Transamin

Transamin

tranexamic acid

Manufacturer:

Daiichi Sankyo

Distributor:

First Pharmaceutical
Full Prescribing Info
Contents
Tranexamic acid.
Description
Each capsule also contains sodium bisulfite, sodium lauryl sulfate and Yellow No.5 (Sunset Yellow FCF) as inactive ingredients. Each 5% w/v ampoule contains tranexamic acid 250 mg/5 mL, has a pH of 7-8 and an osmotic pressure ratio (with respect to physiological saline) of about 1.
Each 10% w/v ampoule contains tranexamic acid 250 mg/2.5 mL, has a pH of 7-8 and an osmotic pressure ratio (with respect to physiological saline) of about 2.
Tranexamic acid is trans-4-aminomethylcyclohexanecarboxylic acid. It has a molecular formula of C8H15NO2, molecular weight of 157.21 and melting point of 386-390°C (decomposition). It occurs as white crystals or powder, odorless and has 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 TS.
Capsule Size: No.2, total length of 17.6 mm and weight of about 350 mg.
Action
Antiplasmin agent.
Pharmacology: In physiological conditions, fibrinolysis affects enhancements of vascular permiability, 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, occur. Even 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 hemorrhages.
Antiallergic and Anti-inflammatory Action: Tranexamic acid inhibits plasmin-induced production of kinin and other active peptides, that cause enhancement of vascular permeability, allergy and anti-inflammatory lesions (as demonstrated in guinea pigs and rats).
Pharmacokinetics: Blood Concentrations: Capsule: The concentrations in the blood, when 250 and 500 mg of tranexamic acid were administered orally to healthy adults, reached peak values of 3.9 mcg/mL (250-mg administration) and 6 mcg/mL (500-mg administration) 2-3 hrs after administration. The biological half-lives were 3.1 and 3.3 hrs, respectively.
Injection: When a single dose of tranexamic acid 500 mg was administered IM or 1000 mg was administered IV to healthy adults, the time-plasma concentration were as follows. (See table.)
Plasma Concentration after Single IV and IM Doses of Tranexamic Acid: See figure.

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Excretion: Capsule: When 250 mg/500 mg of tranexamic acid was administered orally to healthy adults, urinary excretion rate was 40-70% by 24 hrs after administration.
Clinical Studies: Antihemorrhagic Action: Capsule: In an open-labelled clinical trial performed on 2802 patients with hemorrhagic tendencies during leukemia, aplastic anemia or purpura thought to involve systemic hyperfibrinolysis or with pulmonary, genital or renal hemorrhage or abnormal hemorrhage during or after prostate operation thought to involve local hyperfibrinolysis, Transamin showed hemostatic effects in 73.6% (2063 cases).
Injection: A hemostatic effect of Transamin was observed in 594 out of 709 patients (83.8%) with a bleeding tendency eg, leukemia, aplastic anemia and purpura, which are considered to be associated with systemic hyperfibrinolysis or abnormal bleeding eg, pulmonary, nasal, vaginal, renal, prostatic hemorrhage, and intra- and postoperative bleeding.
Antiallergic and Anti-inflammatory Actions: Capsule: Skin Disorders: The effects of Transamin against pruritus, rubor and swelling were compared to placebo in a double-blind clinical trial in 67 patients (Transamin 35, placebo 32) with skin disorders (eczema or similar diseases, toxicoderma and/or drug eruption) were examined.
The result showed that 22 patients (62.9%) in the Transamin group and 10 patients (31.3%) in the placebo group had a response more than good and a significant difference was recognized between these groups (p<0.05).
An open-labelled clinical study in 223 patients with skin diseases (eczema or similar diseases, urticaria, drug rash, toxicoderma) showed that this drug was effective against pruritus, swelling and erythema in 135 patients (60.5%).
Injection: Symptoms of skin disorders eg, eczema and similar conditions or urticaria, improved in 220 out of 283 patients (77.7%).
Otolaryngological Disorders: Capsule: The effects against pain, swelling and rubor, in a double-blind clinical trial in 168 patients (Transamin 84, placebo 84) with otolaryngological disorders (acute laryngopharyngitis, acute tonsillitis and stomatitis) were examined.
The result showed that 44 patients (52.4%) in Transamin group and 22 patients (26.2%) in placebo group had a response more than good and a significant difference was recognized between these groups (p<0.05). In an open-labelled clinical trial performed on 168 patients with tonsillitis, laryngopharyngitis, stomatitis and gingivitis, the effects against pain, swelling, rubor, were observed in 119 patients (70.8%).
Adverse Reactions: Capsule: The major adverse reactions reported in 2954 patients in clinical trial (including double-blind clinical trial) were anorexia in 0.61% (18 cases), nausea in 0.41% (12 cases), vomiting in 0.2% (6 cases), heartburn in 0.17% (5 cases), itching 0.07% (2 cases) and rash in 0.07% (2 cases).
Injection: The major adverse reactions reported in 2972 patients administered Transamin were anorexia in 0.07% (2 cases), vomiting in 0.17% (5 cases), nausea in 0.03% (1 case), diarrhea in 0.07% (2 cases) and drowsiness in 0.03% (1 case).
Nonclinical Studies: Metabolism: When 14C-tranexamic acid was administered IV to rats, it was almost all excreted in the unchanged form.
Distribution: Capsule: When 14C-tranexamic acid was orally administered to rats, the concentrations in most organs reached peak values as well as the blood concentrations after 2 hrs.
Levels in kidney and liver were higher and those of other organs were lower than that of the blood.
Injection: When 14C-tranexamic acid was administered IV or IM to mice, the distribution in the tissues 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: Injection: When a single dose of tranexamic acid 500 mg 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 unchanged form in the urine within 24 hrs of administration.
Toxicology: Single-Dose Toxicity: Capsule: The LD50 values of oral administration were >10 g/kg in mice and rats and >5 g/kg in dogs.
Injection: The LD50 values of IV administration were 1.35 g/kg in mice and 1.41 g/kg in rats.
The LD50 values of SC administration were 5.31 g/kg in mice and 4.62 g/kg in rats.
Repeated-Dose Toxicity: When tranexamic acid was orally administered to rats for 6 months continuously and their general condition, blood, organs were examined, no abnormalities were seen up to a dose of 1.5 g/kg, but at doses of ≥3 g/kg, diarrhea appeared and at 4 g/kg the body weight gain was inhibited only in males.
Teratogenicity: Fetal Test: Capsule: In oral administration test, no teratogenic action was seen at dose of 1.5 g/kg in mice and rats.
Mutagenicity: No mutagenicity was seen in the Rec-assay, Ames test, chromosome test or dominant lethality test.
Carcinogenicity: In a carcinogenicity test performed by administering 2.5% or 5% of tranexamic acid mixed with the feed for 19 months, no carcinogenicity was observed.
Indications/Uses
Bleeding tendencies in which systemic hyperfibrinolysis is considered to be involved (leukemia, aplastic anemia, purpura and abnormal bleeding during or after operation).
Abnormal bleeding in which local hyperfibrinolysis is considered to be involved (pulmonary, nasal, vaginal or renal hemorrhage, abnormal bleeding during or after prostate surgery).
Symptoms eg, erythema, swelling or pruritus in the following diseases: Eczema or similar diseases, urticaria, drug eruptions or toxicoderma.
Symptoms eg, pharyngalgia, redness, hyperemia or swelling in the following diseases: Tonsillitis, pharyngolaryngitis.
Pain in the oral cavity or mucosal aphtha in cases of stomatitis.
Dosage/Direction for Use
Capsule: Adults: 750-2000 mg/day orally in 3-4 divided doses. The dosage may be adjusted depending on the patient's age and symptoms.
Following are the doses of each of the preparation: Daily Dosage: 3-8 cap in 3-4 divided doses.
Injection: Adults: 250-500 mg/day IV or IM in 1-2 divided doses. 500-1000 mg each time IV or 500-2500 mg by IV drip infusion as required during or after surgery.
Amp 5%: 1-2 amp (5-10 mL) per day IV or IM in 1-2 divided doses.
2-10 mL amp (10-50 mL) each time by IV drip infusion as required.
Amp 10%: 2.5-5 mL/day IV or IM in 1-2 divided doses.
5-10 mL each time IV or 5-25 mL by IV drip infusion as required.
The dosage should be adjusted depending on the patient's age and conditions.
Special Precautions
Careful Administration: Patients with thrombosis (cerebral thrombosis, myocardial infarction, thrombophlebitis) and patients at risk of thrombosis.
Transamin may stabilize thrombosis.
Patients with consumption coagulopathy (use concomitantly with heparin). It may stabilize thrombus.
Patients with a history of hypersensitivity to Transamin.
Others: Retinal degeneration has been reported with tranexamic acid in dogs after long-term, high-dose administration.
Use in pregnancy: Placental Transfer: When 14C-tranexamic acid was administered IV to pregnant rats, transfer to the fetuses was confirmed and the concentrations in whole blood of the fetal tissue and fetal were the same as or less than those in the whole blood of the mothers.
Use in lactation: Transfer to Mother's Milk: When 40 mg/kg of 14C-tranexamic acid was administered IV to rats, transfer to mother's milk was seen at concentrations of 6.1 mcg/mL 1 hr and 0.2 mcg/mL 24 hrs after administration.
Use in the elderly: Since the elderly often have reduced physiological hypofunction, careful supervision and measures eg, reducing the dose are recommended.
Use In Pregnancy & Lactation
Use in pregnancy: Placental Transfer: When 14C-tranexamic acid was administered IV to pregnant rats, transfer to the fetuses was confirmed and the concentrations in whole blood of the fetal tissue and fetal were the same as or less than those in the whole blood of the mothers.
Use in lactation: Transfer to Mother's Milk: When 40 mg/kg of 14C-tranexamic acid was administered IV to rats, transfer to mother's milk was seen at concentrations of 6.1 mcg/mL 1 hr and 0.2 mcg/mL 24 hrs after administration.
Adverse Reactions
Capsule: Rarely: <0.1%, infrequently: 0.1% to <5%, no specific designation: ≥5% or frequency unknown.
Other Adverse Reactions: Hypersensitivity: Symptoms eg, itching or skin rash may occur rarely. In the event of such symptoms, treatment should be discontinued.
Digestive: Symptoms eg, anorexia, nausea and/or vomiting may occur infrequently. Symptoms eg, diarrhea and heartburn may occur rarely.
Ophthalmic: Transient defective color vision may occur rarely following IV injection.
Others: Drowsiness and headache may occur rarely. There have been reports of retinal changes when large doses were administered to dogs over long periods.
Injection: The most frequently observed adverse reactions reported in a total of 2972 patients surveyed were anorexia in 0.07% (2 cases), vomiting in 0.17% (5 cases), nausea in 0.03% (1 case), diarrhea in 0.07% (2 cases) and drowsiness in 0.03% (1 case) [based on data obtained from the literature (outside the scope of 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 the drug if necessary.
Hypersensitivity: <0.1%: Pruritus, skin rash, etc.
Gastrointestinal: 0.1% to <1%: Nausea, vomiting. <0.1%: Anorexia, diarrhea.
Ocular: Unknown(*): Transient defective color vision.
Others: <0.1%: Drowsiness, headache.
(*)The incidence of adverse reactions on the basis of spontaneous reports or overseas resources is unknown.
Drug Interactions
Careful Co-Administration: Hemostatic organ preparation, hemocoagulase. (High-dose co-administration may cause a thrombosis tendency.)
Mechanism and Risk Factors: Fibrin clots formed by these drugs may persist in the bloodstream for a relatively long period due to the antiplasmin action of Transamin, so that a thrombotic state is prolonged.
Caution For Usage
Instructions for Use/Handling: IV: With regard to IV administration, inject Transamin 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 and nerves.
1. Inject Transamin carefully to avoid contact with nerves.
2. 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.
3. 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.
4. Precautions When Opening the Ampoule: To avoid contamination with foreign matter, wipe them off with an alcohol swab before opening the ampoule.
A "one-point cut ampoule" is used for Transamin/Transamin S. Hold the ampoule with the mark on the neck upwards and break it open by applying pressure in the opposite direction.
Storage
Store at room temperature.
ATC Classification
B02AA02 - tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.
Presentation/Packing
Cap 250 mg (orange and opaque cap, white and opaque body, identification code D605) x 50 x 10's. Inj (amp) 5% x 5 mL x 50's. 10% x 10 mL x 50's.
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