Consumer medicine information

Cyklokapron Tablets

Tranexamic acid

BRAND INFORMATION

Brand name

Cyklokapron Tablets

Active ingredient

Tranexamic acid

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Cyklokapron Tablets.

SUMMARY CMI

Cyklokapron® Tablets

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I taking Cyklokapron?

Cyklokapron contains the active ingredient tranexamic acid. Cyklokapron is used to prevent or reduce excessive bleeding in patients: who experience bleeding inside the eye; that have heavy periods; that experience periodic severe swelling of the throat; after prostate surgery; are undergoing minor surgery and have a blood clotting disorder. For more information, see Section 1. Why am I using Cyklokapron? in the full CMI.

2. What should I know before I take Cyklokapron?

Do not use if you have ever had an allergic reaction to tranexamic acid or any of the ingredients listed at the end of the CM I, are being treated for stroke or blood clots or have a problem with colour vision that developed after you were born.

Tell your doctor if you, or someone in your family has ever suffered from blood clots, severe bruising, convulsion, fits or seizures; kidney disease with or without blood in the urine, unexplained irregular periods. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take Cyklokapron? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Cyklokapron and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take Cyklokapron?

Your doctor will decide how many tablets you need. It will depend on why you are taking this medicine and if you have kidney disease.

More instructions can be found in Section 4. How do I use Cyklokapron? in the full CMI.

5. What should I know while taking Cyklokapron?

Things you should do

Tell your doctor or dentist that you are taking Cyklokapron.

Seek medical attention immediately if you develop a sudden severe headache as this may require urgent medical attention and your doctor may stop Cyklokapron.

Driving or using machinesCyklokapron may cause dizziness or seizures in some people and may influence the ability to drive or use machines.
Drinking alcoholNo information available.
Looking after your medicineStore below 30°C

For more information, see Section 5. What should I know while using Cyklokapron? in the full CMI.

6. Are there any side effects?

The side effects include allergic reactions such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing; unexpected pain, swelling, warmth or redness in your legs or arms; convulsions, fits or seizures; giddiness or dizziness; changes in your eyesight including colour vision; blood clot or bleeding in the eye or loss of vision; itchy, red or swollen skin; nausea; vomiting; diarrhoea.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Cyklokapron® Tablets

Active ingredient(s): tranexamic acid

Consumer Medicine Information (CMI)

This leaflet provides important information about using Cyklokapron. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking Cyklokapron.

Where to find information in this leaflet:

1. Why am I taking Cyklokapron?
2. What should I know before I take Cyklokapron?
3. What if I am taking other medicines?
4. How do I take Cyklokapron?
5. What should I know while taking Cyklokapron?
6. Are there any side effects?
7. Product details

1. Why am I taking Cyklokapron?

Cyklokapron contains the active ingredient tranexamic acid. Cyklokapron is used to prevent or reduce excessive bleeding in patients: who experience bleeding inside the eye; who have heavy periods; who experience periodic severe swelling of the throat; after prostate surgery; who are undergoing minor surgery and have a blood clotting disorder.

2. What should I know before I take Cyklokapron?

Warnings

Do not use Cyklokapron if you:

  • are allergic 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.

Check with your doctor if you:

  • or someone in your family has ever suffered from blood clots
  • severe bruising
  • have or have ever suffered from convulsion, fits or seizures
  • kidney disease with or without blood in the urine
  • unexplained irregular periods.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

3. What if I am taking other medicines?

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

Some medicines may interfere with Cyklokapron and affect how it works.

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

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Cyklokapron.

4. How do I take Cyklokapron?

How much to take

Follow the instructions provided to you by your doctor or pharmacist and use Cyklokapron until your doctor tells you to stop. Swallow the tablets with water.

Traumatic hyphaema (bleeding inside the eye)

Take 2 or 3 tablets every 8 hours, for 6 to 7 days.

Heavy periods

Take 2 or 3 tablets 4 times a day for four days. Start taking the tablets when you first notice the bleeding. Take CYKLOKAPRON 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.

Hereditary Angioneurotic Oedema (periodic severe swelling of the throat)

The usual dose is 2 or 3 tablets, 2 to 3 times a day. Your doctor will tell you how long to take the tablets.

For those undergoing prostate surgery

The usual dose is 2 tablets 6 hours before surgery, and then 2 tablets 3 to 4 times a day. Your doctor will tell you how long to take the tablets.

For those with a clotting disorder, having minor surgery

The usual dose is 2 or 3 tablets, 2 to 3 times a day. Your doctor will tell you how long to take the tablets.

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.

When to take Cyklokapron

Cyklokapron should be taken regularly at the same time each day.

If you forget to take Cyklokapron

If you miss your dose at the usual time, take your tablet(s) as soon as you remember and then go back to taking it as you 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 take a double dose to make up for the dose you missed.

If you have taken too much Cyklokapron

If you think that you have used too much Cyklokapron, you may need urgent medical attention.

Symptoms from taking too much or being given too much Cyklokapron include:

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

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or pharmacist
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking Cyklokapron?

Things you should do

Remind any doctor or dentist you visit that you are using Cyklokapron.

Seek medical attention immediately if you develop a sudden severe headache as this may require urgent medical attention and your doctor may stop Cyklokapron.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Cyklokapron affects you.

Cyklokapron may cause dizziness or seizures in some people

Drinking alcohol

No data available.

Looking after your medicine

Store below 30°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Do not use this medicine after the expiry date.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Side effects

Side effectsWhat to do
  • Nausea or vomiting
  • diarrhoea
Speak to your doctor if you have any of these common side effects and they worry you.

Side effects

Side effectsWhat to do
  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing, unexpected pain
  • convulsions, fits or seizures
  • swelling, warmth or redness in your legs or arms
  • giddiness or dizziness
  • changes with eyesight including colour vision
  • blood clot or bleeding in the eye or loss of vision
  • itchy, red or swollen skin
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Cyklokapron contains

Active ingredient
(main ingredient)		tranexamic acid
Other ingredients
(inactive ingredients)

Tablet core

  • microcrystalline cellulose
  • hyprolose
  • purified talc
  • magnesium stearate
  • colloidal anhydrous silica
  • povidone
  • water.

Tablet coating

  • Eudragit E100
  • titanium dioxide
  • macrogol 8000
  • vanillin

Do not take this medicine if you are allergic to any of these ingredients.

What Cyklokapron looks like

Cyklokapron are white, capsule shaped film-coated tablets that are marked with a line on one side and 'CY' on the other.

Cyklokapron Tablets: AUST R 14463.

Who distributes Cyklokapron

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizermedicalinformation.com.au

This leaflet was prepared in December 2023.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Cyklokapron Tablets

Active ingredient

Tranexamic acid

Schedule

S4

 

1 Name of Medicine

Tranexamic acid.

2 Qualitative and Quantitative Composition

Each Cyklokapron tablet contains 500 mg of tranexamic acid.

3 Pharmaceutical Form

Cyklokapron is available as film coated tablets. Cyklokapron is a white, capsule shaped tablet with a score on one side and "CY" within upper and lower arcs on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Oral administration.

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.
In Australia, there is no documented clinical evidence to support the use of Cyklokapron solution for injection for traumatic hyphaema, menorrhagia, hereditary angioneurotic oedema, prostatectomy, conisation of the cervix and dental operations or extractions. Cyklokapron tablets should be used in these clinical settings.

Dosage adjustment in renal impairment for orally administered Cyklokapron.

See Table 1.

Method of administration.

Orally administered.

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 Cyklokapron 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 Cyklokapron 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 Section 5.1 Pharmacodynamic Properties, Clinical trials; 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 reduction in dosage is necessary, unless there is evidence of renal failure.

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 Cyklokapron 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 (~ 1.7 times the maximum recommended daily human oral dose on a body surface area basis).
There are no clinical data in humans supporting the impact of tranexamic acid on fertility.
(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.
Available data from published studies, case series and case reports with tranexamic acid use in pregnant women in the second and third trimester and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. There are cases of fetal structural abnormalities that resulted in death of the newborn following administration of tranexamic acid to the mother during conception or the first trimester of pregnancy; however, due to other confounding factors the risk of major birth defects with use of tranexamic acid during pregnancy is not clear.
The estimated background risk for major birth defects and miscarriage for the indicated human population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
It is not known whether tranexamic acid use in pregnant women may cause a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. For decisions regarding the use of tranexamic acid during pregnancy, the potential risk of tranexamic acid administration on the fetus should always be considered along with the mother's clinical need for tranexamic acid; an accurate risk-benefit evaluation should drive the treating physician's decision.
Tranexamic acid passes through the placenta. The concentration in cord blood after an intravenous injection of 10 mg/kg to pregnant women is about 30 mg/L, as high as in the maternal blood.
There were 13 clinical studies that described fetal and/or neonatal functional issues such as low Apgar score, neonatal sepsis, cephalohematoma and 9 clinical studies that discussed alterations to growth including low birth weight and preterm birth at 22-36 weeks of gestation in fetuses and infants exposed to tranexamic acid in utero.
Studies in rats (at up to 1000 mg/kg/day PO; 2 times the maximum recommended daily human oral dose on a body surface area basis) showed no effects of tranexamic acid on embryonic or neonatal development. In rabbits, increased fetal losses and lower litter weights were noted at 200 mg/kg IV and 400 mg/kg PO (1.6 times the maximum recommended daily human oral dose on a body surface area basis) (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).
 Published literature reports the presence of tranexamic acid in human milk. There are no data on the effects of tranexamic acid on the breastfed child or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tranexamic acid and any potential adverse effects on the breastfed child from tranexamic acid or from the underlying maternal condition.

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

Each Cyklokapron tablet contains the following inactive ingredients: microcrystalline cellulose, purified talc, magnesium stearate, colloidal anhydrous silica, povidone, hyprolose, titanium dioxide, macrogol 8000, vanillin and the proprietary ingredient, Eudragit E100 (ID Number 1753).

6.2 Incompatibilities

No data available.

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 30°C.

6.5 Nature and Contents of Container

Cyklokapron Tablets are available in a HDPE bottle of 20 and 100 tablets.
*Not all pack sizes are distributed in Australia.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

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.
The pKa: 4.3 and 10.6.

Chemical structure.

The chemical structure of tranexamic acid is:
Chemical name: trans-4-aminomethylcyclohexane-carboxylic acid.
The molecular formula of tranexamic acid is C8H15NO2 and its molecular weight is 157.2.

CAS number.

1197-18-8.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (S4).

Summary Table of Changes