Tranexamic Acid Tablets (Lysteda™)
Pharmacology Update
Tranexamic Acid Tablets (Lysteda)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
The FDA has approved tranexamic acid, an antifibrinolytic drug, for the treatment of cyclic heavy menstrual bleeding. The drug was originally approved in 1986 (as Cyclokapron) for hemophiliac patients undergoing tooth extraction. The new formulation is marketed by Xanodyne Pharmaceuticals as Lysteda.
Indications
Tranexamic acid is indicated for the treatment of cyclic heavy menstrual bleeding.1
Dosage
The recommended dose is 1300 mg (two 650 mg tablets) three times a day for a maximum of 5 days with each monthly menstruation.1 The dose should be reduced due to renal dysfunction utilizing serum creatinine concentration as an indicator. The dose is 1300 mg twice a day for SCr > 1.4 mg/dL to 2.8 mg/dL; 1300 mg once daily for SCr > 2.8 mg/dL to 5.7 mg/dL; and 650 mg once daily for SCr > 5.7 mg/dL.
Potential Advantages
Tranexamic acid treatment resulted in a 38%-39% reduction in menstrual blood loss compared to a 5%-12% for placebo.1 It is more effective than intranasal desmopressin (DDAVP) in patients with menorrhagia with abnormal laboratory hemostasis.2
Potential Disadvantages
Tranexamic acid may be associated with an increased risk of venous thromboembolism and the risk is enhanced with use of oral contraceptives.1,3 Adverse events include headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, joint pain, muscle cramp, migraine, anemia, and fatigue. Tranexamic acid may also cause visual or ocular adverse events, cerebral edema, and cerebral infarction.1
Comments
Tranexamic acid is a synthetic lysine derivative that reversibly blocks the lysine binding site on plasminogen. This prevents the activated form of plasminogen (plasmin) from binding to the lysine residue on fibrin, inhibiting its degradation. Women with menorrhagia may have higher fibrinolytic activity in utero than women with normal menstrual blood loss.4 The efficacy and safety of tranexamic acid in the treatment of heavy menstrual bleeding was shown in one 3-cycle treatment and 6-cycle treatment, randomized, double-blind, placebo-controlled study.1 Study participants were age 18-49 years, with an average BMI of 32 kg/m2, history of heavy menstrual bleeding of approximately 10 years, and an average menstrual blood loss of 80 mL or greater. Those randomized to tranexamic acid 3900 mg/day (n = 112) had a 39% reduction in menstrual blood flow compared to 5% for those randomized to placebo (n = 67). Similar results were reported for the 6-cycle study (n = 187), 38% vs 12%. In patients (n = 116) with menorrhagia and abnormal laboratory hemostasis (e.g., abnormal platelet aggregation or subnormal level of coagulation factors), tranexamic acid (4 g/day for the first 5 days) was significantly more effective than intranasal DDAVP (300 mg on days 2 and 3 of menstrual bleeding). It is also more effective than mefenamic acid and flurbiprofen.4 Tranexamic acid appears to be well tolerated.
Clinical Implications
Menorrhagia is believed to affect 5%-30% of women of reproductive age.5,6 Menorrhagia is a common reason for hysterectomies. A sizable number of these women may have an underlying hemostatic defect (e.g., von Willebrand's disease, platelet defects).7,8 A smaller number may have coagulation deficiencies or defect in fibrinolysis. Tranexamic acid provides a new therapeutic option for this condition. Mechanistically, tranexamic acid may benefit those with defect in fibrinolysis. It appears to be more effective than NSAIDs or DDAVP.
References
1. Lysteda Prescribing Information. Newport, KY: Xanodyne Pharmaceuticals; November 2009.
2. Kouides PA, et al. Multisite management study of menorrhagia with abnormal laboratory haemostasis: A prospective crossover study of intranasal desmopressin and oral tranexamic acid. Br J Haematol 2009;145:212-220.
3. Sundstrom A, et al. The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs used to treat menorrhagia: A case-control study using the General Practice Research Database. BJOG 2009;116:91-97.
4. Wellington K, Wagstaff AJ. Tranexamic acid: A review of its use in the management of menorrhagia. Drugs 2003;63:1417-1433.
5. El-Hemaidi I, et al. Menorrhagia and bleeding disorders. Curr Opin Obstet Gynecol 2007;19:513-520.
6. Kouides PA. Bleeding symptom assessment and hemostasis evaluation of menorrhagia. Curr Opin Hematol 2008;15:465-472.
7. Philipp CS, et al. Platelet functional defects in women with unexplained menorrhagia. J Thromb Haemost 2003;1:477-484.
8. Shankar M, et al. von Willebrand disease in women with menorrhagia: A systematic review. BJOG 2004;111:734-740.
The FDA has approved tranexamic acid, an antifibrinolytic drug, for the treatment of cyclic heavy menstrual bleeding.Subscribe Now for Access
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