 mm, minor axis 7.2 mm, thickness 5 mm and weighs about 572 mg.
Transamin ampoule has a pH of 7-8 and an osmotic pressure ratio (with respect to physiological saline) of about 1 (250-mg/5 mL ampoule) and about 2 (250-mg/2.5 mL and 1000-mg/10 mL ampoule).
Tranexamic acid is trans-4-aminomethylcyclohexanecarboxylic acid. It has a molecular formula of C₈H₁₅NO₂, molecular weight of 157.21 and a melting point of 386-390°C (decomposition). It occurs as white crystals or powder, odorless and has a bitter taste. It is freely soluble in water or glacial acetic acid; very slightly soluble in ethanol; practically insoluble in ether; soluble in sodium hydroxide test solution.

Antiplasmin agent.
Pharmacology: In physiological and pathologic conditions, fibrinolysis affects enhancement of vascular permeability, and relevant to the development, progression and healing of hemorrhage, allergy and other biological reactions induced by plasmin. Tranexamic acid inhibits the activity of plasmin, thereby exhibiting antihemorrhagic, antiallergic and anti-inflammatory effects.
Antiplasmin Action: Tranexamic acid inhibits the binding of plasmin or plasminogen to fibrin by strongly binding to the lysine binding site (LBS) of fibrin which is also the binding site for plasmin and plasminogen. Therefore, tranexamic acid strongly inhibits fibrinolysis induced by plasmin. In addition, in the presence of antiplasmins eg, α₂-macroglobulin in the plasma, the antifibrinolytic action of tranexamic acid is even further strengthened.
Hemostatic Action: When the blood level of plasmin is abnormally elevated, various phenomena occur eg, inhibition of platelet aggregation and decomposition of coagulation factors. Even a slight elevation in the blood level of plasmin specifically induces fibrinolysis. Tranexamic acid is considered to exhibit a hemostatic effect by inhibiting fibrinolysis in common types of hemorrhage.
Antiallergic and Anti-Inflammatory Action: Tranexamic acid inhibits plasmin-induced production of kinins and other active peptides, that cause enhancement of vascular permeability, allergy and inflammatory lesions (as demonstrated in guinea pigs and rats).
Clinical Studies: Hemostatic Action: A hemostatic effect of Transamin was observed in 2063 out of 2802 patients (73.6%) (capsule and tablet) and in 594 out of 709 patients (83.8%) (ampoule) with a bleeding tendency caused by diseases eg, leukemia, aplastic anemia and purpura, which are considered to be associated with systemic hyperfibrinolysis, or abnormal bleeding eg, pulmonary, nasal, vaginal and renal hemorrhage, prostatic hemorrhage (ampoule only), and intra- and postoperative bleeding.
Antiallergic and Anti-Inflammatory Actions: Skin Disorders: Capsule/Tablet: Transamin was effective for symptoms eg, pruritus, swelling and erythema in 135 out of 223 patients (60.5%) in an open-labeled clinical study conducted to evaluate its effect on skin disorders (eg, eczema and similar conditions, urticaria, drug eruptions and toxidermia).
In a double-blind comparative study conducted to evaluate the effects of Transamin on pruritus, redness, swelling and other symptoms in 67 patients with skin disorders (eczema and similar conditions, drug eruptions and toxidermia), 35 patients were assigned to Transamin and 32 to placebo. The efficacy rate (good to excellent responses) was 62.9% (22 cases) for Transamin vs 31.3% (10 cases) for placebo (p<0.05).
Ampoule: Symptoms of skin disorders eg, eczema and similar conditions or urticaria, etc improved in 220 out of 283 patients (77.7%). Otorhinolaryngological Diseases: Capsule/Tablet: In an open-labeled clinical study performed on 168 patients with tonsillitis, laryngopharyngitis, stomatitis and gingivitis, the effects against pain, swelling and redness, etc were observed in 119 patients (70.8%).
In a double-blind comparative study performed to determine effects of Transamin in 168 patients with otorhinolaryngological diseases (eg, acute pharyngolaryngitis, acute tonsillitis, stomatitis), 84 patients were assigned to Transamin and 84 to placebo. The efficacy rate (good to excellent responses) was 52.4% (44 cases) for Transamin vs 26.2% (22 cases) for placebo (p<0.05).
Pharmacokinetics: Blood Concentration: Capsule/Tablet: When a single dose of tranexamic acid was administered orally to healthy adults, the pharmacokinetic parameters were as shown as follows: Pharmacokinetic Parameters After a Single Oral Dose of Tranexamic Acid (n=5): T_max: 2-3 hrs; C_max: 5.5 mcg/mL (capsule), 6 mcg/mL (tablet); t_½: 3.3 hrs.
Blood concentration-time profile after a single oral dose of tranexamic acid. Capsule: See Figure 1.

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Tablet: See Figure 2.

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Ampoule: When a single dose of 500 mg tranexamic acid was administered IM or 1000 mg was administered IV to healthy adults, the time plasma concentration were as follows: See Figure 3.

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Pharmacokinetic parameters after a single IV or IM dose of tranexamic acid are as follows: 500-mg Dose (IM): T_max: 0.5 hr; C_max: 21.2 mcg/mL; t_½: 2 hrs.
1000-mg Dose (IV): C_max: 60 mcg/mL (15 min after administration); t_½: 1.9 hrs; V_d: 42.4 L.
Distribution: Reference Information (Animal Study):
Capsule/Tablet: When a single dose of ¹⁴C-tranexamic acid was administered orally to rats, the concentration in most organs reached peak values as well as the blood concentration after 2 hrs.
Levels in kidney and liver were higher, and those of other organs were lower than that of the blood.
Ampoule: When ¹⁴C-tranexamic acid was administered IV or IM to mice, the distribution in the tissue was highest in the liver, kidneys and pulmonary, followed by pancreas, adrenals, spleen, prostate, colon, uterus, heart and muscle. Levels in the brain were low.
Metabolism and Excretion: Capsule/Tablet: When a single dose (250 or 500 mg) of tranexamic acid was administered orally to healthy adults, it was rapidly absorbed and about 40-70% of the administered dose was excreted as unchanged form in the urine within 24 hrs.
Ampoule: When a single dose of 500 mg tranexamic acid was administered IM or 1000 mg was administered IV to healthy adults, it was rapidly absorbed, and about 80% and 76% of the administered dose, was respectively, excreted as unchanged form in the urine within 24 hrs of administration.

Abnormal bleeding in which local hyperfibrinolysis is considered to be involved. (Pulmonary, nasal, vaginal and renal hemorrhage, abnormal bleeding during or after prostate surgery.)
Bleeding tendencies in which systemic hyperfibrinolysis is considered to be involved. (Leukemia, aplastic anemia, purpura, etc, abnormal bleeding during or after operation.)
Symptoms eg, pharyngalgia, redness, hyperemia or swelling in the following diseases: Tonsillitis and pharyngolaryngitis.
Symptoms eg, erythema, swelling or pruritus in the following diseases: Eczema or similar conditions, urticaria, drug eruptions or toxicoderma.
Pain in the oral cavity or mucosal aphtha in cases of stomatitis.

Adults: Capsule/Tablet: The usual dosage for oral use is 750-2000 mg tranexamic acid (as the base) daily in 3 or 4 divided doses. The dosage should be adjusted to individuals according to the patient's age and symptoms.
Daily Dose: 3-8 capsules or 2-4 tablets. To be divided into 3 or 4 portions.
Ampoule: The usual daily dosage for IV or IM injection is 250-500 mg of tranexamic acid in 1 or 2 divided doses. During or after surgery, 500-1000 mg IV or 500-2500 mg by IV drip infusion are administered each time as required.
250 mg/5 mL Ampoule: The usual daily dosage for IV or IM injection is 5-10 mL (1-2 amps) in 1 or 2 divided doses. During or after surgery, 10-50 mL (2-10 amps) are administered each time by IV drip infusion as required.
250 mg/2.5 mL and 1000 mg/10 mL Ampoule: The usual daily dose for IV or IM injection is 2.5-5 mL of tranexamic acid in 1 or 2 divided doses. During or after surgery, 5-10 mL IV or 5-25 mL by IV drip infusion are administered each time as required.
The dosage should be adjusted to individuals according to the patient's age and conditions.
Administration: IV: With regard to IV administration, inject the drug slowly. (Symptoms eg, nausea, chest discomfort, palpitations and a fall in blood pressure may rarely occur.)
IM: With regard to IM injection, pay careful attention to the following points to avoid injuring tissues, nerves, etc.
Inject the drug carefully to avoid contact with nerves.
If repeated injection is required, change the injection site (eg, alternate between the right and left arms). Special care should be observed when the drug is administered to premature infants, newborns, suckling infants and children.
If insertion of the injection needle induces intense pain or if blood flows back into the syringe, withdraw the needle immediately and perform injection at a different site.

Careful Administration: Transamin should be administered with care in the following patients:
Patients with thrombosis (cerebral thrombosis, myocardial infarction or thrombophlebitis, etc) and patients at risk of thrombosis. (Transamin may stabilize thrombosis.)
Patients with consumption coagulopathy (use concomitantly with heparin, etc). (Transamin may stabilize thrombosis.)
Patients with a history of hypersensitivity to tranexamic acid.
Others: Retinal degeneration has been reported with tranexamic acid in dogs after long-term, high-dose administration.
Use in the elderly: Since elderly patients often have reduced physiological function, careful supervision and measures eg, reducing the dose are recommended.

Summary of the incidence of adverse reactions:
Capsule/Tablet: The most frequently observed adverse reactions reported in a total of 2954 patients were anorexia (18 events) in 0.61%, nausea (12 events) in 0.41%, vomiting (6 events) in 0.2%, heartburn (5 events) in 0.17%, itching (2 events) in 0.07% and skin rash (2 events) in 0.07% (based on data obtained from the literature [outside the scope of re-examination]).
The following adverse reactions may occur. If any abnormalities occur, appropriate action should be taken eg, discontinuing Transamin if necessary.
0.1% to <1%: Gastrointestinal: Anorexia, nausea, vomiting, diarrhea and heartburn.
<0.1%: Hypersensitivity: Pruritus, skin rash, etc.
Others: Drowsiness.
Ampoule: The most frequently observed adverse reactions reported in a total of 2972 patients surveyed were anorexia (2 events) in 0.07%, vomiting (5 events) in 0.17%, nausea (1 event) in 0.03%, diarrhea (2 events) in 0.07% and drowsiness (1 event) in 0.03% [based on data obtained from the literature (outside the scope of re-examination)].
Clinically significant adverse reactions (frequency unknown*): Shock: Since shock may occur, the patient should be carefully monitored. If any signs of shock are observed, administration of Transamin should be discontinued and appropriate therapeutic measures taken.
Others: The following adverse reactions may occur. If any abnormalities occur, appropriate action should be taken eg, discontinuing Transamin if necessary.
0.1% to <1%: Gastrointestinal: Nausea and vomiting.
<0.1%: Hypersensitivity: Pruritus, skin rash, etc.
Gastrointestinal: Anorexia and diarrhea.
Others: Drowsiness and headache.
Unknown*: Ocular: Transient defective color vision.
*The incidence of adverse reactions on the basis of spontaneous reports or overseas resources is unknown.

Transamin should be administered with care when co-administered with the following drugs:
Hemostatic Organ Preparation, Hemocoagulase: High-dose co-administration may cause a thrombosis tendency. Fibrin clots formed by these drugs may persist in the bloodstream for a relatively long period due to the antiplasmin action of the product, so that a thrombotic state is prolonged.

Capsule/Tablet: For drugs that are dispensed in a press-through-package (PTP), instruct the patient to remove the drug from the package prior to use. (It has been reported that, if the PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa, resulting in severe complications eg, mediastinitis.)
Ampoule: To avoid contamination with foreign matter, wipe the ampoule with an alcohol swab before opening. Since a 'one-point cut ampoule is used, hold the ampoule with the mark on the neck upwards and break it open by pressure in the opposite direction.

Store at room temperature.

Haemostatics

B02AA02 - tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.

P₁S₁S₃