Tranexamic acid

Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from major trauma, postpartum bleeding, surgery, tooth removal, nosebleeds, and heavy menstruation.[1][2] It is also used for hereditary angioedema.[1][3] It is taken either by mouth or injection into a vein.[1]

Tranexamic acid
Clinical data
Pronunciation\ˌtran-eks-ˌam-ik-\
Trade namesCyklokapron, others
AHFS/Drugs.comFDA Professional Drug Information
Pregnancy
category
  • B
Routes of
administration		By mouth, injection, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability34%
Elimination half-life3.1 h
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
ECHA InfoCard100.013.471
Chemical and physical data
FormulaC8H15NO2
Molar mass157.21 g/mol g·mol−1
3D model (JSmol)
  (verify)

Side effects are rare.[3] Some include changes in color vision, blood clots, and allergic reactions.[3] Greater caution is recommended in people with kidney disease.[4] Tranexamic acid appears to be safe for use during pregnancy and breastfeeding.[3][5] Tranexamic acid is in the antifibrinolytic family of medications.[4]

Tranexamic acid was first made in 1962 by Japanese researchers Shosuke and Utako Okamoto.[6] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] Tranexamic acid is available as a generic medication.[8] The wholesale cost in the developing world is about 4.38 to US$4.89 for a course of treatment.[9] In the United States, a course of treatment costs between 100 and US$200.[8]

Medical uses
A one gram vial of TXA

Tranexamic acid is frequently used following major trauma.[10] Tranexamic acid is used to prevent and treat blood loss in a variety of situations, such as dental procedures for hemophiliacs, heavy menstrual bleeding, and surgeries with high risk of blood loss.[11][12]

Trauma

Tranexamic acid has been found to decrease the risk of death in people who have significant bleeding due to trauma.[13][14] Its main benefit is if taken within the first three hours.[15] It has been shown to reduce death due to any cause and death due to bleeding.[16] Further studies are assessing the effect of tranexamic acid in isolated brain injury.[17] Given within three hours of a head injury it also decreases the risk of death.[18]

Vaginal bleeding

Tranexamic acid is used to treat heavy menstrual bleeding.[12] When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding and improves quality of life.[19][20][21] Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16.[19]

Child birth

Tranexamic acid is used after delivery to reduce bleeding, often with oxytocin.[22] Death due to postpartum bleeding was reduced in women receiving tranexamic acid.[2]

Surgery
  • Tranexamic acid is used in orthopedic surgery to reduce blood loss, to the extent of reducing or altogether abolishing the need for perioperative blood collection. It is of proven value in clearing the field of surgery and reducing blood loss when given before or after surgery. Drain and number of transfusions are reduced.[23][24][25]
  • In surgical corrections of craniosynostosis in children it reduces the need for blood transfusions.[26]
  • In spinal surgery (e.g., scoliosis), correction with posterior spinal fusion using instrumentation, to prevent excessive blood loss.[27]
  • In cardiac surgery, both with and without cardiopulmonary bypass (e.g., coronary artery bypass surgery), it is used to prevent excessive blood loss.[23]

Dentistry

In the United States, tranexamic acid is FDA approved for short-term use in people with severe bleeding disorders who are about to have dental surgery.[28] Tranexamic acid is used for a short period of time before and after the surgery to prevent major blood loss and decrease the need for blood transfusions.[29]

Tranexamic acid is used in dentistry in the form of a 5% mouth rinse after extractions or surgery in patients with prolonged bleeding time; e.g., from acquired or inherited disorders.[30]

Hematology

There is not enough evidence to support the routine use of tranexamic acid to prevent bleeding in people with blood cancers.[31] However, there are several trials that are currently assessing this use of tranexamic acid.[31] For people with inherited bleeding disorders (e.g. von Willebrand's disease), tranexamic acid is often given.[17] It has also been recommended for people with acquired bleeding disorders (e.g., directly acting oral anticoagulants (DOACs)) to treat serious bleeding.[32]

Nosebleeds

The use of tranexamic acid, applied directly to the area that is bleeding or taken by mouth, appears useful to treat nose bleeding compared to packing the nose with cotton pledgets alone.[33][34][35] It decreases the risk of rebleeding within 10 days.[36]

Other uses
  • Tentative evidence supports the use of tranexamic acid in hemoptysis.[37][38]
  • In hereditary angioedema[39]
  • In hereditary hemorrhagic telangiectasia - Tranexamic acid has been shown to reduce frequency of epistaxis in patients suffering severe and frequent nosebleed episodes from hereditary hemorrhagic telangiectasia.[40]
  • In melasma - tranexamic acid is sometimes used in skin whitening as a topical agent, injected into a lesion, or taken by mouth, both alone and as an adjunct to laser therapy; as of 2017 its safety seemed reasonable but its efficacy for this purpose was uncertain because there had been no large scale randomized controlled studies nor long term follow-up studies.[41][42]
  • In hyphema - Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in people with traumatic hyphema.[43]

Contraindications
  • Allergic to tranexamic acid
  • History of seizures
  • History of venous or arterial thromboembolism or active thromboembolic disease
  • Severe kidney impairment due to accumulation of the medication, dose adjustment is required in mild or moderate kidney impairment[1]

Adverse effects

Side effects are rare.[3] Some include changes in color vision, blood clots, and allergic reactions.[3]

Blood clots may include venous thromboembolism (deep vein thrombosis and pulmonary embolism), anaphylaxis.[19] These rare side effects were reported in post marketing experience and frequencies cannot be determined.[19] Despite the mode of action, large studies of the use of tranexamic acid have not shown an increase in the risk of venous or arterial thrombosis.[44]

Special populations
  • Tranexamic acid is categorized as pregnancy category B. No harm has been found in animal studies.[19]
  • Small amounts appears in breast milk if taken during lactation.[19] If it is required for other reasons, breastfeeding may be continued.[45]
  • In kidney impairment, tranexamic acid is not well studied. However, due to the fact that it is 95% excreted unchanged in the urine, it should be dose adjusted in patients with renal impairment.[19]
  • In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver.[19]

Mechanism of action

Tranexamic acid is a synthetic analog of the amino acid lysine. It serves as an antifibrinolytic by reversibly binding four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, preventing fibrin degradation and preserving the framework of fibrin's matrix structure.[19] Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid. Tranexamic acid also directly inhibits the activity of plasmin with weak potency (IC50 = 87 mM),[46] and it can block the active-site of urokinase plasminogen activator (uPA) with high specificity (Ki = 2 mM) among all the serine proteases.[47]

Society and culture

Tranexamic acid was first synthesized in 1962 by Japanese researchers Shosuke and Utako Okamoto.[6] It has been included in the WHO list of essential medicines.[48] TXA is inexpensive and treatment would be considered highly cost effective in high, middle and low income countries.[49]

Brand names

Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in Australia and Jordan it is marketed in an IV form and tablet form as Cyklokapron, in the UK as Cyclo-F and Femstrual, in Asia as Transcam, in Bangladesh as Tracid, in India as Pause, in Pakistan as Transamin, in South America as Espercil, in Japan as Nicolda, in France, Belgium and Romania as Exacyl and in Egypt as Kapron. In the Philippines, its capsule form is marketed as Hemostan and In Israel as Hexakapron.

Approval

The U.S. Food and Drug Administration (FDA) approved tranexamic acid oral tablets (brand name Lysteda) for treatment of heavy menstrual bleeding on 13 November 2009.

In March 2011 the status of tranexamic acid for treatment of heavy menstrual bleeding was changed in the UK, from PoM (Prescription only Medicines) to P (Pharmacy Medicines)[50] and became available over the counter in UK pharmacies under the brand names of Cyklo-F and Femstrual, initially exclusively for Boots pharmacy, which has sparked some discussion about availability.[51] (In parts of Europe it had then been available OTC for over a decade.) Regular liver function tests are recommended when using tranexamic acid over a long period of time.[52]

References
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