Consumer medicine information

APO-Tranexamic Acid

Tranexamic acid

BRAND INFORMATION

Brand name

APO-Tranexamic Acid

Active ingredient

Tranexamic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Tranexamic Acid.

What is in this leaflet

This leaflet answers some common questions about APO-TRANEXAMIC ACID.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking APO-TRANEXAMIC ACID against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine. You may need to read it again.

What this medicine is used for

APO-TRANEXAMIC ACID is used to prevent bleeding in patients with:

Traumatic hyphaema (bleeding into the front part of the eye)

Blood clotting disorders, who are having minor surgery

Heavy periods

Hereditary angioneurotic oedema (periodic swelling of the throat)

APO-TRANEXAMIC ACID contains tranexamic acid. Tranexamic acid is an antifibrinolytic that works by slowing the processes that cause bleeding.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • have an allergy to tranexamic acid or any of the ingredients listed at the end of this leaflet
  • are being treated for stroke
  • are being treated for blood clots in your legs, lungs or anywhere else in your body
  • have a problem with colour vision that developed after you were born.
  • the expiry date (Exp.) printed on the pack has passed.
  • the packaging is torn or shows signs of tampering.

Do not use APO-TRANEXAMIC ACID to treat any other complaint unless your doctor tells you to.

Before you start to take it

Tell your doctor if you have any of the following:

  • you, or someone in your family, has ever suffered from blood clots
  • severe bruising
  • kidney disease with or without blood in the urine
  • irregular periods and the reason is not known

Tell your doctor if you have or have ever suffered from convulsion, fits or seizures before you start taking APO-TRANEXAMIC ACID. Convulsions, fits or seizures have been reported with APO-TRANEXAMIC ACID treatment.

Tell your doctor if you are allergic to any other medicines, foods, dyes or preservatives.

Tell your doctor if you are pregnant or plan to become pregnant. Your doctor will discuss the risks and benefits of taking APO-TRANEXAMIC ACID during pregnancy.

Tell your doctor if you are breastfeeding or wish to breastfeed. Your doctor will discuss the risks and benefits of taking APO-TRANEXAMIC ACID when breastfeeding.

If you have not told your doctor about any of the above, tell them before you start taking APO-TRANEXAMIC ACID.

Do not give this medicine to anyone else even if they have the same condition as you.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines may be affected by APO-TRANEXAMIC ACID, or may affect how well it works. These include:

  • other medicines used to prevent bleeding
  • medicines used to thin blood.

Your doctor can tell you what to do if you are taking any of these medicines.

If you are not sure whether you are taking any of these medicines, check with your doctor or pharmacist. Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking APO-TRANEXAMIC ACID.

How to take this medicine

Follow carefully all directions given to you by your doctor or pharmacist. Their instructions may be different to the information in this leaflet.

How much to take

Traumatic hyphaema (bleeding to the front part of the eye)
Take two or three tablets every 8 hours, for six to seven days. Swallow the tablets with water.

Heavy periods
Take two or three tablets four times a day for four days. Start taking the tablets when you first notice the bleeding. Take APO-TRANEXAMIC ACID tablets for the first four days of your period. See your doctor for a check up after three months of treatment. If the bleeding is not reduced, talk to your doctor. Swallow the tablets with water.

Hereditary Angioneurotic Oedema (periodic swelling of the throat)
The usual dose is two or three tablets, 2 to 3 times a day. Your doctor will tell you how long to take the tablets. Swallow the tablets with water.

For those with a clotting disorder, having minor surgery
The usual dose is two or three tablets, 2 to 3 times a day. Your doctor will tell you how long to take the tablets. Swallow the tablets with water.

The directions your doctor gives you should be strictly followed.

If you do not understand the instructions in this leaflet, ask your doctor or pharmacist for help.

If you forget to take it

Take your APO-TRANEXAMIC ACID Tablets as soon as you remember and then go back to taking it as normally would.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not try to make up for missed doses by taking more than one dose at a time because this may increase the chance of you getting an unwanted side effect.

If you have any questions about this, check with your doctor or pharmacist.

If you take too much (overdose)

Symptoms from taking too much APO-TRANEXAMIC ACID include:

  • dizziness
  • headache
  • nausea
  • diarrhoea
  • low blood pressure
  • convulsions, fits or seizures.

Immediately telephone your doctor, or the Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much APO-TRANEXAMIC ACID. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

While you are taking this medicine

Things you must do

Before starting any new medicine, tell your doctor or pharmacist that you are taking APO-TRANEXAMIC ACID.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking APO-TRANEXAMIC ACID.

Possible side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking APO-TRANEXAMIC ACID.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • nausea
  • vomiting
  • diarrhoea.

There are the more common side effects of APO-TRANEXAMIC ACID. Mostly these are mild and short-lived.

Following cardiac surgery, total knee replacement or total hip replacement surgery, tell your doctor or nurse immediately if you experience any of the following:


  • irregular and often rapid heart beat
  • heart attack
  • slow or irregular heart beat
  • cardiogenic shock caused by very low blood pressure. The symptoms are dizziness and light headedness, rapid, weak pulse, white skin, sweating, restlessness, loss of consciousness, fainting, rapid, shallow breathing, cold clammy skin and weakness
  • stroke. The symptoms of stroke are numbness or weakness of the arms or legs, headache, dizziness and confusion, visual disturbance, difficulty swallowing, slurred speech and loss of speech
  • kidney problems where you pass little or no urine, drowsiness, nausea, vomiting and breathlessness
  • difficulty breathing
  • a condition called deep vein thrombosis (DVT). The symptoms of DVT are pain and swelling in the large veins, usually in your legs. DVT may lead to complications such as blood clots in your lungs
  • bowel infarction caused by a restriction of blood supply to the bowels. You may experience severe abdominal pains and may pass bloody stools.

These are serious side effects. You may need urgent medical attention.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • unexpected pain
  • unexpected swelling in your legs or arms
  • giddiness or dizziness
  • allergic skin reactions
  • changes in your eyesight
  • convulsions, fits or seizures.

These may be serious side effects. You may need urgent medical attention.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything that is making you feel unwell.

Storage and disposal

Storage

Keep APO-TRANEXAMIC ACID where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Keep your tablets in the pack until it is time to take them. If you take the tablets out of the pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store APO-TRANEXAMIC ACID or any other medicine in the bathroom or near a sink.

Do not leave APO-TRANEXAMIC ACID in the car or on window sills. Heat and dampness can destroy some medicines.

Disposal

If your doctor tells you to stop taking APO-TRANEXAMIC ACID, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What APO-TRANEXAMIC ACID tablet looks like

500mg tablet: Tranexamic acid is a white to slightly yellowish, film coated, capsule shaped, biconvex, 18 mm x 8 mm, with a break-line and embossed "TXA 500"

Each pack contains 100 tablets.

Ingredients

The active ingredient in APO-TRANEXAMIC ACID is tranexamic acid. Each 500 mg tablet contains 500 mg of tranexamic acid.

The tablet also contains:

  • microcrystalline cellulose
  • povidone
  • croscarmellose sodium
  • colloidal anhydrous silica
  • purified talc
  • magnesium stearate
  • titanium dioxide
  • macrogol 8000
  • vanillin
  • eudragit E100.

The tablets do not contain gluten, lactose, sucrose, tartrazine or any other azo dyes.

Australian Registration Numbers

APO-Tranexamic acid 500mg tablets (blister pack): AUST R 272732

APO-Tranexamic acid 500mg tablets (bottle pack): AUST R 272727

Sponsor

Southern Cross Pharma Pty Ltd
Suite 2 Level 2
19-23 Prospect Street
VIC 3128

APO and APOTEX are registered trademarks of Apotex Inc.

Distributor

Arrotex Pharmaceuticals
15 – 17 Chapel St
Cremorne VIC 3121
www.arrotex.com.au

This leaflet was last updated in:
February 2023

Published by MIMS June 2023

BRAND INFORMATION

Brand name

APO-Tranexamic Acid

Active ingredient

Tranexamic acid

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals

1 Name of Medicine

Tranexamic acid.

2 Qualitative and Quantitative Composition

APO-Tranexamic Acid tablets contain the active ingredient tranexamic acid.
Each APO-Tranexamic Acid tablet contained 500 mg of tranexamic acid.
Tranexamic acid is a white crystalline powder that is odourless or almost odourless. It is freely soluble in water and in glacial acetic acid, practically insoluble in methanol, ethanol, acetone, diethyl ether and benzene.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

The tablets contain 500 mg tranexamic acid. Tablets are white to slightly yellowish, film coated, capsule shaped, biconvex, 18 mm x 8 mm, with a break-line and embossed "TXA 500".
The tablets are packed in PVC/aluminium foil blister packs of 100 tablets and bottles of 100 tablets (white HDPE bottles with PP child-resistant tamper evident screw cap and silica gel desiccant).

4 Clinical Particulars

4.1 Therapeutic Indications

Hereditary angioneurotic oedema.
Short term use in the treatment of hyphaema and in patients with established coagulopathies who are undergoing minor surgery.
Menorrhagia.

4.2 Dose and Method of Administration

Oral administration.

Traumatic hyphaema.

1.0 to 1.5 g every 8 hours for six to seven days.

Menorrhagia.

Two tablets (1 g) four times a day, increasing to three tablets (1.5 g) four times a day if needed, for four days. Treatment should be initiated at the onset of visible bleeding, and continued for the first 4 days of the menstrual cycle. Patients should be assessed after three months of treatment.
No efficacy data are available from randomised, controlled clinical trials for treatment beyond three menstrual cycles.

Hereditary angioneurotic oedema.

Patients who can sense the onset of attacks are best treated intermittently with 2-3 tablets, 2-3 times a day until symptoms subside. Others should be treated continuously with the same dose.

Prostatectomy.

1 g orally six hours pre-operatively followed by 1 g orally 3 to 4 times a day until macroscopic haematuria is no longer present. Treatment beyond two weeks is not recommended.

Patients with established coagulopathies undergoing minor surgery conisation of the cervix.

1.0 to 1.5 g (2 to 3 tablets) every 8 to 12 hours for 12 days post-operatively.

Dental operations/extraction.

25 mg/kg is given orally two hours before operation. Factor VIII and Factor IX should be given as well as tranexamic acid. After the operation, 25 mg/kg of tranexamic acid is given 3 to 4 times a day for 6 to 8 days.

Dosage adjustment in renal impairment for orally administered tranexamic acid.

See Table 1.

4.3 Contraindications

Patients with a history or risk of thrombosis should not be given tranexamic acid, unless at the same time it is possible to give treatment with anticoagulants.
Active thromboembolic disease such as deep vein thrombosis (DVT), pulmonary embolism and cerebral thrombosis.
The preparation should not be given to patients with acquired disturbances of colour vision. If disturbances of colour vision arise during the course of treatment the administration of the preparation should be discontinued.
Patients with subarachnoid haemorrhage should not be given tranexamic acid as anecdotal experience indicates that cerebral oedema and cerebral infarction may be caused in such cases.
Hypersensitivity to tranexamic acid or any of its excipients.

4.4 Special Warnings and Precautions for Use

The dose of tranexamic acid should be reduced in patients with renal impairment because of the risk of accumulation (see Section 4.2 Dose and Method of Administration). Isolated cases of obstruction of the urinary tract due to blood clots have been observed when tranexamic acid has been used to treat severe bleeding from the upper urinary tract.
Tranexamic acid therapy is not indicated in haematuria caused by diseases of the renal parenchyma. Intravascular precipitation of fibrin frequently occurs in these conditions and may aggravate the disease. In addition, in cases of massive renal haemorrhage of any cause, antifibrinolytic therapy carries the risk of clot retention in the renal pelvis.
Although clinical evidence shows no significant increase in thrombosis, possible risk of thrombotic complications cannot be ruled out. Venous and arterial thrombosis or thromboembolism has been reported in patients treated with tranexamic acid. In addition, cases of central retinal artery and central retinal vein obstruction have been reported. A few patients have developed intracranial thrombosis with tranexamic acid but further investigation is needed to assess the significance of this potential hazard.
Patients with a high risk for thrombosis (a previous thromboembolic event and a family history of thromboembolic disease) should use tranexamic acid only if there is a strong medical indication and under strict medical supervision. The risk for thromboembolic events may be increased in patients using hormonal contraceptives. If tranexamic acid has to be used in these patients, advise them to use an effective alternative (nonhormonal) contraceptive method.
Tranexamic acid should not be administered concomitantly with Factor IX Complex Concentrates or Anti-inhibitor Coagulant Concentrates, as the risk of thrombosis may be increased.
Blood in body cavities such as pleural space, joint spaces and urinary tract (e.g. renal, pelvis, bladder) may develop 'indissoluble clots' in these cavities due to extravascular blood clots which may be resistant to physiological fibrinolysis.
Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of the irregularity has been established. If menstrual bleeding is not adequately reduced by tranexamic acid, an alternative treatment should be considered.
There are no data on the use of tranexamic acid in women taking oral contraceptive agents.
Patients with disseminated intravascular coagulation (DIC) who require treatment with tranexamic acid must be under the strict supervision of a physician experienced in treating this disorder.
Focal areas of retinal degeneration have developed in cats, dogs and rats following oral or intravenous tranexamic acid at doses between 250 to 1600 mg/kg/day (6 to 40 times the recommended usual human dose) from 6 days to 1 year. The incidence of such lesions has varied from 25% to 100% of animals treated and was dose related. At lower doses some lesions appeared to be reversible.
Limited data in cats and rabbits showed retinal changes in some animals with doses as low as 126 mg/kg/day (about 3 times the recommended human dose) administered for several days to two weeks.
No retinal changes have been reported or noted in eye examinations in patients treated with tranexamic acid for weeks to months in clinical trials. However, visual abnormalities, often poorly characterised, represent the most frequently reported postmarketing adverse event in Sweden. For patients who are to be treated continually for longer than several days, an ophthalmological examination, including visual acuity, colour vision, eye-ground and visual fields, is advised before commencing and at regular intervals during the course of treatment. Tranexamic acid should be discontinued if changes in examination results are found.
Convulsions have been reported in association with tranexamic acid treatment.

Use in hepatic impairment.

Pharmacokinetic data from patients with pre-existing hepatic impairment, who were treated with tranexamic acid, are not available. As tranexamic acid is excreted unchanged, dose adjustment due to hepatic impairment is not required.

Use in renal impairment.

Patients with impaired renal function may experience an increased elimination half-life for the drug. The need for dose reduction is recommended in adult patients with renal impairment.
Dose reduction is recommended in children ≥ 2 years old who are mildly or moderately renally impaired. Tranexamic acid is not recommended in children who are severely impaired see Clinical trials and see Section 4.2 Dose and Method of Administration.
For both the adult and the paediatric patient, an eGFR ≥ 90 mL/min/1.73 m2 usually indicates kidney function within a 'normal range', but does not exclude patients with early kidney damage. If renal impairment is suspected, informed dose alterations decision may include other estimates of renal function including consultation with an experienced renal physician.

Use in the elderly.

No data available.

Paediatric use.

Clinical experience with tranexamic acid in menorrhagic females under 15 years of age is not available.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Clinically important interactions have not been observed with tranexamic acid tablets. There are no specific drug-drug interactions data for tranexamic acid. Because of the absence of interaction studies, simultaneous treatment with anticoagulants must take place under the strict supervision of a physician experienced in this field.
Avoid concomitant use of tranexamic acid with medical products that are prothrombotic because concomitant use can further increase the risk of thromboembolic adverse reactions associated with tranexamic acid (see Section 4.4 Special Warnings and Precautions for Use).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility was not affected in male or female rats at high oral doses (up to 850-880 mg/kg/day).
(Category B1)
Drugs which have been taken by only a limited number or pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed.
Previous studies in rats (at up to 1000 mg/kg/day PO) showed no effects of tranexamic acid on embryonic or neonatal development. In rabbits, increased foetal losses and lower litter weights were noted at 200 mg/kg IV and 400 mg/kg PO (but not at 100 mg/kg IV or 200 mg/kg PO). There was no effect on rat or rabbit young survival (including one IV teratology study in rabbits at 50-200 mg/kg).
The long-term clinical experience is limited to 21 pregnant women, treated for one to 18 weeks, in most cases to prevent further haemorrhage in connection with abruptio placentae. Whilst premature births were reported in infants who were born, all of these infants were born healthy. The short-term experience comprises 67 women with abruptio placentae treated with a single dose just before delivery by caesarean section. All deliveries went well and were not further complicated by haemorrhage.
There are no adequate and well-controlled studies in pregnant women. However, tranexamic acid is known to cross the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Because animal reproduction studies are not always predictive of human response, tranexamic acid should be used during pregnancy only if clearly needed.
 Tranexamic acid is secreted in the mother's breast milk at a concentration of about a hundredth of the corresponding serum levels. While an anti-fibrinolytic effect in the infant is unlikely at therapeutic doses, caution should be exercised when tranexamic acid is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

Tranexamic acid may cause dizziness and therefore may influence the ability to drive or use machines.

4.8 Adverse Effects (Undesirable Effects)

Oral administration.

Gastrointestinal discomfort occurs in more than 30% of patients after oral administration of 6 g/day. The discomfort disappears when the dose is reduced.
Common side effects (≥ 1 to < 10%).

Gastrointestinal disorders.

Nausea, vomiting, diarrhoea.
Uncommon side effects (≥ 0.1 to < 1%).

Immune system disorders.

Dermatitis allergic.

Post-marketing experience.

Immune system disorders.

Hypersensitivity including anaphylactic reaction.

Central nervous system disorders.

Convulsion, dizziness.

Eye disorders.

Chromatopsia, visual impairment.

Vascular disorders.

Embolism.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Overdose data are limited. There is one report of overdosage in which a seventeen year old ingested 37 g of tranexamic acid and after receiving treatment with gastric lavage, mild intoxication was reported.
Symptoms of overdose may include dizziness, headache, nausea, vomiting, diarrhoea, orthostatic symptoms, hypotension and convulsions.
There is no known antidote for tranexamic acid overdose. In the event of overdose, the patient should be treated symptomatically and supportive measures should be instituted as required.
Activated charcoal may reduce absorption of tranexamic acid if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube once the airway is protected.
In addition to this, monitor vital signs to detect a possible hypotensive episode. Monitor fluid and electrolyte status in patients with severe vomiting or diarrhoea and administer IV fluids and replace electrolytes as necessary. Monitor urine output and maintain adequate diuresis. Monitor for clinical evidence of thromboembolic complications (e.g. chest pain, shortness of breath, flank pain, extremity pain). Because there is a risk of thrombosis in predisposed individuals, anticoagulant therapy should be considered in these patients.
In symptomatic patients, support respiratory and cardiac function. Monitor blood count, renal function, pulse oximetry and/or blood gases and obtain a chest x-ray. Obtain an ECG and institute continuous cardiac monitoring.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Tranexamic acid is a competitive inhibitor of plasminogen activation and at much higher concentrations a noncompetitive inhibitor of plasmin, thus implying that tranexamic acid interferes with the fibrinolytic process in the same way as aminocaproic acid. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid.
Tranexamic acid binds more strongly than aminocaproic acid to both the strong and weak sites of the plasminogen molecule in a ratio corresponding to the difference in potency between the compounds.
Tranexamic acid in a concentration of 1 mg/mL does not aggregate platelets in vitro. Tranexamic acid in concentrations up to 10 mg/mL blood has no influence on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood in normal subjects. On the other hand tranexamic acid in concentrations of 1 mg/mL and 10 mg/mL blood prolongs the thrombin time.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Absorption from the gastrointestinal tract is only about 50% at reasonably low oral doses. However, a parallel intake of food has no effect on the gastrointestinal absorption of the drug following a dose of 2 g or on the maximum plasma concentration.

Distribution.

Tranexamic acid does not bind to serum albumin. The plasma protein binding is about 3% at therapeutic plasma levels and seems to be fully accounted for by its binding to plasminogen.
Three hours after a single oral dose of 25 mg/kg, the peak serum level was 15.4 g/L and the aqueous humour level was 1.6 g/L. The plasma peak level after 1 g orally is 8 mg/L and after 2 g, 15 mg/L, both obtained three hours after dosing.
When administered 36 to 48 hours before surgery in 4 doses of 10 to 20 mg/kg, an antifibrinolytically active concentration (10 microgram/mL) of tranexamic acid remains in different tissues for about 17 hours and in the serum for up to seven or eight hours.
Tranexamic acid passes through to the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to women could be fairly high, about 30 microgram/mL of foetal serum.
The concentration in breast milk is about one hundredth of the serum peak concentration obtained.
Tranexamic acid passes to semen and inhibits its fibrinolytic activity but does not influence the sperm migration.
Tranexamic acid crosses the blood-brain barrier.
Tranexamic acid concentration in cerebrospinal fluid is about one tenth that of plasma. The drug passes into the aqueous humour, the concentration being about one tenth of the plasma concentration.
Tranexamic acid diffuses rapidly to the joint fluid and the synovial membrane, and in the joint fluid the same concentration is obtained as in the serum. The biological half-life in the joint fluid is about three hours.

Metabolism.

Only a small fraction of the drug is metabolised. The total amount of metabolites excreted in urine during 72 hours is less than 5%. Possible routes of biotransformation are acetylation or deamination followed by oxidation or reduction. After oral administration approximately 50% of the parent compound, 2% of the deaminated dicarboxylic acid and 0.5% of the acetylated product are excreted.

Excretion.

After an intravenous dose of 1 g, the plasma concentration time curve shows a triexponential decay with a half-life of about 2 hours for the terminal elimination phase. The initial volume of distribution is about 9 to 12 litres.
Urinary excretion is the main route of elimination via glomerular filtration. Overall renal clearance is equal to overall plasma clearance (110 to 116 mL/min) and more than 95% of the dose is excreted in urine as the unchanged drug. Excretion of tranexamic acid by glomerular filtration is about 90% at 24 hours after intravenous administration of 10 mg/kg bodyweight.
After oral administration of 10 to 15 mg/kg body weight the urinary excretion at 24 hours is 39% and at 48 hours is 41% of the ingested dose or 78% of the absorbed material.

Special populations.

Renal impairment.

Adults.

Tranexamic acid is eliminated unchanged in urine. Patients with impaired renal function may experience an increased elimination half-life for the drug. Immediately after a dose of tranexamic acid was given, plasma levels of tranexamic acid were similar in all cardiac surgery patients. This reflects distribution into body fluid. A linear increase in plasma levels was observed with decreasing renal function (increasing serum creatinine levels) at 24 hours, confirming the need for dose reduction in renally impaired patients (see Section 4.2 Dose and Method of Administration).
Hepatic impairment. Pharmacokinetic data from patients with pre-existing hepatic impairment, who were treated with tranexamic acid, are not available. As tranexamic acid is excreted unchanged, dose adjustment due to hepatic impairment is not required.

5.3 Preclinical Safety Data

Genotoxicity.

Tranexamic acid was not mutagenic in B. subtilis and had no chromosomal effects in Chinese hamster cells. The incidence of chromosomal breakage was increased at 3 g/kg in rat bone marrow. No lethal mutagenicity was detected in a dominant lethal test at 100 mg/kg and 3 g/kg. The weight of evidence in a limited range of mutagenicity tests suggests that tranexamic acid is not mutagenic.

Carcinogenicity.

A dietary carcinogenicity study in Shermann-Wyckoff rats showed an increase in the incidence of biliary hyperplasia, cholangioma and adenocarcinoma of the liver at high doses. However, these findings have not been reproduced in a number of other lifetime studies in either SD or CDF1 mice. A possible treatment-related increase in the incidence of leukaemia was noted in mice receiving dietary tranexamic acid at doses equivalent to up to 5 g/kg/day for 20 months.

6 Pharmaceutical Particulars

6.1 List of Excipients

APO-Tranexamic Acid, each tablet contains the excipients microcrystalline cellulose, povidone, croscarmellose sodium, colloidal anhydrous silica, purified talc, magnesium stearate, Eudragit E 100, titanium dioxide, macrogol 8000 and vanillin.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C and Protect from light.

6.5 Nature and Contents of Container

PVC/aluminium foil blister packs of 100 tablets and bottles of 100 tablets (white HDPE bottles with PP child-resistant tamper evident screw cap and silica gel desiccant).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


CAS number.

1197-18-8.
Chemical Name: trans-4-aminomethylcyclohexane-carboxylic acid.
Molecular Formula: C8H15NO2.
Molecular Weight: 157.2 g/mol.
pKa: 4.3 and 10.6.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes