Contents

TEXAKIND (Tranexamic Acid Injection BP)

Tranexamic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin.

Tranexamic acid is a competitive inhibitor of plasminogen activation, and at much higher concentrations, a noncompetitive inhibitor of plasmin, i.e., actions similar to aminocaproic acid. The antifibrinolytic activity of tranexamic acid is about 10 times more potent in vitro than aminocaproic acid.

Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak receptor sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds. Tranexamic acid in a concentration of 1mg/ml does not aggregate platelets in vitro.

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.

In vitro studies showed that high tranexamic dosages decreased the activity of complement.

Therapeutic indications

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.

Dosage and administration

Adults: unless otherwise prescribed, the following doses are recommended

Standard treatment of local fibrinolysis: o.5g (1 ampoule of 5ml) to 1g (2 ampoules of 5ml) tranexamic acid by slow intravenous injection (=1ml/minute) 2 to 3 times daily
Standard treatment of general fibrinolysis: 1g (2 ampoules of 5ml) tranexamic acid by slow intravenous injection (=1ml/minute) every 6 to 8 hours, equivalent to 15mg/kg BW
Renal impairment: renal insufficiency leading to a risk of accumulation, the use of tranexamic acid is contraindicated in patients with severe renal impairment. For patients with mild to moderate renal impairment, the dosage of tranexamic acid should be reduced according to the serum creatinine level:

Serum Creatinine	µmol/l	Mg/10ml	Dose IV	Administration
120-249	1.35-2.82	10mg/kg BW	Every 12 hours
250-500	2.82-5.65	10mg/kg BW	Every 24 hours
>500	>5.65	5mg/kg BW	Every 24 hours

Hepatic impairment: No dose adjustment is required in patients with hepatic impairment.

Paediatric population

In children from 1 year, the dosage is in the region of 20mg/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.

Mode of administration: The administration is strictly limited to slow intravenous injection.

Contraindications

TEXAKIND is contraindicated in patients with known hypersensitivity to active substance

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)

Special warnings and precautions

The above indications and method of administration indicated below 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 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 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 disease 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.

Interactions with other medicinal products and other forms of interactions

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 antagonized with thrombolytic drugs.

Pregnancy and lactation

Women of childbearing potential have to use effective contraception during treatment.

Pregnancy: there is insufficient clinical data on the use of tranexamic acid in pregnant women.

Although studies in animals do not indicate teratogenic effects, as precaution for use, tranexamic acid is not recommended during the first trimester of pregnancy.

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, breast-feeding is not recommended.

Fertility: there are no clinical data on the effects of tranexamic acid on fertility.

Effects on ability to drive and use machines: no studies have been performed on the ability to drive and use machines.

Overdose

No case of overdose has been reported.

Signs and symptoms may include dizziness, headache, hypotension and convulsions. It has been shown that convulsions tend to occur at higher frequency with increasing dose.

Management of ovardose should be supportive.

TEXAKIND (Tranexamic Acid Injection BP)

TEXAKIND (Tranexamic Acid Injection BP)