Tranexamic Acid 500mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
TRANEXAMIC ACID 500 mg TABLETS
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 500 mg of tranexamic acid.
Refer to section 6.1 for excipients.
3 PHARMACEUTICAL FORM
Film-coated tablet.
Description: White to off white capsule shaped tablet marked ‘TA 500’ on one face and with a central division line on the reverse.
4 CLINICAL PARTICULARS
Tranexamic acid is an antifibrinolytic agent used to prevent bleeding. It achieves this action by competitively inhibiting the activation of plasminogen to plasmin.
4.1 Therapeutic indications
Short-term use for haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis.
• Local fibrinolysis occurs in the following conditions:
Prostatectomy
Menorrhagia
Epistaxis
Conisation of the cervix Traumatic hyphaema
Management of dental extraction in haemophiliacs
Hereditary angioneurotic oedema
4.2 Posology and method of administration
Route of Administration Oral
Posology
Adults:
The recommended standard dose is 15-25 mg / kg body weight (which generally equates to 2 to 3 tablets), two to three times a day.
The following doses are also suggested for the listed indications:
Prostatectomy:
Prophylaxis and treatment of haemorrhage in high-risk patients should commence pre or post operatively with tranexamic acid injection (also available commercially). Thereafter 2 tablets should be dosed three to four times a day until macroscopic haematuria is no longer present.
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.
Epistaxis:
2 tablets should be dosed three times a day for seven days where recurrent bleeding is anticipated.
Conisation of the cervix:
3 tablets should be dosed three times a day.
Traumatic hyphaema:
2 to 3 tablets should be dosed three times a day. This dose should be based on a dose of 25 mg / kg body weight three times a day.
Haemophilia:
2 to 3 tablets should be dosed three times a day in the management of dental extractions. Again, this dose should be based on a dose of 25 mg / kg body weight.
Hereditary angioneurotic oedema:
2 to 3 tablets should generally be dosed two to three times a day. In some patients this dosing should be continuous, but intermittent treatment can be used where patients are aware of the onset of the illness.
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.
Serum Creatinine (pmol/1) - Dose tranexamic acid 120-249 15 mg/kg body weight/twice daily 250-500 15 mg/kg body weight/day.
Elderly:
No reduction in dosage is necessary unless there is any evidence of renal failure.
Children:
In children, for current approved indications as described in section 4.1, the dosage is in the region of 20 mg/kg/day. However, data on efficacy, posology and safety for these indications are limited.
4.3 Contraindications
Tranexamic acid is contraindicated in patients with:
• Active thromboembolic disease or a history of venous or arterial thrombosis
• Hypersensitivity to tranexamic acid or any of the other ingredients
• Severe renal impairment because of risk of accumulation
• Fibrinolytic conditions following disseminated intravascular coagulation
• History of convulsions
4.4 Special Warnings and Precautions for Use
The blood levels are increased in patients with renal insufficiency. Therefore a dose reduction is recommended (see section 4.2 Posology).
In cases of haematuria of renal origin, there is a risk of mechanical anuria due to formation of a ureteral clot. Caution is advised in the treatment of patients suffering massive haematuria from the upper urinary tract (especially in haemophilia) since, in a few cases, ureteric obstruction has been reported.
A very small number of cases of acute renal failure have been reported with both intravenous and oral therapy, possibly due to renal microthrombi or infarction. Although other risk factors were present in several patients, the inhibitory effect of tranexamic acid on dissolution of blood clots in the kidney could be a contributory factor.
Regular eye examination (e.g. visual acuity, slit lamp, intra-ocular pressure, visual fields) and liver function tests should be performed during long-term treatment of patients with hereditary angioneurotic oedema (see 4.8). Patients who experience visual disturbance should be withdrawn from treatment.
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.
Before use of tranexamic acid, risk factors for thromboembolic disease should be investigated. 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 use of tranexamic acid in cases of increased fibrinolysis due to disseminated intravascular coagulations is not recommended (see Section 4.3).
Tranexamic acid should be administered with care in patients receiving oral contraceptives because of the increased risk of thrombosis.
Clinical experience with tranexamic acid in menorrhagic children under 15 years of age is not available.
4.5 Interaction with other medicinal products and other forms of interaction
Concomitant chlorpromazine and tranexamic acid therapy of subarachnoid haemorrhage has been reported to result in cerebral vasospasm and cerebral ischemia, and possibly a reduction in cerebral blood flow.
It is not recommended to use tranexamic acid concomitantly with highly activated prothrombin products.
Tranexamic acid will counteract the thrombolytic effect of fibrinolytic preparations.
4.6 Pregnancy and lactation
Tranexamic acid crosses the placenta
Although animal studies show no evidence of any teratogenic effect, the usual precautions associated with the use of drugs during pregnancy should be observed.
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
None reported
4.8 Undesirable Effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common ( >1/l0), 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).
|
System Organ Class | |
|
Immune system disorders |
Very rare: Hypersensitivity reactions including anaphylaxis |
|
Nervous system disorders |
Very rare: Convulsions |
|
Eye disorders |
Rare: Colour vision disturbances, retinal vein/artery occlusion |
|
Patients who experience disturbance of colour vision should be withdrawn from treatment. | |
|
Vascular disorders |
Rare : Thromboembolic events (arterial or venous thrombosis). Hypotension, with or without loss of consciousness. This generally occurs as a consequence of rapid intravenous injection, but may occur exceptionally after oral administration. |
|
Gastrointestinal disorders |
Very rare: Nausea, vomiting diarrhoea. These may disappear on dose reduction. |
|
Skin and subcutaneous tissue disorders |
Rare: Allergic skin reactions |
|
Renal and urinary disorders |
Not known: Renal infarct, acute renal failure |
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.
4.9 Overdose
No cases of overdose have been reported.
Symptoms of overdose 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 produces antifibrinolytic effects via complex interactions with plasminogen, displacing plasminogen from the fibrin surface. Tranexamic acid exerts its antifibrinolytic effects primarily by forming a reversible complex with a modified plasminogen and the associated conformational changes of this proenzyme. In effect, tranexamic acid saturates the lysine binding sites of human plasminogen, displacing plasminogen from the fibrin surface which results in inhibition of fibrinolysis. Fibrinolysis is inhibited no matter how rapidly plasmin is formed, since plasmin is unable to bind to fibrinogen or fibrin monomers, precluding proteolytic action by the serine-histidine enzyme site.
Tranexamic acid also inhibits the proteolytic activity of plasmin via blockade of the lysine binding sites of plasmin, making inactivation by alpha-2-antiplasmin impossible. Recurrent or excessive bleeding can occur with defective fibrin formation or excessive rapid dissolution of fibrin; tranexamic acid can prevent the dissolution of haemostatic fibrin by stabilising fibrin structures. The drug also increases collagen synthesis and tensile strength within granulation tissue, most likely by preserving the fibrin matrix.
Tranexamic acid and other antifibrinolytic agents cross the blood-brain barrier and counteract the increased fibrinolytic activity of cerebrospinal fluid. Tranexamic acid competitively inhibits the activation of enterokinase and noncompetitively inhibits the proteolytic activity of trypsin at four-fold greater concentrations.
5.2 Pharmacokinetic properties
Absorption
Absorption of tranexamic acid from the GI tract is 30 to 40%. Peak plasma concentrations are achieved about 3 hours after dosing and the plasma half-life of the drug is between 1 and 3 hours.
Elimination
Tranexamic acid is excreted in urine as unchanged compound. Approximately 90% of an intravenous administered dose is excreted by the kidney in the first twelve hours after administration (glomerular excretion without tubular reabsorption).
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 SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
The tablet also contains:
Microcrystalline cellulose Povidone
Croscarmellose sodium Talc
Magnesium stearate Colloidal silica
The coating contains:
Methacrylic co-polymer Titanium dioxide (E171)
Talc
Magnesium stearate Macrogol 8000
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 25 °C. Store in the original pack.
6.5 Nature and contents of container
Blister packs composed of PVC covered by an aluminium lidding foil.
The blister packs are contained in an outer carton containing 60 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Manx Healthcare Limited Taylor Group House Wedgnock Lane Warwick CV34 5YA United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 14251/0011
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
26/07/2002 / 26/03/2009
10 DATE OF REVISION OF THE TEXT
19/12/2013