Website: October 2003
Prescriber Update 2003;24(2):26-27
Dr Ruth Savage, Medical Assessor, New Zealand Pharmacovigilance Centre, Dunedin
Tranexamic acid is an effective treatment for heavy menstrual bleeding and can now be prescribed for this indication without specialist recommendation. Tranexamic acid has the potential to cause thrombotic disorders and is contraindicated in patients with active thrombotic or embolic disorders. It should not be prescribed for patients with risk factors for thromboembolic disease unless the potential benefits clearly outweigh the potential for harm. Patients should be made aware of symptoms suggestive of venous or arterial thrombosis or embolism.
New Zealand report of fatal pulmonary embolism
Link with thrombosis mainly supported by case reports
Avoid tranexamic acid if active thromboembolic disease is present
The Centre for Adverse Reactions Monitoring (CARM) has received nine reports of adverse reactions with tranexamic acid, including one report of a fatal pulmonary embolism and one of parietal haemorrhage followed by a venous sinus thrombosis in a patient taking both mefenamic acid and tranexamic acid.
Tranexamic acid (Cyklokapron®) is an antifibrinolytic agent used to treat or prevent haemorrhage in a variety of bleeding disorders. It has been shown to reduce menstrual blood loss in menorrhagia. The New Zealand Guidelines Group's guideline on heavy menstrual bleeding1 considered effectiveness, side effects and patient acceptability when assessing medical interventions for menorrhagia. Using these criteria tranexamic acid, as well as non-steroidal anti-inflammatory agents, ranked second to the levonorgestrel intrauterine device. Tranexamic acid for heavy menstrual bleeding can now be prescribed by general practitioners without specialist recommendation.
There are several published case reports of thrombotic or embolic disorders occurring with tranexamic acid use. These include three reports of deep vein thrombosis or pulmonary embolism.2-4 Two of these patients had bleeding disorders,2,4 and the other had a subarachnoid haemorrhage.3 Amongst the case reports of arterial thrombosis are two young women who developed cerebral artery thromboses while taking tranexamic acid for menorrhagia.5 The World Health Organisation's international drug monitoring database holds 528 reports of suspected reactions to tranexamic acid. There are 56 reports of deep vein thrombosis, pulmonary embolism or both and these include reports of cerebral and retinal vein thrombosis. Additionally there are 22 reports of cerebral embolism and nine of arterial thrombosis.
In contrast to the above reports, a study of 256 pregnant women taking tranexamic acid, of whom 169 delivered by caesarean section, found no increased risk of thrombosis.6 However, a Cochrane review7 of antifibrinolytics for the treatment of menorrhagia noted the absence of randomised control trial data to assess the risk of thromboembolic events with tranexamic acid.
The New Zealand product data sheet8 states that tranexamic acid is contraindicated in patients with active thromboembolic disease such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis. While there are no formal epidemiological studies demonstrating a link between tranexamic acid and thrombotic disorders, with respect to its use for menorrhagia prescribers should be aware of the possible link suggested by the case reports. Information about a personal or family history of thromboembolic disease, or the presence of other thrombosis risk factors should be elicited; where these are present, the risks of tranexamic acid compared with its potential benefit need to be carefully considered. Patients should be informed about the symptoms of thrombotic or embolic disorders, as well as short-term risk factors such as surgery and immobility.
Prescribers should also be aware that other treatments used for heavy menstrual bleeding, such as progestogens in doses greater than those used for contraception, can also increase the risk of venous thromboembolism. If a patient is at risk of thrombosis, then an alternative agent should be used.
Competing interests (author): none declared.
Correspondence to Dr Ruth Savage, New Zealand Pharmacovigilance Centre, PO Box 913, Dunedin.