Tranexamic acid

Tranexamic acid

Clinical data
Pronunciation	\ˌtran-eks-ˌam-ik-\
AHFS/Drugs.com	Consumer Drug Information
Pregnancy category	B
Routes of administration	Injection and oral
ATC code	B02AA02 (WHO)
Legal status
Legal status	P (UK)
Pharmacokinetic data
Bioavailability	34%
Biological half-life	3.1 h
Identifiers
IUPAC name trans-4-(aminomethyl)cyclohexanecarboxylic acid
CAS Number	1197-18-8 Y
PubChem (CID)	5526
IUPHAR/BPS	6573
DrugBank	DB00302 Y
ChemSpider	10482000 Y
UNII	6T84R30KC1 Y
KEGG	D01136 Y
ChEBI	CHEBI:48669 Y
ChEMBL	CHEMBL877 Y
ECHA InfoCard	100.013.471
Chemical and physical data
Formula	C8H15NO2
Molar mass	157.21 g/mol
3D model (Jmol)	Interactive image
SMILES NC[C@@H]1CC[C@H](CC1)C(O)=O
InChI InChI=1S/C8H15NO2/c9-5-6-1-3-7(4-2-6)8(10)11/h6-7H,1-5,9H2,(H,10,11)/t6-,7- Y Key:GYDJEQRTZSCIOI-LJGSYFOKSA-N Y
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Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss from trauma, surgery, and in various medical conditions including hemophilia and heavy menstrual bleeding.^[1] It comes in oral and intravenous forms.^[1]

Side effects are uncommon and include gastrointestinal effects, dizziness, fatigue, headache, and hypersensitivity reactions.^[2] The medication needs to be used cautiously in people with kidney disease and who are at a high risk for blood clots.^[1] Tranexamic is safe to use in pregnant women. However, caution should be used in lactating women.^[1] It is an antifibrinolytic.

It was discovered in 1962 by Utako Okamoto^[3] and has been on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[4]

Medical uses

Tranexamic acid is frequently used following major trauma.^[5] 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.^[6][7]

Trauma

Tranexamic acid has been found to decrease the risk of death in people who have significant bleeding due to trauma.^[8][9] Its main benefit is if taken within the first three hours.^[10]

Heavy menstrual bleeding

Tranexamic acid is used to treat heavy menstrual bleeding.^[7] When taken by mouth it both safely and effectively treats regularly occurring heavy menstrual bleeding.^[2][11] Another study demonstrated that the dose does not need to be adjusted in females who are between ages 12 and 16.^[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.
• In surgical corrections of craniosynostosis in children it reduces the need for blood transfusions.^[12]
• In spine surgery, e.g. scoliosis correction with posterior spinal fusion using instrumentation, to prevent excessive blood loss.^[13]
• In cardiac surgery, both with and without cardiopulmonary bypass e.g. coronary artery bypass surgery, it is used to prevent excessive blood loss. It replaces aprotinin.

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.^[1] 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.^[14] In people with hemophilia, combinations of tranexamic acid and factor VII or IX have effectively decreased blood loss and the need for transfusions after dental surgery In one person with mild hemophilia, a combination of tranexamic acid and demopressin effectively stopped bleeding^[15]

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.

Other uses

• In obstetrics, tranexamic acid is used after delivery to reduce bleeding, often with syntocinon/oxytocin and fundal massage. Since 2010, the WOMAN (World Maternal Antifibrinolytic) trial has been in progress worldwide to establish the efficacy of the drug to arrest postpartum haemorrhage (PPH) in 15 000 women, due to be completed in 2016.^[16] Since the drug can be administered orally, it has great potential to reduce maternal mortality rates in developing countries where primary healthcare is often unavailable.
• In hereditary angioedema^[17]
• 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.^[18]
• In melasma - Tranexamic acid has shown to provide rapid and sustained lightening in melasma by decreasing melanogenesis in epidermal melanocytes.^[19]
• In hyphema - Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in patients with traumatic hyphema.^[20]

Adverse effects

Common side effects include:^[2]

• Headaches (50.4 - 60.4%)
• Back aches (20.7 - 31.4%)
• Nasal sinus problem (25.4%)
• Abdominal pain (12 - 19.8%)
• Diarrhea (12.2%)
• Fatigue (5.2%)
• Anemia (5.6%)

Rare side effects include:^[2]

• Pulmonary embolism
• Deep vein thrombosis
• Anaphylaxis
• Visual disturbances

These rare side effects were reported in post marketing experience and frequencies cannot be determined.^[2]

Special populations

• Tranexamic acid is categorized as pregnancy category B. No harm has been found in animal studies.^[2]
• Small amounts appears in breast milk if taken during lactation.^[2] If it is required for other reasons, breastfeeding may be continued.^[21]
• Tranexamic acid is also not indicated for postmenopausal women and geriatrics.^[2]
• 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.^[2]
• In liver impairment, dose change is not needed as only a small amount of the drug is metabolized through the liver.^[2]

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 or plasmin. This prevents plasmin from binding to and degrading fibrin and preserves the framework of fibrin's matrix structure.^[2] Tranexamic acid has roughly eight times the antifibrinolytic activity of an older analogue, ε-aminocaproic acid.

Society and culture

TXA was discovered in 1962 by Utako Okamoto.^[3] It has been included in the WHO list of essential medicines.^[4] TXA is inexpensive and treatment would be considered highly cost effective in high, middle and low income countries.^[22]

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 Traxyl, in India as Pause, in South America as Espercil, in Japan as Nicolda, in France 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)^[23] 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.^[24] (In parts of Europe - like Sweden - 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.^[25]

References

External links

• CRASH-2: tranexamic acid and trauma patients
• Patient Experience with tranexamic acid
• Tranexamic acid, UK patient information leaflet