Side Effects of Lysteda (tranexamic acid)

Lysteda (tranexamic acid) is a man-made amino acid derivative that promotes the clotting of blood and thereby reduces bleeding due to heavy menstruation. It is also used off-label (uses not approved by the FDA) hereditary angioedema (a condition similar to hives), nosebleeds, cone biopsy, and hyphema (an eye condition).

Lysteda increases blood clotting by preventing the breakdown of fibrin. Fibrin is a protein and an important component of blood clots. It is broken down by another protein called plasmin. Lysteda blocks the action of plasmin on fibrin and thereby prevents the breakdown of fibrin. This leads to stabilization and preservation of fibrin in blood clots, and this helps reduce bleeding during a heavy menstrual cycle.

Common side effects of Lysteda include

• abdominal and back pain,
• anemia,
• joint pain,
• muscle cramps and spasms,
• musculoskeletal pain,
• headache,
• migraine,
• nasal and sinus problems, and
• fatigue.

Serious side effects of Lysteda include increased risk of forming blood clots.

Drug interactions of Lysteda include and birth control medications, because concomitant use can increase the risk of blood clots.

Concomitant use with tissue plasminogen activators (used to prevent or treat blood clots) can reduce the effectiveness of Lysteda.

Concomitant use with Factor IX complex concentrates or anti-inhibitor coagulant concentrates that promote blood clots is not recommended due to the increased risk of blood clots.

Lysteda is not approved for use in pregnant women. Moreover, there no adequate studies of Lysteda to determine safe and effective use in pregnant women.

Lysteda is present in breast milk in trace amounts; therefore, caution must be exercised before considering its use in breastfeeding mothers.

Side effects of this drug include:

• Abdominal and back pain
• Anemia
• Joint pain
• Muscle cramps and spasms
• Musculoskeletal pain
• Headache
• Migraine
• Nasal and sinus problems
• Fatigue

Tranexamic acid may increase the risk of forming blood clots.

Clinical Trial Experience

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.
• 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/m² .
• 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.

Table 2: Adverse Events Reported by ≥ 5% of Subjects Treated with Lysteda and More Frequently in Lysteda-treated Subjects

Long-term Studies

• Long-term safety of Lysteda was studied in two open-label studies. In one study, subjects with physician-diagnosed heavy menstrual bleeding (not using the alkaline hematin methodology) were treated with 3900 mg/day for up to 5 days during each menstrual period for up to 27 menstrual cycles.
• A total of 781 subjects were enrolled and 239 completed the study through 27 menstrual cycles. A total of 12.4% of the subjects withdrew due to adverse events.
• Women using hormonal contraception were excluded from the study.
• The total exposure in this study to 3900 mg/day Lysteda was 10,213 cycles. The average duration of Lysteda use was 2.9 days per cycle.
• A long-term open-label extension study of subjects from the two short-term efficacy studies was also conducted in which subjects were treated with 3900 mg/day for up to 5 days during each menstrual period for up to 9 menstrual cycles.
• A total of 288 subjects were enrolled and 196 subjects completed the study through 9 menstrual cycles. A total of 2.1% of the subjects withdrew due to adverse events.
• The total exposure to 3900 mg/day Lysteda in this study was 1,956 cycles. The average duration of Lysteda use was 3.5 days per cycle.
• The types and severity of adverse events in these two long-term open-label trials were similar to those observed in the double-blind, placebo-controlled studies although the percentage of subjects reporting them was greater in the 27-month study, most likely because of the longer study duration.
• A case of severe allergic reaction to Lysteda was reported in the extension trial, involving a subject on her fourth cycle of treatment, who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment.

Postmarketing Experience

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 US and worldwide postmarketing reports, the following have been reported in patients receiving tranexamic acid for various indications:

• Nausea, vomiting, and diarrhea
• Allergic skin reactions
• Anaphylactic shock and anaphylactoid reactions
• Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction); cases have been associated with concomitant use of combination hormonal contraceptives
• Impaired color vision and other visual disturbances
• Dizziness

No drug-drug interaction studies were conducted with Lysteda.

Hormonal Contraceptives

Because Lysteda is antifibrinolytic, concomitant use of hormonal contraception and Lysteda may further exacerbate the increased thrombotic risk associated with combination hormonal contraceptives. For this reason, concomitant use of Lysteda with combination hormonal contraceptives is contraindicated.

Tissue Plasminogen Activators

Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both Lysteda and tissue plasminogen activators. Therefore, exercise caution if a woman taking Lysteda therapy requires tissue plasminogen activators.

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.

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.