Tranexamic acid
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| Systematic (IUPAC) name |
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trans-4-(aminomethyl)cyclohexanecarboxylic acid
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| Clinical data |
| Pronunciation |
\ˌtran-eks-ˌam-ik-\ |
| AHFS/Drugs.com |
Consumer Drug Information |
Pregnancy
category |
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| Legal status |
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Routes of
administration |
Injection and oral |
| Pharmacokinetic data |
| Bioavailability |
34% |
| Biological half-life |
3.1 h |
| Identifiers |
| CAS Registry Number |
1197-18-8 Y |
| ATC code |
B02AA02 |
| PubChem |
CID: 5526 |
| IUPHAR/BPS |
6573 |
| DrugBank |
DB00302 Y |
| UNII |
6T84R30KC1 Y |
| KEGG |
D01136 Y |
| ChEBI |
CHEBI:48669 Y |
| ChEMBL |
CHEMBL877 Y |
| Chemical data |
| Formula |
C8H15NO2 |
| Molecular mass |
157.21 g/mol |
SMILES
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NC[C@@H]1CC[C@H](CC1)C(O)=O
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InChI
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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
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Key:GYDJEQRTZSCIOI-LJGSYFOKSA-N Y
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| Y (what is this?) (verify) |
Tranexamic acid (TXA) is 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] This 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 on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[3]
Contents
- 1 Medical uses
- 1.1 Trauma
- 1.2 Heavy menstrual bleeding
- 1.3 Surgery
- 1.4 Dentistry
- 1.5 Other uses
- 2 Adverse effects
- 3 Mechanism of action
- 4 Society and culture
- 4.1 Brand names
- 4.2 Approval
- 5 References
- 6 External links
Medical uses
Tranexamic acid is frequently used following major trauma.[4] 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.[5][6]
Trauma
Tranexamic acid has been found to decrease the risk of death in people who have significant bleeding due to trauma.[7] However, its benefit only appears to be within the first three hours.[8]
Heavy menstrual bleeding
Tranexamic acid is used treat heavy menstrual bleeding.[6] When taken by mouth it is both safely and effectively treated regularly occurring heavy menstrual bleeding.[2][9] Another study demonstrated that the dose does not need to be adjusted in people 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. However, the hidden blood loss is not reduced. Still, it is becoming an important tool in the anaesthetist's arsenal. It is commonly used in joint replacement surgery.
Use of tranexamic acid in surgical corrections of craniosynostosis in children reduces the need for blood transfusions.[10]
Tranexamic acid is commonly used in cardiac surgery, both with and without cardiopulmonary bypass. 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] Transexamic 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.[11] 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[12]
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. A major trial is in progress worldwide to establish the efficacy of the drug to arrest postpartum haemorrhage (PPH). 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 cardiac surgery, e.g. coronary artery bypass surgery, it is used to prevent excessive blood loss.
- In spine surgery, e.g. scoliosis correction with posterior spinal fusion using instrumentation, to prevent excessive blood loss.[13]
- In hereditary angioedema[14]
- 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.[15]
- In melasma - Tranexamic acid has shown to provide rapid and sustained lightening in melasma by decreasing melanogenesis in epidermal melanocytes.[16]
- In hyphema - Tranexamic acid has been shown to be effective in reducing risk of secondary hemorrhage outcomes in patients with traumatic hyphema.[17]
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]
- Tranexamic acid is indicated for lactating women and is not well studied nor intended for use in premenarchial girls (<12 years of age).[2]
- 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 has been included in the WHO list of essential medicines.[3] TXA is inexpensive and treatment would be considered highly cost effective in high, middle and low income countries.[18]
Brand names
Tranexamic acid is marketed in the U.S. and Australia in tablet form as Lysteda and in IV form as Cyklokapron and Transamin, 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)[19] 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.[20] (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.[21]
References
- ^ a b c d e "Cyklokapron (tranexamic acid) Product Information" (PDF). Retrieved 3 November 2015.
- ^ a b c d e f g h i j k l m "Lysteda (tranexamic acid) Package Insert" (PDF). accessdata.FDA.gov. Retrieved 2 November 2015.
- ^ a b "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
- ^ Binz, S; McCollester, J; Thomas, S; Miller, J; Pohlman, T; Waxman, D; Shariff, F; Tracy, R; Walsh, M (2015). "CRASH-2 Study of Tranexamic Acid to Treat Bleeding in Trauma Patients: A Controversy Fueled by Science and Social Media.". Journal of blood transfusion 2015: 874920. PMID 26448897.
- ^ Melvin, JS; Stryker, LS; Sierra, RJ (22 October 2015). "Tranexamic Acid in Hip and Knee Arthroplasty.". The Journal of the American Academy of Orthopaedic Surgeons. PMID 26493971.
- ^ a b Tengborn, L; Blombäck, M; Berntorp, E (February 2015). "Tranexamic acid--an old drug still going strong and making a revival.". Thrombosis research 135 (2): 231–42. PMID 25559460.
- ^ Cherkas, David (Nov 2011). "Traumatic Hemorrhagic Shock: Advances In Fluid Management". Emergency Medicine Practice 13 (11).
- ^ Napolitano, Lena M.; Cohen, Mitchell J.; Cotton, Bryan A.; Schreiber, Martin A.; Moore, Ernest E. (2013). "Tranexamic acid in trauma". Journal of Trauma and Acute Care Surgery 74 (6). doi:10.1097/TA.0b013e318292cc54. PMID 23694890.
- ^ Lukes, AS; Moore, KA; Muse, KN (2010). "Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial". Obstet Gynecol 116 (4): 865–875. doi:10.2147/IJWH.S13840. Retrieved 3 November 2015.
- ^ RCPCH. "Evidence Statement Major trauma and the use of tranexamic acid in children Nov 2012" (PDF). Retrieved 17 December 2012.
- ^ Forbes CD, Barr RD, Reid G; et al. (1972). "Tranexamic acid in control of haemorrhage after dental extraction in haemophilia and Christmas disease". Br Med J 2 (809): 311–313.
- ^ Shankar S & Lee R (1984). "DDAVP and tranexamic acid for dental extractions in a mild hemophiliac". Br Dent J 156 (12): 450–452.
- ^ Sethna, N. F.; Zurakowski, D; Brustowicz, R. M.; Bacsik, J; Sullivan, L. J.; Shapiro, F (2005). "Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery". Anesthesiology 102 (4): 727–32. PMID 15791100.
- ^ Rod Flower; Humphrey P. Rang; Maureen M. Dale; Ritter, James M. (2007). Rang & Dale's pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-06911-5. [page needed]
- ^ Klepfish, A; Berrebi, A; Schattner, A (2001). "Intranasal tranexamic acid treatment for severe epistaxis in hereditary hemorrhagic telangiectasia". Archives of internal medicine 161 (5): 767. PMID 11231712.
- ^ Karn, D; Kc, S; Amatya, A; Razouria, E. A.; Timalsina, M (2012). "Oral tranexamic acid for the treatment of melasma". Kathmandu University Medical Journal 10 (40): 40–3. PMID 23575051.
- ^ Gharaibeh, Almutez; Savage, Howard I; Scherer, Roberta W; Goldberg, Morton F; Lindsley, Kristina (2011). "Medical interventions for traumatic hyphema". Cochrane Database of Systematic Reviews (1): CD005431. doi:10.1002/14651858.CD005431.pub2. PMC 3437611. PMID 21249670.
- ^ Guerriero, Carla; Cairns, John; Perel, Pablo; Shakur, Haleema; Roberts, Ian; Crash 2 Trial, Collaborators (2011). "Cost-Effectiveness Analysis of Administering Tranexamic Acid to Bleeding Trauma Patients Using Evidence from the CRASH-2 Trial". PLoS ONE 6 (5). Bibcode:2011PLoSO...618987G. doi:10.1371/journal.pone.0018987. PMC 3086904. PMID 21559279.
- ^ Tranexamic Acid to be available OtC[full citation needed]
- ^ In defence of multiple pharmacies[full citation needed]
- ^ Allen, Helen (June 13, 2012). "Tranexamic acid for bleeding". Patient UK.
External links
- [1] (PoM to P in the UK)
- CRASH-2: tranexamic acid and trauma patients
- Patient Experience with tranexamic acid
- Tranexamic acid, UK patient information leaflet
- Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial (The Lancet)
- Drug will save lives of accident victims, says study, BBC News
- Types of Angioedema and treatments, Hereditary Angioedema Association
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Antihemorrhagics (B02)
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Antihemorrhagics
(coagulation) |
| Systemic |
| Vitamin K |
- Phytomenadione (K1)
- Menadione (K3)
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Coagulation
factors |
- intrinsic: IX/Nonacog alfa
- VIII/Moroctocog alfa/Turoctocog alfa
- extrinsic: VII/Eptacog alfa
- common: X
- II/Thrombin
- I/Fibrinogen
- combinations: Prothrombin complex concentrate (II, VII, IX, X, protein C and S)
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Other
systemic |
- Etamsylate
- Carbazochrome
- Batroxobin
- thrombopoietin receptor agonist (Romiplostim
- Eltrombopag)
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| Local |
- Absorbable gelatin sponge
- Oxidized cellulose
- Tetragalacturonic acid hydroxymethylester
- Thrombin
- Collagen
- Calcium alginate
- Epinephrine/Adrenalone
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| Antifibrinolytics |
- amino acids (Aminocaproic acid
- Tranexamic acid
- Aminomethylbenzoic acid)
serpins (Aprotinin
- Alfa1 antitrypsin
- C1-inhibitor
- Camostat)
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Index of cells from bone marrow
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| Description |
- Immune system
- Cells
- Physiology
- coagulation
- proteins
- granule contents
- colony-stimulating
- heme and porphyrin
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| Disease |
- Red blood cell
- Monocyte and granulocyte
- Neoplasms and cancer
- Histiocytosis
- Symptoms and signs
- Blood tests
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| Treatment |
- Transfusion
- Drugs
- thrombosis
- bleeding
- other
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