Lysteda Information
Lysteda ()
Lysteda () Indications And Usage
Lysteda () (tranexamic acid) Tablets is indicated for the treatment of cyclic heavy menstrual bleeding [see ].
Prior to prescribing Lysteda () , exclude endometrial pathology that can be associated with heavy menstrual bleeding.
Lysteda () Dosage Forms And Strengths
Lysteda () Contraindications
Do not prescribe Lysteda () to women who are known to have the following conditions:
Venous and arterial thrombosis or thromboembolism, as well as cases of retinal artery and retinal vein occlusions, have been reported with tranexamic acid.
Lysteda () Warnings And Precautions
Concomitant Use of Hormonal Contraceptives
Combination hormonal contraceptives are known to increase the risk of venous thromboembolism, as well as arterial thromboses such as stroke and myocardial infarction. Because Lysteda () is antifibrinolytic, the risk of venous thromboembolism, as well as arterial thromboses such as stroke, may increase further when hormonal contraceptives are administered with Lysteda () . This is of particular concern in women who are obese or smoke cigarettes, especially smokers over 35 years of age [see and ].
Women using hormonal contraception were excluded from the clinical trials supporting the safety and efficacy of Lysteda () , and there are no clinical trial data on the risk of thrombotic events with the concomitant use of Lysteda () with hormonal contraceptives. There have been U.S. postmarketing reports of venous and arterial thrombotic events in women who have used Lysteda () concomitantly with combined hormonal contraceptives. Women using hormonal contraception, especially those who are obese or smoke, should use Lysteda () only if there is a and the benefit of treatment will outweigh the potential increased risk of a thrombotic event. Do not use Lysteda () in women who are taking more than the approved dose of a hormonal contraceptive.
Factor IX Complex Concentrates or Anti-Inhibitor Coagulant Concentrates
Lysteda () is not recommended for women taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased [see and ].
All-Trans Retinoic Acid (Oral Tretinoin)
Exercise caution when prescribing Lysteda () to women with acute promyelocytic leukemia taking all‑trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid [see and ].
Ocular Effects
Retinal venous and arterial occlusion has been reported in patients using tranexamic acid. Patients should be instructed to report visual and ocular symptoms promptly. In the event of such symptoms, patients should be instructed to discontinue Lysteda () immediately and should be referred to an ophthalmologist for a complete ophthalmic evaluation, including dilated retinal examination, to exclude the possibility of retinal venous or arterial occlusion.
Lysteda () Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Short-term Studies
The safety of Lysteda () in the treatment of heavy menstrual bleeding (HMB) was studied in two randomized, double-blind, placebo-controlled studies [see ]. One study compared the effects of two doses of Lysteda () (1950 mg and 3900 mg given daily for up to 5 days during each menstrual period) versus placebo over a 3-cycle treatment duration. A total of 304 women were randomized to this study, with 115 receiving at least one dose of 3900 mg/day of Lysteda () . A second study compared the effects of Lysteda () (3900 mg/day) versus placebo over a 6-cycle treatment duration. A total of 196 women were randomized to this study, with 117 receiving at least one dose of Lysteda () . In both studies, subjects were generally healthy women who had menstrual blood loss of ≥ 80 mL.
In these studies, subjects were 18 to 49 years of age with a mean age of approximately 40 years, had cyclic menses every 21-35 days, and a BMI of approximately 32 kg/m. On average, subjects had a history of HMB for approximately 10 years and 40% had fibroids as determined by transvaginal ultrasound. Approximately 70% were Caucasian, 25% were Black, and 5% were Asian, Native American, Pacific Islander, or Other. Seven percent (7%) of all subjects were of Hispanic origin. Women using hormonal contraception were excluded from the trials.
The rates of discontinuation due to adverse events during the two clinical trials were comparable between Lysteda () and placebo. In the 3-cycle study, the rate in the 3900 mg Lysteda () dose group was 0.8% as compared to 1.4% in the placebo group. In the 6-cycle study, the rate in the Lysteda () group was 2.4% as compared to 4.1% in the placebo group. Across the studies, the combined exposure to 3900 mg/day Lysteda () was 947 cycles and the average duration of use was 3.4 days per cycle.
A list of adverse events occurring in ≥ 5% of subjects and more frequently in Lysteda () treated subjects receiving 3900 mg/day compared to placebo is provided in Table 2.
The following adverse reactions have been identified from postmarketing experience with tranexamic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Based on U.S. and worldwide postmarketing reports, the following have been reported in patients receiving tranexamic acid for various indications:
Lysteda () Drug Interactions
No drug-drug interaction studies were conducted with Lysteda () .
Lysteda () Use In Specific Populations
Lysteda () is not indicated for use in pregnant women. Reproduction studies have been performed in mice, rats and rabbits and have revealed no evidence of impaired fertility or harm to the fetus due to tranexamic acid. However, tranexamic acid is known to cross the placenta and appears in cord blood at concentrations approximately equal to the maternal concentration. There are no adequate and well-controlled studies in pregnant women [see ].
An embryo-fetal developmental toxicity study in rats and a perinatal developmental toxicity study in rats were conducted using tranexamic acid. No adverse effects were observed in either study at doses up to 4 times the recommended human oral dose of 3900 mg/day based on mg/m (actual animal dose 1500 mg/kg/day).
Lysteda () is indicated for women of reproductive age and is not intended for use in premenarcheal girls.
Lysteda () has not been studied in adolescents under age 18 with heavy menstrual bleeding.
Lysteda () Overdosage
There are no known cases of intentional overdose with Lysteda () and no subjects in the clinical program took more than 2 times the prescribed amount of Lysteda () in a 24-hour period (>7800 mg/day). However, cases of overdose of tranexamic acid have been reported. Based on these reports, symptoms of overdose may include gastrointestinal (nausea, vomiting, diarrhea); hypotensive (e.g., orthostatic symptoms); thromboembolic (arterial, venous, embolic); visual impairment; mental status changes; myoclonus; or rash. No specific information is available on the treatment of overdose with Lysteda () . In the event of overdose, employ the usual supportive measures (e.g., clinical monitoring and supportive therapy) as dictated by the patient's clinical status.
Lysteda () Description
Lysteda () is an antifibrinolytic drug. The chemical name is trans-4-aminomethyl-cyclohexanecarboxylic acid. The structural formula is:
Tranexamic acid is a white crystalline powder. It is freely soluble in water and in glacial acetic acid and is very slightly soluble in ethanol and practically insoluble in ether. The molecular formula is CHN0 and the molecular weight is 157.2.
Tranexamic acid tablets are provided as white oval-shaped tablets and are not scored. Each tablet is debossed with the marking “XP650.” The active ingredient in each tablet is 650 mg tranexamic acid. The inactive ingredients contained in each tablet are: microcrystalline cellulose, colloidal silicon dioxide, pregelatinized corn starch, povidone, hypromellose, stearic acid, and magnesium stearate.
Lysteda () Clinical Pharmacology
Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin's matrix structure.
The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen. Native human plasminogen contains 4 to 5 lysine binding sites with low affinity for tranexamic acid (K = 750 μmol/L) and 1 with high affinity (K = 1.1 μmol/L). The high affinity lysine site of plasminogen is involved in its binding to fibrin. Saturation of the high affinity binding site with tranexamic acid displaces plasminogen from the surface of fibrin. Although plasmin may be formed by conformational changes in plasminogen, binding to and dissolution of the fibrin matrix is inhibited.
Tranexamic acid, at concentrations of 25 - 100 μM, reduces by 20 - 60% the maximal rate of plasmin lysis of fibrin catalyzed by tissue plasminogen activator (tPA).
Elevated concentrations of endometrial, uterine, and menstrual blood tPA are observed in women with heavy menstrual bleeding (HMB) compared to women with normal menstrual blood loss. The effect of tranexamic acid on lowering endometrial tPA activity and menstrual fluid fibrinolysis is observed in women with HMB receiving tranexamic acid total oral doses of 2-3 g/day for 5 days.
In healthy subjects, tranexamic acid at blood concentrations less than 10 mg/mL has no effect on the platelet count, the coagulation time or various coagulation factors in whole blood or citrated blood. Tranexamic acid, however, at blood concentrations of 1 and 10 mg/mL prolongs the thrombin time.
Cardiac Electrophysiology
The effect of Lysteda () on QT interval was evaluated in a randomized, single-dose, 4-way crossover study in 48 healthy females aged 18 to 49 years. Subjects received (1) Lysteda () 1300 mg (two 650 mg tablets), (2) Lysteda () 3900 mg (six 650 mg tablets; three times the recommended single dose), (3) moxifloxacin 400 mg, and (4) placebo. There was no significant increase in the corrected QT interval at any time up to 24 hours after the administration of either dose of Lysteda () . Moxifloxacin, the active control, was associated with a maximum 14.11 msec mean increase in corrected QT interval (moxifloxacin – placebo) at 3 hours after administration.
Lysteda () Nonclinical Toxicology
Carcinogenesis
Carcinogenicity studies with tranexamic acid in male mice at doses as high as 6 times the recommended human dose of 3900 mg/day showed an increased incidence of leukemia which may have been related to treatment. Female mice were not included in this experiment.
The dose multiple referenced above is based on body surface area (mg/m). Actual daily dose in mice was up to 5000 mg/kg/day in food.
Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in a different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver.
Mutagenesis
Tranexamic acid was neither mutagenic nor clastogenic in the Bacterial Reverse Mutation Assay (Ames test), chromosome aberration test in Chinese hamster cells, and in chromosome aberration tests in mice and rats.
Impairment of Fertility
Reproductive studies performed in mice, rats and rabbits have not revealed any evidence of impaired fertility or adverse effects on the fetus due to tranexamic acid.
In a rat embryo-fetal developmental toxicity study, tranexamic acid had no adverse effects on embryo-fetal development when administered during the period of organogenesis (from gestation days 6 through 17) at doses 1, 2 and 4 times the recommended human oral dose of 3900 mg/day. In a perinatal-postnatal study in rats, tranexamic acid had no adverse effects on pup viability, growth or development when administered from gestation day 6 through postnatal day 20 at doses 1, 2 and 4 times the recommended human oral dose of 3900 mg/day.
The dose multiples referenced above are based on body surface area (mg/m). Actual daily doses in rats were 300, 750 or 1500 mg/kg/day.
Ocular Effects
In a 9-month toxicology study, dogs were administered tranexamic acid in food at doses of 0, 200, 600, or 1200 mg/kg/day. These doses are approximately 2, 5, and 6 times, respectively, the recommended human oral dose of 3900 mg/day based on AUC. At 6 times the human dose, some dogs developed reversible reddening and gelatinous discharge from the eyes. Ophthalmologic examination revealed reversible changes in the nictitating membrane/conjunctiva. In some female dogs, the presence of inflammatory exudate over the bulbar conjunctival mucosa was observed. Histopathological examinations did not reveal any retinal alteration. No adverse effects were observed at 5 times the human dose.
In other studies, focal areas of retinal degeneration were observed in cats, dogs and rats following oral or intravenous tranexamic acid doses at 6-40 times the recommended usual human dose based on mg/m (actual animal doses between 250-1600 mg/kg/day).
Lysteda () Clinical Studies
The efficacy and safety of Lysteda () in the treatment of heavy menstrual bleeding (HMB) was demonstrated in one 3-cycle treatment and one 6-cycle treatment, randomized, double-blind, placebo-controlled study [see ]. In these studies, HMB was defined as an average menstrual blood loss of ≥ 80 mL as assessed by alkaline hematin analysis of collected sanitary products over two baseline menstrual cycles. Subjects were 18 to 49 years of age with a mean age of approximately 40 years, had cyclic menses every 21-35 days, and a BMI of approximately 32 kg/m. On average, subjects had an HMB history of approximately 10 years and 40% had fibroids as determined by transvaginal ultrasound. Approximately 70% were Caucasian, 25% were Black, and 5% were Asian, Native American, Pacific Islander, or Other. Seven percent (7%) of all subjects were of Hispanic origin.
In these studies, the primary outcome measure was menstrual blood loss (MBL), measured using the alkaline hematin method. The endpoint was change from baseline in MBL, calculated by subtracting the mean MBL during treatment from the mean pretreatment MBL.
The key secondary outcome measures were based on specific questions concerning limitations in social or leisure activities (LSLA) and limitations in physical activities (LPA). Large stains (soiling beyond the undergarment) were also included as a key secondary outcome measure.
Lysteda () How Supplied/storage And Handling
Lysteda () (tranexamic acid) tablets are provided as white oval-shaped tablets. Each tablet is debossed with the marking "XP650" and are supplied as:
Store at room temperature 25° C (77° F); excursions permitted to 15-30° C (59-86° F). [See USP Controlled Room Temperature].
Lysteda () Patient Counseling Information
See FDA-approved patient labeling (Patient Information)
Instruct patients that the usual schedule is to take two tablets with liquids, three times a day during menstruation. Patients should be instructed not to exceed 3 doses (6 tablets) in a 24-hour period or to take for more than 5 days in any menstrual cycle.
Inform patients that they should immediately stop Lysteda () if they notice any eye symptoms or change in their vision. Instruct them to report any such problems promptly to their physician and to follow-up with an ophthalmologist for a complete ophthalmic evaluation, including dilated retinal examination of the retina.
Inform patients that they should stop Lysteda () and seek immediate medical attention if they notice symptoms of a severe allergic reaction (e.g., shortness of breath or throat tightening).
Instruct patients that common side effects of Lysteda () include headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, joint pain, muscle cramps, migraine, anemia and fatigue.
Advise patients to contact their healthcare provider if their heavy menstrual bleeding symptoms persist or worsen.
Remind patients to read the Patient Labeling carefully.
Read the Patient Information that comes with Lysteda () before you start using the drug and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical condition or your treatment.
Lysteda () is a prescription medicine used to treat your heavy monthly period (menstruation) when your bleeding gets in the way of social, leisure and physical activities. Lysteda () does not contain any hormones. On average, Lysteda () has been shown to lower the amount of blood lost during your monthly period by about one-third, but it is not meant to stop your period.
Lysteda () is taken only during your period and is not meant to treat pre-menstrual symptoms (symptoms that occur before your bleeding starts). Lysteda () does not affect your fertility and cannot be used as birth control. Lysteda () does not protect you against diseases that you may get if you have unprotected sex.
Lysteda () has not been studied in adolescents younger than 18 years of age.
Do not take Lysteda () if you:
Before taking Lysteda () , tell your healthcare provider about all of your medical conditions, including whether:
Ask your healthcare provider if you are not sure if your medicine is one that is described above.
The most common side effects of Lysteda () include:
Tell your healthcare provider if you have any side effect that bothers you or does not go away.
These are not all of the possible side effects of Lysteda () . For more information, ask your healthcare provider or pharmacist.
Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464).
Store Lysteda () at room temperature between 59°F to 86°F (15°C to 30°C).
Medicines are sometimes prescribed for conditions that are not mentioned in Patient Information Leaflets. Do not use Lysteda () for a condition for which it was not prescribed. Do not give Lysteda () to other people, even if they have the same symptoms that you have. It may harm them.
This patient information leaflet summarizes the most important information about Lysteda () . If you would like more information about Lysteda () , talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about Lysteda () that is written for healthcare professionals. For more information, go to www.Lysteda () .com or call 1-888-FERRING (1-888-337-7464).
Active ingredient: tranexamic acid
Inactive ingredients: microcrystalline cellulose, colloidal silicon dioxide, pregelatinized corn starch, povidone, hypromellose, stearic acid, and magnesium stearate.
Manufactured for:
Ferring Pharmaceuticals Inc.
Parsippany, NJ 07054
By:
Mikart, Inc.
Atlanta, GA 30318
Rev. 4/2011
Lysteda () Package Label - Bottle Label Count
(tranexamic acid) tablets
30 tablets
Lysteda () Package Label - Carton Count
(tranexamic acid) tablets
30 tablets
