Tranexamic Acid

Registered South African indications:

• Short term use in the treatment of haemorrhage or risk of haemorrhage in increased fibrinolysis or fibrinogenolysis. Local fibrinolysis occurs in the following conditions
  - Prostatectomy and bladder surgery
  - Epistaxis
  - Conisation of the cervix
  - Traumatic hyphaema
• Management of dental extraction in haemophiliacs
• Hereditary angioedema
• Menorrhagia

Registered South African contraindications

Injection and infusion

• Hypersensitivity to the active ingredient or any of its excipient
• In cases of massive upper urinary tract haemorrhage, tranexamic acid should be avoided to reduce the risk of ureteric obstruction
• Patients with pronounced thrombotic tendency or colour vision disorder
• Thrombophlebitis
• Impaired liver function
• Subarachnoid bleeding
• Fibrinolytic conditions following consumption coagulopathy except in those with predominant activation of the fibrinolytic system with acute severe bleeding
• History of convulsions
• History of acute venous or arterial thrombosis
• Severe renal impairment (risk of accumulation)
• Active intravascular clotting
• Intrathecal and intraventricular injection, intracerebral application (risk of cerebral oedema and convulsions)

Film-coated tablet

• Hypersensitivity to the active ingredient or any of its excipient
• In cases of massive upper urinary tract haemorrhage, tranexamic acid should be avoided to reduce the risk of ureteric obstruction
• Patients with a pronounced thrombotic tendency or colour vision disorder should not be given tranexamic acid
• Thrombophlebitis
• Impaired liver function
• Subarachnoid bleeding
• History of arterial or venous thromboembolism
• Active intravascular clotting
• Patients with hypercoagulopathies

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Haematuria of renal or upper urinary tract origin
• Haemophilia  
• Long-term treatment of hereditary angioneurotic oedema (tab)
• Current administration with oral contraceptives
• Previous thromboembolic event or a family history of thromboembolic disease (patients with thrombophilia)
• Increased fibrinolysis due to disseminated intravascular coagulation
• Menorrhagia in children under 15 years (tab)
• Coronary artery bypass graft surgery (inj)
• High doses (inj)
• Continuous long-term use (inj)
• Ophthalmic changes in diseases of the retina (inj)

Forms avail. in SA and covered in this monograph: fct, tab, inf, inj

South African registered indications and dosages

Short term use for haemorrhage or risk of haemorrhage in those with increased fibrinolysis or fibrinogenolysis

Standard treatment of local fibrinolysis

• IV: 0.5-1g given by slow injection or infusion at 1ml/min, 2-3 times dly

OR

• Oral (fct, tab): 0.5-1g, 2-3 times dly

Standard treatment of general fibrinolysis

• IV: 1g given by slow injection or infusion at 1ml/min, every 6-8hrs (equivalent to 15mg/kg body weight)

OR

• Oral (fct, tab): 1g, 6hrly

Specific doses based on individual indications

Prostatectomy and bladder surgery

• IV: 0.5-1g given by slow injection or infusion at 1ml/min, 2-3 times dly (the first injection being given during the operation); Duration: First 3 days of surgery

THEN

• Oral (fct, tab): 1-1.5 g, 2 - 3 times daily as a continuation after IV treatment

Epistaxis

• IV: 1-1.5g, 8-12hrly for 10 days

OR

• Oral (fct, tab): 1-1.5g, 8-12hrly for 10 days

Conisation of the cervix

• IV: 1-1.5g, 8-12hrly for 12 days post-operatively

OR

• Oral (fct, tab): 1-1.5g, 8-12hrly for 12 days post-operatively

Traumatic hyphaema

• IV: 1-1.5g, 8hrly for 6-7 days

OR

• Oral (fct, tab): 1-1.5g, 8hrly for 6-7 days

Management of dental extraction in haemophiliacs (Additional agents required)

• IV: Initial: 25mg/kg, admin. 2hrs before the operation (as well as Factor VIII and Factor IX.); Then: 25mg/kg, admin. 3-4 times a day for 6-8 days
• Oral (fct, tab): 25mg/kg, given 3-4 times a day for 6-8 days

Hereditary angioedema

• IV: 1-1.5g, 2-3 dly for some days; Some patients are aware of the onset of illness, while other patients are treated continually at this dosage
• Oral (fct, tab): 1-1.5g, 2-3 dly for some days; Some patients are aware of the onset of illness, while other patients are treated continually at this dosage

Menorrhagia

• Oral (fct, tab): 1-1.5g, 3-4 times dly, given at the onset of heavy bleeding for the duration of the period

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Method of administration

Tranexamic acid IV is given orally or by slow intravenous infusion/injection. Administration by injection is usually changed to oral administration after a few days

For the injection 
Tranexamic acid solution for injection is strictly limited to slow intravenous infusion, or slow injection over a period of at least five minutes, i.e. 1 ml/minute
For intravenous injection, use immediately after opening. Diluted infusion solutions are stable in the refrigerator at 2 - 8 °C for up to 24 hours

Not established for use in children

Pregnancy 

• Caution
• Tranexamic acid crosses the placenta. There are no or limited amount of data from the use of tranexamic acid in pregnant women
• As a result, although studies in animals do not indicate teratogenic effects, as precaution for use, tranexamic acid is not recommended during the first trimester of pregnancy
• Limited clinical data of the use of tranexamic acid in different clinical haemorrhagic settings during the second and third trimesters did not identify deleterious effect for the foetus
• Tranexamic acid should be used throughout pregnancy only if the expected benefit justifies the potential risk
• Women of childbearing potential have to use effective contraception during treatment

Breastfeeding 

• Caution
• 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
• However, breastfeeding is not recommended

Fertility 

• There is no clinical data on the effects of tranexamic acid on fertility

South African recommendations

Film-coated tablet

• Mild to severe: Caution; dose adjustment recommended

Injection and infusion

• Mild to moderate: Caution; dose adjustment recommended
• Severe: Contraindicated

Serum creatinine (micromole/l)	Oral dose	Intravenous dose
120 - 250	15mg/kg body weight twice daily	10mg/kg body weight twice daily
250 - 500	15mg/kg body weight daily	10mg/kg body weight daily
> 500	7.5mg/kg body weight daily	5mg/kg body weight daily

South African recommendations

• Contraindicated

• No dose adjustment recommended

Central Nervous System Disorders

• Seizures
• Malaise

Cardiovascular Disorders

• Thromboembolic events
• Arterial or venous thrombosis at any site
• Hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions
• Allergic dermatitis (inj)

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylaxis

Sensory Disorders

• Impaired colour vision
• Retinal vein/artery occlusion (tab)
• Visual disturbances

• Oral contraceptives
• Oestrogens
• Anticoagulants
• Thrombolytic agents
• Fibrinolytic agents (tab)

None routine. Specific cases may require

• Ophthalmic exam
• Renal function

Additional observations

• Signs/symptoms of:
  - Hypersensitivity reactions
  - Seizures
  - Thrombotic events

Tranexamic acid exerts an anti haemorrhagic activity by inhibiting the fibrinolytic properties of plasmin. A complex involving tranexamic acid, plasminogen is constituted; the tranexamic acid being linked to plasminogen when transformed into plasmin. The activity of the tranexamic acid-plasmin complex on the activity on fibrin is lower than the activity of free plasmin alone. In vitro studies showed that high tranexamic dosages decreased the activity of complement.

Tablet 500mg 

• Bio Tranexamic acid (Biotech Laboratories)
• Cyklokapron (Pfizer) originator
• Fibtin (Pharmacare Limited)
• Morwak (Dr Reddy's Laboratories)
• Tranexamic Acid Medwich (Medwich)
• Tranic (Litha)

Injection (per 5ml) 500mg

• Cyclokapron  (Pfizer) originator
• Cynex (Pharmaplan)
• Haemostop (Equity Pharmaceuticals)
• Klotigo 500 (Pharma Dynamics)
• Morwak IV 500 (Dr Reddy's Laboratories)
• Tranexamic acid 100mg/ml PharmC (Pharmacorp)
• Transun IV (Litha Pharma)