Tranexamic Acid

Pronunciation

Pronunciation: TRAN-ex-AM-ik AS-id
Class: Hemostatic

Trade Names

Cyklokapron
- Injection 100 mg/mL

Lysteda
- Tablets 650 mg

Pharmacology

Inhibits fibrinolysis to stop bleeding.

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Pharmacokinetics

Absorption

Absolute bioavailability is 45%. T max is approximately 3 h and C max is approximately 16 mcg/mL following multiple oral doses. Food increased C max and AUC by 7% and 16%, respectively. Tranexamic acid may be given without regard to meals.

Distribution

Protein binding is 3%, with no apparent binding to albumin. Vd is about 0.39 L/kg (oral) and 9 to 12 L (IV). Tranexamic acid crosses the placenta; concentration in cord blood after IV injection is as high as in maternal blood.

Metabolism

Only a small fraction is metabolized.

Elimination

Renally eliminated. 95% is recovered in the urine as unchanged drug. Cl is 110 to 116 mL/min. Half-life is about 2 h.

Special Populations

Renal Function Impairment

Following administration of a single IV injection, the 24-h urinary fractions of tranexamic acid with serum creatinine concentrations 1.4 to 2.8, 2.8 to 5.7, and more than 5.7 mg/dL were 51%, 39%, and 19%, respectively. The 24-h plasma concentrations demonstrated a direct relationship to degree of renal impairment.

Hepatic Function Impairment

The effect of hepatic impairment has not been evaluated. Because only a small fraction of tranexamic acid is metabolized, no dosage adjustment is needed in patients with hepatic impairment.

Elderly

Not intended for use by postmenopausal women (oral).

Children

Tranexamic acid has not been studied in adolescents younger than 18 years of age with heavy menstrual bleeding.

Indications and Usage

For short-term use in patients with hemophilia to reduce or prevent hemorrhage and reduce the need for replacement therapy during and following tooth extraction (injection only); treatment of cyclic heavy menstrual bleeding (oral only).

Unlabeled Uses

Treatment of GI hemorrhage, hereditary angioneurotic edema, primary or intrauterine device–induced menorrhagia, or recurrent epistaxis; prevention of perioperative bleeding or rebleeding after subarachnoid hemorrhage.

Contraindications

Injection

Acquired defective color vision; subarachnoid hemorrhage; active intravascular clotting.

Oral

Active thromboembolic disease (eg, deep vein thrombosis, pulmonary embolism, cerebral thrombosis); history of thrombosis or thromboembolism, including retinal vein or artery occlusion; intrinsic risk of thrombosis or thromboembolism (eg, thrombogenic valvular disease, thrombogenic cardiac rhythm disease, hypercoagulopathy); hypersensitivity to tranexamic acid.

Dosage and Administration

Cyclic Heavy Menstrual Bleeding
Adults

PO 1,300 mg 3 times daily for a max of 5 days during monthly menstruation.

Dental Extraction in Hemophilia Patients
Adults and Children

IV 10 mg/kg immediately before dental extraction, followed by 10 mg/kg 3 to 4 times daily for 2 to 8 days, together with replacement therapy.

Renal Function Impairment
  • PO
  • Serum creatinine 1.5 to 2.8 mg/dL: 1,300 mg twice daily;
  • serum creatinine 2.9 to 5.7 mg/dL: 1,300 mg once daily;
  • serum creatinine greater than 5.7 mg/dL: 650 mg once daily.
  • IV
  • Serum creatinine 1.36 to 2.83 mg/dL: 10 mg/kg twice daily;
  • serum creatinine 2.83 to 5.66 mg/dL: 10 mg/kg once daily;
  • serum creatinine greater than 5.66: 10 mg/kg every 48 h or 5 mg/kg every 24 h.

General Advice

  • IV infusion
  • Compatible with most solutions for infusion. Heparin may be added to tranexamic acid injection.
  • Do not mix tranexamic acid injection with blood or solutions containing penicillin.
  • Do not inject at a more rapid rate than 1 mL/min.
  • Oral
  • Administer without regard to meals.
  • Swallow tablets whole; do not break, chew, or crush.

Storage/Stability

Store at 59° to 86°F. Tranexamic acid injection should be prepared the same day the solution is to be infused.

Drug Interactions

Factor IX complex concentrates, anti-inhibitor coagulant concentrates

Coadministration of tranexamic acid and factor IX complex concentrates or anti-inhibitor coagulant concentrates may increase the risk of thrombosis. Avoid coadministration.

Hormonal contraceptives

Coadministration of tranexamic acid and hormonal contraceptives may exacerbate the increased thrombotic risk associated with combination hormonal contraceptives. Coadminister only if there is a strong medical need and if the benefit of treatment outweighs the potential for the increased risk of a thrombotic event. Additional clinical monitoring is warranted.

Tissue plasminogen activators

Coadministration may decrease the efficacy of both tranexamic acid and tissue plasminogen activators. Use with caution. Additional clinical monitoring is warranted.

Tretinoin

Coadministration of tretinoin with tranexamic acid may increase the risk of severe thromboembolic reactions. Use with caution. Additional clinical monitoring is warranted.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (with rapid IV infusion); thromboembolic events (eg, acute renal cortical necrosis, central retinal artery and vein obstruction, cerebral thrombosis, deep venous thrombosis, pulmonary embolism) (postmarketing).

CNS

Headache (50%); migraine (6%); fatigue (5%).

EENT

Impaired color vision and visual disturbances (postmarketing)

GI

Abdominal pain (20%); diarrhea, nausea, vomiting.

Hematologic-Lymphatic

Anemia (6%).

Musculoskeletal

Back pain (21%); musculoskeletal pain (11%); arthralgia, muscle cramps and spasms (7%).

Respiratory

Nasal and sinus symptoms (25%).

Miscellaneous

Anaphylactic shock and anaphylactoid reactions (postmarketing).

Precautions

Monitor

Monitor for symptoms of severe allergic reaction and changes in vision. Patients treated continually for longer than several days should undergo ophthalmologic evaluation (eg, visual acuity, color vision, eye-ground and visual fields) prior to starting therapy and at regular intervals.


Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established for cyclic heavy menstrual bleeding.

Elderly

Not intended for use by postmenopausal women (oral).

Hypersensitivity

Severe allergic reaction (dyspnea, facial flushing, tightening of throat) and anaphylactic shock have been reported.

Renal Function

Dosage adjustment needed because of the risk of accumulation.

Cerebral edema/infarction

May be caused by use of tranexamic acid in patients with subarachnoid hemorrhage.

DIC

Patients with DIC must be under strict supervision of a health care provider while on therapy with tranexamic acid.

Ocular effects

Retinal venous and arterial occlusion has been reported. Discontinue therapy if suspected and refer patient to ophthalmologist for evaluation.

Ureteral obstruction

Has been reported in patients with upper urinary tract bleeding treated with tranexamic acid.

Overdosage

Symptoms

Arterial, embolic, or venous thromboembolism; diarrhea, nausea, vomiting; hypotension or orthostatic symptoms; mental status changes; myoclonus; rash; visual impairment.

Patient Information

  • Inform patients that they should immediately stop therapy if they notice any eye symptoms or changes in vision. Instruct them to report such problems promptly to their health care provider and to follow up with an ophthalmologist.
  • Inform patients that they should stop therapy and seek immediate medical attention if they notice symptoms of severe allergic reaction (eg, shortness of breath, throat tightening).
  • Instruct patients to report any of the following symptoms to their health care provider: chest pain, leg pain or swelling, shortness of breath, sudden severe headache, or vision changes.
  • Oral
  • Instruct patients not to exceed 6 tablets in a 24 h period or to take for more than 5 days in a menstrual cycle.
  • Advise patients to contact their health care provider if heavy menstrual bleeding symptoms persist or worsen.

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