Document: spc-doc_PL 06464-1373 change

• spc-doc_PL 04416-0391
• spc-doc_PL 06464-1373
• spc-doc_PL 14251-0011
• spc-doc_PL 17780-0095

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Tranexamic Acid 500 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Tranexamic acid 500 mg

For excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablet for oral administration.

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

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

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 and method of administration

For oral administration.

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. 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.

Serum Creatinine (frmol/l) Dose Tranexamic acid

120-249 15 mg/kg body weight twice daily

250-500 15 mg/kg body weight/day

Children's dosage:

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

Elderly patients dosage:

No reduction in dosage is necessary unless there is evidence of renal failure (see guidelines below).

4.3 Contraindications

Severe renal failure because of risk of accumulation, Hypersensitivity to tranexamic acid or any of the excipients, Active thromboembolic disease.

4.4 Special warnings and precautions for use

In massive haematuria from the upper urinary tract (especially in haemophilia) since, in a few cases, ureteric obstruction has been reported.

When disseminated intravascular coagulation is in progress.

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.

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 increase 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.

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

4.5. Interactions with other Medicaments and other forms of Interaction

Tranexamic acid counteracts the thrombolytic effect of fibrinolytic preparations.

4.6 Pregnancy and lactation

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.

Lactation

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.

4.7. Effects on Ability to Drive and Use Machines

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

4.8 Undesirable effects

Gastrointestinal disorders (nausea, vomiting, diarrhoea) may occur but disappear when the dosage is reduced.

Rare instances of colour vision disturbances have been reported. Patients who experience disturbance of colour vision should be withdrawn from treatment.

Rare cases of thromboembolic events have been reported.

Rare cases of allergic skin reactions have also been reported.

4.9 Overdose

No cases of overdosage have been reported. Symptoms may be nausea, vomiting, orthostatic symptoms and / or hypotension. 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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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.

5.2. Pharmacokinetic Properties

Following oral administration, 1.13% and 39% of the administered dose were recovered after 3 and 24 hours respectively. Tranexamic acid administered parenterally is distributed in a two compartment model.

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

Following intravenous administration, the biological half-life of tranexamic acid has been determined to be 1.9 hours and 2.7 hours.

5.3 Preclinical Safety Data

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

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

MARKETING AUTHORISATION NUMBER(S)

PL 06464/1373

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18^th August 2003

DATE OF REVISION OF THE TEXT

05/02/2007