Tranexamic Acid 500 mg Tablets

Each film-coated tablet contains Tranexamic acid 500 mg

For the full list of excipients, see section 6.1

Film-coated tablet

Each film-coated tablet is white to off-white, oblong, biconvex with a break line and marked “TA” on one side of the break line.

The breakline is not intended for breaking the tablet.

1. Short-term use for haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Local fibrinolysis as occurs in the following conditions:

a) Prostatectomy and bladder surgery

b) Menorrhagia

c) Epistaxis

d) Conisation of the cervix

e) Traumatic hyphaema

2. Hereditary angioneurotic oedema

3. Management of dental extraction in haemophiliacs

Posology

1. Local fibrinolysis

The recommended standard dosage is 15-25 mg /kg bodyweight (i.e. 2- 3 tablets) two to three times daily. For the indications listed below the following doses may be used:

a) Prostatectomy: Prophylaxis and treatment of haemorrhage in high risk patients should commence pre- or post-operatively with intravenous tranexamic acid injection; thereafter 2 tablets three to four times daily until macroscopic haematuria is no longer present.

b) Menorrhagia: Recommended dosage is 2 tablets 3 times daily as long as needed for up to 4 days. If very heavy menstrual bleeding, dosage may be increased. A total dose of 4g daily (8 tablets) should not be exceeded. Treatment with Tranexamic acid should not be initiated until menstrual bleeding has started.

c) Epistaxis: Where recurrent bleeding is anticipated oral therapy (2 tablets three times daily) should be administered for 7 days.

d) Conisation of the cervix: 3 tablets three times daily.

e) Traumatic hyphaema: 2-3 tablets three times daily. The dose is based on 25 mg /kg three times a day.

2. Hereditary angioneurotic oedema

Some patients are aware of the onset of the illness; suitable treatment for these patients is intermittently 2-3 tablets two to three times daily for some days. Other patients are treated continuously at this dosage.

3. Haemophilia

In the management of dental extractions 2-3 tablets every eight hours. The dose is based on 25 mg /kg bodyweight.

Renal insufficiency: By extrapolation from clearance data relating to the intravenous dosage form, the following reduction in oral dosage is recommended for patients with mild to moderate renal insufficiency.

Children's dosage:

This should be calculated according to body weight at 25 mg /kg per dose.

However, data on efficacy, posology and safety for these indications are limited.

Elderly patient's dosage:

No reduction in dosage is necessary unless there is evidence of renal insufficiency (see above).

Method of administration

For oral administration

Severe renal impairment because of risk of accumulation.

Hypersensitivity to tranexamic acid or any of the excipients, listed in section 6.1.

Active thromboembolic disease.

History of venous or arterial thrombosis.

Fibrinolytic conditions following consumption coagulopathy.

History of convulsions.

In case of haematuria of renal origin (especially in haemophilia) there is a risk of mechanical anuria due to the formation of a ureteral clot.

In the long-term treatment of patients with hereditary angioneurotic oedema, regular eye examinations (e.g. visual acuity, slit lamp, intraocular pressure, visual fields) and liver function tests should be performed.

Patients with irregular menstrual bleeding should not use Tranexamic acid until the cause of irregular bleeding has been established. If menstrual bleeding is not adequately reduced by Tranexamic acid, an alternative treatment should be considered.

Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.

Patients with a previous thromboembolic event and a family history of thromboembolic disease (patients with thrombophilia) should use Tranexamic acid only if there is a strong medical indication and under strict medical supervision.

The blood levels are increased in patients with renal insufficiency. Therefore, a dose reduction is recommended (see section 4.2).

The use of Tranexamic acid in cases of increased fibrinolysis due to disseminated intravascular coagulation is not recommended.

Patients who experience visual disturbance should be withdrawn from treatment.

Clinical experience with Tranexamic acid in menorrhagic children under 15 years of age is not available.

Cases of convulsions have been reported in association with tranexamic acid treatment. In cardiac surgery, most of these cases were reported following intravenous (i.v.) injection of tranexamic acid in high doses.

Tranexamic acid counteracts the thrombolytic effect of fibrinolytic preparations.

Pregnancy

Although there is no evidence from animal studies of a teratogenic effect, the usual caution with the use of drugs in pregnancy should be observed.

Tranexamic acid crosses the placenta.

Breast-feeding

Tranexamic acid passes into breast milk to a concentration of approximately one hundredth of the concentration in the maternal blood. An antifibrinolytic effect in the infant is unlikely.

Tranexamic acid has no or negligible influence on the ability to drive and use machines.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥ 1/10,000 and <1/1000) and very rare (<1/10,000) including isolated reports, not known (cannot be estimated from the available data).

Immune system disorders

Very rare: Hypersensitivity reactions including anaphylaxis

Eye disorders

Rare: Colour vision disturbances, retinal/artery occlusion

Vascular disorders

Rare: Thromboembolic events

Very rare: Arterial or venous thrombosis at any sites

Gastro-intestinal disorders

Very rare: Digestive effects such as nausea, vomiting and diarrhoea, may occur but disappear when the dosage is reduced.

Skin and subcutaneous tissue disorders

Rare: Allergic skin reactions

Nervous system disorders

Frequency not known: Convulsions particularly in cases of misuse (refer to sections 4.3 and 4.4)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Signs and symptoms may include nausea, vomiting, orthostatic symptoms and/or hypotension, dizziness, headache and convulsions. Initiate vomiting, then stomach lavage, and charcoal therapy. Maintain a high fluid intake to promote renal excretion. There is a risk of thrombosis in predisposed individuals. Anticoagulant treatment should be considered.

Pharmacotherapeutic group: Antihemorrhagics, Antifibrinolytics. ATC code: B02AA02

Tranexamic acid is an antifibrinolytic compound which is a potent competitive inhibitor of the activation of plasminogen to plasmin. At much higher concentrations it is a non-competitive inhibitor of plasmin. The inhibitory effect of tranexamic acid in plasminogen activation by urokinase has been reported to be 6-100 times and by streptokinase 6-40 times greater than that of aminocaproic acid. The antifibrinolytic activity of tranexamic acid is approximately ten times greater than that of aminocaproic acid.

Absorption

Peak plasma Tranexamic acid concentration is obtained immediately after intravenous administration (500mg). Then concentration decreases until the 6th hour.

Distribution

Tranexamic acid administered parenterally is distributed in a two compartment model. Tranexamic acid is delivered in the cell compartment and the cerebrospinal fluid with delay. The distribution volume is about 33% of the body mass.

Tranexamic acid crosses the placenta, and may reach one hundredth of the serum peak concentration in the milk of lactating women.

Elimination

Elimination half-life is about 3 hours.

Tranexamic acid is excreted in urine as unchanged compound. 90% of the administered dose is excreted by the kidney in the twelve first hours after administration (glomerular excretion without tubular reabsorption).

Following oral administration, 1.13% and 39% of the administered dose were recovered after 3 and 24 hours respectively.

Plasma concentrations are increased in patients with renal insufficiency.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the Summary of Product Characteristics.

Tablet core:

Microcrystalline cellulose

Povidone K90

Croscarmellose sodium

Colloidal anhydrous silica

Talc

Magnesium Stearate

Film coating:

Magnesium stearate

Methacrylate polymers

Titanium dioxide (E171)

Macrogol 8000

Vanillin

Not applicable.

36 months.

Do not store above 25°C.

Store in the original package.

Blister pack of 25 μm, aluminium foil and 250μm, white opaque or transparent PVC.

Pack sizes: 12 and 60.

Not all pack sizes may be marketed.

No special requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Waymade Plc t/a Sovereign Medical

Sovereign House

Miles Gray Road

Basildon

Essex

SS14 3FR

United Kingdom

PL 06464/1373

18^th August 2003

05/11/2018