- Approval Id
- 1f990170212ce20d
- Drug Approval Emc Name
- Tranexamic Acid 500 mg Tablets
- Drug Name
- Tranexamic Acid 500 mg Tablets
- Company Name
- Sovereign Medical
- Company Address
- Sovereign House, Miles Gray Road, Basildon, Essex, SS14 3FR
- Company Telephone
- +44 (0)1268 535 200
- Company Medical Info Direct Line
- +44 (0) 1748 827 299
- Company Medical Info Email
- medinfo@waymade.co.uk
- Company Medical Info Fax
- +44 (0)1268 535 299
- Atc Code
- B02AA02
- Legal Category
- Prescription only medicine
- Authorisation Holder
- Waymade Plc t/a Sovereign Medical
Sovereign House
Miles Gray Road
Basildon
Essex
SS14 3FR
United Kingdom
- Authorisation Number
- PL 06464/1373
- Authorisation Date
- 18th August 2003
- Instruction Authorisation Holder
- Waymade Plc t/a Sovereign Medical
Sovereign House
Miles Gray Road
Basildon
Essex
SS14 3FR
United Kingdom
- Instruction Authorisation Number
- PL 06464/1373
- Instruction Authorisation Date
- 18th August 2003
- Instruction Composition
- Each film-coated tablet contains Tranexamic acid 500 mg
For the full list of excipients, see section 6.1
- Instruction Dosage Form
- 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.
- Instruction 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 haemophiliacs4.2 Posology and method of administration
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.
| | |
| --- | --- |
| Serum Creatinine (μmol/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.
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 administration4.3 Contraindications
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.4.4 Special warnings and precautions for use
In case of haematuria of renal origin (especially in haemophilia) there is a risk for urinary obstruction at the lower levels of the tract. If left untreated, urinary obstruction may lead to serious consequences such as renal insufficiency, urinary tract infection, hydronephrosis, and anuria. Therefore, close monitoring is recommended for those patients with haematuria or risk of haematuria from the upper urinary tract.
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.4.5 Interaction with other medicinal products and other forms of interaction
Tranexamic acid counteracts the thrombolytic effect of fibrinolytic preparations.4.6 Fertility, 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.
\*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.4.7 Effects on ability to drive and use machines
Tranexamic acid has no or negligible influence on the ability to drive and use machines. Visual disturbances may occur following administration of tranexamic acid.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
\*\*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.4.9 Overdose
Signs and symptoms may include nausea, diarrhoea, 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.
- Instruction Pharmacology
- 5.1 Pharmacodynamic properties
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.5.2 Pharmacokinetic properties
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.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.
- Instruction 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
Vanillin6.2 Incompatibilities
Not applicable.6.3 Shelf life
36 months.6.4 Special precautions for storage
Do not store above 25ºC.
Store in the original package.6.5 Nature and contents of container
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.6.6 Special precautions for disposal and other handling
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
- Instruction Content
- ## Composition
Each film-coated tablet contains Tranexamic acid 500 mg
For the full list of excipients, see section 6.1
## Pharmaceutical Form
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.
## 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 haemophiliacs4.2 Posology and method of administration
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.
| | |
| --- | --- |
| Serum Creatinine (μmol/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.
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 administration4.3 Contraindications
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.4.4 Special warnings and precautions for use
In case of haematuria of renal origin (especially in haemophilia) there is a risk for urinary obstruction at the lower levels of the tract. If left untreated, urinary obstruction may lead to serious consequences such as renal insufficiency, urinary tract infection, hydronephrosis, and anuria. Therefore, close monitoring is recommended for those patients with haematuria or risk of haematuria from the upper urinary tract.
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.4.5 Interaction with other medicinal products and other forms of interaction
Tranexamic acid counteracts the thrombolytic effect of fibrinolytic preparations.4.6 Fertility, 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.
\*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.4.7 Effects on ability to drive and use machines
Tranexamic acid has no or negligible influence on the ability to drive and use machines. Visual disturbances may occur following administration of tranexamic acid.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
\*\*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.4.9 Overdose
Signs and symptoms may include nausea, diarrhoea, 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.
## Pharmacological Properties
5.1 Pharmacodynamic properties
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.5.2 Pharmacokinetic properties
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.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.
## 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
Vanillin6.2 Incompatibilities
Not applicable.6.3 Shelf life
36 months.6.4 Special precautions for storage
Do not store above 25ºC.
Store in the original package.6.5 Nature and contents of container
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.6.6 Special precautions for disposal and other handling
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
