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  • CLASSES

    Synthetic Antifibrinolytics

    DEA CLASS

    Rx

    DESCRIPTION

    Oral and injectable antifibrinolytic
    Used for bleeding prophylaxis during tooth extraction in patients with hemophilia and for treatment of cyclic heavy menstrual bleeding
    May increase the risk of thromboembolic events

    COMMON BRAND NAMES

    Cyklokapron, Lysteda

    HOW SUPPLIED

    Cyklokapron/Tranexamic Acid/Tranexamic Acid, Sodium Chloride Intravenous Inj Sol: 1mL, 100mg, 10-0.7%
    Lysteda/Tranexamic Acid Oral Tab: 650mg

    DOSAGE & INDICATIONS

    For the treatment of cyclic menorrhagia (heavy menstrual bleeding).
    NOTE: Before initiating therapy, exclude any endometrial pathology that can be associated with heavy menstrual bleeding.[37613]
    Oral dosage
    Adults

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

    Children and Adolescents 12 to 17 years

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

    For the treatment of symptomatic intracranial bleeding† occurring within 24 hours after administration of IV alteplase for treatment of acute ischemic stroke.
    Intravenous dosage
    Adults

    1,000 mg IV as a single dose. There is potential for benefit in all patients, but particularly when blood products are contraindicated or declined by patient/family or if cryoprecipitate is not available in a timely manner.

    For the treatment of active hemorrhage in trauma patients†.
    For the treatment of active hemorrhage in hospitalized trauma patients†.
    Intravenous
    Adults

    1 g IV over 10 minutes beginning within 3 hours of injury followed by 1 g IV over 8 hours.   

    For the treatment of active hemorrhage in trauma patients in combat or field setting†.
    Intravenous
    Adults

    2 g IV or IO as a single dose as soon as possible and within 3 hours of injury.

    For bleeding prophylaxis, including after ocular trauma (hyphema)†.
    For short-term use to reduce or prevent hemorrhage and reduce the need for replacement therapy during and after tooth extraction in hemophilia A and hemophilia B patients.
    Intravenous dosage
    Adults

    10 mg/kg IV as a single dose immediately before procedure, then 10 mg/kg/dose IV 3 to 4 times daily for 2 to 8 days.[56752]

    Children and Adolescents

    10 mg/kg IV as a single dose immediately before procedure, then 10 mg/kg/dose IV 3 to 4 times daily for 2 to 8 days.[56752]

    For bleeding prophylaxis after ocular trauma (hyphema)†.
    Oral dosage
    Adults

    25 mg/kg/dose PO 3 times daily for 5 to 7 days.

    For intracranial bleeding prophylaxis† after traumatic brain injury.
    Intravenous dosage
    Adults

    1 g IV over 10 to 30 minutes beginning within 8 hours of injury followed by 1 g IV over 8 hours.

    For the treatment of epistaxis†.
    Nasal dosage
    Adults

    Soak gauze or a cotton pledget in the injectable solution (500 mg/5 mL) and place in the affected nostril(s) until bleeding stops.

    Oral dosage
    Adults

    1 to 4.5 g/day PO in 2 to 4 divided doses.

    For angioedema prophylaxis† in patients with hereditary angioedema.
    Oral dosage
    Adults

    0.5 to 3 g/day PO in divided doses for longer-term prophylaxis. Usual dose: 1 g PO twice daily (range: 0.25 to 1.5 g PO twice daily).[34510] [58445] [58446] For perioperative prophylaxis, 1 g PO every 6 hours beginning 48 hours before oropharyngeal or general surgery procedures and continuing for an additional 48 hours.[58444]

    For intracranial rebleeding prophylaxis after recent aneurysmal subarachnoid hemorrhage†.
    Intravenous dosage
    Adults

    1 g IV every 2 hours for 2 doses followed by 1 g IV every 6 hours until early aneurysm occlusion or for up to 72 hours.[58119] Alternately, 1 g IV every 4 hours for 1 week followed by oral therapy for up to 2 additional weeks with treatment discontinued preoperatively or when endovascular therapy begins.[58120] Guidelines recommend short-term (less than 72 hours) tranexamic acid therapy to reduce the risk of early aneurysm rebleeding for patients with unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications.[58117]

    Oral dosage
    Adults

    1.5 g PO every 6 hours for up to 2 weeks after initial first week of IV therapy with treatment discontinued preoperatively or when endovascular therapy begins.[58120] Guidelines recommend short-term (less than 72 hours) tranexamic acid therapy to reduce the risk of early aneurysm rebleeding for patients with unavoidable delay in obliteration of aneurysm, a significant risk of rebleeding, and no compelling medical contraindications.[58117]

    For surgical bleeding prophylaxis† in orthopedic or cardiac surgery†.
    For topical use for surgical bleeding prophylaxis in primary total hip or knee arthroplasty.
    Topical dosage
    Adults

    2 g in 100 mL of 0.9% Sodium Chloride Injection topically into the joint space as bath for 2 minutes after final surgical washout and prior to closure, or alternately, 3 g in 150 mL of 0.9% Sodium Chloride Injection topically as 50 mL gauze soak to acetabulum for 3 minutes after acetabular preparation, 50 mL gauze soak in the femoral canal for 3 minutes after femoral canal broach preparation, and 50 mL injected into the hip joint after fascia closure using a drain and clamped for 30 minutes.

    For intravenous use for surgical bleeding prophylaxis in primary total hip or knee arthroplasty.
    Intravenous dosage
    Adults

    10 or 15 mg/kg IV bolus before start of procedure followed by a second bolus 3 hours later or 1 mg/kg/hour continuous IV infusion until skin closure or for 6 hours after surgery.

    For intravenous use for surgical bleeding prophylaxis in cardiac surgery.
    Intravenous dosage
    Adults

    50 mg/kg or less IV bolus or 10 mg/kg IV followed by 1 mg/kg/hour continuous IV infusion. Guidelines recommend tranexamic acid to reduce blood loss and blood transfusion during cardiac procedures.

    For the treatment of postpartum bleeding†.
    Intravenous dosage
    Adults

    1 g IV as a single dose, initially, within 3 hours of hemorrhage recognition; may give a second dose of 1 g IV if bleeding continues after 30 minutes or stops and restarts within 24 hours of the first dose.

    Adolescents 16 to 17 years

    1 g IV as a single dose, initially, within 3 hours of hemorrhage recognition; may give a second dose of 1 g IV if bleeding continues after 30 minutes or stops and restarts within 24 hours of the first dose.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    3,900 mg/day PO; 40 mg/kg/day IV.

    Geriatric

    3,900 mg/day PO; 40 mg/kg/day IV.

    Adolescents

    3,900 mg/day PO; 40 mg/kg/day IV has been used after tooth extraction in hemophilia patients.

    Children

    12 years: 3,900 mg/day PO; 40 mg/kg/day IV has been used after tooth extraction in hemophilia patients.
    1 to 11 years: Safety and efficacy have not been established for oral dosing; 40 mg/kg/day IV has been used after tooth extraction in hemophilia patients.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Oral tranexamic acid (e.g., Lysteda):
    SCr 1.4 mg/dL or less: No dosage adjustment needed.
    SCr 1.5 to 2.8 mg/dL: 1,300 mg PO twice daily for a maximum of 5 days during menstruation.
    SCr 2.9 to 5.7 mg/dL: 1,300 mg PO once daily for a maximum of 5 days during menstruation.
    SCr more than 5.7 mg/dL: 650 mg PO once daily for a maximum of 5 days during menstruation.[37613]
     
    Intravenous tranexamic acid (e.g., Cyklokapron):
    SCr less than 1.36 mg/dL: No dosage adjustment needed.
    SCr 1.36 to 2.82 mg/dL: 10 mg/kg/dose IV twice daily.
    SCr 2.83 to 5.66 mg/dL: 10 mg/kg/dose IV once daily.
    SCr more than 5.66 mg/dL: 10 mg/kg/dose IV every 48 hours or 5 mg/kg/dose IV every 24 hours.[56752]

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Administer without regard to meals.
    Swallow tablets whole; do not chew or break apart.[37613]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    Tranexamic acid injection is indicated for intravenous use only. Inadvertent intrathecal administration of tranexamic acid injection may result in serious life-threatening injuries. Careful handling of tranexamic acid injection is important to prevent medication errors that could result in serious injury or death. Clearly label syringes containing tranexamic acid with the intravenous route of administration.

    Intravenous Administration

    Administer at a rate not to exceed 100 mg/minute to avoid hypotension.[56752]
    Tranexamic acid may be mixed with most solutions for infusion (e.g., electrolyte, carbohydrate, amino acid, and dextran solutions). Heparin may be added.
    Do not mix with blood or solutions containing penicillin.
    ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 100 mg/mL (undiluted).
    Storage: Diluted admixture may be stored for up to 4 hours at room temperature.[56752]

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in moisture barrier overwrap until time of use
    Cyklokapron:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store diluted product in accordance with package insert instructions
    Lysteda :
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Tranexamic acid is contraindicated in patients with a known hypersensitivity to tranexamic acid or any of the ingredients. Severe allergic reactions have been reported.[37613] [56752]

    Thromboembolic disease, thrombosis

    Injectable tranexamic acid is contraindicated in patients with active intravascular clotting.[56752] Oral tranexamic acid is contraindicated in patients with active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, or cerebral thrombosis), a history of thrombosis or thromboembolism, including retinal vein or artery occlusion, or an intrinsic risk of thrombosis or thromboembolism (e.g., thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy).[37613]

    Intracranial bleeding

    Injectable tranexamic acid is contraindicated in patients with subarachnoid hemorrhage (intracranial bleeding).[56752] Cerebral edema and cerebral infarction may be caused by the use of tranexamic acid in patients with subarachnoid hemorrhage.[37613] [56752]

    Visual disturbance

    Retinal venous and arterial occlusions have been reported in patients receiving tranexamic acid.[37613] [56752] Discontinue tranexamic acid immediately if visual disturbance or ocular symptoms occur and refer the patient to an ophthalmologist for a complete ophthalmological evaluation, including dilated retinal examination.[37613] In patients who are expected to be treated for more than 3 months with intravenous tranexamic acid, consider ophthalmic monitoring, including visual acuity and optical coherence tomography, at regular intervals. Discontinue tranexamic acid if changes in ophthalmological exam occur.[56752] [64570]

    Renal impairment

    Tranexamic acid is substantially excreted by the kidneys, and the risk of adverse reactions may be greater in patients with renal impairment. Reduce the dosage of tranexamic acid in patients with renal insufficiency due to the risk of accumulation.[37613] [56752]

    Seizure disorder, surgery

    Seizures have been reported with tranexamic acid use, particularly in patients receiving tranexamic acid during cardiovascular surgery (which is not FDA-approved and uses doses up to 10-fold higher than the recommended human dose) and in those inadvertently given tranexamic acid into the neuraxial system. Consider dosage reduction during surgery and dose adjustments in patients with renal dysfunction. Closely monitor patients during surgery. Consider EEG monitoring in patients with a history of seizure disorder or who experience myoclonic movements, twitching, or show evidence of focal seizures. Discontinue tranexamic acid if seizures occur.[56752] [64570]

    Driving or operating machinery

    Tranexamic acid may cause dizziness. Concomitant use with other drugs that may also cause dizziness may worsen this effect. Advise patients to avoid driving or operating machinery until they know how the drug affects them.[56752]

    Geriatric

    Use caution in dose selection for the geriatric patient, usually starting at the low end of the dosage range, reflecting the greater frequency of decreased renal function in this population. Because tranexamic acid is substantially excreted by the kidney, risk of toxicity may be greater. It may be useful to monitor renal function. Clinical experience has not identified differences in response to injectable tranexamic acid between geriatric and younger patients; clinical studies did not include sufficient numbers of patients aged 65 years and older.[56752]

    Intrathecal administration

    Tranexamic acid injection is indicated for intravenous use only. Inadvertent intrathecal administration of tranexamic acid injection may result in serious life-threatening injuries, including seizures, cardiac arrhythmias, paraplegia, permanent neurological injury, and death. Careful handling of tranexamic acid injection is important to prevent medication errors that could result in serious injury or death. Clearly label syringes containing tranexamic acid with the intravenous route of administration.

    Pregnancy

    Available data with tranexamic acid use in pregnant women in the second and third trimesters and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Clinical studies in fetuses and infants exposed to tranexamic acid in utero describe fetal and/or neonatal functional issues, such as low Apgar score, neonatal sepsis, cephalohematoma, and alterations to growth, including low birth weight and preterm birth at 22 to 36 weeks of gestation. Also, there are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors, the risk of major birth defects with the use of tranexamic acid during pregnancy is not clear. Consider the potential risk of tranexamic acid administration on the fetus along with the mother's clinical need for tranexamic acid during pregnancy; an accurate risk-benefit evaluation should drive the decision to use tranexamic acid.[56752]

    Breast-feeding

    Tranexamic acid is present in the mother's milk at a concentration about one-hundredth of the corresponding serum concentration. The amount of tranexamic acid a breast-feeding infant would absorb is not known. There are no data available on the effects of tranexamic acid on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tranexamic acid and any potential adverse effects on the breast-fed infant from tranexamic acid or the underlying maternal condition. [56752] An international consensus panel recommends against using tranexamic acid during breast-feeding in patients with hereditary angioedema caused by C1 inhibitor deficiency.[48655]

    ADVERSE REACTIONS

    Severe

    anaphylactoid reactions / Rapid / 0-1.0
    anaphylactic shock / Rapid / 0-1.0
    thrombosis / Delayed / 0-1.0
    thromboembolism / Delayed / 0-1.0
    pulmonary embolism / Delayed / 0-1.0
    retinal thrombosis / Delayed / 0-1.0
    seizures / Delayed / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    migraine / Early / 6.0-6.0
    anemia / Delayed / 5.6-5.6
    dyspnea / Early / 0-1.0
    hypotension / Rapid / Incidence not known
    dyschromatopsia / Delayed / Incidence not known

    Mild

    headache / Early / 50.4-50.4
    back pain / Delayed / 20.7-20.7
    abdominal pain / Early / 19.8-19.8
    musculoskeletal pain / Early / 11.2-11.2
    myalgia / Early / 11.2-11.2
    arthralgia / Delayed / 6.9-6.9
    muscle cramps / Delayed / 6.5-6.5
    fatigue / Early / 5.2-5.2
    flushing / Rapid / 0-1.0
    sinusitis / Delayed / 10.0
    nasal congestion / Early / 10.0
    dizziness / Early / Incidence not known
    nausea / Early / Incidence not known
    vomiting / Early / Incidence not known
    diarrhea / Early / Incidence not known
    rash / Early / Incidence not known

    DRUG INTERACTIONS

    Alteplase: (Contraindicated) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Anti-inhibitor Coagulant Complex: (Major) Use of tranexamic acid within approximately 6 to 12 hours after the administration of anti-inhibitor coagulant complex (human) is not recommended, due to the increased risk of thrombosis.
    Conjugated Estrogens: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Conjugated Estrogens; Bazedoxifene: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Conjugated Estrogens; Medroxyprogesterone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Desogestrel; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Dienogest; Estradiol valerate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Diethylstilbestrol, DES: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Drospirenone; Estetrol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Drospirenone; Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Drospirenone; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Esterified Estrogens: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Esterified Estrogens; Methyltestosterone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol Cypionate; Medroxyprogesterone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol; Levonorgestrel: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol; Norethindrone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol; Norgestimate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estradiol; Progesterone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estrogens: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Estropipate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethinyl Estradiol; Norelgestromin: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethinyl Estradiol; Norethindrone Acetate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethinyl Estradiol; Norgestrel: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Etonogestrel; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Factor IX: (Major) Tranexamic acid should not be administered concomitantly with factor IX complex, Factor IX Fc fusion protein, recombinant, or Factor IX concentrates, due to the increased risk of thrombosis.
    Levonorgestrel; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
    Mestranol; Norethindrone: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Norethindrone; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Norgestimate; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Prothrombin Complex Concentrate, Human: (Major) Tranexamic acid should not be administered concomitantly with factor IX complex, Factor IX Fc fusion protein, recombinant, or Factor IX concentrates, due to the increased risk of thrombosis.
    Relugolix; Estradiol; Norethindrone acetate: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Reteplase, r-PA: (Contraindicated) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Segesterone Acetate; Ethinyl Estradiol: (Contraindicated) Tranexamic acid is contraindicated in women who are using combination hormonal contraception containing an estrogen and a progestin. Use with other estrogens is also not recommended. Estrogens increase the hepatic synthesis of prothrombin and factors VII, VIII, IX, and X and decrease antithrombin III; estrogens also increase norepinephrine-induced platelet aggregability. A positive relationship of estrogens to thromboembolic disease has been demonstrated, and the US FDA has suggested class labeling of combined OCs and non-oral combination contraceptives in accordance with this data. OC products containing >= 50-mcg ethinyl estradiol are associated with the greatest risk of thromboembolic complications. Therefore, do not coadminister estrogens, combined hormonal oral contraceptives, or non-oral combination contraceptives together with tranexamic acid. Tranexamic acid is an antifibrinolytic agent, and concomitant use can further exacerbate the thrombotic risk associated with these estrogen-containing hormonal products; in post-market use of tranexamic acid, cases of thromboembolic events have been reported, with cases occurring in those patients concomitantly receiving combined hormonal contraceptives containing both an estrogen and a progestin.
    Tenecteplase: (Contraindicated) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Thrombolytic Agents: (Contraindicated) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
    Tretinoin, ATRA: (Major) Rare cases of fatal thrombotic complications have been reported in patients treated with systemic all-trans retinoic acid (ATRA) or tretinoin and the use of antifibrinolytic agents, like tranexamic acid. This is thought to be due to the persistent procoagulant tendency often associated with systemic tretinoin therapy.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data with tranexamic acid use in pregnant women in the second and third trimesters and at the time of delivery have not clarified whether there is a drug-associated risk of miscarriage or adverse maternal or fetal outcomes. Tranexamic acid is known to pass the placenta and appears in cord blood at concentrations approximately equal to maternal concentration. Clinical studies in fetuses and infants exposed to tranexamic acid in utero describe fetal and/or neonatal functional issues, such as low Apgar score, neonatal sepsis, cephalohematoma, and alterations to growth, including low birth weight and preterm birth at 22 to 36 weeks of gestation. Also, there are 2 (0.02%) infant cases with structural abnormalities that resulted in death when tranexamic acid was used during conception or the first trimester of pregnancy; however, due to other confounding factors, the risk of major birth defects with the use of tranexamic acid during pregnancy is not clear. Consider the potential risk of tranexamic acid administration on the fetus along with the mother's clinical need for tranexamic acid during pregnancy; an accurate risk-benefit evaluation should drive the decision to use tranexamic acid.[56752]

    Tranexamic acid is present in the mother's milk at a concentration about one-hundredth of the corresponding serum concentration. The amount of tranexamic acid a breast-feeding infant would absorb is not known. There are no data available on the effects of tranexamic acid on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tranexamic acid and any potential adverse effects on the breast-fed infant from tranexamic acid or the underlying maternal condition. [56752] An international consensus panel recommends against using tranexamic acid during breast-feeding in patients with hereditary angioedema caused by C1 inhibitor deficiency.[48655]

    MECHANISM OF ACTION

    Tranexamic acid is a hemostatic agent and is a synthetic derivative of the amino acid lysine. Tranexamic acid binds to the lysine binding site for fibrin on the plasminogen/plasmin molecule. Plasminogen has 4 to 5 binding sites with low affinity for tranexamic acid and 1 high-affinity binding site. The high-affinity binding site is involved with the binding of plasminogen to fibrin. Saturation of this high-affinity binding site by tranexamic acid displaces plasminogen from the surface of fibrin. This prevents the binding of fibrin to plasmin and preserves and stabilizes the matrix structure of fibrin and diminishes the ability of plasmin to lyse fibrin clots. Tranexamic acid is about 10 times more potent in vitro than aminocaproic acid, binding more strongly to both the high and low-affinity binding sites of plasminogen.
     
    Elevated concentrations of endometrial, uterine, and menstrual blood tissue plasminogen activator (tPA) are observed in women with heavy menstrual bleeding compared to women with normal menstrual blood loss. In women with heavy menstrual bleeding and after receiving oral doses of 2 to 3 g/day for 5 days, the effect of tranexamic acid on lowering endometrial tPA concentrations and menstrual fluid fibrinolysis is observed.
     
    At blood concentrations as low as 1 mg/mL, tranexamic acid can prolong the thrombin time. However, at blood concentrations up to 10 mg/mL, tranexamic acid has no effect on platelet count, coagulation time, or various coagulation factors in whole blood or citrated blood in healthy subjects.

    PHARMACOKINETICS

    Tranexamic acid is administered orally and intravenously. Tranexamic acid is minimally bound to plasma proteins (3%) and binds exclusively to plasminogen (no apparent binding to albumin).[37613] [56752] Apparent steady-state Vd is 0.39 L/kg.[37613] Tranexamic acid distributes into various tissues. It diffuses rapidly into joint fluid and the synovial membrane. Concentrations in the joint fluid are similar to those seen in the serum.[56752] It is also distributed in both the cerebrospinal fluid and the aqueous humor of the eye at one-tenth the plasma concentration.[37613] [56752] Only a small amount of tranexamic acid is metabolized. Tranexamic acid is eliminated by urinary excretion primarily via glomerular filtration. Overall clearance is equivalent to plasma clearance (110 to 116 mL/minute) with more than 95% of the dose excreted unchanged.[37613] [56752] The biological half-life of tranexamic acid in synovial fluid is approximately 3 hours.[56752] The elimination half-life of tranexamic acid is approximately 2 hours, and the mean terminal half-life is approximately 11 hours.[37613] Antifibrinolytic concentrations remain in tissues for about 17 hours and in the serum for 7 to 8 hours.[56752]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Oral Route

    Peak plasma concentration is attained approximately 3 hours after a single oral dose. Absolute bioavailability is approximately 45%. Cmax increases approximately 19% after 5 days of multiple doses (13.83 to 16.41 mcg/mL), while AUC remains unchanged (77.96 and 77.67 mcg/mL x hour). Food does not significantly affect absorption. At in vitro concentrations of 25 to 100 micromolar, tranexamic acid reduces the maximal rate of plasmin lysis of fibrin catalyzed by tissue plasminogen activator (tPA) by 20% to 60%. After receiving oral doses of 2 to 3 g/day for 5 days, endometrial tPA concentrations are lowered and menstrual fluid fibrinolysis is observed in women with heavy menstrual bleeding.[37613]

    Intravenous Route

    After an intravenous dose of 10 mg/kg, excretion of tranexamic acid is approximately 90% at 24 hours, with most elimination occurring during the first 10 hours.