TRANEXAMIC ACID TILLOMED 500 MG FILM-COATED TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Tranexamic acid Tillomed 500 mg film-coated tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Tranexamic acid 500 mg as the active ingredient.

Excipients with known effect:

Each tablet contains 3.50 mg castor oil, hydrogenated and 0.648 mg propylene glycol

For a full list of excipients, see section 6.1.

Film-coated tablets

Off white to pale yellow, oval shaped film-coated tablet, plain on both sides, for oral use.

4.1 Therapeutic indications

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

Prostatectomy and bladder surgery

Menorrhagia

Severe Epistaxis

Conisation of the cervix

Prevention of recurrent hemorrhage in Traumatic hyphaema

Hereditary angioneurotic oedema

Management of dental extraction in haemophiliacs

4.2 Posology and method of administration Route of administration: O­ral.

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:

1a. Prostatectomy: Prophylaxis and treatment of haemorrhage in high risk patients should commence pre- or post-operatively with Tranexamic Acid Injection; thereafter 2 tablets three to four times daily until macroscopic haematuria is no longer present.

1b. 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.

1c. Severe Epistaxis: Where recurrent bleeding is anticipated oral therapy (2 tablets three times daily) should be administered for 7 days.

1d. Conisation of the cervix: 3 tablets three times daily for 12–14 days.

1e. Prevention of recurrent hemorrhage in Traumatic hyphaema: 2–3 tablets three times daily for 7 days. 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 prevention and treatment of hemorrhages in the management of dental extractions 2–3 tablets every eight hours for 6–8 days. The dose is based on 25 mg/kg.

Renal insufficiency: By extrapolation from clearance data relating to the intravenous dosage form, the following reduction in the 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 patients: No reduction in dosage is necessary unless there is evidence of renal failure (see guidelines below).

4.3 Contraindications

Hypersensitivity to tranexamic acid or any of the other excipients listed in section 6.

Severe renal impairment (Serum Creatinine > 500 jimol/l) because of risk of accumulation

Active thromboembolic disease.

History of venous or arterial thrombosis

Fibrinolytic conditions following consumption coagulopathy

History of convulsions

4.4 Special warnings and precautions for use

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

Tranexamic acid Tillomed 500 mg film-coated tablets contain castor oil. The presence of castor oil may cause stomach upset and diarrhoea.

4.5 Interaction with other medicinal products and other forms of interaction Tranexamic acid will counteract the thrombolytic effect of fibrinolytic preparations. Drugs that exert effects on hemostasis should be given with caution to patients taking tranexamic acid. There is a theoretical risk of increased formation potential thrombi, for example with estrogen.

4.6 Fertility, pregnancy and lactation

Pregnancy

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

Tranexamic acid crosses the placenta.

Breastfeeding

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.

Fertility

There are no clinical data on the effects of tranexamic acid on fertility.

4.7 Effects on ability to drive and use machines

Tranexamic Acid 500 mg Tablets has no known influence on the ability to drive and use machines.

4.8 Undesirable effects

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

Nervous system disorders

Very rare: convulsions, particularly in case of misuse

Eye disorders

Rare: Colour vision disturbances, retinal/artery occlusion

Cardiac disorders

Very rare: malaise with hypotension, with or without loss of consciousness (usually followed by an intravenous too fast, exceptionally after oral administration)

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

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 national reporting system listed in the Yellow Card Scheme www.mhra.gov.uk/yellowcard.

4.9 Overdose

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

Pharmacotherapeutic group: Antihemorrhagics, Antifibrolytics, Aminoacids

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.

5.2 Pharmacokinetic properties

Absorption

Peak plasma Tranexamic acid concentration is obtained immediately after intravenous administration (500mg). Then concentration decreases until the 6th hour. Elimination half-life is about 3 hours.

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

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.

5.3 Preclinical safety data

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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Core:

Cellulose microcrystalline (E460)

Starch pregelatinised

Low substituted hydroxypropyl cellulose (E463)

Silica colloidal anhydrous (E551)

Povidone (E1201)

Talc (E553b)

Castor oil hydrogenated

Magnesium stearate (E572)

Coating:

Hypromellose (E464)

Titanium dioxide (E171)

Macrogol (E1521)

Propylene glycol (E1520)

Sodium lauryl sulfate (E487)

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

In use shelf life for HDPE bottle pack: 25 days

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

HDPE bottle: For storage conditions after first opening of the medicinal product, see section 6.3

6.5 Nature and contents of container

Blister consisting of aluminium forming (OPA/Alu/PVC) and aluminium lidding foil.

Pack sizes of 10, 20, 30, 50, 60 and 100 tablets.

White High Density Polyethylene (HDPE) bottle fitted with a Polypropylene closure with liner/induction seal. Pack size of 100 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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