Ranesan

Clear, colorless solution.
Each mL contains: Tranexamic Acid 100 mg.

Antifibrinolytic.
Pharmacology: Pharmacodynamics: Tranexamic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin. A complex involving tranexamic acid, plasminogen is constituted; the tranexamic acid being linked to plasminogen when transformed into plasmin. The activity of the tranexamic acid-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone.
Pharmacokinetics: Absorption: Peak plasma concentrations of tranexamic acid are obtained rapidly after a short intravenous infusion after which plasma concentrations decline in a multi-exponential manner.
Distribution: 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. The initial volume of distribution is about 9 to 12 liters.
Tranexamic acid passes through the placenta. Following administration of an intravenous injection of 10 mg/kg to 12 pregnant women, the concentration of tranexamic acid in serum ranged 10-53 μg/mL while that in cord blood ranged 4-31 μg/mL. Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. Following administration of an intravenous injection of 10 mg/kg to 17 patients undergoing knee surgery, concentrations in the joint fluids were similar to those seen in corresponding serum samples. The concentration of tranexamic acid in a number of other tissues is a fraction of that observed in the blood (breast milk, one hundredth; cerebrospinal fluid, one tenth; aqueous humor, one tenth). Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity but does not influence sperm migration.
Elimination: It is excreted mainly in the urine as unchanged drug. Urinary excretion via glomerular filtration is the main route of elimination. Renal clearance is equal to plasma clearance (110 to 116 mL/min). Excretion of tranexamic acid is about 90% within the first 24 hours after intravenous administration of 10 mg/kg body weight. Half-life of tranexamic acid is approximately 3 hours.
Special populations: Plasma concentrations increase in patients with renal failure.
No specific PK study has been conducted in children.

Prevention and treatment of haemorrhages due to general or local fibrinolysis in adults and children from one year. Specific indications include: Haemorrhage caused by general or local fibrinolysis such as: Menorrhagia and metrorrhagia; Gastrointestinal bleeding; Haemorrhagic urinary disorders, further to prostate surgery or surgical procedures affecting the urinary tract; Ear Nose Throat surgery (adenoidectomy, tonsillectomy, dental extractions); Gynaecological surgery or disorders of obstetric origin; Thoracic and abdominal surgery and other major surgical intervention such as cardiovascular surgery; Management of haemorrhage due to the administration of a fibrinolytic agent.

Adults: Unless otherwise prescribed, the following doses are recommended: Standard treatment of local fibrinolysis: 0.5 g (1 ampoule of 5 mL) to 1 g (2 ampoules of 5 mL) tranexamic acid by slow intravenous injection (= 1 mL/minute) two to three times daily.
Standard treatment of general fibrinolysis: 1 g (1 ampoule of 10 mL or 2 ampoules of 5 mL) tranexamic acid by slow intravenous injection (= 1 mL/minute) every 6 to 8 hours, equivalent to 15 mg/kg BW.
Renal impairment: In renal insufficiency leading to a risk of accumulation, the use of tranexamic acid is contra-indicated in patient with severe renal impairment (see Contraindications). For patient with mild to moderate renal impairment, the dosage of tranexamic acid should be reduced according to the serum creatinine level: See Table 1.

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Hepatic impairment: No dose adjustment is required in patient with hepatic impairment.
Paediatric Population: In children from 1 year, for current approved indications, the dosage is in the region of 20 mg/kg/day. However, data on efficacy, posology and safety for these indications are limited.
The efficacy, posology and safety of tranexamic acid in children undergoing cardiac surgery have not been fully established.
Elderly: No reduction in dosage is necessary unless there is evidence of renal failure.
Method of administration: The administration is strictly limited to slow intravenous injection.

No cases of overdose have been reported.
Signs and symptoms may include nausea, vomiting, dizziness, headache, hypotension, and convulsions. It has been shown that convulsions tend to occur at higher frequency with increasing dose. Management of overdose should be supportive. Maintain a high fluid intake to promote renal excretion. Anticoagulant treatment should be considered. There is a risk of thrombosis in predisposed individuals.

Hypersensitivity to the active substance or to any of the excipients.
Acute venous or arterial thrombosis.
Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding.
Severe renal impairment (risk of accumulation).
History of convulsions.
Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions).

The indications and method of administration indicated previously should be followed strictly: Intravenous injections should be given very slowly.
Tranexamic acid should not be administered by the intramuscular route.
Convulsions: Cases of convulsions have been reported in association with tranexamic acid treatment. In coronary artery bypass graft (CABG) surgery, most of these cases were reported following intravenous (I.V.) injection of tranexamic acid in high doses. With the use of the recommended lower doses of Tranexamic Acid, the incidence of post-operative seizures was the same as that in untreated patients.
Visual Disturbances: Attention should be paid to possible visual disturbances including visual impairment, vision blurred, impaired colour vision and if necessary the treatment should be discontinued. With continuous long-term use of Tranexamic Acid solution for injection, regular ophthalmologic examinations (eye examinations including visual acuity, colour vision, fundus, visual field etc.) are indicated. With pathological ophthalmic changes, particularly with diseases of the retina, the physician must decide after consulting a specialist on the necessity for the long-term use of Tranexamic Acid solution for injection in each individual case.
Haematuria: In case of haematuria from the upper urinary tract, there is a risk for urethral obstruction.
Thromboembolic events: Before use of Tranexamic Acid, risk factors of thromboembolic disease should be considered. In patients with a history of thromboembolic diseases or in those with increased incidence of thromboembolic events in their family history (patients with a high risk of thrombophilia), Tranexamic acid solution for injection should only be administered if there is a strong medical indication after consulting a physician experienced in hemostaseology and under strict medical supervision. Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.
Disseminated Intravascular Coagulation: Patients with disseminated intravascular coagulation (DIC) should in most cases not be treated with tranexamic acid. If tranexamic acid is given it must be restricted to those in whom there is predominant activation of the fibrinolytic system with acute severe bleeding. Characteristically, the haematological profile approximates to the following: reduced euglobulin clot lysis time; prolonged prothrombin time; reduced plasma levels of fibrinogen, factors V and VIII, plasminogen fibrinolysin and alpha-2 macroglobulin; normal plasma levels of P and P complex; i.e. factors II (prothrombin), VIII and X; increased plasma levels of fibrinogen degradation products; a normal platelet count. The foregoing presumes that the underlying disease state does not of itself modify the various elements in this profile. In such acute cases a single dose of 1 g tranexamic acid is frequently sufficient to control bleeding. Administration of Tranexamic acid in DIC should be considered only when appropriate haematological laboratory facilities and expertise are available.
This product contains sodium metabisulfite, a sulfite that may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episode in certain susceptible persons.

Women of childbearing potential have to use effective contraception during treatment.
Pregnancy: There are insufficient clinical data on the use of tranexamic acid in pregnant women. As a result, although studies in animals do not indicate teratogenic effects, as a precaution for use, tranexamic acid is not recommended during the first trimester of pregnancy. Limited clinical data on the use of tranexamic acid in different clinical haemorrhagic settings during the second and third trimesters did not identify deleterious effect for the foetus. Tranexamic acid should be used throughout pregnancy only if the expected benefit justifies the potential risk.
Lactation: Tranexamic acid is excreted in human milk. Therefore, breastfeeding is not recommended.

The ADRs reported from clinical studies and post-marketing experience are listed as follows according to system organ class.
Tabulated List of Adverse Reactions: Adverse reactions reported are presented in the table as follows. Adverse reactions are listed according to MedDRA primary system organ class. Within each system organ class, adverse reactions are ranked by frequency.
Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.
Frequencies were defined as follows: Common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100), not known (can not be estimated from the available data). (See Table 2.)

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No interaction studies have been performed. Simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field. Medicinal products that act on haemostasis should be given with caution to patients treated with tranexamic acid. There is a theoretical risk of increased thrombus-formation potential, such as with oestrogens. Alternatively, the antifibrinolytic action of the drug may be antagonised with thrombolytic drugs.

Store at temperatures not exceeding 30°C.

Haemostatics

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

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