Tranexamic Acid Approved by FDA – A new tool for treatment of mennorhagia
Tranexamic acid was recently approved by the FDA for treatment of fibroid related mennoraghia, under the trade name Lysteda. Being ignorant of this drug, I wanted to do a little research. Being a blogger, I want to share this research.
Apparently, this drug has been available in Europe for quite a long time, and there is substantial evidence of its efficacy and safety for treatment of a wide variety of bleeding issues, both gynecologic and otherwise. Tranexamic acid (Wiki, WA) is in class of drugs called antifibrinolytics. It is related to the drug Amicar (ε-aminocaproic acid) which is used in the US most notably after dental procedures as a mouthwash in patients with bleeding disorders. These drugs function by blockade of lysine binding sites on plasminogen, thus blocking degradation of plasminogen into plasmin (sort of an anti-tPA). Through this mechanism it stabilizes clots and prevents clot breakdown, thus augmenting the clotting system and decreasing bleeding.
Tranexamic acid has been studied in a wide variety of medical applications, all in situations where improved blood clotting is required. Some studied applications include reduction of blood loss in CABG surgery, decreasing blood loss during and after cesarean delivery, and control of severe upper GI bleeding.
The use of tranexamic acid for control of mennoraghia has also been thoroughly studied, and based on the data already in press it appears to be effective in this use.
Here are a few studies that support the efficacy of the drug:
Gultekin et al did a study of 132 women who presented to the hospital with disfunctional uterine bleeding who were put on 500 mg of tranexamic acid. Patients were used as their own control group, comparing pre-treatment labs and history with post treatment labs and history. On treatment, bleeding days decreased from a median 9 days to 5 days, and median hemoglobins rose from 10.6 to 12.1. 66% of patients required no other treatment. The study’s major methodologic concern is that the pretreatment control is affected by recall bias in comparison to contemporaneously gathered treatment arm data.
Senthong et al conducted a randomized trial of tranexamic acid for women who had problematic bleeding while on DMPA. 88% of the women in the treatment arm had cessation of bleeding by 4 weeks, against only 8% in the placebo arm. Four weeks after cessation of treatment, the treatment arm still had better bleeding profiles than the placebo arm, with 68% having bleeding free intervals of > 20 days vs 0% with the nontreatment arm.
Wellington et al reviewed the use of tranexamic acid, with favorable results: “In a number of small clinical studies in women with idiopathic menorrhagia, tranexamic acid 2-4.5 g/day for 4-7 days reduced menstrual blood loss by 34-59% over 2-3 cycles, significantly more so than placebo, mefenamic acid, flurbiprofen, etamsylate and oral luteal phase norethisterone at clinically relevant dosages. Intrauterine administration of levonorgestrel 20 microg/day, however, produced the greatest reduction (96% after 12 months) in blood loss; 44% of patients treated with levonorgestrel developed amenorrhoea. Tranexamic acid 1.5 g three times daily for 5 days also significantly reduced menstrual blood loss in women with intrauterine contraceptive device-associated menorrhagia compared with diclofenac sodium (150 mg in three divided doses on day 1 followed by 25 mg three times daily on days 2-5) or placebo…. tranexamic acid may be considered as a first-line treatment for the initial management of idiopathic menorrhagia, especially for patients in whom hormonal treatment is either not recommended or not wanted.”
A Cochrane review addressed tranexamic acid in meta-analysis for heavy menstrual bleeding, and found it effective in reducing blood loss. “Antifibrinolytic therapy compared to placebo showed a significant reduction in mean blood loss (WMD -94.0 [-151.4, -36.5]) and significant change in mean reduction of blood loss (WMD -110.2 [-146.5, -73.8]).”
So overall, there appears to be strong evidence of efficacy of the drug. The only catch for me is that as a competitive inhibitor of plasminogen activity, it acts as a pro-coagulant and potentially increases the risk of thrombotic event. There are a number of case reports of unusual thrombosis (CVA in a 28 year old woman, recurrent pulmonary embolism in another woman), but there is a no clear increased risk of thrombosis described in the larger studies. Most likely this drug does increase the risk of thrombosis a small amount, and this is likely affected by host genetic factors as well. The alternatives also increase thrombotic risk somewhat (OCPs predominantly), though a Mirena IUD is able to achieve the same effect without the thrombotic risk.
For me, I will consider the use of this drug in my patients with mennorhagia, but will hold off on anybody with a defined thrombotic risk. My use will also be very dependent on the cost of the drug. I cannot see using this drug at this time if it costs $100 a month or is not being adequately covered by insurers.
Any thoughts from the viewers?
Role of a non-hormonal oral anti-fibrinolytic hemostatic agent (tranexamic acid) for management of patients with dysfunctional uterine bleeding. Gultekin M, Diribas, K, Buru E,Gökçeoğlu MA. Clin Exp Obstet Gynecol. 2009;36(3):163-5.
The risk of venous thromboembolism associated with the use of tranexamic acid and other drugs use to treat menorrhagia: a case-control study using the General Practice Research Database. Sundstrom A, Seaman H, KielerH, Alfredsson L. BJOG. 2009 Jan;116(1):91-7. Epub 2008 Nov 11.