Ácido Tranexamico - Acesso 03.05.17 Micromedex

201753 Drug details MICROMEDEX®
TRANEXAMIC ACID
Avaliações do DRUGDEX®
DOSING/ADMINISTRATION
Adult Dosing
Normal Dosage
Intraarticular route
Arthroplasty of knee Postoperative hemorrhage; Prophylaxis
a) Various regimens have been used in clinical trials to decrease the incidence of
bleeding and the need for transfusion during knee arthroplasty:
1.5 g or 3 g diluted in 100 mL NS; apply topically intraarticularly to open joint
surfaces with bulb syringe after all components cemented; keep in contact with
tissues for 5 minutes then suction excess solution prior to closure [51]

1.5 g diluted in 100 mL NS; infuse intraarticularly during closure [52]

Intravenous route
Acute myeloid leukemia Hemorrhage
a) A continuous IV infusion of tranexamic acid (2000 mg in 500 mL of D5W, given
every 8 hours for 6 days) was reported effective in reducing hemorrhagic episodes
and transfusion requirements in 12 patients with acute promyelocytic leukemia in a
small, doubleblind study [102]. The drug was initiated at the same time as the
start of antileukemic therapy and there were no thromboembolic complications.
bleeding and the need for transfusion during total knee arthroplasty:
15 mg/kg IV (max dose, 1.2 g) at the time of anesthesia induction [37]

10 mg/kg IV just before tourniquet deflation and then 3 hours later [53]

15 mg/kg IV just before tourniquet deflation and 10 mg/kg administered 3 to 4
hours later for 2 doses [54]

15 mg/kg IV 30 minutes before surgery then every 8 hours for 3 days [56]

15 mg/kg IV over 30 minutes then 10 mg/kg/hr IV infusion for 12 hours [55]

Operation on heart Postoperative hemorrhage; Prophylaxis
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a) Offlabel Dosage
1) Dosage: Bolus of 10 mg/kg IV followed by 1 mg/kg/hr IV infusion (lowdose)
OR 30 mg/kg IV bolus followed by 16 mg/kg/hr IV infusion (highdose). Bolus
doses were administered 15 minutes after anesthesia induction, and the infusions
were continued until end of surgery; 1 mg/kg was added to the priming solution
prior to cardiopulmonary bypass for the low dose, and 2 mg/kg was added to the
priming solution for the high dose [58].

2) Dosage: Loading dose of 15 mg/kg IV followed by 1 mg/kg/hr IV infusion for 5
[60] or 6 hours [59]

3) Dosage: Preoperative dose of 100 mg/kg IV over 20 minutes with additional 50
mg/kg IV postoperatively [63]

4) Dosage: Single preoperative dose of 10 g IV infused over 20 [62] or 30 minutes
[61]

5) Dosage: A dose of 2.5 g IV prior to skin incision with 2.5 g added to the bypass
priming solution [64]

Postoperative hemorrhage; Prophylaxis Total replacement of hip
a) Dose: 15 mg/kg IV at the time of anesthesia induction was used in a clinical
study [37]
b) Maximum Dose: 1.2 g [37]
Postpartum hemorrhage; Prophylaxis
a) Offlabel Dosage
1) Dosage: 1 g diluted in 20 mL D5W given IV over 5 to 10 minutes (offlabel
dosage) [101]

2) Dosage: 10 mg/kg in 200 mL NS given IV over 10 minutes (offlabel dosage)
[101]

3) Dosage: 10 to 15 mg/kg in 20 mL D5W given IV over 20 minutes (offlabel
dosage) [101]

4) Dosage: 0.5 to 1 g IV 2 to 3 minutes after delivery (offlabel dosage) [101]

5) Timing of administration (cesarean section): Administered 10 to 20 minutes
prior to anesthesia induction, at the time of induction, 20 minutes after induction,
or 10 minutes before skin incision (offlabel dosage) [101]

Oral route
a) Dose: 25 mg/kg orally 2 hours prior to procedure was used in a clinical study
[37]

b) Maximum Dose: 2 g [37]
Menorrhagia
a) The recommended tranexamic acid dose for the treatment of cyclic heavy
menstrual bleeding is 1300 mg 3 times daily (3900 mg/day) for a maximum of 5
days during monthly menstruation [16].
[37]

Traumatic hyphema
a) Doses of tranexamic acid 1 g 3 times daily orally have been effective in reducing
the frequency of secondary hemorrhage following traumatic hyphema [91][89].

Parenteral route
Hemophilia Hemorrhage; Prophylaxis Tooth extraction
a) In hemophilia patients, the recommended dosage is 10 mg/kg tranexamic acid
IV prior to tooth extraction, combined with factor VIII or IX concentrate. Following
surgery, tranexamic acid 10 mg/kg IV 3 to 4 times daily for 2 to 8 days is
recommended. No further therapy with coagulation factor concentrates is generally
required postsurgery [4][6].

Dosage in Renal Failure
For oral administration in renal impairment, the following adjustments should be made [16]:
Serum Creatinine Total Daily
Adjusted Dose
(mg/dL) Dose
1300 mg (two 650mg tablets) twice daily, maximum of
above 1.4 to 2.8 2600 mg
5 days during menstruation
1300 mg (two 650mg tablets) once daily, maximum of
above 2.8 to 5.7 1300 mg
650 mg (one 650mg tablet) once daily, maximum of 5
above 5.7 650 mg
days during menstruation
For IV administration in renal impairment, the following adjustments should be made [4][113]
[114]:
Serum creatinine (mcmol/L) IV dose
120 to 250 (1.36 to 2.83 mg/dL) 10 mg/kg twice daily
250 to 500 (2.83 to 5.66 mg/dL) 10 mg/kg once daily
over 500 (over 5.66 mg/dL) 10 mg/kg every 48 hours or 5 mg/kg every 24 hours
Dosage in Hepatic Insufficiency
A) Dosage adjustment in patients with hepatic impairment is not needed, as only a small
fraction of the drug is metabolized [16].
Pediatric Dosing
Normal Dosage
Intravenous route
a) Offlabel Dosage
1) Dosage (6 months to 12 years): 100 mg/kg IV over 15 minutes followed by a
continuous IV infusion of 10 mg/kg/hour until transport to the ICU [65]

Oral route
Menorrhagia

Oral tranexamic acid (Lysteda(TM)) is not intended for use in premenarcheal girls; it has
not been studied in pediatric patients younger than 12 years with heavy menstrual
bleeding [16].
Adjusted Dose
(mg/dL) Dose
above 1.4 to 2.8 1300 mg (two 650mg tablets) twice daily, maximum of 2600 mg

above 2.8 to 5.7 1300 mg
above 5.7 650 mg
[114]:
[114]:
FDA Uses
FDA Labeled Indication
1) Overview
FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective

Recommendation: Adult, Class IIa

Strength of Evidence: Adult, Category B

See Drug Consult reference: RECOMMENDATION AND EVIDENCE RATINGS

2) Summary:
For shortterm use in hemophilia patients undergoing dental extractions [4]
3) Adult:
a) To prevent hemorrhage and reduce the need for replacement therapy, tranexamic acid is
indicated for shortterm use (2 to 8 days) during and after tooth extractions in hemophilia
patients. IV tranexamic acid, 10 mg/kg as the recommended dosage, is administered with
substitution therapy immediately prior to tooth extraction, followed by 10 mg/kg IV after tooth
extraction 3 to 4 times per day for 2 to 8 days [4].

b) Tranexamic acid has been effective in reducing blood loss and transfusion requirements
when given in conjunction with factor VIII or IX following dental extractions in hemophilia
patients [5][6]. An IV dose of 25 mg/kg tranexamic acid has been recommended prior to
dental extraction (together with factor VIII or IX concentrate), followed by oral doses of 25
mg/kg 3 to 4 times daily for 8 days [6].

c) A combination of desmopressin and tranexamic acid was effective in achieving adequate
hemostasis for tooth extractions in a patient with mild hemophilia [7]. Two hours prior to
surgery, the patient was given desmopressin 0.4 mcg/kg IV followed by tranexamic acid 1 g
IV. Extractions were completed with minimal tissue trauma and the patient as given oral
tranexamic acid 1 g every 6 hours for 7 days postsurgery. There was minimal bleeding and no
tranexamic acid 1 g every 6 hours for 7 days postsurgery. There was minimal bleeding and no
complications occurred.

Menorrhagia
FDA Labeled Indication
1) Overview
FDA Approval: Adult, yes; Pediatric, yes (after menarche)

Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy

Recommendation: Adult, Class IIb; Pediatric, Class IIb

Strength of Evidence: Adult, Category B; Pediatric, Category B


2) Summary:
Tranexamic acid is indicated for the treatment of cyclic heavy menstrual bleeding [16].

Based on a pharmacokinetic study in patients 12 to 16 years old (n=20), dose adjustment is
not needed in the adolescent population [16].

The safety and efficacy of tranexamic acid tablets in the treatment of cyclic heavy menstrual
bleeding was demonstrated in 2 randomized, doubleblind, placebocontrolled studies over 3
cycle treatment (n=294) and 6cycle treatment (n=187) periods [17][18].

Tranexamic acid has been effective in the treatment of menorrhagia, including menorrhagia
secondary to intrauterine devices (IUDs), in several studies (Lakhani, 1998)[19][20].

Four patients with menorrhagia related to von Willebrand disease were successfully treated
with highdose tranexamic acid (Ong, 1998).

3) Adult:
a) The safety and efficacy of tranexamic acid tablets in the treatment of cyclic heavy
menstrual bleeding was demonstrated in 2 randomized, doubleblind, placebocontrolled
studies. The studies involved generally healthy women aged 18 to 49 years (mean 40 years),
who had cyclic menses every 21 to 35 days with an average menstrual blood loss of 80 mL or
greater over 2 baseline menstrual cycles assessed by alkaline hematin analysis of collected
sanitary products. Study 1 (n=294) was a 3cycle treatment comparing the effects of 2 doses
of tranexamic acid (1950 mg and 3900 mg total daily dose) versus placebo, and study 2
(n=187) was a 6cycle treatment duration comparing the effects of tranexamic acid tablets 3
times daily of 1.3 g per dose, (2 tablets, 650 mg each, maximum 3900 mg/day) versus
placebo. In both studies, the doses were given daily for up to 5 days during each menstrual
period. The results of study 1 did not show clinical significance in the 1950mg/day dose.
Mean reduction in menstrual blood loss from baseline (primary endpoint) was 7 mL, 44 mL,
and 65 mL in the placebo, 1950mg, and 3900mg groups, respectively, (p less than 0.001,
3900mg group versus placebo). In study 2, mean reduction in menstrual blood loss from
baseline was 17.8 mL and 66.3 mL in the placebo and 3900mg groups, respectively (p less
than 0.001) [17]. The rates of discontinuation in study 1 were 0.8% in the 3900 mg
tranexamic acid group compared with 1.4% in the placebo group; in study 2, the
discontinuation rates were 2.4% and 4.1%, respectively. The average duration of use was 3.4
days per cycle across the studies. Longterm safety trials of tranexamic acid were also
conducted in openlabel studies, which showed similar results in types and severity of adverse
events, although the percentage of patients reporting them was greater in the 27month
study. There was one case report of severe allergic reaction to tranexamic acid requiring
emergency medical treatment in one of the longterm trials [16].
In Study 2, women with heavy menstrual bleeding treated with tranexamic acid achieved the
prespecified 3part primary efficacy outcome (mean reduction in menstrual blood loss from
baseline with tranexamic acid must be greater than placebo, greater than 50 mL, and greater
than predetermined meaningful threshold of 36 mL or higher). There was significant greater
reduction in menstrual blood loss of 69.6 mL in the tranexamic acid treatment group (n=115)
reduction in menstrual blood loss of 69.6 mL in the tranexamic acid treatment group (n=115)
compared with 12.6 mL in the placebo group (n=72) (40.4% and 8.2%, respectively; p less
than 0.001), a reduction of menstrual blood loss exceeding the prespecified 50 mL (56% and
19%, respectively; p less than 0.001), and a reduction of menstrual blood loss of at least 36
mL, which was considered meaningful to women (69% and 29%, respectively; p less than
0.001). Lysteda(TM) was used in this study and this formulation of tranexamic acid was
generally well tolerated with the frequency of gastrointestinalrelated adverse events similar
between the 2 groups. The most common adverse events reported were menstrual discomfort
or cramps, headache, and back pain. Sinus headache and anemia were reported more
frequently with tranexamic acid than with placebo [17].

b) Tranexamic acid was safe and effectively reduced blood loss during menstrual periods in
women with ovulatory menorrhagia; in contrast, norethisterone (norethindrone) was
associated with increased blood loss, based on a doubleblind, controlled study (n=46).
Ovulatory menorrhagia was defined as menstrual blood loss greater than 80 mL per cycle with
midluteal serum progesterone greater than 9 nanomoles/liter. During the first 2 cycles, study
subjects received placebo and served as their own controls. After those 2 cycles, the cohort
was randomized to 2 cycles of either tranexamic acid (1 g 4 times daily on days 1 to 4; n=25)
or norethisterone (5 mg twice daily on days 19 to 26; n=21). Blood loss was assessed after
each of the 2 cycles. Tranexamic acid was associated with a blood loss reduction of 45% from
mean 175 to 97 mL (p less than 0.0001). Norethisterone was associated with a 20% increase
in blood loss from mean 173 to 208 mL (p=0.26). Fourteen women (56%) in the tranexamic
acid group achieved a menstrual loss of less than 80 mL of blood per cycle, compared with 2
(9.5%) who reached that level in the norethisterone group. No serious side effects were
reported for either drug [21].

c) Four patients with menorrhagia related to von Willebrand disease were successfully treated
with highdose tranexamic acid. Patients reported reduced fatigue, likely related to resolution
of iron deficiency. No adverse effects were reported. Prior trials of oral contraceptives, blood
products, and lowdose tranexamic acid had failed to control excessive bleeding in any patient.
Single daily doses of tranexamic acid 4 g, administered on days 1 to 3 of the menstrual cycle,
was the regimen used in 2 patients. A third received 4 g on days 1 through 5, and a fourth
received a single dose only (Ong, 1998).
d) A significant reduction in mean menstrual blood loss was reported with oral tranexamic acid
in women with an intrauterine device and exhibiting heavy menstrual bleeding (greater than
70 mL) was reported. Tranexamic acid 1.5 g 3 times daily for 5 days reduced mean menstrual
blood flow by 54% as compared with placebo. In this study, tranexamic acid was compared
with diclofenac sodium (50 mg 3 times per day for the first day of each cycle followed by 25
mg 3 times per day for 4 days). Diclofenac was less effective than tranexamic acid, reducing
menstrual blood loss by 20%; however, side effects were greater with tranexamic acid [19].

e) Tranexamic acid 6 g daily reduced the incidence of uterine blood loss following insertion of
a copperreleasing intrauterine device from 83% to 11% [22].
4) Pediatric:
a) In a randomized, crossover study in pediatric patients (12 to 16 years old; n=20) with
heavy menstrual bleeding, the Cmax and AUC values after a single tranexamic acid 1300mg
dose were 20% to 25% less than the Cmax and AUC values of adults given a single 1300mg
dose in another study [16].

NonFDA Uses
Abruptio placentae
1) Overview
FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category C


2) Summary:
Reduced perinatal mortality in small study
3) Adult:
a) A retrospective review of medical records of pregnant women with various bleeding
disorders failed to demonstrate a relationship between the administration of tranexamic acid
and an increased risk of thromboembolism. Data from 2102 case records involving abruptio
placenta, placenta previa and unspecified antepartum hemorrhage revealed that 256 patients
had received tranexamic acid until delivery, for an average duration of 46 days. Of these 256
patients, 169 were delivered by cesarean section. Pulmonary embolism occurred in 2 patients,
1 of which was delivered by cesarean section. The odds ratio for developing a thromboembolic
event during tranexamic acid therapy in the highrisk pregnant patient delivered by cesarean
section was 0.65 (95% CI, 0.1 to 5.8) (Lindoff, 1993).

b) Placental abruption is primarily characterized by activation of the fibrinolytic system [40].
Bleeding secondary to placental abruption is associated with a 3 to 4fold increase in perinatal
mortality [6]. Tranexamic acid reduced perinatal mortality in cases of abruptio placentae [6]
[40][41].

c) Tranexamic acid 1 g was administered IV just prior to delivery by cesarean section in 67
women with a diagnosis of abruptio placentae. In 6 other women who were in the early stage
of pregnancy with less pronounced symptoms, the drug was given orally in doses of 1 g 4
times daily, continuing until delivery (also by cesarean section). Perinatal mortality for the
entire group was 8%, with only minimal maternal mortality. No case was complicated by a
hemorrhagic diathesis or thrombosis [40].
1) Overview

Efficacy: Adult, Evidence favors efficacy

Recommendation: Adult, Class IIb



2) Summary:
Limited data indicate reduction in hemorrhage and transfusion requirements
3) Adult:
a) A continuous IV infusion of tranexamic acid (2000 mg in 500 mL of D5W, given every 8
hours for 6 days) was effective in reducing hemorrhagic episodes and transfusion
requirements in 12 patients with acute promyelocytic leukemia in a small, doubleblind study
[102]. The drug was initiated at the same time as the start of antileukemic therapy and there
were no thromboembolic complications.

Alpha2antiplasmin deficiency
1) Overview





2) Summary:
Useful for surgical prophylaxis
3) Adult:
a) Two patients with congenital alpha2plasmin inhibitor deficiency underwent successful
surgery for intramedullary multiple hematomas of the long bones with the IV administration of
tranexamic acid. In one patient, tranexamic acid was infused at 10 mg/kg/hr during surgery,
followed by 2 g/day for the next 2 weeks, and finally decreased to 1 g/day given orally on an
intermittent basis. The other patient was treated with topical tranexamic acid combined with
fibrin glue applied to the bone lesion, followed by IV (or oral) administration of tranexamic
acid 40 mg/kg/day. Use of tranexamic acid prior to surgery was of no benefit, thus the surgery
became necessary. Further study of surgical prophylaxis in this setting is needed, but the
congenital condition is very rare [42].

Angioedema
1) Overview





2) Summary:
Has reduced frequency of attacks in patients with nonhereditary and hereditary angioneurotic
edema

3) Adult:
a) In a controlled crossover study, oral tranexamic acid 1.5 g 3 times daily for 3 months was
beneficial in the treatment of nonhereditary angioedema. Nine of 10 patients became
symptomfree or substantially improved with tranexamic acid therapy. At a 4year followup, 8
of the 9 responders were contacted and indicated that 6 were still taking the drug in doses
from 1 to 4.5 g daily which was still necessary to prevent relapse. Two patients stopped
tranexamic acid, one due to the infrequency of attacks (1 to 2 yearly) and one had no further
attacks. In cases of nonhereditary angioedema, tranexamic acid should be initiated in doses of
3 to 4.5 g daily in 3 to 4 divided doses, with meals, and continued for a period long enough
for at least 3 to 4 attacks to have normally occurred [43].

b) Tranexamic acid therapy (1 g every 6 hours for 48 hours prior to surgery and for 48 hours
postoperatively) was effective for enabling patients with angioneurotic edema to undergo
dental and surgical procedures [44].

c) Tranexamic acid 1 g 3 times daily was effective in treating 7 of 18 patients with hereditary
angioneurotic edema [45]. Four patients had less severe attacks and one patient showed no
improvement; 6 others did not complete both drugs and placebo studies in this report.

d) Hereditary angioneurotic edema has also been successfully treated with tranexamic acid in
other studies [46][47][48][45].

1) Overview





2) Summary:
Evidence
A metaanalysis of 33 randomized trials found that tranexamic acid administered IV, orally,
topically, or intraarticularly significantly reduced total blood loss and reduced the need for
blood transfusions by 85% in patients undergoing total hip or knee arthroplasty, without
increasing the risk of postoperative DVT. However, important differences between the studies
included in the analysis may affect the validity of some of the reported findings [38].

Both oral [37] and intraarticular [52] administration have been associated with significantly
less blood loss and lower transfusion rates compared with IV administration [37][52].

3) Adult:
a) Oral vs IV Administration
1) In a retrospective study of patients undergoing knee or hip replacement surgery
(N=3000), the odds of receiving a transfusion were 52% lower in patients who received oral
tranexamic acid compared with IV tranexamic acid. Patients received tranexamic acid 15
mg/kg IV (max dose, 1.2 g) at the time of anesthesia induction (n=2698), or oral tranexamic
acid 25 mg/kg (max dose, 2 g) 2 hours prior to the procedure (n=302). Transfusion was
required in 7.9% of those who received IV tranexamic acid and in 4.6% who received oral
tranexamic acid. There were no differences between groups in readmission rates for up to 30
days or in rates of postoperative DVT or pulmonary embolism for up to 60 days [37].

b) Intraarticular vs IV Administration
1) Intraarticular tranexamic acid administration to patients undergoing knee arthroplasty was
associated with less blood loss and fewer blood transfusions compared with IV administration
in a randomized trial (N=150). Patients received tranexamic acid 1.5 g in 100 mL NS intra
articularly during closure suturing, tranexamic acid 1.5 g IV after closure, or placebo. There
was a significant difference in mean blood loss between the groups (intraarticular, 426 mL;
IV, 528 mL; placebo, 833 mL), and transfusion rates were 20% for the intraarticular group,
34% for the IV group, and 94% for the placebo group [52].

Colitis Hemorrhage; Prophylaxis
1) Overview





2) Summary:
Reduction in bleeding reported with tranexamic acid administered orally or rectally
3) Adult:
a) A significant reduction in rectal bleeding was reported following tranexamic acid 1.5 g orally
3 times daily for 3 weeks in a placebocontrolled, crossover study of 12 patients with leftsided
proctocolitis [74]. Rectal bleeding was reduced in 50% of patients with minimal toxicity and
improvement of the rectal mucosa was demonstrated through sigmoidoscopic grading.

b) A tranexamic acid enema (5 g dissolved in 100 mL of warm water administered twice daily
for 6 months) was beneficial in a study involving five patients with ulcerative colitis. In 4 of the
patients with elevated mucosal fibrinolysis, complete remission was observed in 2 with
tranexamic acid enemas alone; one remission was achieved with combination oral
prednisolone therapy. In the fourth patient with slightly elevated mucosal fibrinolysis, clinical
improvement was observed without radiological changes. In one patient with normal tissue
fibrinolysis, no response was seen with tranexamic acid. Successful treatment of a case of 9/77
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fibrinolysis, no response was seen with tranexamic acid. Successful treatment of a case of
penicillininduced pseudomembranous colitis with tranexamic acid was also reported [75].

Craniosynostosis syndrome Hemorrhage, Perioperative; Prophylaxis Surgical
procedure
1) Overview

Efficacy: Pediatric, Evidence favors efficacy

Recommendation: Pediatric, Class IIb

Strength of Evidence: Pediatric, Category B


2) Summary:
In 2 doubleblind, placebocontrolled trials (n=43, n=39) in children undergoing
craniosynostosis surgery, compared with tranexamic acid significantly reduced transfusion
requirements [2],[3], and reduced blood loss [2].
3) Pediatric:
a) In a doubleblind, placebocontrolled trial (n=43) tranexamic acid significantly reduced
perioperative blood loss and transfusion requirements in children undergoing craniosynostosis
surgery. Patients who were 2 months to 6 years old were randomly assigned to receive either
tranexamic acid IV 50 mg/kg over 15 minutes as a loading dose followed by 5 mg/kg/hr of IV
infusion or placebo (1:1 ratio). The patients were mostly Caucasian (79%) and male (60%).
The primary endpoint of perioperative blood loss for patients receiving tranexamic acid
compared with placebo was 65 +/ 26 mL/kg and 119 +/ 67 mL/kg, respectively (p less than
0.001). The mean total packed erythrocyte volume transfusion in the tranexamic acid group
compared with placebo was 33 +/ 13 mL/kg and 56 +/ 35 mL/kg, respectively (p=0.006).
Patients in both groups did not report any thromboembolic or neurologic complications [2].

b) In a randomized doubleblind, placebocontrolled study (n=39) tranexamic acid was
effective in reducing transfusion requirements in children undergoing craniosynostosis surgery
who were pretreated with erythropoietin and elemental iron supplementation. Patients
received either an IV loading dose of 15 mg/kg over 15 minutes, followed by 10 mg/kg/hr IV
infusion of tranexamic acid or placebo until skin closure. The median age and male/female
ratio of the studied population was 7 and 6 years old, and 17:2 and 17:3 in the tranexamic
acid group and placebo, respectively. In the tranexamic acid and placebo groups 7 of 19
children and 14 of 20 children, respectively, received blood transfusions. The mean total
packed erythrocyte volume transfusion was 7.2 +/ 10.8 mL/kg and 16.6 +/ 13.5 mL/kg in
the tranexamic acid group compared with the placebo group (p=0.03). The amount of blood
loss between the 2 groups was not significantly different. No patient in the study reported any
adverse effects [3].

Cystic fibrosis Hemoptysis, Recurrence; Prophylaxis
1) Overview

Efficacy: Pediatric, Evidence is inconclusive

Recommendation: Pediatric, Class III

Strength of Evidence: Pediatric, Category C


2) Summary:
Limited data available

Useful adjunct to bronchial artery embolization, but may not control hemoptysis indefinitely 10/77
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Useful adjunct to bronchial artery embolization, but may not control hemoptysis indefinitely

3) Pediatric:
a) Tranexamic acid was a useful adjunct to bronchial artery embolization (BAE) in preventing
the recurrence of hemoptysis in an 8yearold girl with cystic fibrosis. Following 2 BAEs within
2 weeks on the larger bronchial artery which did not completely stop bleeding, therapy was
initiated with IV tranexamic acid 60 mg/kg/day in 4 divided doses. After the bleeding stopped
within 1 day, the patient was changed to oral tranexamic acid 500 mg 4 times a day (90
mg/kg/day). When tapering of the dose was attempted, hemoptysis recurred 1 month after
tranexamic acid was stopped, necessitating a third BAE. Afterward, the patient resumed
therapy with tranexamic acid 500 mg 3 times a day and, over 3 years of followup, the
tranexamic acid has been welltolerated and 2 attempts to stop or even reduce the dosage
resulted in recurrence of hemoptysis [77].

b) Only temporary control of hemoptysis was achieved after bronchial artery embolization of
multiple arteries in a 13yearold boy with tranexamic acid 500 mg 3 times a day. The boy's
hemoptysis stopped 2 days after beginning tranexamic acid therapy and was temporarily
controlled with the same dosage. After 5 months, however, hemoptysis recurred and a right
upper lobectomy was necessary [78].

Dental procedure, In patients on anticoagulant therapy Postoperative hemorrhage;
Prophylaxis
1) Overview





2) Summary:
Mixed results reported for tranexamic mouthwash for the prevention of bleeding after oral
surgery in patients on anticoagulant therapy [49][50]

3) Adult:
a) Tranexamic acid mouthwash provided no additional benefit to resorbable gelatin sponge
and sutures used for dental extractions in patients receiving coumarin products. One hundred
and fifty patients receiving coumarin received 1 of 3 different hemostatic modalities to prevent
postoperative bleeding after extraction. Patients presenting on day 1 (n=50) received
resorbable gelatin sponge and multiple sutures. Patients on day 2 (n=50) received gelatin
sponge, multiple sutures, and mouthwash with tranexamic acid 500 mg for 2 minutes and 4
times daily for 4 days. Patients on day 3 (n=50) received fibrin glue, resorbable gelatin
sponge, and multiple sutures. On the day of the procedure, patients had an INR of 1.5 to 4.
Postoperative bleeding occurred in 3 patients in the day 1 group, in 6 patients in the day 2
group, and in 4 patients in the day 3 group. The difference was not significant. The authors
conclude that local hemostasis with resorbable gelatin sponges and sutures are sufficient after
meticulous curettage of the extraction site [49].

b) In a randomized, doubleblind, placebocontrolled trial the administration of tranexamic
mouthwash was associated with a significantly lower rate of postoperative bleeding compared
with placebo in 93 anticoagulated patients undergoing dental surgery. Ten patients in the
control group, but none in the tranexamic acid group, developed bleeding episodes requiring
treatment with tranexamic mouthwashes and soaked gauze pads (n=3), tranexamic soaks
plus a topical hemostatic and sutures (n=6), or additionally, vitamin K 5 mg (n=1) (p greater
than 0.05). Coagulation studies verified that all patients were within the therapeutic range
preoperatively. Prior to suturing, the surgically treated area was irrigated with 10 mL
tranexamic acid solution 4.8% or placebo. Following surgery, patients were instructed to use
the solution as a mouthwash every 6 hours for the next 7 days. There were no differences in
treatment groups regarding the number of surgically treated or extracted teeth or the
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treatment groups regarding the number of surgically treated or extracted teeth or the
therapeutic range of coagulation studies at which surgery was performed. Treatment with
tranexamic mouthwash was well tolerated (Ramstrom, 1993).

c) Tranexamic acid mouthwash 4.8% was effective in preventing bleeding following oral
surgery in patients receiving anticoagulants for cardiac valvular stenosis, prosthetic cardiac
valves or vascular prosthesis. Patients were given either placebo or tranexamic acid
mouthwash in a randomized fashion. Prior to application of sutures, the operative field was
irrigated with 10 mL of mouthwash or placebo. Surgery was followed by a 7day course of
mouth rinsing with 10 mL of the assigned solution (2 minutes, 4 times daily). Bleeding which
required therapy occurred in 1 of 20 tranexamic acidtreated patients, as compared with 8 of
20 patients (10 occasions) receiving placebo. No systemic adverse effects were observed [50].

Dental surgical procedure Hemophilia Hemorrhage
1) Overview


Recommendation: Adult, Class IIa



2) Summary:
Tranexamic acid mouthwash preferred over systemic therapy for control of bleeding
3) Adult:
a) Local tranexamic acid therapy (a mouth rinse of 10 mL of a 5% solution, for 2 minutes 4
times daily) was effective in the treatment of spontaneous gingival bleeding or bleeding
following subgingival scaling in hemophiliac patient [79]. In this study, local therapy was
superior to systemic therapy in controlling bleeding. Local antifibrinolytic therapy should be
included in the treatment of gingival hemorrhage in hemophiliac patients.

Dysfunctional uterine bleeding
1) Overview





2) Summary:
The effects of tranexamic acid on uterine vascular resistance and menstrual blood loss were
mixed in a longitudinal, prospective study of women with menorrhagia caused by
dysfunctional uterine bleeding (n=24) and uterine fibroids (n=12) (Lakhani, 1998).
Tranexamic acid significantly reduced menstrual blood loss and endometrial fibrinolytic enzyme
levels as compared with baseline in 15 women with dysfunctional uterine bleeding (Gleeson,
1994).
3) Adult:
a) The effects of tranexamic acid on uterine vascular resistance and menstrual blood loss were
mixed in a longitudinal, prospective study of women with menorrhagia caused by
dysfunctional uterine bleeding (n=24) and uterine fibroids (n=12). Pulsatility index (PI) and
resistance index (RI), measures of uterine vascular resistance, were significantly reduced in
patients with dysfunctional uterine bleeding, but unchanged in those with uterine fibroids.
Similarly, menstrual blood loss was reduced by 30% in patients with dysfunctional uterine
bleeding (p=0.0001), but only minimally decreased in women with uterine fibroids. All patients
bleeding (p=0.0001), but only minimally decreased in women with uterine fibroids. All patients
received tranexamic acid 1 g 3 times daily during menstruation for 2 menstrual cycles. The
authors suggest that decreases in uterine resistance due to tranexamic acid are likely
incidental to its effect of reducing menstrual blood loss, as decreases in vascular resistance
should enhance blood flow. The results observed in women with fibroids may be due to a
lesser effect in this population, or may be the result of an inadequate sample size (Lakhani,
1998).

b) Tranexamic acid significantly reduced menstrual blood loss and endometrial fibrinolytic
enzyme levels as compared with baseline in 15 women with dysfunctional uterine bleeding.
Menstrual blood loss was decreased from a median of 145 mL in untreated cycles to 61 mL
during cycles treated with tranexamic acid (p less than 0.05). Endometrial biopsies before and
after treatment revealed reductions in tissue plasminogen activator activity as well as tissue
plasminogen activator antigen levels (p less than 0.001). Patients received tranexamic acid
500 mg every 6 hours for the first 5 days of menstruation. Nausea and leg cramps occurred
more frequently in patients taking tranexamic acid. No thrombotic complications were
observed (Gleeson, 1994).

Epistaxis
1) Overview





2) Summary:
Oral doses of 1.5 g 3 times per day effective for treatment of recurrent epistaxis in a
controlled study (Petruson, 1974)

Has been used in the treatment of hereditary hemorrhagic telangiectasia

Extracorporeal membrane oxygenation Hemorrhage; Prophylaxis
1) Overview





2) Summary:
Reduced bleeding and transfusion requirements in patients requiring extracorporeal membrane
oxygenation
3) Pediatric:
a) Tranexamic acid was used to reduce bleeding during congenital diaphragmatic hernia
(CDH) repairs in which extracorporeal membrane oxygenation (ECMO) was necessary. The
study was unblinded and used historical controls, comparing 9 patients who underwent CDH
repair without tranexamic acid to 10 who received tranexamic acid during their CDH repairs.
The repair was performed in all study patients during ECMO and, with the exception of the
addition of tranexamic acid, the ECMO protocol did not differ between groups. The first 2
patients experienced severe thrombotic complications and the tranexamic acid dosage was
reduced. The recommended duration of the postoperative infusion was also reduced from that
reduced. The recommended duration of the postoperative infusion was also reduced from that
used in the study. The authors' final determination was that the appropriate dosage and
administration for the tranexamic acid was a 4mg/kg IV bolus 30 minutes prior to CDH repair
followed by a continuous IV infusion of 1 mg/kg/hour over 24 hours postoperatively. The
tranexamic acidtreated patients experienced significantly less bleeding than their historical
counterparts (57 mL vs 390 mL, respectively) and had significantly lower transfusion
requirements (1.13 mL/kg/hour vs 2.95 mL/kg/hour, respectively) [76].

Gastrointestinal hemorrhage
1) Overview





2) Summary:
Reduced transfusion requirements and/or mortality in patients with upper gastrointestinal
hemorrhage
3) Adult:
a) Chronic, severe rectal bleeding due to colonic angiodysplasias was resolved after treatment
with tranexamic acid in a 58yearold man with ESRD. Prior to hospital admission for
symptoms of hematochezia and melena, the patient experienced occasional painless episodes
of bloodtinged stools over a 6month period. Transfusions of packed RBCs were required for
the next 7 months. Following that time, a massive rectal hemorrhage resulted in
hospitalization. Mesenteric angiography revealed multiple, patchy sites of bleeding,
characteristic of angiodysplasia. As estrogen treatment was refused by the patient, a trial of
tranexamic acid was initiated at 20 mg/kg every 48 hours. The bleeding resolved in 24 hours
and stool tests were negative at 48 hours. Therapy was continued for 4 weeks, and then
tapered to 10 mg/kg every 48 hours for an additional month. No bleeding was observed
during the treatment period. Two months following the discontinuation of tranexamic acid,
massive rectal bleeding recurred. Tranexamic acid was reinstituted at 10 mg/kg every 48
hours and continued for 2 months. The rectal bleeding ceased with 24 hours and did not
reappear, despite later discontinuance of therapy. No complications related to tranexamic acid
were observed. Recurrence of the bleeding upon discontinuation of tranexamic acid supports
its efficacy in the treatment of angiodysplastic lesions [8].

b) Resolution of severe gastrointestinal (GI) bleeding due to cirrhosis and gastric antral
vascular ectasia is reported following the initiation of tranexamic acid therapy in a 66yearold
woman. Symptomatic iron deficiency anemia (Hb 4.7 g/L) resulted in multiple hospital
admissions for transfusion over a 3year period. The GI bleeding was resistant to multiple
interventions, including omeprazole, sucralfate, betablockers, and transjugular intrahepatic
portosystemic shunting. Tranexamic acid was administered in a dosage of 500 mg 3 times
daily for 2 months, and then increased to 1 g 3 times daily. Hb values have since remained
stable and no further blood transfusions have been required for more than 18 months
(McCormick, 1998).

c) Based upon a review of 5 controlled studies, one author indicated that tranexamic acid is
effective in lowering mortality in patients with acute upper gastrointestinal bleeding and
recommends use of the drug in this clinical setting [9].

d) Tranexamic acid has been effective in reducing blood transfusion requirements in patients
with gastric and duodenal bleeding secondary to verifiable benign lesions [10]. The drug was
also effective in reducing the need for emergency surgery, as compared with placebo.
Although the incidence of rebleeding was also reduced with tranexamic acid, this was not
statistically significant as compared with placebo. Tranexamic acid was IV administered in
doses of 1 g every 4 hours for 3 days, followed by 1.5 g orally every 6 hours for 3 further
days. Three of 72 tranexamic acidtreated patients developed complications (phlebitis at the
injection site in 2; uncomplicated DVT in 1) and no patients receiving placebo developed
injection site in 2; uncomplicated DVT in 1) and no patients receiving placebo developed
complications.

e) Plasminogen activator is present in high amounts in the gastric wall and free plasmin is
found more often in gastric venous blood in peptic ulcer patients than in control patients
undergoing laparotomy and these findings have led to the use of tranexamic acid in the
treatment of upper gastrointestinal hemorrhage [6]. Several controlled studies have
demonstrated benefits of the drug in reducing transfusion requirements in upper
gastrointestinal hemorrhage, most often related to gastritis and erosive gastroduodenitis [11]
[12][13][14].

f) Tranexamic acid reduced the mortality rate in patients with upper gastrointestinal (GI) tract
bleeding in a controlled study comparing the drug with cimetidine and placebo. This study
involved 775 patients with a primary diagnosis of hematemesis and/or melena. Tranexamic
acid was IV administered in doses of 1 g every 6 hours for 48 hours and then 1 g orally every
6 hours; therapy was continued for 7 days or until discharge, withdrawal from the trial,
surgery or mortality. Cimetidine was given IV in doses of 400 mg every 6 hours for 48 hours
then 400 mg by mouth every 6 hours for five days. The mortality rate was reduced by 7.2%
with tranexamic acid and by 5.7% with cimetidine when compared with placebotreated
patients; however, neither tranexamic acid or cimetidine affected rebleeding or operation
rates. Exclusion of the results of 99 patients who withdrew from the study for various causes
shifted the mortality difference between tranexamic acid and placebo to 6.9%, while
significantly decreasing the difference between cimetidine and placebo (2.7%). It was
concluded that tranexamic acid should be indicated in elderly patients (older than 60 years)
for the treatment of upper gastrointestinal tract bleeding, since the highest risk of death
occurs in these patients. It is also suggested that mortality be used as the main endpoint in
future studies evaluating treatments for upper GI tract bleeding since tranexamic acid did
have an effect on mortality even though it did not reduce rebleeding rates and severity [11].

Hemodialysis Hemorrhage; Prophylaxis
1) Overview





2) Summary:
Decreases bleeding time in hemodialysis patients

Increases ultrafiltration volume in continuous ambulatory peritoneal dialysis patients

3) Adult:
a) A 65yearold hemodialysis patient with intracranial bleeding benefited from tranexamic
acid treatment. On admission, the man complained of severe headache, fatigue, nausea, and
vomiting. Computed tomography showed regions of hypodense/hyperdense subdural fluid
collections. Conservative measures were followed until day12 when he became somnolent
and a burr hole excavation of the hematoma was performed. Unfortunately, reconstitution of
the blood collection occurred within a few days and the patient deteriorated. A new computed
tomography scan showed a large intracerebral parietooccipital hemorrhage in addition to the
frontoparietal subdural hematoma. Tranexamic acid 20 mg/kg/48 hours IV was initiated. After
4 days of therapy, the patient was completely alert with only a mild leftsided hemiparesis.
The continuous bleeding into the subdural space had stopped and a rapid resolution of the
subdural and intracerebral hematomas occurred. After 4 weeks of therapy, the tranexamic
acid was changed to 10 mg/kg/48 hours orally for an additional 4 weeks. Repeat computed
tomography showed no neurological deficits [71].

b) Tranexamic acid may be a useful agent for increasing ultrafiltration volume in patients
receiving continuous ambulatory peritoneal dialysis (CAPD). CAPD patients with (n=5) or
without (n=10) ultrafiltration loss received tranexamic acid 250 mg orally after breakfast for 2
weeks. In those patients with ultrafiltration loss, tranexamic acid therapy increased
ultrafiltration volume nearly 2fold (p less than 0.01). In those without ultrafiltration loss,
ultrafiltration volume increased in 7 out of 10 patients. Tranexamic acid also produced a
significant increase in peritoneal clearance of urea and creatinine. The authors suggest that
tranexamic acid could prevent the need for hypertonic dialysate and thus may be beneficial to
CAPD patients [72].

c) Tranexamic acid shortened bleeding time and improved platelet function in patients with
advanced chronic renal failure (CRF). Before initiating hemodialysis, patients with advanced
CRF (n=37) received tranexamic acid 20 to 25 mg/kg daily for 6 days. Dalteparin 2500 units
subQ on days 1, 3, and 5 was also given to 24 of the patients. Combination therapy shortened
bleeding time in 71% of patients. Nine patients actually normalized bleeding time. Tranexamic
acid alone shortened bleeding time in 62% of patients with values normalized in 6 patients.
Tranexamic acid therapy alone was not significantly different from combined therapy. In both
groups, reduction of bleeding time was associated with improvement of platelet aggregation
and secretion, substantial decrease in circulating plasminogen, and increase in plasmin
antiplasmin complexes. Treatment did not significantly reduce indices of activation of
coagulation [73].

Hemophilia Hemorrhage, Spontaneous; Prophylaxis
1) Overview





2) Summary:
Limited, conflicting data

Possible prophylactic benefits

3) Adult:
a) Some data suggest the benefits of tranexamic acid therapy for prevention of spontaneous
bleeding episodes in hemophiliac patients. Tranexamic acid 3 g daily reduced the incidence of
spontaneous bleeding episodes in one study [80], but another controlled study failed to show
any benefits of the drug [81]. More wellcontrolled studies are needed to determine the
usefulness of the drug in hemophilia for prevention of spontaneous bleeding episodes.

Hemorrhage Malignant mesothelioma
1) Overview





2) Summary:
Shortterm therapy controlled bleeding in 2 patients

3) Adult:
a) Two patients with malignant mesothelioma (not associated with asbestos exposure) with
bleeding pleural effusions were successfully treated with oral tranexamic acid 1 g 4 times daily
in addition to 2 daily doses of tranexamic acid 5 g given intrapleurally [87]. Shortterm
management effectively controlled bleeding and transfusion requirements were reduced;
however both patients eventually died without autopsy followup.
Hemorrhage Neoplastic disease
1) Overview





2) Summary:
Suppressed capillary ooze associated with cancerous tumors in a small study
3) Adult:
a) In a 16patient pilot study, 2 antifibrinolytic agents, tranexamic acid and aminocaproic acid,
were useful in palliative care for the suppression of tumorassociated hemorrhage. Eight
patients received initial oral doses of tranexamic acid 1.5 g followed by 1 g 3 times a day and
6 received initial oral doses of aminocaproic acid 5 g followed by 1 g 4 times a day. Two
tranexamic acidtreated patients did not want further oral therapy and instead received topical
tranexamic acid solutions, one for application to a skin wound and the other for use as a
bladder instillation. Bleeding improved in 15 patients and completely ceased in 14. The
average time to improvement was 2 days and 4 days was the average time for cessation of
bleeding. Patients were advised empirically to continue therapy for 7 days after cessation of
bleeding and could continue antifibrinolytic therapy after that as they wished. None of the
patients were being treated for major vessel bleeding; most had low pressure capillary ooze
[57].

Intracranial hemorrhage Traumatic brain injury
1) Overview





2) Summary:
Evidence
Tranexamic acid significantly reduced the risk of progression of intracranial hemorrhage by
24% compared with placebo (pooled analysis; N=510), in a metaanalysis of 2 highquality
randomized trials in patients with or at risk of traumatic brain injury. There was a trend toward
decreased mortality that was not significant (risk reduction, 36%). Outcomes could not be
assessed in patients with isolated head injury due to a small number of such patients in the
included studies, and almost all patients in 1 study had significant extracranial injuries. No
adverse events related to tranexamic acid were reported [1].

KasabachMerritt syndrome
1) Overview



Strength of Evidence: Pediatric, Category C


2) Summary:
Case report indicates usefulness as secondline medication
3) Pediatric:
a) Tranexamic acid in doses of 20 to 25 mg/kg/day orally (in combination with highdose
prednisone) was effective in treating KasabachMerritt syndrome in 1 infant [82]. Tranexamic
acid therapy improved the hematological and clinical status of the patient, as well as enabling
earlier tapering of prednisone therapy and fewer transfusions. Tranexamic acid should be
considered as secondline medication in severe KasabachMerritt syndrome in the newborn.

KlippelTrenaunayWeber syndrome
1) Overview





2) Summary:
Effective in 1 case report
3) Adult:
a) A 39yearold man with KlippelTrenaunayWeber syndrome had his intestinal variceal
bleeding controlled by tranexamic acid. Manifestations of this congenital disorder include
vascular nevus formation, deep venous thrombosis, varicosities, and hypertrophy of the
affected tissues. This patient had thrombosis of his splanchnic circulation and presented with
lifethreatening hemorrhage from rectosigmoid varices. The bleeding did not respond to blood
transfusions, cryoprecipitate, fresh frozen plasma, vitamin K, propranolol, or somatostatin.
Tranexamic acid 2 g daily was initiated and then increased to 2 g every 12 hours. His
hematochezia stopped. For home IV therapy, an implantable venous access port was initiated
through the right internal jugular vein. Abnormal bleeding continued and tranexamic acid was
increased to 2 g every 8 hours. This therapy was maintained for 6 months until his death from
a massive variceal bleed [83].

Operation on cervix Postoperative hemorrhage; Prophylaxis
1) Overview





2) Summary:
Reduced postoperative hemorrhage
3) Adult:
a) Tranexamic acid (1.5 g daily for at least 12 days postoperatively) has been effective in
reducing blood loss following cervical conization [68][69]. Tranexamic acid (1 g IV during
surgery followed by 1 g orally 3 times daily for 2 weeks postoperatively) was effective in
reducing postoperative hemorrhage in patients undergoing laser conization or miniconization
of the cervix [70]. In 68 patients administered tranexamic acid, no postoperative hemorrhage
was observed, compared with hemorrhage occurring in 8 of 72 laser conizations (11%) in
untreated patients. The frequency of postoperative hemorrhage following laser miniconization
was also significantly decreased, from 9.1% in 110 patients not receiving tranexamic acid to
5.5% in 110 tranexamic acidtreated patients.

1) Overview


Recommendation: Adult, Class IIb; Pediatric, Class IIb



2) Summary:
Evidence (Adult)
Tranexamic acid with or without aspirin compared with placebo did not significantly affect the
composite outcome of death or thrombotic events during the first 30 days after coronary
artery surgery (16.7% vs 18.1%) in a randomized trial of adults with increased risk of
perioperative complications (N=4631). There were no significant betweengroup differences
in the proportion of individual thrombotic events (myocardial infarction, stroke, renal failure,
pulmonary embolism, or bowel infarction), but tranexamic acid significantly reduced the
number of patients with blood loss during surgery, the number of patients who required blood
transfusions (37.9% vs 54.7%), the number of units of red cells and other blood products
transfused (median of 3 vs 4 units), and rates of reoperation within 30 days due to major
hemorrhage or cardiac tamponade (1.4% vs 2.8%; number needed to treat, 71).
Postoperative seizures occurred in significantly more patients with tranexamic acid (0.7% vs
0.1%, number needed to harm, 177) [66].

Tranexamic acid use during cardiac surgery with cardiopulmonary bypass (CPB) has reduced
perioperative blood loss, transfusion requirements, or other complications in a number of
clinical trials, although specific regimens have varied widely [64][60][61][63][62]; optimal
dosage regimen has not been established.

The need for at least 1 unit of blood product up to day 7 was similar with low or highdose
tranexamic acid (63% vs 60%; N=569). The lowdose regimen was 10 mg/kg IV bolus
followed by 1 mg/kg/hr IV infusion and the highdose regimen was 30 mg/kg IV bolus
followed by 16 mg/kg/hr IV infusion. However, in patients at high risk for transfusion because
of dual antiplatelet use or complex surgical procedures, the difference between the low and
high dose was more pronounced (highrisk group, 75.8% vs 68%; lowrisk group, 56.6% vs
54.2%) [58].

Evidence (Pediatric)
Perioperative blood loss was reduced by 24% and transfusion volume by 38% compared with
placebo in patients 6 months to 12 years old who were undergoing repeat cardiac surgeries
with CPB (N=43) [65].

Evidence (Combination Therapy)
Blood transfusion or blood products were required in 24% of patients who received
tranexamic acid plus desmopressin, compared with 74% who received desmopressin
monotherapy (N=100), during elective CABG surgery with CPB [67].

Operative procedure on spinal structure Postoperative hemorrhage; Prophylaxis
1) Overview





2) Summary:
Tranexamic acid reduced blood transfusion requirements related to pediatric scoliosis surgery
3) Pediatric:
a) In pediatric patients 9 to 18 years of age with scoliosis, peri operative tranexamic acid
reduced blood transfusion requirements for spinal fusion surgery. In this doubleblind,
controlled study, subjects were randomly assigned to tranexamic acid (n=22) or to placebo
(isotonic saline, n=18). Tranexamic acid was given as an initial dose of 10 mg/kg administered
over 15 minutes followed by a maintenance infusion of 1 mg/kg/hour continuing until skin
closure. A uniform threshold was established for transfusion of any type of RBC product; the
threshold was a Hb level of 7 g/dL or less. Patients could receive a unit of blood if the
anesthesiologist or surgeon deemed it clinically unsafe to withhold blood, even if the threshold
level was not met. Also, a cell saver was used and the threshold was not applied to cellsaved
blood. Total blood transfused was 1253 mL for tranexamictreated subjects and 1784 mL for
placebotreated subjects (p=0.045). Intraoperative blood loss was 2453 mL and 2703 mL for
the tranexamic acid and control groups, respectively (p=0.58, not significant). Tranexamic
acid was well tolerated. There were no thrombotic complications or other druginduced
adverse effects [109].

Ovarian carcinoma
1) Overview





2) Summary:
Some efficacy in arresting tumor growth
3) Adult:
a) A 60yearold woman with ovarian carcinoma was treated with oral tranexamic acid 1.5 to
2 g 3 times daily, in addition to periodic infusions of the drug (3 to 5 g) into the peritoneal
cavity or IV administration [96]. Following 3 months of treatment, there was arrest of ascites
and tumor growth and exploratory laparotomy revealed encapsulation of fibrinoid substances
and proliferation of connective tissue around tumor cells.

b) An inhibitory effect on tumor growth was reported in a 55yearold woman with
metastasizing ovarian carcinoma with oral tranexamic acid 4 to 6 g daily for 2 years [97].
Heparin was administered as adjuvant therapy (12,500 international units subQ 2 times per
day). Therapy prevented dissolution and removal of residual fibrin around the tumor and
suppressed tumor growth. Over a 2year period, the patient improved with regression of
clinical symptoms and ascites. The tumor masses were observed to be encapsulated by a
white fibrinlike material.

c) Malignant ovarian tumors possess both coagulative and fibrinolytic properties. High
amounts of fibrinogenfibrin degradation products have been observed in serum and ascitic
fluid of patients with ovarian tumors [98][99].

Perinatal periventricular hemorrhage; Prophylaxis
1) Overview





2) Summary:
Not effective in preventing periventricular hemorrhage in premature infants
3) Pediatric:
a) Tranexamic acid was ineffective in preventing periventricular hemorrhage in 100 preterm,
lowbirthweight infants in a controlled study [100]. Infants were administered tranexamic acid
(100 mg/mL) in doses of 0.25 mL/kg IV every 6 hours for 5 days. Periventricular hemorrhage
occurred in 22 tranexamic acidtreated patients and 20 patients receiving placebo. Excessive
fibrinolytic activity is not an important consideration in the pathogenesis of periventricular
hemorrhage in newborn infants.

Postoperative hemorrhage; Prophylaxis Prostatectomy
1) Overview





2) Summary:
Not recommended for routine use

Intravesicular blood clots formed in 50% of patients in small study

3) Adult:
a) Although tranexamic acid 1 g orally 3 times daily for several weeks has been effective in
reducing the frequency of secondary hemorrhage following prostatectomy [103][104], 3 of 6
patients in one report developed insoluble intravesicular blood clots in the bladder following
pre and postoperative tranexamic acid therapy to reduce blood loss after prostatectomy.
These clots persisted until they were evacuated surgically between 5 and 17 days after
withdrawal of tranexamic acid [105]. Similar clot formation in the bladder following tranexamic
acid therapy has been reported by others [106] and it is not recommended for routine use
after prostatectomy [105].

Postoperative hemorrhage; Prophylaxis Tonsillectomy
1) Overview





2) Summary:
Effective in prevention of perioperative blood loss, most common complication of tonsillectomy
(Verstraete, 1985; Verstraete et al, 1977)
3) Adult:
a) Tranexamic acid prevented blood loss during and after tonsillectomy in 80 patients in a
controlled study. Forty patients received tranexamic acid 250 mg IV 2 hours preoperatively
and 2 and 4 hours postoperatively; 500 mg 3 times daily was then administered orally for 3
days. Intraoperative blood loss was reduced by 28% with the incidence of postoperative
bleeding also significantly reduced. Postoperative bleeding occurred in 27% of the tranexamic
acid group as compared with 67% of the 40 control patients [111].

1) Overview





2) Summary:
A metaanalysis of 33 randomized controlled trials found that tranexamic acid significantly
reduced total blood loss and the need for allogeneic blood transfusions in patients undergoing
total hip or knee arthroplasty without increasing the risk of postoperative DVT. However,
important differences between the studies included in the analysis may affect the validity of
some of the reported findings [38].

Topical intraarticular administration of tranexamic acid resulted in a 2.6fold reduction in the
odds of needing a transfusion compared with placebo in patients undergoing hip replacement
surgery in the doubleblind, randomized TRANXH study (n=161) [39].

The odds of requiring a transfusion were 52% lower in patients administered oral tranexamic
acid compared with IV tranexamic acid in a retrospective study of patients undergoing knee or
hip replacement surgery (n=3000) [37].

3) Adult:
a) A metaanalysis found that tranexamic acid significantly reduced total blood loss and the
need for allogeneic blood transfusions in patients undergoing total hip or knee arthroplasty
without increasing the risk of postoperative DVT. Randomized controlled trials in which
patients underwent unilateral total knee or hip replacement were included in the analysis. Of
the 33 studies included, 21 were considered of high quality. Tranexamic acid was administered
IV in 29 of the studies, intraarticularly in 3 studies, orally in 1 study, and topically in 1 study.
The results for patients undergoing hip replacement follow [38].
1) Total Blood Loss
a) Total blood loss in patients undergoing hip replacement was significantly lower in
tranexamic acidtreated patients compared with those in the control group, as measured by
the weighted mean difference (0.504; 95% CI, 0.672 to 0.336; p less than 0.001).
However, important differences between the studies included in this analysis may affect the
validity of this finding [38].

2) Transfusion Requirements
a) Among patients undergoing hip replacement, patients treated with tranexamic acid had a
67% reduction in the odds of needing allogeneic transfusions compared with those in the
control group (odds ratio, 0.327; 95% CI, 0.208 to 0.515; p less than 0.001). However,
important differences between the studies included in this analysis may affect the validity of
this finding [38].

3) Rates of Postoperative DVT
a) There was no difference in the rate of postoperative DVT among patients undergoing hip
replacement who received tranexamic acid or placebo/no treatment (odds ratio, 1.07; 95%
CI, 0.393 to 2.911; p=0.895) [38].

4) Topical Administration in Total Hip Arthroplasty
a) Topical intraarticular administration of tranexamic acid resulted in significantly lower
transfusion rates compared with placebo in patients undergoing hip replacement surgery in
the doubleblind, randomized TRANXH study (n=161). Patients undergoing unilateral
primary total hip replacement received topical intraarticular administration of tranexamic
acid or placebo. Blood transfusion was necessary in 12.5% of the tranexamic acid group and
32.1% of the placebo group, for an absolute risk reduction of 19.6% (p=0.004). An analysis
found a 2.6fold reduction in the odds of needing a transfusion with tranexamic acid
compared with placebo (95% CI, 1.6 to 6.6; p=0.032). Mean drain blood loss was also
significantly lower in the tranexamic acid group. Two patients from each treatment group
developed postoperative DVT and no patients developed pulmonary embolism [39].

5) Oral vs IV Administration in Total Hip or Knee Arthroplasty
a) In a retrospective study of patients undergoing knee or hip replacement surgery
(n=3000), the odds of receiving a transfusion were significantly lower in patients who
received oral tranexamic acid compared with IV tranexamic acid. Patients received either
tranexamic acid 15 mg/kg IV (max dose, 1.2 g) at the time of anesthesia induction (n=2698)
or oral tranexamic acid 25 mg/kg (max dose, 2 g) 2 hours prior to the procedure (n=302).
Transfusion was required in 7.9% of those receiving IV tranexamic acid and 4.6% of those
receiving oral tranexamic acid (p=0.05). The odds of requiring a transfusion were 52% lower
in the group administered oral tranexamic acid compared with IV tranexamic acid (odds
ratio, 0.48; 95% CI, 0.26 to 0.89; p=0.019). There were no differences between groups in
readmission rates for up to 30 days or in rates of postoperative DVT or pulmonary embolism
for up to 60 days [37].

Postoperative hemorrhage; Prophylaxis Transplantation of liver
1) Overview





2) Summary:
Data on the utility of tranexamic acid to reduce bleeding with liver transplantation are
conflicting.

Prophylactic tranexamic acid 10 mg/kg/hour reduced packed RBC requirements compared with
aminocaproic acid 16 mg/kg/hour in a doubleblind, placebocontrolled study (n=132) of
patients undergoing orthotopic liver transplantation, although effects were not maintained
during the first 24 hours postoperatively [84].

In a prospective, doubleblind, placebocontrolled trial, lowdose IV infusion of tranexamic acid
did not reduce intraoperative or postoperative blood transfusion requirements in patients
undergoing orthotopic liver transplantation (n=32) although fibrinolysis was significantly
reduced (Kaspar, 1997).
reduced (Kaspar, 1997).

In a doubleblind, placebocontrolled study, highdose tranexamic acid (40 mg/kg/hr, max 20
g) IV infusion significantly reduced intraoperative blood loss and perioperative donor exposure
in patients undergoing liver transplantation (n=45) [85].

3) Adult:
a) The prophylactic use of tranexamic acid 10 mg/kg/hour was significantly more effective
than aminocaproic acid 16 mg/kg/hour in reducing packed RBC requirements in a double
blind, placebocontrolled study (n=132) of patients undergoing orthotopic liver
transplantation. This effect was not maintained during the first 24 hours postoperatively [84].

b) In a prospective, doubleblind, placebocontrolled trial, a lowdose IV infusion of
tranexamic acid did not reduce the intraoperative or postoperative blood transfusion
requirements in 32 patients undergoing orthotopic liver transplantation. Fibrinolysis, as
measured by the clot lysis index, fibrin degradation products, and Ddimer levels, was
significantly reduced during the anhepatic and neohepatic phases of surgery in patients
receiving tranexamic acid (p less than 0.05). Patients were randomized to receive either a
continuous infusion of tranexamic acid 2 mg/kg/hr (n=16) or NS, beginning after anesthesia
induction and ending at the completion of surgery. No loading dose was administered. Patients
received an average total dose of 830 mg (566 to 1667 mg). A 5g rescue dose of epsilon
aminocaproic acid was administered postreperfusion to 9 of 16 (56%) control patients and 3
of 16 (19%) tranexamic acid patients for significant fibrinolysis. No patient demonstrated
evidence of disseminated intravascular coagulopathy. One patient in the tranexamic acid
group who did not receive epsilon aminocaproic acid developed a hepatic artery thrombosis
postoperatively. The authors therefore caution against the routine prophylactic use of
tranexamic acid in centers with low transfusion requirements (Kaspar, 1997).

c) Highdose tranexamic acid (40 mg/kg/hr infused IV up to a maximum dose of 20 g)
significantly reduced intraoperative blood loss and perioperative donor exposure in patients
undergoing liver transplantation in a 45patient, doubleblind, placebocontrolled study.
Patients were randomized to receive a continuous infusion of either tranexamic acid in NS or
NS alone which was started after induction of anesthesia and discontinued when portal veins
were unclamped. Additionally, all patients received dipyridamole 150 mg and heparin 5000
units in 250 mL of D5W, infused at 10 mL/hr beginning after hepatic arterial anastomosis was
completed and continuing for 24 hours. Median intraoperative blood loss was 4.3 L for patients
receiving tranexamic acid and 8 L for placebotreated patients (p=0.006) and median
postoperative drainage was 0.8 L and 1.2 L, respectively (p=0.39). Median intraoperative
donor exposure was 18 units for tranexamic acidtreated patients and 35 units for controls
(p=0.01) and median postoperative donor exposure was 1 unit and 7.5 units, respectively
(p=0.01) [85]. This study did not include patients with increased risk of thrombosis. The
authors did not search for hepatic artery or portal vein thromboses nor was the study
sufficiently powered to detect a difference in this measure of safety [86].

1) Overview





2) Summary:
Evidence
In a systematic review and metaanalysis of 12 trials (N=3285), lowrisk women undergoing
cesarean section (n=2453) or vaginal delivery (n=832) who received tranexamic acid
demonstrated a 48% reduced risk of postpartum blood loss greater than 400 or 500 mL, and a
60% reduced risk of blood loss greater than 1000 mL compared to those who received
placebo or no intervention. Mean blood loss was lower, and the need for additional medical 24/77
placebo or no intervention. Mean blood loss was lower, and the need for additional medical
interventions and blood transfusions was lower in women who received tranexamic acid. There
was an increase in the incidence of minor side effects with tranexamic acid use [101].

Rectal hemorrhage
1) Overview





2) Summary:
Tranexamic acid delivered via enemas useful for hemostasis
3) Adult:
a) Enemas containing tranexamic acid 5 g/50 mL was used successfully to stop persistent
rectal bleeding . The bleeding was secondary to a large prostatic tumor pushing on the rectal
wall. Enemas administered twice daily for 10 days virtually eliminated bleeding. The frequency
of administration was gradually reduced and finally eliminated, but rectal bleeding
subsequently returned necessitating chronic tranexamic acid enemas 3 times weekly [107].

Rheumatoid arthritis
1) Overview

Efficacy: Adult, Ineffective




2) Summary:
No effect observed on clinical status or disease markers
3) Adult:
a) Tranexamic acid 0.5 to 1.5 g 3 times daily was reported to be ineffective in the treatment
of rheumatoid arthritis in a placebocontrolled study. There were no differences observed in
any of the variables between treatment and placebo groups. Tranexamic acid had no effect on
clinical status or general markers of disease activity. Levels of immune complexes and
concentrations of complement split group product C3d remained high, and C4 and C1q levels
did not change throughout treatment [108].

Subarachnoid hemorrhage; Prophylaxis
1) Overview





2) Summary:
Not recommended due to association with ischemic complications

No effect on improving outcome although reduced incidence of rebleeding

May have some benefit combined with nimodipine

3) Adult:
a) A retrospective review of patients with subarachnoid hemorrhage suggests the potential
benefit of combined preoperative therapy with lowdose tranexamic acid and nimodipine to
reduce the incidence of rebleeding and delayed vasospasm. Eightyfour of 101 patients with
documented aneurysm received both drugs; of these 8 patients rebled, 42 demonstrated
vasospasm, and 8 developed delayed ischemia. In 21 of 25 patients without aneurysm, 2 re
bled, 10 demonstrated vasospasm, and none had evidence of ischemia. In 126 patients, aged
20 to 80 years, treatment with tranexamic acid 1 g orally 3 times daily or 0.5 g IV 3 times a
day and nimodipine 1 to 3 mg per hour IV was initiated upon admission and continued until
surgery. Patients also routinely received hydration, phenytoin, sedatives, and analgesics.
Ninety percent of the patients studied were admitted within 96 hours of the initial bleed. The
authors conclude, by comparison with other reports, that these doses are effective in the
prevention of rebleeding due to intracranial aneurysm. However, the variations in clinical
management and the policy of late surgical intervention employed in this study make valid
comparisons of outcomes difficult (Stroobandt, 1998).

b) Tranexamic acid and aminocaproic acid are the 2 agents which have been evaluated most
extensively in preventing rebleeding following subarachnoid hemorrhage. However, results of
therapy with both agents have been controversial. Several uncontrolled and controlled studies
have reported the efficacy of tranexamic acid in reducing the rebleeding rate following
subarachnoid hemorrhage [23][24][25][26][27][28][29][30][31]. Of these studies, 4 were
randomized, controlled trials [23][24][27][25]. However, other controlled clinical trials have
failed to demonstrate any benefit of tranexamic acid on preventing rebleeding [32][33][34]
[35].

c) Although tranexamic acid may reduce the incidence of rebleeding, the drug does not
appear to improve outcome by preventing recurrent hemorrhage [6][23][36]; (Ramirez
Lassepas, 1981)[32]. In addition, ischemic complications may occur during drug treatment.
[23]. In a multicenter, randomized, doubleblind trial, involving 479 patients with subarachnoid
hemorrhage, the authors evaluated the efficacy of tranexamic acid on improving outcome by
the prevention of rebleeding. In this study, treatment was initiated with tranexamic acid or
placebo within 72 hours after the occurrence of subarachnoid hemorrhage and the maximum
duration of therapy was 4 weeks. In 2 of the 4 participating centers, the drug was given by IV
bolus injection in doses of 6 g daily (in 6 divided doses) during the first week, followed by 4 g
daily given IV in 4 doses thereafter. In 2 other centers, the drug was given by IV bolus
injections for 2 weeks, followed by oral therapy thereafter; in these centers, 6 g daily was
given IV in 6 doses during the first week, followed by 4 g daily in 4 IV doses during the second
week, with the oral equivalent of 6 g daily in 4 doses being given for the third and fourth
weeks. Most episodes of rebleeding were confirmed by CT scans. At 3 months, there were no
statistical difference between the outcomes in the tranexamic acid group and the control
group.

d) In the preoperative management of patients with aneurysmal subarachnoid hemorrhage,
tranexamic acid was associated with an increased incidence of severe vasospasm, fatal
delayed cerebral ischemia, pulmonary embolism and myocardial infarction, as compared with
the control group. Although tranexamic acid may protect patients with ruptured aneurysms
from rebleeding for 1 to 2 weeks, it may also produce cerebral ischemic complications. In this
series of 59 patients (30 receiving tranexamic acid and 29 serving as controls), the incidence
of mortality from cerebral ischemia was higher in tranexamic acidtreated patients as
compared with the control group (5 patients and 2 patients, respectively) [32].

Sudden hearing loss
1) Overview





2) Summary:
Limited data indicate possible efficacy
3) Adult:
a) One controlled study reported the successful use of tranexamic acid in the treatment of
sudden deafness. Doses of 250 mg daily given IV plus 1.5 g orally 3 times per day for periods
of 7 to 40 days were effective in achieving complete or marked recovery of hearing in 44% of
25 ears (in 19 patients) following sudden deafness [110]. However, controlled studies are
required to evaluate this therapy.

Traumatic hemorrhage
1) Overview





2) Summary:
In the multicenter, randomized, placebocontrolled Clinical Randomization of an Antifibrinolytic
in Significant Hemorrhage 2 (CRASH2) trial (n=20,127), tranexamic acid therapy significantly
reduced allcause mortality and death due to bleeding compared with placebo in adult trauma
patients [15].

3) Adult:
a) In the multicenter, randomized, placebocontrolled Clinical Randomization of an
Antifibrinolytic in Significant Hemorrhage 2 (CRASH2) trial (n=20,127), tranexamic acid
therapy significantly reduced allcause mortality compared with placebo in adult trauma
patients. Patients who presented with or who were at risk for significant hemorrhage (systolic
blood pressure (SBP) below 90 mmHg and/or heart rate greater than 110 beats/min) arriving
at the hospital within 8 hours of injury were eligible for enrollment. Patients were selected for
randomization if the responsible doctor was not sure if the patient should receive tranexamic
acid (uncertainty principle), assuming there were no contraindications to therapy. Patients
received tranexamic acid 1 g over 10 minutes followed by 1 g over 8 hours IV (n=10,060;
mean age, 34.6 +/ 14.1 years; mean time since injury, 2.8 +/ 2.2 hours; blunt injury,
67.5%; penetrating injury, 32.5%) or a 0.9% saline infusion (n=10,067; mean age, 34.5 +/
14.4 years; mean time since injury, 2.9 +/ 2.6 hours; blunt injury, 67.7%; penetrating injury,
32.3%). Patient characteristics (timing and type of injury, vital signs, and Glasgow Coma Score
(GCS)) were similar in both groups. All cause mortality within 4 weeks of injury (primary
endpoint) was significantly reduced in the tranexamic acid arm (n=1463; 14.5%) compared
with placebo (n=1613; 16%); corresponding to a relative risk (RR) of 0.91 (95% CI, 0.85 to
0.97; p=0.0035). Additionally, the risk of death due to bleeding was significantly reduced
(n=489 (4.9%) vs n=574 (5.7%); RR 0.85 (95% CI, 0.76 to 0.96; p=0.0077). A subgroup
analysis revealed no significant difference between groups in all cause mortality when the
treatment arms were separated by time from injury, SBP, GCS, and injury type (except
patients with SBP 75 mmHg or less; tranexamic acid arm, 30.6%; placebo arm, 35.1%; RR,
0.87; 95% CI, 0.76 to 0.99). Death from other causes (vascular occlusion, multiorgan failure,
head injury, or other cause) were not significantly different between the 2 groups.
head injury, or other cause) were not significantly different between the 2 groups.
Furthermore, there was no significant difference between groups for the incidence of vascular
occlusive events and the need for a blood transfusion or surgery. There were no adverse
events suspected to be related to study treatment reported in the study [15].

Traumatic hyphema
1) Overview


Recommendation: Adult, Class III; Pediatric, Class III



2) Summary:
Has been useful in the treatment of hyphema and in several ophthalmic surgery procedures
3) Adult:
a) Tranexamic acid was more effective than oral prednisolone in preventing rebleeding in
patients with traumatic hyphema. Patients admitted with traumatic hyphema were randomized
to receive tranexamic acid 75 mg/kg orally, divided into 3 daily doses (n=80), prednisolone
0.75 mg/kg orally divided in 2 daily doses (n=78), or placebo 3 times daily (n=80), each given
for 5 days. Secondary bleeding occurred in 43 patients after 2 to 6 days (median 3 days).
Rebleeding occurred in 10% of the tranexamic acid group, in 18% in the prednisolone group,
and in 26% of the placebo group. Rebleeding in the tranexamic group was significantly less
than in the placebo group (p=0.008). Rebleeding in the prednisolone and placebo groups was
not significantly different. No patient had to discontinue tranexamic acid or prednisolone due
to adverse effects. There were no rapid increases in intraocular pressure after discontinuation
of tranexamic acid. The authors conclude that tranexamic acid should be the drug of choice
for the prevention of rebleeding after traumatic hyphema (Rahamani & Jahadi, 1999).

b) Tranexamic acid 0.5 to 1 g 3 times daily for 3 to 7 days was effective in preventing
secondary hemorrhage in patients with traumatic hyphema [88]. None of 58 patients given
tranexamic acid in these doses developed secondary hemorrhage. However, 3 of 55 patients
(5.5%) treated without antifibrinolytic therapy developed secondary hemorrhage. In this
series, the activities of these patients were not restricted and eye patches were not utilized. In
a previous series of 126 patients with traumatic hyphema that were confined to bed and
treated without tranexamic acid, none (7.1%) developed secondary hemorrhage. Tranexamic
acid significantly delays resorption of the hyphema and effectively prevents secondary
hemorrhage following traumatic hyphema without bed rest and binocular patching. It has also
been effective in decreasing the incidence of rebleeding in traumatic hyphema in other studies
[89][90][91][92]. The usual dosage is 0.5 to 1 g 3 times daily for 3 to 7 days.

c) Oral tranexamic acid 1 g 3 times daily for 7 days resulted in a decrease in central corneal
thickness in healthy subjects [93]. In contrast, aspirin therapy resulted in an increase in
corneal thickness. These data suggest that the fibrinolytic system is involved in normal corneal
thickness regulation.

d) Two studies demonstrated benefits in reducing corneal edema after cataract surgery and
trabeculectomy surgery [94][95].
4) Pediatric:
a) In an open, prospective study of 163 pediatric patients with traumatic hyphema, the
administration of tranexamic acid 25 mg/kg orally every 8 hours for 5 days significantly
reduced the incidence of secondary hemorrhage as compared with an historic cohort not
treated with antifibrinolytic therapy. A 3% incidence (5 of 163) of rebleeding occurred in
patients receiving tranexamic acid while in patients not receiving tranexamic acid, a 10%
incidence of rebleeding was observed (33 episodes in 24 of 316 patients) (p less than 0.008).
The size of the secondary hemorrhage was also greater in the group not receiving tranexamic
acid. Eight of 33 bleeding episodes produced total (grade 4) hyphema, while the hemorrhages
in the treated group involved 10% or less of the anterior chamber (grade 1 or microscopic).
The patients, aged 6 months to 17 years in age, were hospitalized for an average of 6.8 days.
The patients, aged 6 months to 17 years in age, were hospitalized for an average of 6.8 days.
Length of stay in the cohort not receiving antifibrinolytic treatment was not reported (Deans,
1992).

Urticaria
1) Overview





2) Summary:
Not effective for treatment of chronic urticaria

Limited data available

3) Adult:
a) One controlled study reported the ineffectiveness of tranexamic acid 1 g orally 3 times a
day for 9 weeks in the treatment of chronic urticaria in patients with decreased levels of C1
esterase inhibitor [112].

Dose Adjustments
Adult Dosage
Normal Dosage
Intraarticular route
bleeding and the need for transfusion during knee arthroplasty:
1.5 g or 3 g diluted in 100 mL NS; apply topically intraarticularly to open joint
surfaces with bulb syringe after all components cemented; keep in contact with
tissues for 5 minutes then suction excess solution prior to closure [51]

1.5 g diluted in 100 mL NS; infuse intraarticularly during closure [52]

Intravenous route
a) A continuous IV infusion of tranexamic acid (2000 mg in 500 mL of D5W, given
every 8 hours for 6 days) was reported effective in reducing hemorrhagic episodes
and transfusion requirements in 12 patients with acute promyelocytic leukemia in a
small, doubleblind study [102]. The drug was initiated at the same time as the
start of antileukemic therapy and there were no thromboembolic complications.
bleeding and the need for transfusion during total knee arthroplasty:
15 mg/kg IV (max dose, 1.2 g) at the time of anesthesia induction [37]

10 mg/kg IV just before tourniquet deflation and then 3 hours later [53]

15 mg/kg IV just before tourniquet deflation and 10 mg/kg administered 3 to 4
hours later for 2 doses [54]

15 mg/kg IV 30 minutes before surgery then every 8 hours for 3 days [56]

15 mg/kg IV over 30 minutes then 10 mg/kg/hr IV infusion for 12 hours [55]

a) Offlabel Dosage
1) Dosage: Bolus of 10 mg/kg IV followed by 1 mg/kg/hr IV infusion (lowdose)
OR 30 mg/kg IV bolus followed by 16 mg/kg/hr IV infusion (highdose). Bolus
doses were administered 15 minutes after anesthesia induction, and the infusions
were continued until end of surgery; 1 mg/kg was added to the priming solution
prior to cardiopulmonary bypass for the low dose, and 2 mg/kg was added to the
priming solution for the high dose [58].

2) Dosage: Loading dose of 15 mg/kg IV followed by 1 mg/kg/hr IV infusion for 5
[60] or 6 hours [59]

3) Dosage: Preoperative dose of 100 mg/kg IV over 20 minutes with additional 50
mg/kg IV postoperatively [63]

4) Dosage: Single preoperative dose of 10 g IV infused over 20 [62] or 30 minutes
[61]

5) Dosage: A dose of 2.5 g IV prior to skin incision with 2.5 g added to the bypass
priming solution [64]

a) Dose: 15 mg/kg IV at the time of anesthesia induction was used in a clinical
study [37]
b) Maximum Dose: 1.2 g [37]
a) Offlabel Dosage
1) Dosage: 1 g diluted in 20 mL D5W given IV over 5 to 10 minutes (offlabel
dosage) [101]

2) Dosage: 10 mg/kg in 200 mL NS given IV over 10 minutes (offlabel dosage)
[101]

3) Dosage: 10 to 15 mg/kg in 20 mL D5W given IV over 20 minutes (offlabel
dosage) [101]

4) Dosage: 0.5 to 1 g IV 2 to 3 minutes after delivery (offlabel dosage) [101]

5) Timing of administration (cesarean section): Administered 10 to 20 minutes
prior to anesthesia induction, at the time of induction, 20 minutes after induction,
or 10 minutes before skin incision (offlabel dosage) [101]

Oral route
[37]

Menorrhagia

[37]

Traumatic hyphema
a) Doses of tranexamic acid 1 g 3 times daily orally have been effective in reducing
the frequency of secondary hemorrhage following traumatic hyphema [91][89].

Parenteral route
a) In hemophilia patients, the recommended dosage is 10 mg/kg tranexamic acid
IV prior to tooth extraction, combined with factor VIII or IX concentrate. Following
surgery, tranexamic acid 10 mg/kg IV 3 to 4 times daily for 2 to 8 days is
required postsurgery [4][6].

Adjusted Dose
(mg/dL) Dose
above 1.4 to 2.8 2600 mg
above 2.8 to 5.7 1300 mg
above 5.7 650 mg
[114]:
Dosage in Hepatic Insufficiency
A) Dosage adjustment in patients with hepatic impairment is not needed, as only a small
fraction of the drug is metabolized [16].
Pediatric Dosage
Normal Dosage
Intravenous route
a) Offlabel Dosage
1) Dosage (6 months to 12 years): 100 mg/kg IV over 15 minutes followed by a
continuous IV infusion of 10 mg/kg/hour until transport to the ICU [65]

Oral route
Menorrhagia

Oral tranexamic acid (Lysteda(TM)) is not intended for use in premenarcheal girls; it has
not been studied in pediatric patients younger than 12 years with heavy menstrual
bleeding [16].
Adjusted Dose
(mg/dL) Dose
above 1.4 to 2.8 2600 mg
above 2.8 to 5.7 1300 mg
above 5.7 650 mg
[114]:
[114]:
Administration
A) Preparation
1) Intravenous route
a) Injection may be mixed with electrolyte solutions, carbohydrate solutions, amino acid solutions,
and dextran solutions; heparin may be added to Cyklokapron(R) injection[4].

b) Do not mix injection with blood or solutions containing penicillin [4].

c) To avoid hypotension, do not inject more rapidly than 1 mL/min [4].
2) Oral route
a) Tablets may be given without regard to meals [16].

b) Tablets should be swallowed whole; do not chew or break tablets [16].

B) Intravenous route
1) Solution
a) Store at controlled room temperature, 25 degrees C (77 degrees F), with excursions permitted
between 15 and 30 degrees C (59 and 86 degrees F) [4].

b) Solution stored between 20 and 50 degrees C was stable for up to 12 weeks. However, glass
ampoules that contained the solution cracked when frozen. Therefore, the authors suggest
packaging the solution in something other than glass or not allowing the product to freeze [168].

C) Oral route
1) Tablet

Comparative Efficacy
Aminocaproic Acid
a) In a doubleblind, randomized and placebocontrolled clinical trial of 127 patients
undergoing total knee replacement, antifibrinolytic agents (tranexamic acid (TXA) and
epsilonaminocaproic acid (EACA)) greatly reduced blood loss and the number of blood
transfusions required. Patients were assigned to two parallel surgical groups; the study
group patients (n=68, one lost to followup; ANTIF) were randomized to receive either
TXA 10 milligrams/kilogram (mg/kg) intravenously just before the tourniquet was
deflated and 3 hours later (n=35); or EACA 100 mg/kg intravenously before tourniquet
deflation followed by continuous perfusion (1 gram (g)/hr) for 3 hours (n=32). The
control group patients (CONT) were treated with placebo (n=60). Total blood loss [mean
(SD)] was 1099 milliliters (mL) (535) in the ANTIF group (TXA 1095 mL (473) and EACA
1104 mL (603); p=0.998) and 1784 mL (660) in the CONT group (p < 0.001). Blood
transfusions were required in 5 patients (7.5%) in the ANTIF group (TXA 2.8% and EACA
12.5%; p=0.185) and 23 (38.3%) in the CONT group (p < 0.001). Mean reduction in
hemoglobin levels (g/dL) between preoperative and fifth day postoperative readings were
2.5 (0.9) and 3.4 (1.2) in the ANTIF group and CONT group (p < 0.001), respectively.
Overall, no significant differences were observed between the EACA and TXA groups for
any of the outcome measures (total blood losses, the reduction in hemoglobin and
hematocrit levels, the number of patients receiving transfusions). No postoperative
complications were observed [53].

a) ADULTS:

b) During a randomized trial, patients who received aminocaproic acid or tranexamic acid
during cardiac surgery demonstrated no significant betweengroup differences in
postoperative blood loss or blood product usage, while both treatments were superior to
no antifibrinolytic therapy (N=120). Patients scheduled for cardiac surgery were
randomly allocated to receive intraoperative aminocaproic acid 100 mg/kg after induction
of anesthesia, 100 mg/kg on bypass, and 100 mg/kg after protamine reversal of heparin
, tranexamic acid 10 mg/kg at induction of anesthesia, 10 mg/kg on bypass, and 10
mg/kg after protamine reversal of heparin, or no fibrinolytic therapy . The cumulative
postoperative blood loss at 24 hours was 360 mL in the aminocaproic acid group, 342 mL
in the tranexamic acid group (a difference that was not significant), and 780 mL in the
control group . Compared with either the aminocaproic acid group or the tranexamic acid
group, the mean volume of packed red blood cells, fresh frozen plasma, or platelet
concentrate administered by 24 hours were all significantly greater in the control group .
Reexploration for mediastinal bleeding was required in 8 control patients, compared with
2 patients in each active treatment group [181].

c) In a randomized trial in subjects undergoing firsttime coronary artery bypass graft
surgery (N=59), use of tranexamic acid was associated with reduced blood loss
compared with use of aminocaproic acid, although both fibrinolytics demonstrated
compared with use of aminocaproic acid, although both fibrinolytics demonstrated
reduced blood loss and fewer elevations in Ddimer levels compared with NS. Patients
were randomized to receive tranexamic acid with a loading dose of 15 mg/kg plus
continuous infusion 1 mg/kg/hr for 6 hours , aminocaproic acid with a loading dose of
150 mg/kg plus continuous infusion 10 mg/kg/hr for 6 hours , or NS infusion for 6 hours
; all treatments were initiated immediately following induction of anesthesia.
Postoperative blood loss at 6 and 12 hours was significantly reduced in the tranexamic
acid group compared with the aminocaproic acid and NS groups . At 24 hours, the
tranexamic acid group mean cumulative postoperative blood loss (measured by chest
tube drainage) of 600 mL was significantly lower when compared with 961 mL in the
aminocaproic acid group and 1060 mL in the NS group . An intraoperative Ddimer level
of 2 mcg/mL or less was observed in 19 and 18 patients in the aminocaproic acid and
tranexamic acid groups, respectively, compared with 7 patients in the placebo group ;
postsurgery Ddimer levels remained elevated in the control group at 6, 12, and 24 hours
[59].

d) Highdose tranexamic acid and epsilon aminocaproic acid, administered
prophylactically during cardiopulmonary bypass, were equally effective in reducing
transfusion requirements in patients undergoing firsttime, coronary artery bypass
grafting with cardiopulmonary bypass. In this randomized trial, the estimated median
intraoperative blood loss was significantly reduced in patients receiving tranexamic acid
(450 milliliters (mL)) over control patients (600 mL) , but not different from patients
receiving epsilon aminocaproic acid (500 mL). Postoperative mediastinal chest drainage
was significantly lower in both tranexamic acid (438 mL) and epsilon aminocaproic acid
(538 mL) groups as compared with control (700 mL). Total exposure to blood products
was significantly higher in the control group (7.5 units) than in either treatment group (2
units each) . Multivariate analysis of the treatment groups combined revealed that
treatment produced a statistically and clinically significant reduction in the number of
severe bleeders over placebo (13/88, 15% versus 14/44, 32%, respectively). The
incidence of postoperative complications was similar between groups. Patients received
either epsilon aminocaproic acid (15 grams (g) by intravenous (IV) bolus over 20
minutes, followed by a 1 g per hour (g/hr) infusion), tranexamic acid (10 g bolus IV over
20 minutes, followed by a normal saline placebo infusion), or normal saline placebo
(bolus plus infusion) (Hardy, 1998).
e) PEDIATRICS:

f) In a randomized trial (N=150; mean age 4 years), there was no significant difference
between aminocaproic acid and tranexamic acid for reducing postoperative blood loss or
the need for blood products in pediatric patients with cyanotic congenital heart disease
undergoing firsttime corrective surgery on cardiopulmonary bypass (CPB). Patients were
randomized to receive aminocaproic acid (100 mg/kg IV after anesthetic induction,
during CPB, and after protamine reversal of heparin) or tranexamic acid (10 mg/kg IV
after anesthetic induction, during CPB, and after protamine reversal of heparin) or no
drug. There was no significant difference among patients in the aminocaproic acid group
and tranexamic acid group with regards to sternal closure time and other intraoperative
parameters; patients in the control group had a longer sternal closure time. There was
no significant difference between aminocaproic acid and tranexamic acid therapy,
respectively, for cumulative blood loss in the ICU at 24 hours (28 mL/kg/24 hours and 27
mL/kg/24 hours); blood loss was highest in the control group (36 mL/kg/24 hr. As
expected, there was a significant increased requirement for blood and blood products in
the control group compared with aminocaproic acid and tranexamic acid (no significant
difference). No renal or nervous system complications were reported in the study [181].
g) In an observational study in pediatric patients undergoing cardiac surgery with
cardiopulmonary bypass, there was no significant difference in blood loss 24 hours
postoperatively between epsilon aminocaproic acid and tranexamic acid (N=234).
Pediatric patients weighing less than 20 kg either received tranexamic acid 50 mg/kg
bolus or epsilon aminocaproic acid 75 mg/kg bolus at the beginning and end of surgery.
Additionally, tranexamic acid 100 mg/100 mL or aminocaproic acid 75 mg/100 mL were
added to the corresponding priming fluid of the cardiopulmonary bypass system. Median
blood loss at 24 hours postoperatively was aminocaproic acid (21 mL/kg) vs tranexamic
acid (29 mL/kg). Although the study was underpowered to detect a difference, incidences
of seizure (3.5% vs 0.8%) were higher in the tranexamic acid group and incidences of
renal failure (4.2% vs 1.8%) were higher in the aminocaproic acid group [182].
Postoperative hemorrhage; Prophylaxis Transplantation of liver
a) The prophylactic use of tranexamic acid (10 milligrams per kilogram per hour
(mg/kg/hour) was significantly more effective than aminocaproic acid (16 mg/kg/hour) in
reducing packed red blood cell requirements in a doubleblind, placebocontrolled study
(n=132) of patients undergoing orthotopic liver transplantation. This effect was not
maintained during the first 24 hours postoperatively [84].
Subarachnoid hemorrhage
a) SUMMARY: Although tranexamic acid is NOT indicated in subarachnoid hemorrhage
due to a high incidence of ischemic complications, it was as effective as aminocaproic
acid in preventing rebleeding hemorrhage following subarachnoid hemorrhage in 1
report. Tranexamic acid may have more sustained antifibrinolytic effects and is 6 to 10
times more potent than aminocaproic acid in fibrinolytic activity [172][173][174]. In
addition, tranexamic acid has greater and more sustained antifibrinolytic activity in
tissues than aminocaproic acid [173] and appears to have the same order of acute and
chronic toxicity [172].

b) Tranexamic acid (36 g daily) was equal in efficacy to aminocaproic acid (6 g daily),
oral and intravenous, in the prevention of recurrent hemorrhage and delayed ischemic
deficits following subarachnoid hemorrhage [175]. Recurrent hemorrhage occurred in 8%
and 10% of patients given tranexamic acid and aminocaproic acid, respectively; the
corresponding incidence of delayed ischemic deficits was 7% and 5%, respectively, with
the total preoperative mortality in both groups being 11%. The most common side
effects were nausea, vomiting, and diarrhea with both agents, with detectable deep vein
thrombosis occurring in 6% of patients in each group.

c) Due to a high incidence of ischemic complications, tranexamic acid is not
recommended in patients with subarachnoid hemorrhage [183]. This study did not
demonstrate any improvement in outcome with tranexamic acid. Insufficient data is
available to determine whether aminocaproic acid will be effective and possess fewer side
effects than tranexamic acid for this purpose.
Adverse Effects
a) In a retrospective cohort review of subjects who underwent open heart surgery (n=604),
administration of tranexamic acid was associated with more frequent seizures compared with
use of aminocaproic acid, although 24hour postoperative blood loss and the incidence of
transient renal dysfunction were greater in the aminocaproic acid cohort. Patients in the
tranexamic acid cohort (n=275) received a 2 g bolus at the start of surgery followed by a
continuous infusion of 0.5 g/hr until chest closure, and 2 g were added to the priming fluid of
the cardiopulmonary bypass system (CPB). Patients in the aminocaproic acid cohort (n=329)
received a 10 g bolus at the start of surgery, followed by a continuous infusion of 2.5 g/hr
until chest closure, and 10 g were added to the priming fluid of CPB. Heart valve surgery and
coronary artery bypass graft surgery were the most common procedures, performed at similar
rates; no significant differences in medical history, patient characteristics, or bleeding risks
were identified between the groups. Postoperative seizure occurred in 11 patients who
received aminocaproic acid, compared with 21 patients who received tranexamic acid (3.3%
vs 7.6%; Relative Risk (RR), 0.44; 95% CI, 0.89 to 0.22; p=0.019), with multiple episodes
reported in 8 and 13 patients, respectively. Transient renal dysfunction occurred in 30.1% and
20% of subjects who received aminocaproic acid and tranexamic acid, respectively (RR, 1.49;
95% CI, 2 to 1.12; p=0.005), although the rate of renal failure was not significantly different
(9.7% vs 8.4%; p=0.562). Postoperative blood loss at 24 hours was 809 +/ 940 mL in the
aminocaproic acid cohort compared with 620 +/ 573 mL in the tranexamic acid cohort
(p=0.015). The transfusion rate and revision rate for bleeding did not differ significantly [180].

Aprotinin
Operation on heart
a) Tranexamic acid had equal hemostatic effectiveness and less renal dysfunction
compared with aprotinin during cardiac surgery with cardiopulmonary bypass in high
transfusionalrisk patients according to a prospective, casecontrol study. Out of a pool of
10,870 patients, 449 patients (following a test dose) received aprotinin 2 x 10(6) units
intravenously over 30 minutes after anesthesia induction, in the pump prime, and infused
over 4 hours. By use of a propensity score derivation model, which included 20 variables,
a matched group of 449 patients received a mean tranexamic acid dose of 74 mg +/ 32
mg/kg (range 50 to 100 mg/kg) intravenously administered over 5 to 10 minutes after 35/77
mg/kg (range 50 to 100 mg/kg) intravenously administered over 5 to 10 minutes after
anesthesia induction. Comparing the aprotinin with the tranexamic acid groups, patients
who received at least 1 RBC unit (354 vs 342 patients, p=0.3), at least 5 RBC units (157
vs 135 patients, p=0.1), and at least 10 RBC units (60 vs 46 patients, p=0.2),
respectively. There was a higher incidence of renal effects in the aprotinin group
compared with the tranexamic acid group, renal dysfunction (107 vs 75 patients,
p=0.01), and renal failure (25 vs 14 patients, p=0.08) [177].

b) Tranexamic acid and aprotinin were equally effective in reducing postoperative blood
loss, frequency of transfusion, and volume of blood products transfused in 150 patients
undergoing elective primary coronary artery bypass grafting, and were superior in
producing these outcomes when compared with 30 placebotreated patients receiving
otherwise similar management. Median mediastinal chest tube drainage was 708
milliliters (mL), 600 mL, and 1020 mL for tranexamic acid, aprotinin, and control groups,
respectively (p less than 0.05 for control versus treatments groups). Allogeneic blood
products were required in 25% of the tranexamic acid group, 27% of the aprotinin
group, and 66% of patients in the control group. Median number of units of blood
products administered were 0, 0, and 4.5, respectively (p=0.007 for the control
compared with treatment groups). Patients were randomly assigned to receive
tranexamic acid (1 gram (g) as an intravenous (IV)loading dose, followed by a 2
milligram per kilogram (mg/kg/hr) IV infusion for 6 hours) or aprotinin (2 million KIU IV
loading dose), plus 2 million KIU for cardiopulmonary bypass priming, followed by an IV
infusion at 500,000 KIU/hr for 6 hours. Adverse events were infrequent, and included re
exploration (2), stroke (1), and myocardial infarction (5) [178].

Bevacizumab
Epistaxis Osler hemorrhagic telangiectasia syndrome
a) In the randomized NOSE trial in adults with hereditary hemorrhagic telangiectasia
related epistaxis (N=121), during weeks 5 to 12 with twice daily topical nasal spray
treatment, there was no significant difference in patientreported median weekly
epistaxis frequency in patients receiving bevacizumab 1% (7 episodes), estriol 0.1% (8
episodes), or tranexamic acid 10% (7.5 episodes) compared with placebo (normal saline;
8 episodes). All 4 groups significantly decreased the epistaxis severity score from
baseline with no significant betweengroup difference. There was also no significant
betweengroup differences in epistaxis duration, hemoglobin or ferritin levels, or
transfusion requirements [184].

Cimetidine
Gastrointestinal hemorrhage
a) Tranexamic acid was reported at least as effective as cimetidine in reducing mortality
in acute upper gastrointestinal tract bleeding in a doubleblind, randomized study
involving 775 patients with hematemesis or melena, or both. In this study, 99 patients
were withdrawn prior to breaking of the code, primarily because their primary illness was
not considered secondary to acute upper GI bleeding. Mortality among those withdrawn
was high (22%). Their exclusion reduced the death rates to 4% in tranexamic acid
treated patients, 8% in cimetidinetreated patients, and 11% in placebotreated patients.
The authors suggest that the routine use of tranexamic acid is indicated in patients over
the age of 60, the group considered to be at highest risk of death from upper
gastrointestinal tract hemorrhage [176].

Cinnarizine
Hereditary angioedema
a) A study in 7 patients compared the efficacy of tranexamic acid (AMCA) 1 gram (g)
twice daily to 1.5 g three times daily in 4 patients to cinnarizine 20 to 30 mg daily in 3
patients for the treatment of hereditary angioneurotic edema (HANE). During continuous
therapy, AMCA kept 2 out of 3 patients almost symptomfree, and the third patient had
milder and fewer attacks. Cinnarizine provided relief to 2 out of 3 patients. One of these
milder and fewer attacks. Cinnarizine provided relief to 2 out of 3 patients. One of these
patients was an AMCA treatment failure [190].

Desmopressin Acetate
Menorrhagia
a) Women with menorrhagia and identifiable hemostatic abnormalities treated with oral
tranexamic acid experienced significantly greater decreases in menstrual blood loss
assessed by pictorial blood assessment chart (PBAC) scores compared with nasal
desmopressin acetate, according to a prospective, randomized crossover study (n=116).
Women (mean age of 36 years) with regular menstrual periods at least every 39 days, a
negative pelvic exam, a negative Papanicolaou (PAP) smear within the last 12 months,
and a PBAC score of 100 or greater were included in the study. At baseline, diagnostic
blood analysis revealed abnormal platelet aggregation and/or releases in 70% (47/67) of
tranexamic acidtreated patients and in 82% (40/49) of desmopressin acetatetreated
patients and baseline median PBAC scores of 229 +/ 163.7 and 218 +/ 199.3,
respectively. Patients were randomized to receive either desmopressin acetate 300
micrograms intranasally on days 2 and 3 of menstrual bleeding for 2 cycles (n=39), and
subsequently receive tranexamic acid 1 gram orally 4 times daily for the first 5 days of
menstrual bleeding for 2 cycles (n=28), or patients received tranexamic acid (n=51)
followed by desmopressin acetate (n=45). No washout period was required between
treatment regimens. In a crossover analysis the decrease in PBACscore from baseline
was 105.7 (95% confidence interval (CI), 130.5 to 81) in tranexamic acidtreated
patients and was 64.1 (95% CI, 88 to 40.3) in desmopressin acetatetreated patients,
for a difference of 41.6 (CI 19.6 to 63.6) p=0.0002. Mean PBAC scores at baseline had a
significant effect on improvement; for every unit increase in baseline PBAC score, the
change in PBAC decreased by 0.36. Neither treatment groups fully controlled
menorrhagia by decreasing PBAC scores under 100. Quality of life showed improvements
in both tranexamic acid and desmopressin acetatetreated patients. There was a high
dropout rate, 43% in desmopressin acetatetranexamic acid sequence and 33% in the
tranexamic aciddesmopressin acetate sequence. The study did not include a placebo
arm and utilized PBAC score rather than the gold standard of alkaline hematin
spectrophotometrics for measuring menstrual blood loss [194].

Diclofenac
Menorrhagia
a) One controlled study reported the superiority of tranexamic acid over diclofenac in the
treatment of menorrhagia in women with an intrauterine device and heavy menstrual
bleeding [185]. Mean menstrual blood loss was significantly reduced by tranexamic acid
(54%) after treatment with 1.5 g by mouth three times per day for five days of each
cycle. Diclofenac reduced menstrual blood loss by 20% with doses of 50 mg by mouth
three times per day for the first day followed by 25 mg by mouth three times per day for
four days of each cycle. However, side effects were more frequent with tranexamic acid.
b) Although tranexamic acid was more effective than diclofenac, diclofenac is
recommended over tranexamic acid for the initial treatment of menorrhagia due to the
lower incidence of side effects observed [185]. Tranexamic acid could be considered if
diclofenac is ineffective.

Estriol
Epistaxis Osler hemorrhagic telangiectasia syndrome
a) In the randomized NOSE trial in adults with hereditary hemorrhagic telangiectasia
related epistaxis (N=121), during weeks 5 to 12 with twice daily topical nasal spray
treatment, there was no significant difference in patientreported median weekly
epistaxis frequency in patients receiving bevacizumab 1% (7 episodes), estriol 0.1% (8
episodes), or tranexamic acid 10% (7.5 episodes) compared with placebo (normal saline;
8 episodes). All 4 groups significantly decreased the epistaxis severity score from
baseline with no significant betweengroup difference. There was also no significant 37/77
baseline with no significant betweengroup difference. There was also no significant
betweengroup differences in epistaxis duration, hemoglobin or ferritin levels, or
transfusion requirements [184].

Ethamsylate
Menorrhagia
a) Tranexamic acid was significantly superior to ethamsylate and mefenamic acid in
improving menorrhagia in a randomized, comparative study involving 76 women with
objective evidence of dysfunctional uterine bleeding. Before treatment, all women had
menstrual loss greater than 80 milliliters (mL) (mean of 3 consecutive menses as
control). During 3 consecutive menstrual cycles, women were treated for 5 bleeding days
with either ethamsylate 500 mg every 6 hours, mefenamic acid 500 mg every 8 hours, or
tranexamic acid 1 gram (g) every 6 hours. Ethamsylate did not significantly reduce
menstrual blood loss, whereas reductions achieved by mefenamic acid and tranexamic
acid were 20% and 54%, respectively. There was no significant difference in the duration
of bleeding between treatment groups (approximately 5.5 days). A significant reduction
in sanitary napkins use was evident in the mefenamic acid and tranexamic acid groups
[188].

Tonsillectomy and adenoidectomy
a) During a controlled trial of 64 children undergoing adenotonsillectomy, tranexamic
acid and ethamsylate each failed to decrease operative blood loss compared to placebo.
Patients in the ethamsylate group received 2 oral doses of 12 milligrams/kilogram
(mg/kg) at 12 and 2 hours before surgery, then the same dose intravenously at the time
of surgery. Tranexamic acid 50 mg/kg was administered 2 hours before surgery [186].
b) Other placebocontrolled studies suggest lack of efficacy of either agent given
intravenously in reducing bleeding in patients undergoing adenoidectomy, tonsillectomy,
or adenotonsillectomy [187].

Flurbiprofen
Menorrhagia
a) A levonorgestrelreleasing intrauterine device, flurbiprofen, and tranexamic acid were
evaluated in a comparative study involving 31 women with menstrual blood loss well in
excess of 80 mL each cycle [189]. A significant reduction in menstrual blood loss was
seen in the group treated with levonorgestrol (16 women), decreasing from a mean
blood loss in control cycles of 203 mL to a mean blood loss of 9 mL (a 96% reduction)
after 12 months of therapy . Some intermenstrual bleeding or spotting was noted during
the initial three menstrual cycles, but was considered to be very minimal. Amenorrhea
occurred frequently (in 7 women or 44% of study subjects). Flurbiprofen and tranexamic
acid were evaluated in crossover fashion in 15 women, two cycles with each drug.
Although both agents achieved significant decreases in menstrual blood loss, no washout
period was provided between the two treatments, and both were significantly less
effective than levonorgestrel. All three agents appear to provide therapeutic benefit
which may thus provide useful alternatives to surgical intervention in certain patients.

Levonorgestrel
Menorrhagia
a) In a prospective, randomized, parallelgroup, multicenter clinical trial in 571 women
with menorrhagia, treatment with levonorgestrel intrauterine system (IUS) significantly
improved Menorrhagia MultiAttribute Scale (MMAS) scores compared with standard
medical therapy over a 2year period. Patients between 25 and 50 years old were
randomized to receive levonorgestrel IUS (n=285) or standard medical treatment
specified prior to randomization (n=286: tranexamic acid, mefenamic acid,
norethindrone, combined estrogen/progesterone, progesterone, or medroxyprogesterone
acetate injection). Treatments could be changed to another standard medical treatment
or levonorgestrel IUS or discontinued according to usual practice. MMAS scores (primary
outcome; selfevaluation of 6 domains of daily life, from 1 (severely affected) to 100 (not
outcome; selfevaluation of 6 domains of daily life, from 1 (severely affected) to 100 (not
affected)) improved from baseline for both treatment groups, but improvements were
significantly greater for women assigned to the levonorgestrel IUS group compared with
standard medical therapy (mean difference in scores at 2years, 13.4 points; 95% CI, 9.9
to 16.9; p less than 0.001). When women who switched treatments were excluded,
additional improvement was demonstrated in the levonorgestrel IUS group compared
with standard medical therapy (mean difference in scores at 2years, 17.8 points; 95%
CI, 14.1 to 21.5; p less than 0.001). The most common reasons for discontinuation of
levonorgestrel IUS treatment (occurring in 26 patients) were lack of effectiveness (37%),
and irregular or prolonged bleeding (28%), and discontinuation of standard medical
therapies (occurring in 57 patients) was lack of efficacy (53%); 49% of patients who
discontinued medical therapies switched to levonorgestrel IUS [191].

b) A levonorgestrelreleasing intrauterine device, flurbiprofen, and tranexamic acid were
evaluated in a comparative study involving 31 women with menstrual blood loss well in
excess of 80 mL each cycle . A significant reduction in menstrual blood loss was seen in
the group treated with levonorgestrel (16 women), decreasing from a mean blood loss in
control cycles of 203 mL to a mean blood loss of 9 mL (a 96% reduction) after 12
months of therapy . Some intermenstrual bleeding or spotting was noted during the
initial 3 menstrual cycles, but was considered to be very minimal. Amenorrhea occurred
frequently (in 7 women or 44% of study subjects). Flurbiprofen and tranexamic acid
were evaluated in crossover fashion in 15 women, 2 cycles with each drug. Although
both agents achieved significant decreases in menstrual blood loss, no washout period
was provided between the two treatments, and both were significantly less effective than
levonorgestrel. All 3 agents appear to provide therapeutic benefit which may thus provide
useful alternatives to surgical intervention in certain patients [192].

Norethindrone
Menorrhagia
a) TRANEXAMIC ACID was safe and effectively reduced blood loss during menstrual
periods in women with ovulatory menorrhagia; in contrast, NORETHISTERONE
(NORETHINDRONE) was associated with increased blood loss, based on a doubleblind,
controlled study (n=46). Ovulatory menorrhagia was defined as menstrual blood loss
greater than 80 milliliters (mL) per cycle with midluteal serum progesterone greater than
9 nanomoles/liter. During the first 2 cycles, study subjects received placebo and served
as their own controls. After those 2 cycles, the cohort was randomized to 2 cycles of
either tranexamic acid (1 gram 4 times daily on days 1 to 4; n=25) or norethisterone (5
milligrams twice daily on days 19 to 26; n=21). Blood loss was assessed after each of the
2 cycles. Tranexamic acid was associated with a blood loss reduction of 45% from mean
175 to 97 mL (p less than 0.0001). Norethisterone was associated with a 20% increase in
blood loss from mean 173 to 208 mL (p=0.26). Fourteen women (56%) in the
tranexamic acid group achieved a menstrual loss of less than 80 mL of blood per cycle,
compared with 2 (9.5%) who reached that level in the norethisterone group. No serious
side effects were reported for either drug [193].

Prednisolone
Traumatic hyphema
a) Tranexamic acid was more effective than oral prednisoLONE in preventing rebleeding
in patients with traumatic hyphema. Patients admitted with traumatic hyphema were
randomized to receive tranexamic acid 75 milligrams/kilogram (mg/kg) orally, divided
into 3 daily doses (n=80), prednisoLONE 0.75 mg/kg orally divided in 2 daily doses
(n=78), or placebo 3 times daily (n=80). Each medication was given for 5 days.
Secondary bleeding occurred in 43 patients after 2 to 6 days (median 3 days).
Rebleeding occurred in 10% of the tranexamic acid group, in 18% in the prednisoLONE
group, and in 26% of the placebo group. Rebleeding in the tranexamic group was
significantly less than in the placebo group (p=0.008). Rebleeding in the prednisoLONE
and placebo groups was not significantly different. No patient had to discontinue
tranexamic acid or prednisoLONE due to adverse effects. There were no rapid increases
in intraocular pressure after discontinuation of tranexamic acid. The authors conclude
that tranexamic acid should be the drug of choice for the prevention of rebleeding after39/77
that tranexamic acid should be the drug of choice for the prevention of rebleeding after
traumatic hyphema [179].

Place In Therapy
A) Oral tranexamic acid is indicated for the treatment of cyclic heavy menstrual bleeding [16].
Intravenous tranexamic acid is indicated for the shortterm use in hemophiliacs undergoing dental
extractions [4].
B) Cardiac Surgery
1) In a retrospective cohort analysis in children and neonates undergoing heart surgery (n=22,258;
median age, 7.6 months), tranexamic acid was associated with a reduced risk of hospital mortality
or bleeding requiring surgical intervention compared with aprotinin (odds ratio (OR), 0.47; 95% CI,
0.3 to 0.74; p=0.001). The advantage of tranexamic acid over aprotinin was more pronounced in a
subgroup of neonates (OR, 0.3; 95% CI, 0.15 to 0.58; p=0.0004). No difference in the risk of
hospital mortality or bleeding requiring surgical intervention was detected between patients who
received aprotinin compared with aminocaproic acid [169].

2) A metaanalysis reported that lysine analogues, such as tranexamic acid, decrease perioperative
blood loss in cardiac surgery patients. Treatment with lysine analogues also decreased the
frequency of surgical reexploration (odds ratio, 0.44; CI, 0.22 to 0.9). These agents appear to have
no effect on the risk of perioperative myocardial infarction [170].
C) KasabachMerritt Syndrome In The Newborn
1) Tranexamic acid is considered a secondline medication in severe KasabachMerritt syndrome in
the newborn [171].

D) Subarachnoid Hemorrhage
1) Although tranexamic acid is not indicated in subarachnoid hemorrhage due to a high incidence
of ischemic complications, it was as effective as aminocaproic acid in preventing rebleeding
hemorrhage following subarachnoid hemorrhage in 1 report. Tranexamic acid may have more
sustained antifibrinolytic effects and is 6 to 10 times more potent than aminocaproic acid in
fibrinolytic activity [172][173][174]. In addition, tranexamic acid has greater and more sustained
antifibrinolytic activity in tissues than aminocaproic acid [173] and appears to have the same order
of acute and chronic toxicity [172].

2) Tranexamic acid (36 g daily) was equal in efficacy to aminocaproic acid (6 g daily), oral and
intravenous, in the prevention of recurrent hemorrhage and delayed ischemic deficits following
subarachnoid hemorrhage. The most common side effects were nausea, vomiting, and diarrhea
with both agents, with detectable deep vein thrombosis occurring in 6% of patients in each group
[175].

MEDICATION SAFETY
Contraindications
A) Women using hormonal contraception with oral administration [115]
B) Acquired defective color vision with IV administration [116]
C) Hypersensitivity to tranexamic acid [115] or other components of the product [116]
D) Active intravascular clotting with IV administration [116]
E) Subarachnoid hemorrhage; cerebral edema or infarction may occur with IV administration [116]
F) Active thromboembolic disease (eg, DVT, pulmonary embolism, or cerebral thrombosis) with oral
administration [115]
G) History of thrombosis or thromboembolism, including retinal vein or artery occlusion with oral
H) Intrinsic risk of thrombosis or thromboembolism (eg, thrombogenic valvular disease,
thrombogenic cardiac rhythm disease, or hypercoagulopathy) with oral administration [115]
Precautions
A) Cardiovascular: Thrombosis and thromboembolism, venous or arterial, have been reported with
IV administration, especially in patients with a history of thromboembolic disease [116]
B) Cardiovascular: Treatment of patients with DIC requires strict supervision of experienced
physician with IV administration [116]
C) Concomitant use: Not recommended with factor IX complex concentrates or antiinhibitor
coagulant concentrates [116][115]
D) Immunologic: Anaphylactic shock and severe allergic reaction have been reported with oral
E) Neurologic: Convulsions have been reported with IV administration; increased risk with
cardiovascular surgery or inadvertent neuraxial system administration [116]
F) Ophthalmic: Retinal occlusion, arterial and venous, has been reported [116]; discontinuation may
be required [115]
G) Ophthalmic: Ligneous conjunctivitis has been reported with oral administration [115]
H) Ophthalmic: Visual abnormalities may occur with IV administration; monitoring recommended
[116]
I) Renal: Ureteral obstruction, due to clot formation from upper urinary tract bleeding, has been
reported with IV administration [116]
J) Renal: Risk of accumulation with IV administration in patients with impaired renal function; dose
adjustment recommended [116]
Adverse Effects
Cardiovascular Effects
Hypotension
1) Hypotension has been reported occasionally with the use of tranexamic acid, primarily
when intravenous administration of the drug is too rapid (ie, administered at a rate
greater than 1 mL/min) [119]. Hypotension has not been reported with oral
administration of tranexamic acid [18].

Dermatologic Effects
Atopic dermatitis
1) Allergic dermatitis has been occasionally reported in patients treated with IV
tranexamic acid [119].
Fixed drug eruption
1) Adult Case Reports
a) Generalized fixed drug eruption on the back, thigh, and groin was reported in a 39
yearold woman following use of numerous commercial and prescription drugs
containing tranexamic acid. The patient presented with recurring episodes of erythema
and postinflammatory pigmentation. Closed patch testing produced negative results. An
oral challenge test was performed with tranexamic acid 250 mg and within 1 hour of
administration erythema appeared, including new lesions in previously unaffected areas.
Although the regular dose of tranexamic acid was used in this case, the authors
recommend initiating an oral test with a low dose and titrating up until the first objective
symptoms occur, or until the maximum single dose is reached without symptoms. The
skin lesions regressed with oral prednisoLONE treatment for 3 days; no recurrence was
noted [140].

Purpuric rash
1) Adult Case Reports
a) A 33yearold woman who received tranexamic acid for persistent microscopic
hematuria following pyeloplasty of her right kidney, developed a patchy, itchy rash. The
woman had tolerated tranexamic acid 1 g 3 times daily for 8 years. Her other
medications included furosemide and ibuprofen. The rash started on her hands and
progressed to her trunk and limbs. There was no response to terfenadine, miconazole
cream, or oral doxycycline. Prednisolone provided some relief. With the discontinuation
of tranexamic acid, the rash resolved within days. After rechallenge, the rash recurred
within 2 to 3 hours. After 4 months without drug therapy, desensitization with
tranexamic acid 25 mcg was attempted; however, the rash recurred after 5 days [141].

Toxic epidermal necrolysis
1) A 67yearold man with alcoholrelated liver cirrhosis, ascitic decompensation,
esophageal varices, and renal insufficiency developed toxic epidermal necrolysis (TEN)
following oral tranexamic acid treatment for rectal bleeding. Hemorrhaging partially
resolved with tranexamic acid 1000 mg therapy given orally every 8 hours together with
band and suture of a bleeding hemorrhoid. However, a purplish, erythematous macular
rash developed on his trunk 10 days after initiation of tranexamic acid. Longterm
concomitant medications included spironolactone, furosemide, omeprazole, lactulose, and
bisoprolol. Despite a tranexamic acid dose reduction to 1000 mg orally every 12 hours
secondary to renal insufficiency, the erythematous lesions spread over the patient's face,
trunk, and extremities over the next week and affected approximately 50% of the body
surface, including oral and genital mucosa. With no history of drug allergies nor previous
exposure to tranexamic acid, the patient was empirically diagnosed with TEN.
Tranexamic acid was withdrawn and the patient was treated with Nacetylcysteine and
10 days of oral prednisone. Though a skin patch test showed no correlation with
tranexamic acid, skin biopsy results were compatible with TEN. The Naranjo probability
scale indicated a probable relationship between the use of tranexamic acid and the
development of TEN in this patient. The skin and mucous lesions resolved and the
epithelium gradually returned with treatment. Two weeks later, however, the patient died
secondary to acute renal failure and multiorgan failure [142].

Gastrointestinal Effects
Abdominal pain
1) Incidence: oral, 12% [118] to 19.8% [18]

2) Abdominal pain, including abdominal tenderness and discomfort, was reported in 46
patients (19.8%) treated with oral tranexamic acid 3900 mg/day (n=232) compared with
25 patients (18%) treated with placebo (n=139) in 2 randomized, doubleblind, placebo
controlled, clinical trials of women 18 to 49 years of age being treated for heavy
menstrual bleeding [18].

3) Abdominal discomfort was one of the most frequently reported treatmentemergent
gastrointestinal adverse events occurring in 12% (87/723) of patients following the
longterm treatment (up to 27 cycles) with tranexamic acid in women with menorrhagia
according to an openlabel, noncontrolled study (n=723). Women, mean 38.3 years of
age, with a mean duration of menorrhagia of 9.8 years received tranexamic acid 1.3 g
orally three times daily for up to 5 days per menstrual cycle for a total of 27 menstrual
cycles. The mean duration of patient exposure to tranexamic acid was 41 days. The
discontinuation rate was 69.5% (n=545) with adverse events accounting for 17.8%. The
majority of treatmentemergent adverse events were mild or moderate in severity [118].
Diarrhea
1) Incidence: 12.2% [118]

2) Diarrhea is one of the primary side effects of tranexamic acid therapy; these
symptoms should abate if the tranexamic acid dosage is reduced [119][129][135][128]
[117][122].

3) Diarrhea was one of the most frequently reported treatmentemergent gastrointestinal
adverse events occurring in 12.2% (88/723) of patients following the longterm treatment
(up to 27 cycles) with tranexamic acid in women with menorrhagia according to an open
label, noncontrolled study (n=723). Women, mean 38.3 years of age, with a mean
duration of menorrhagia of 9.8 years received tranexamic acid 1.3 g orally three times
daily for up to 5 days per menstrual cycle for a total of 27 menstrual cycles. The mean
duration of patient exposure to tranexamic acid was 41 days. The discontinuation rate 42/77
duration of patient exposure to tranexamic acid was 41 days. The discontinuation rate
was 69.5% (n=545) with adverse events accounting for 17.8%. The majority of
treatmentemergent adverse events were mild or moderate in severity [118].
Nausea
1) Incidence: 14.4% [118]

2) Nausea is one of the primary side effects of tranexamic acid therapy; these symptoms
should abate if the tranexamic acid dosage is reduced [119][129][135][128][117][122].
3) Nausea was one of the most frequently reported treatmentemergent gastrointestinal
adverse events occurring in 14.4% (104/723) of patients following the longterm
treatment (up to 27 cycles) with tranexamic acid in women with menorrhagia according
to an openlabel, noncontrolled study (n=723). Women, mean 38.3 years of age, with a
mean duration of menorrhagia of 9.8 years received tranexamic acid 1.3 g orally three
times daily for up to 5 days per menstrual cycle for a total of 27 menstrual cycles. The
mean duration of patient exposure to tranexamic acid was 41 days. The discontinuation
rate was 69.5% (n=545) with adverse events accounting for 17.8%. The majority of
Vomiting
1) Vomiting is one of the primary side effects of tranexamic acid therapy; these
symptoms should abate if the tranexamic acid dosage is reduced [119][129][135][128]
[117][122].

Hematologic Effects
Anemia
1) Incidence: oral, 5.6% [18]

2) Anemia was reported in 13 patients (5.6%) treated with oral tranexamic acid 3900
mg/day (n=232) compared with 5 patients (3.6%) treated with placebo (n=139) in 2
randomized, doubleblind, placebocontrolled, clinical trials of women 18 to 49 years of
age being treated for heavy menstrual bleeding [18].
Blood coagulation disorder
1) Coagulation defects or disorders and abnormal bleeding times have been observed
rarely [117].

Decreased platelet count
1) Thrombocytopenia has been rarely reported [117].

2) The mean decrease in platelet count from baseline to study termination was 13,233
(from 298,791 to 282,689) following longterm treatment (up to 27 cycles) with
tranexamic acid in women with menorrhagia according to an openlabel, noncontrolled
study (n=723). Women, mean 38.3 years of age, with a mean duration of menorrhagia
of 9.8 years received tranexamic acid 1.3 g orally three times daily for up to 5 days per
menstrual cycle for a total of 27 menstrual cycles. The mean duration of patient exposure
to tranexamic acid was 41 days. The discontinuation rate was 69.5% (n=545) with
adverse events accounting for 17.8%. The majority of treatmentemergent adverse
events were mild or moderate in severity [118].
Deep venous thrombosis
1) Thromboembolic events including DVT, pulmonary embolism, cerebral thrombosis,
acute renal cortical necrosis, and central retinal artery and vein obstruction have been
reported during postmarketing use of tranexamic acid for various indications [16][119].
These reports were in patients who were using combination hormonal contraceptives
concomitantly (now contraindicated) [16].

2) Systemic thromboembolic complications have been reported with tranexamic acid,
including thromboembolism, myocardial infarction, and pulmonary embolism [121][122]
[123][124][125]. However, these complications do not appear to be frequent. The
occurrence of preoperative DVT in 2 of 30 patients receiving tranexamic acid; both
patients also had pulmonary embolism and 2 additional cases of pulmonary embolism
were described in tranexamic acidtreated patients [122]. DVT has been associated with
tranexamic acid for the treatment of idiopathic thrombocytopenia purpura [126].
Thromboembolic disorder
1) Thromboembolic events (eg, DVT, pulmonary embolism, cerebral thrombosis, acute
renal cortical necrosis, and central retinal artery and vein obstruction) have been

2) A nested casecontrol study of data from the General Practice Research Database
(GPRD) revealed that the use of tranexamic acid to treat menorrhagia is associated with
the risk of venous thromboembolism (VTE); however the risk was not significant
(adjusted odds ratio (OR), 3.2; 95% CI, 0.65 to 15.78) and the study was underpowered.
Using data from 1992 through 1998, a cohort of 122,237 women between the ages of 15
and 49 years with a diagnosis of menorrhagia were identified from the GPRD (a database
of general practice patient records for approximately 4% of the population in the United
Kingdom). From this cohort, 134 cases of VTE meeting inclusion criteria (women with
known risk factors for VTE were excluded) were identified. For each case, an average of
4 controls were matched by practice, year of birth and index date of event. Cases and
controls were considered to be exposed to tranexamic acid or other medications used to
treat menorrhagia if they had a prescription within 90 days of the index date. Three of
the 134 women experiencing VTE had been exposed to tranexamic acid compared with 4
of the women in the control group (n=552). Details of the specific tranexamic acid
exposure or resulting VTE were not reported. Other treatments for menorrhagia which
included mefenamic acid and norethisterone were shown to have an associated risk of
VTE with a an adjusted odds ratios of 5.54 (95% CI 2.13 to 14.4) and 2.41 (95% CI 1 to
5.78), respectively. A diagnosis of anemia, obesity, and smoking was shown to have
significantly increased the risk of VTE in this casecontrol study [120].

4) Administration of tranexamic acid to decrease blood loss in patients undergoing
transurethral prostatectomy has been associated with intravesical blood clotting. In this
study, 3 of 6 patients who received 1 g by mouth preoperatively and 1 g 3 times per day
postoperatively until macroscopic bleeding subsided developed indissoluble blood clots
adherent to the bladder wall. Irrigation had no effect and surgery was required. The drug
is not recommended for routine use after prostatectomy [127].

Immunologic Effects
Anaphylaxis
1) Anaphylactic reactions and anaphylactic shock have been reported during
postmarketing use of tranexamic acid for various indications [18].
Hypersensitivity reaction (Severe)
1) A case of severe allergic reaction (dyspnea, throat tightening, and facial flushing) that
required emergency medical treatment was reported in a patient on her fourth treatment
cycle in a longterm extension study of women treated with oral tranexamic acid 3900
mg/day for up to 5 days through 9 menstrual cycles (n=288) [18].

Musculoskeletal Effects
Arthralgia

2) Arthralgia, including joint stiffness and swelling, was reported in 16 patients (6.9%)
treated with oral tranexamic acid 3900 mg/day (n=232) compared with 7 patients (5%)
treated with placebo (n=139) in 2 randomized, doubleblind, placebocontrolled, clinical
trials of women 18 to 49 years of age being treated for heavy menstrual bleeding [18].
3) Arthralgia occurred in 14.5% (105/723) of patients following the longterm treatment
label, noncontrolled study (n=723). Women, mean 38.3 years of age, with a mean 44/77
Backache
1) Incidence: oral, 20.7% to 31.4% [118][18]

2) Back pain was reported in 48 patients (20.7%) treated with oral tranexamic acid 3900

3) Back pain occurred in 31.4% (227/723) of patients following the longterm treatment
Cramp

2) Muscle cramps and spasms were reported in 15 patients (6.5%) treated with oral
tranexamic acid 3900 mg/day (n=232) compared with 8 patients (5.8%) treated with
placebo (n=139) in 2 randomized, doubleblind, placebocontrolled, clinical trials of
women 18 to 49 years of age being treated for heavy menstrual bleeding [18].
Musculoskeletal pain

2) Musculoskeletal pain, including musculoskeletal discomfort and myalgia, was reported
in 26 patients (11.2%) treated with oral tranexamic acid 3900 mg/day (n=232)
compared with 4 patients (2.9%) treated with placebo (n=139) in 2 randomized, double
blind, placebocontrolled, clinical trials of women 18 to 49 years of age being treated for
heavy menstrual bleeding [18].

Neurologic Effects
Cerebral ischemia
1) Summary
a) Tranexamic acid has been demonstrated to cause or aggravate cerebral ischemic
complications when administered for the prevention of rebleeding in patients with
subarachnoid hemorrhage [128][122]. Several case reports of cerebral thrombosis and
infarction have been published [129][130][131][132]. A statistically higher incidence of
cerebral infarction was reported in tranexamic acidtreated patients as compared to
placebotreated patients undergoing therapy for subarachnoid hemorrhage [128].
2) An increased incidence of severe vasospasm, fatal delayed cerebral ischemia,
pulmonary embolism and myocardial infarction was reported in tranexamic acidtreated
patients, as compared to control patients, in a randomized controlled study [122]. These
data also support the contention that tranexamic acid may produce cerebral ischemic
complications. Fatal cerebral arterial thrombosis was described in a 26yearold woman
who received tranexamic acid 1.5 g daily for persistent uterine bleeding following
insertion of an intrauterine device (IUD) [130]. Intracranial arterial thrombosis was
described in 2 women who received tranexamic acid for the treatment of menorrhagia.
Both patients received the drug in doses of 0.5 to 4.5 g daily for approximately one year
during periods of menstrual blood loss. One patient was discharged after one month with
no residual symptoms, whereas the other patient retained some leftsided weakness,
dysesthesia, and hemianopia after a period of 3 months [132].
Cerebral thrombosis
1) Thromboembolic events and thromboembolism, including cerebral thrombosis, have
been reported with the postmarketing use of tranexamic acid for various indications [16]
[119]. These reports were in patients who were using combination hormonal
contraceptives concomitantly (now contraindicated) [16].
Dizziness
1) Dizziness has been reported with tranexamic acid use [119].
Headache
1) Incidence: oral, 50.4% to 60.4% [118][18]

2) Headache (including tension headache) was reported in 117 patients (50.4%) treated
with oral tranexamic acid 3900 mg/day (n=232) compared with 65 patients (46.8%)
treated with placebo (n=139) in 2 randomized, doubleblind, placebocontrolled, clinical
trials of women 18 to 49 years of age being treated for heavy menstrual bleeding [18].
3) Headache was one of the most frequently reported treatmentemergent adverse
events occurring in 60.4% (437/723) of patients following the longterm treatment (up to
27 cycles) with tranexamic acid in women with menorrhagia according to an openlabel,
noncontrolled study (n=723). Women, mean 38.3 years of age, with a mean duration of
menorrhagia of 9.8 years received tranexamic acid 1.3 g orally three times daily for up to
5 days per menstrual cycle for a total of 27 menstrual cycles. The mean duration of
patient exposure to tranexamic acid was 41 days. The discontinuation rate was 69.5%
(n=545) with adverse events accounting for 17.8%. The majority of treatmentemergent
adverse events were mild or moderate in severity [118].
Hydrocephalus
1) Since tranexamic acid inhibits fibrinolysis, retained clots around the arachnoid villi may
induce scarring and decrease cerebrospinal fluid (CSF) absorption, predisposing to the
development of hydrocephalus [117].

2) The occurrence of hydrocephalus, requiring drainage of cerebrospinal fluid, was
reported in more patients receiving tranexamic acid than placebo; however, this
difference did not reach a level of statistical significance [128]. Other investigators have
reported the occurrence of hydrocephalus during prophylaxis of rebleeding in
subarachnoid hemorrhage [124].
Migraine
1) Incidence: oral, 6% to 10.8% [118][18]

2) Migraine was reported in 14 patients (6%) treated with oral tranexamic acid 3900

3) Migraine occurred in 10.8% (78/723) of patients following the longterm treatment (up
to 27 cycles) with tranexamic acid in women with menorrhagia according to an open
Seizure
1) Incidence: 0.3% to 2.6% [133][134]
2) General Information
a) Convulsions have been reported with tranexamic acid use [119].
3) Adult Clinical Trials
a) Cardiac surgery (IV route): 0.9%; significantly higher seizure incidence with infusion
(2.6%; cumulative dose, greater than 80 mg/kg (1)) compared with bolus
administration (0.3%; bolus dose, 50 mg/kg (1)) [133]

b) Cardiac surgery (IV route): 2.5% (mean dose, 24 mg/kg (1)) vs 1.2% in patients
who did not receive tranexamic acid [134]

Summary
1) The most serious adverse effects of tranexamic acid are cerebral ischemia and
infarction, which have occurred during use of the drug to prevent rebleeding in
subarachnoid hemorrhage [129][128][130][122][131][132]; other central nervous
subarachnoid hemorrhage [129][128][130][122][131][132]; other central nervous
system (CNS) side effects have included headache and hydrocephalus [18][128][124].

Ophthalmic Effects
Blurred vision
1) Severe blurred vision occurred in one patient which resulted in discontinuation from
the study following longterm treatment (up to 27 cycles) with tranexamic acid in women
with menorrhagia, according to an openlabel, noncontrolled study (n=723). The blurred
vision later resolved upon discontinuation of therapy. Women, mean 38.3 years of age,
with a mean duration of menorrhagia of 9.8 years received tranexamic acid 1.3 g orally
three times daily for up to 5 days per menstrual cycle for a total of 27 menstrual cycles.
The mean duration of patient exposure to tranexamic acid was 41 days. The
discontinuation rate was 69.5% (n=545) with adverse events accounting for 17.8%. The
majority of treatmentemergent adverse events were mild or moderate in severity [118].
Central retinal artery occlusion
1) Central retinal artery obstruction has been reported in patients treated with
tranexamic acid during postmarketing surveillance. Immediate treatment discontinuation
is recommended [16][119]. Some of these reports were in patients who were using
combination hormonal contraceptives concomitantly (now contraindicated) [16].
Chromatopsia
1) Chromatopsia has been rarely reported with the postmarketing use of tranexamic acid
[119].

Color vision deficiency
1) Impaired color vision has been reported during postmarketing use of tranexamic acid
for various indications. Immediate treatment discontinuation is recommended [18][18].
Tranexamic acid IV is contraindicated in patients with acquired defective color vision
[119].

Ligneous conjunctivitis
1) Ligneous conjunctivitis has been reported in patients treated with tranexamic acid,
which resolved after drug cessation [138].
Venous retinal branch occlusion
1) Retinal vein obstruction has been reported in patients treated with tranexamic acid
during postmarketing surveillance. Immediate treatment discontinuation is recommended
[16][119]. Some of these reports were in patients who were using combination hormonal
contraceptives concomitantly (now contraindicated) [16].
Venous stasis retinopathy
1) Two cases of central venous stasis retinopathy were reported in women who received
tranexamic acid for severe menorrhagia. Both cases occurred within 1 week of beginning
use of tranexamic acid 2 g/day, and both resolved within 8 to 10 weeks following
discontinuation of the therapy and administration of prednisone 60 mg/day and
dipyridamole 225 mg/day. No further ophthalmological problems occurred during follow
up (minimum 2 years) [139].
Visual disturbance
1) Visual disturbances have been reported during postmarketing use of tranexamic acid
for various indications. Immediate treatment discontinuation is recommended [119][18].

Psychiatric Effects
Giddiness
1) Giddiness has been occasionally reported in patients treated with IV tranexamic acid
[119].

Psychiatric sign or symptom
1) Psychiatric disturbances may occur during tranexamic acid therapy, which may create
diagnostic difficulties in patients with subarachnoid hemorrhage [117].
Restlessness
1) Restlessness may occur during tranexamic acid therapy, which may create diagnostic
difficulties in patients with subarachnoid hemorrhage [117].

Renal Effects
Occlusion of ureter
1) Ureteral obstruction due to clot formations has been reported in patients treated with
tranexamic acid for upper urinary tract bleeding [119].
Renal cortical necrosis, acute
1) Acute renal cortical necrosis has been reported in patients treated with tranexamic
acid for various indications during postmarketing surveillance [16][119]. Some of these
reports were in patients who were using combination hormonal contraceptives

2) Acute bilateral renal cortical necrosis occurred in a 21yearold man with hemophilia A
who was treated with a 4day course of tranexamic acid 3 g/day for epistaxis. Three days
later, the patient developed oligoanuria and azotemia. Urinary analysis showed no
proteinuria or hematuria. On day 6 of hospitalization, serum creatinine increased to 8.1
mg/dL. He was treated with hemodialysis for 3 weeks. During followup, urine output
decreased below 20 cc/day, and did not increase again. Renal angiography was
performed and a diagnosis of renal cortical necrosis was made [136].

3) A 37yearold man developed acute renal cortical necrosis with glomerular thrombosis
after receiving tranexamic acid therapy for hemoptysis. He had a history of pulmonary
tuberculosis and recently developed hemoptysis for which treatment included tranexamic
acid 3 g daily for 5 days. After 6 days, he suddenly developed anuria and azotemia with a
normal coagulation profile. Light microscopy revealed an infarction with fibrin thrombi in
the intraglomerular capillaries and arterioles. He received hemodialysis for 2 weeks with
slow improvement of his renal function [137].
Respiratory Effects
Nasal sinus problem

2) Nasal and sinus symptoms, including nasal, respiratory tract, and sinus congestion,
sinusitis, acute sinusitis, sinus headache, allergic sinusitis and sinus pain, and multiple
allergies and seasonal allergies were reported in 59 patients (25.4%) treated with oral
tranexamic acid 3900 mg/day (n=232) compared with 24 patients (17.3%) treated with
placebo (n=139) in 2 randomized, doubleblind, placebocontrolled, clinical trials of
women 18 to 49 years of age being treated for heavy menstrual bleeding [18].
Pulmonary embolism
1) Thromboembolic events (eg, DVT, pulmonary embolism, cerebral thrombosis, acute
renal cortical necrosis, and central retinal artery and vein obstruction) have been


Other
Fatigue

2) Fatigue was reported in 12 patients (5.2%) treated with oral tranexamic acid 3900

Black Box Warning
No results available
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Drug Interactions (single)
DrugDrug Combinations
AntiInhibitor Coagulant Complex
1) Interaction Effect: an increased risk of thrombosis

2) Summary: Since limited data are available on the coadministration of highly activated
prothrombin complex products and antifibrinolytic agents, antiinhibitor coagulant
complex not be used concomitantly with tranexamic acid[146].
3) Severity: major
4) Onset: rapid

5) Substantiation: theoretical

6) Clinical Management: Due to the possibility of additive effects on coagulation, this
combination should not be used.
7) Probable Mechanism: unknown
Chlorpromazine
1) Interaction Effect: increased risk of bleeding
2) Summary: In a 2series clinical trial (n=105) of tranexamic acid for treatment of
subarachnoid hemorrhage due to a ruptured aneurysm, one tranexamic acidtreated
patient, who was also taking chlorproMAZINE, experienced a rebleed. The proposed
mechanism of action is the prolongation of bleeding time and increased blood
noradrenaline concentrations by chlorproMAZINE which in turn can increase the
fibrinolytic activity of blood[145]. Caution should be used with concurrent use of
chlorproMAZINE and tranexamic acid.
3) Severity: major
4) Onset: unspecified
5) Substantiation: theoretical
6) Clinical Management: Use caution when prescribing chlorproMAZINE to patients who
take tranexamic acid. Concomitant use of chlorproMAZINE and tranexamic acid may
cause an increased risk of bleeding due to an increased bleeding time chlorproMAZINE.
This may interfere with the antifibrinolytic activity of tranexamic acid resulting in
increased bleeding[145]. Monitor patient for signs and symptoms of bleeding, including
excessive bruising, wounds that will not heal, and blood in the stool or urine.
7) Probable Mechanism: increased bleeding time by chlorproMAZINE
8) Literature Reports
a) In a 2series clinical trial (n=105) of tranexamic acid for treatment of patients with
subarachnoid hemorrhage due to a ruptured aneurysm, one tranexamic acidtreated
patient experienced a rebleed. The patient was also taking chlorproMAZINE.
ChlorproMAZINE can prolong bleeding time and increase blood noradrenaline. The
authors propose that this in turn may increase the fibrinolytic activity of blood leading to
authors propose that this in turn may increase the fibrinolytic activity of blood leading to
increased bleeding in this patient population [145].

Desogestrel
1) Interaction Effect: an increased risk of thrombotic events
2) Summary: Concomitant use of combination contraceptives and tranexamic acid is
contraindicated due to further increased risk of thrombotic events, especially in women
who are obese, or smoke cigarettes, and more so, in smokers over the age of 35 years.
Venous and arterial thrombotic events have been reported during postmarketing
surveillance of women concomitantly treated with combined hormonal contraceptives and
tranexamic acid[16].
3) Severity: contraindicated
5) Substantiation: probable

6) Clinical Management: Due to further increased risk of thrombotic events, especially in
women who are obese, or smoke cigarettes, and more so, in smokers over the age of 35
years, coadministration of combination contraceptives and tranexamic acid is
contraindicated[16].

Dienogest


Drospirenone


Estradiol Cypionate


Estradiol Valerate


Ethinyl Estradiol


Ethynodiol Diacetate


Etonogestrel




Levonorgestrel





Medroxyprogesterone Acetate





Mestranol





Norelgestromin





Norethindrone





Norgestimate





Norgestrel





Tretinoin
1) Interaction Effect: increased risk of thrombosis

2) Summary: Caution should be exercised when treating patients concomitantly with
tretinoin and tranexamic acid.There is a risk of both venous and arterial thrombosis
which can involve any organ system during the first month of treatment with tretinoin.
Cases of fatal thrombotic complications have been reported rarely in patients
concomitantly treated with tretinoin and antifibrinolytic agents[147].
3) Severity: major



6) Clinical Management: Monitor the patient closely for signs or symptoms of
thromboembolic complications.

IV Compatibility (single)
Pregnancy & Lactation
A) Teratogenicity/Effects in Pregnancy
1) U.S. Food and Drug Administration's Pregnancy Category: Category B (All Trimesters)
a) Either animalreproduction studies have not demonstrated a fetal risk but there are no
controlled studies in pregnant women or animalreproduction studies have shown adverse effect
(other than a decrease in fertility) that was not confirmed in controlled studies in women in the
first trimester (and there is no evidence of a risk in later trimesters).

See Drug Consult reference: PREGNANCY RISK CATEGORIES
2) Crosses Placenta: Yes

3) Clinical Management
a) There are no adequate and wellcontrolled studies of tranexamic acid use during pregnancy.
This drug does cross the placenta and the concentration in cord blood is about equal to the
maternal concentration. In animal studies, there is no evidence of impaired fertility or fetal harm
[18][4].

4) Literature Reports
a) Tranexamic acid does cross the placenta. After a tranexamic acid 10mg/kg IV injection, the
concentration in cord blood is about 30 mg/L which is about equal to the maternal concentration
[18]. Limited data using tranexamic acid during pregnancy have revealed no harmful effects on the
fetus [148].
b) In animal reproductive studies, there was no evidence of impaired fertility or fetal harm when
mice, rats and rabbits were exposed to tranexamic acid. No adverse effects were noted in either of
2 studies in which rats were exposed to tranexamic acid at doses up to 1500 mg/kg/day (4 times
the recommended human oral dose of 3900 mg/day based on mg/m(2)) [18].

B) Breastfeeding
1) Micromedex Lactation Rating: Infant risk cannot be ruled out.
a) Available evidence and/or expert consensus is inconclusive or is inadequate for determining
infant risk when used during breastfeeding. Weigh the potential benefits of drug treatment against
potential risks before prescribing this drug during breastfeeding.

2) Clinical Management
a) There are limited data on nursing an infant while on tranexamic acid. Data have shown that
only minimal amounts of the drug are excreted in breast milk. Breast milk concentrations were
reported to be approximately 1% of peak serum levels 1 hour following the last dose of a 2day 54/77
reported to be approximately 1% of peak serum levels 1 hour following the last dose of a 2day
treatment regimen [18][4][148]. Tranexamic acid should only be used in a nursing mother only if
clearly needed and use caution when tranexamic acid is administered to a nursing mother [18][4].

3) Drug Levels in Breastmilk
a) Parent Drug
1) Milk to Maternal Plasma Ratio
a) Levels of tranexamic acid found in breast milk are about one hundredth of those in the
maternal serum [151][18]

Monitoring
A) Therapeutic
1) Physical Findings
a) Hemorrhage in Hemophilic Patients after Tooth Extraction
1) Prevention or reduction in blood loss during and after tooth extraction is evidence of efficacy.

b) Heavy Menstrual Bleeding
1) Reduction in menstrual blood loss is evidence of efficacy.

B) Toxic
1) Physical Findings
a) Intravenous
1) Perform ophthalmologic examination, including visual acuity, color vision, eyeground and
vision fields, prior to initiating tranexamic acid and at regular intervals thereafter in patients who
are to receive continual treatment longer than several days [4].

Do Not Confuse
MECHANISM OF ACTION
Mechanism of Action
A) Mechanism of Action
1) Tranexamic acid is a synthetic lysine amino acid derivative which produces antifibrinolytic effects
via complex interactions with plasminogen. In the presence of tranexamic acid, the lysine receptor
binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus
preserving and stabilizing fibrin's matrix structure. Tranexamic acid is a competitive inhibitor of
plasminogen activation , and at much higher concentrations, a noncompetitive inhibitor of plasmin
(ie, actions similar to aminocaproic acid). Tranexamic acid is about 10 times more potent in vitro
than aminocaproic acid [151][18]. In concentrations up to 10 mg/mL, tranexamic acid has no
influence on the platelet count, the coagulation time or various coagulation factors in whole blood
or citrated blood from normal subjects [18].

PHARMACOKINETICS
Pharmacokinetics
Onset and Duration
A) Duration
1) Single Dose
a) Fibrinolysis inhibition, IV: 17 hours [151]; oral: 24 hours [152].
1) An antifibrinolytic concentration of tranexamic acid persists in various tissues for
approximately 17 hours, and up to 7 or 8 hours in the serum [151].

2) Following a 10mg/kg oral dose, inhibition of urinary fibrinolytic activity persisted for at
least 24 hours [152].

Drug Concentration Levels
A) Therapeutic Drug Concentration
1) Fibrinolysis inhibition, 5 to 10 mcg/mL [159][160][161][162][163].

2) Prolongation of thrombin time, 1 mg/mL [151]
a) Prolongation of thrombin time may occur with tranexamic acid concentrations as low as 1
mg/mL, although tranexamic acid blood concentrations up to 10 mg/mL did not result in
changes in platelet count, coagulation time, or other coagulation factors in normal subjects
(whole or citrated blood samples) [151].

B) Peak Concentration
1) Adults
a) Oral, multipledose: 16.41 mcg/mL (1300 mg 3 times a day); singledose 13.83 mcg/mL
(1300 mg) [18]
1) Mean Cmax following multipledose oral administration of tranexamic acid 1300 mg 3
times a day for 5 days and singledose oral administration of tranexamic acid 1300 mg in 19
healthy women was 16.41 mcg/mL and 13.83 mcg/mL, respectively [18].

2) Pediatrics (12 to 16 years)
a) Oral, singledose: 20% to 25% lower than adult women (1300 mg) [115]
1) In a randomized, crossover study in 20 adolescent patients 12 to 16 years old with heavy
menstrual bleeding, the Cmax values following a single tranexamic acid 650 mg dose were
32% to 36% less than the AUC after a single tranexamic acid 1300 mg dose. The Cmax
values after a single tranexamic acid 1300 mg dose in this study were 20% to 25% lower
than values observed in adult women administered the same dose during a different study
[115].

3) IV, singledose: 81 to 86 mcg/mL (1 g) [154].
a) Plasma levels of 81 to 86 mcg/mL were reported 5 minutes following a 1g IV bolus
injection of tranexamic acid (over 5 minutes). Serum levels at 15 minutes and approximately
1 hour were 63 and 30 mcg/mL, respectively [154].

b) Serum concentrations of 1.3 mcg/mL or less were reported in 3 subjects at 12 hours
following a 1g IV injection of tranexamic acid. Serum levels at 24 hours ranged from 0.27 to
0.5 mcg/mL [154]

c) Serum concentrations at 54 minutes following a 0.5g IV injection were 39 mcg/mL and
less than 1 mcg/mL after 480 minutes [155].

4) IV, infusion: 18 mcg/mL (10 mg/kg) [156][152].
a) Following IV administration of a 10mg/kg dose of tranexamic acid, plasma levels at 1 and
3 hours were 18 and 10 mcg/mL, respectively. Plasma levels at 5 hours were 5 mcg/mL
[152].

5) Rectal, singledose: 0.4 to 1.1 mg/L (2 g) [153]
a) Following rectal instillation of a single 2gram dose of tranexamic acid, the median peak
plasma concentration for healthy volunteers (n=5) was 0.4 mg/L and for patients with
ulcerative colitis (n=5) was 1.1 mg/L [153].

C) Time to Peak Concentration
1) Oral: 2.5 to 3 hours [18][157][158].
a) Following singledose oral administration of tranexamic acid 1300 mg, the peak plasma
concentration occurred at approximately 3 hours [18][157][158].

b) A mean Tmax of 2.5 hours (range, 2 to 3.5 hours) was observed following multipledose
oral administration of tranexamic acid 1300 mg three times a day for 5 days in 19 healthy
women. Mean Tmax following singledose oral administration of 1300 mg, Tmax was also 2.5
hours (range, 1 to 5 hours) [18].

2) IM: 1 hour [155].
a) Peak serum concentrations of 12.4 mcg/mL were reported at 54 minutes following a 0.5g
IM injection of tranexamic acid. Serum concentrations ranged from 1.08 to 1.45 mcg/mL at
480 minutes [155].

3) IV, bolus injection: 5 minutes [154].
a) Plasma levels of 81 to 86 mcg/mL were reported 5 minutes following a 1g IV bolus
injection of tranexamic acid (over 5 minutes). Serum levels at 15 minutes and approximately
1 hour were 63 and 30 mcg/mL, respectively [154].

b) Serum concentrations of 1.3 mcg/mL or less were reported in three subjects at 12 hours
following a 1g IV injection of tranexamic acid. Serum levels at 24 hours ranged from 0.27 to
0.5 mcg/mL [154]

c) Serum concentrations at 54 minutes following a 0.5g intravenous injection were 39
mcg/mL and less than 1 mcg/mL after 480 minutes [155].

4) IV, infusion: 0.5 to 1 hour [156][152].
a) On cardiopulmonary bypass: plasma tranexamic acid concentrations were 27.6 mcg/mL,
31.4 mcg/mL, and 29.2 mcg/mL at 5 minutes (min), 30 min, and 60 min into cardiopulmonary
bypass (CPB). Twentyone patients received a bolus of tranexamic acid 10 mg/kg over 20
minutes, followed by an infusion of 1 mg/kg/hour via a central venous catheter during CPB.
In vitro, fibrinolysis was shown to be inhibited at a tranexamic acid concentration of 10
mcg/mL [156].

b) Following IV administration of a 10mg/kg dose of tranexamic acid, plasma levels at 1 and
3 hours were 18 and 10 mcg/mL, respectively. Plasma levels at five hours were 5 mcg/mL
[152].

5) Rectal: 5 to 6 hours [153].
a) Peak serum levels following rectal instillation of a single 2gram dose of tranexamic acid
occurred 6 hours after administration in healthy volunteers and 5 hours after administration in
patients with ulcerative colitis [153].

D) Area Under the Curve
1) Adults
a) Oral, multipledose: 77.67 mcg x hr/mL (1300 mg 3 times a day); singledose 77.96 mcg x
hr/mL (1300 mg) [18]
1) Mean AUC(0 to 8 hour) following multipledose oral administration of tranexamic acid
1300 mg 3 times a day for 5 days and singledose oral administration of tranexamic acid
1300 mg in 19 healthy women was 77.67 mcg x hr/mL and 77.96 mcg x hr/mL, respectively.
The AUC(0 to infinity) following singledose oral administration of tranexamic acid 1300 mg
was 80.19 mcg x hr/mL [18].

2) Steadystate plasma concentrations are reached on day 2 following the 5th dose of oral
tranexamic acid [18].

2) Pediatrics (12 to 16 years)
a) Oral, singledose: 20% to 25% lower than adult women (1300 mg) [115]
1) In a randomized, crossover study in 20 adolescent patients 12 to 16 years old with heavy
menstrual bleeding, the AUC values following a single tranexamic acid 650 mg dose were
32% to 36% less than the AUC after a single tranexamic acid 1300 mg dose. The AUC values
after a single tranexamic acid 1300 mg dose in this study were 20% to 25% lower than the
AUC observed in adult women administered the same dose during a different study [115].

3) Rectal, singledose: 7.6 to 13.8 mg X hr/L (2 g) [153].
a) The AUC for tranexamic acid following rectal instillation of a single 2gram dose was 7.6
mg X hr/L in healthy volunteers (n=5) and 13.8 mg X hr/L in patients with ulcerative colitis
(n=5) [153].

ADME
Absorption
A) Bioavailability
1) IM: 100% [155].
a) The absolute bioavailability of IM tranexamic acid (0.5 g) was 105.2% [155].

2) Oral, tablet: approximately 45% [18].
a) The absolute bioavailability of tranexamic acid in women 18 to 49 years of age is
approximately 45% [18].

3) Topical, mouth rinse: minimal [164].
a) The systemic absorption of tranexamic acid mouth rinse is small. Thirty healthy
volunteers received either oral tranexamic acid 1gram tablets (n=10) or 10 mL of 5%
tranexamic acid mouth rinse (n=20). Plasma levels and saliva were periodically
examined for tranexamic acid content. The group that received oral tranexamic acid
tablets achieved peak plasma levels of 7 mcg/mL and no detectable levels in the saliva.
The mouth rinse group achieved a peak plasma level less than 2 mcg/mL and very high
saliva levels (200 mcg/mL) which remained in the therapeutic range for 2 hours [164].

B) Effects of Food
1) No significant effect [18].
a) Following singledose oral administration of tranexamic acid 1300 mg with food, the
Cmax and AUC were increased by 7% and 16%, respectively. Tranexamic acid can be
administered without regard to meals [18].

Distribution
A) Distribution Sites
1) Protein Binding
a) Plasminogen, 3% [151][18].
1) Tranexamic acid is about 3% bound to plasminogen at therapeutic plasma levels
[151][18]

2) Tissues and Fluids
a) Aqueous humor: 10% of plasma concentration [151][18]
1) Tranexamic acid passes into the aqueous humor of the eye achieving a
concentration of approximately onetenth of plasma concentrations [151][18].

b) Cerebrospinal fluid: 10% of plasma concentration [151][18]
1) Tranexamic acid crosses the bloodbrain barrier and suppresses fibrinolytic activity,
primarily in the leptomeninges [152][165], and the concentration of tranexamic acid in
the cerebrospinal fluid has been reported to be approximately onetenth the
concentration in plasma [151][18].

c) Placenta: 30 mg/L [151][18]
1) Tranexamic acid passes the placenta readily and achieves high concentrations in
cord blood [166]. Following IV injection of tranexamic acid 10 mg/kg in pregnant
women, the concentration in cord blood is about 30 mg/L, as high as in maternal blood
[151][18].

d) Semen: unknown [151]
1) Tranexamic acid has been detected in semen where it inhibits fibrinolytic activity,
but has no influence on sperm migration [151]

e) Synovial fluid: equivalent to serum [151]
1) Tranexamic acid diffuses rapidly into joint fluid and the synovial membrane. The
concentration reached in the joint fluid is the same concentration that is obtained in
the serum. The biological halflife of tranexamic acid in the joint fluid is about 3 hours
[151].

f) Tissues: amount unknown [151]
1) Tranexamic acid demonstrates considerable antifibrinolytic activity in tissues
(kidneys, intestines, prostate) [167]. Tranexamic acid, at a concentration of
antifibrinolytic activity, persists in serum for up to 7 or 8 hours and in different tissues
for approximately 17 hours [151].

B) Distribution Kinetics
1) Volume of Distribution
a) 9 to 12 L (initial) [151]; 0.39 L/kg [18]
1) The apparent volume of distribution for tranexamic acid at steadystate is 0.39 L/kg
[18]. The initial volume of distribution is 0.18 L/kg (9 to 12 L) [18][151].

Metabolism
A) Metabolism Sites and Kinetics
1) Site not established, less than 10% [154].
a) A small fraction [18] (less than 10%) [154] of tranexamic acid is metabolized [18].

B) Metabolites
1) Acetylated metabolite: inactive [18]
a) One percent and 0.5% of an oral dose of tranexamic acid is excreted as dicarboxylic
acid and acetylated metabolite, respectively [18].

2) Dicarboxylic acid: inactive [18]
a) One percent and 0.5% of an oral dose of tranexamic acid is excreted as dicarboxylic
acid and acetylated metabolite, respectively [18].

Excretion
A) Kidney
1) Renal Clearance (rate)
a) 110 to 116 mL/min [151][18]
1) The overall renal clearance matches the overall plasma clearance at 110 to 116
mL/min [151][18].

2) Renal Impairment
a) Urinary excretion of tranexamic acid declines as renal function decreases. Following
singledose IV administration of tranexamic acid 10 mg/kg in 28 patients, the 24hr
urinary fractions of tranexamic acid with serum creatinine concentrations of 1.4 to 2.8,
2.8 to 5.7 and greater than 5.7 mg/dL were 51%, 39%, and 19%, respectively. Dose
adjustment is needed in patients with renal impairment [18].

2) Renal Excretion (%)
a) 95% unchanged (IV) [151][18]; 39% [152] to 53% (oral) [152]
1) Tranexamic acid is eliminated by urinary excretion primarily via glomerular filtration
with more than 95% of the dose excreted unchanged. Most elimination post IV
administration occurred during the first 10 hours. Following IV administration of
tranexamic acid 10 mg/kg, excretion is about 90% at 24 hours [151][18].

2) Following oral administration (10 to 15 mg/kg), 1%, 13%, and 39% of the dose was
recovered unchanged in the urine at 1, 3, and 24 hours, respectively [152]. Other data
have reported urinary excretion of 53% of an oral dose, with no difference in excretion
occurring between 0.5 and 2g doses [152].

B) Total Body Clearance
1) 110 to 116 mL/min [151][18]
a) Plasma clearance of tranexamic acid is 110 to 116 mL/min [151][18].

Elimination Halflife
A) Parent Compound
1) IV: 2 hours [151][18]
a) Following tranexamic acid 1 g IV administration, the plasma concentration time curve
shows triexponential decay with most elimination occurring within the first 10 hours,
giving an apparent elimination halflife of approximately 2 hours [151][18]. The
biological halflife of tranexamic acid in the joint fluid is about 3 hours [151].

2) Oral, 11 hours [18]
a) Following singledose oral administration of tranexamic acid in 19 healthy women,
the mean terminal halflife was 11.08 hours [18].

PATIENT EDUCATION
Medication Counseling
Patient Handouts
A) Tranexamic Acid (By injection)
Tranexamic Acid
Given before tooth removal to prevent or control bleeding episodes in people who have hemophilia.
When This Medicine Should Not Be Used:
You should not receive this medicine if you have had an allergic reaction to tranexamic acid, or if
you have an eye disorder that causes you to have problems seeing certain colors. You should not
receive this medicine if you have a certain type of head injury or bleeding in your brain. You should
not receive this medicine if you have an active or a history of blood clots.
How to Use This Medicine:
Injectable
Your doctor will prescribe your dose and schedule. This medicine is given through a needle placed
in a vein.

A nurse or other health provider will give you this medicine.

If a Dose is Missed:
This medicine needs to be given on a fixed schedule. Keep all appointments. If you miss a dose,
call your doctor or pharmacist for instructions.

Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthecounter
medicines, vitamins, and herbal products.
Make sure your doctor knows if you are receiving any other medicine to help blood clotting. Tell
your doctor if you are using factor IX complex (such as BeneFIX®, Proplex® T) or antiinhibitor
coagulant concentrates (such as Feiba VH®).

Warnings While Using This Medicine:
Make sure your doctor knows if you are pregnant or breastfeeding, or if you have kidney problems,
any other blood or circulation problems, urinary tract problems, or a history of seizures. Tell your
doctor if you have a blood clotting problem called disseminated intravascular coagulation or DIC.
If you or your child will be receiving this medicine for longer than several days, your doctor may 60/77
If you or your child will be receiving this medicine for longer than several days, your doctor may
want you to have your eyes checked regularly by an eye doctor. This will allow your doctor to check
for unwanted effects that may be caused by this medicine.

This medicine may make you dizzy. Avoid driving, using machines, or doing anything else that
could be dangerous if you are not alert.

Your doctor will check your progress and the effects of this medicine at regular visits. Keep all
appointments. Blood tests will be needed to check for unwanted effects.

Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth
or throat, chest tightness, trouble breathing

Chest pain, shortness of breath, or coughing up blood.

Dark or bloody urine, trouble urinating, or a decrease in how much or how often you urinate.
Lightheadedness, dizziness, or fainting.

Numbness or weakness in your arm or leg, or on one side of your body.
Pain in your lower calf.
Seizures.

Sudden or severe headache, or problems with speech or walking.
Vision changes.

If you notice these less serious side effects, talk with your doctor:
Nausea, vomiting, or diarrhea.
Sudden mood changes.

If you notice other side effects that you think are caused by this medicine, tell your doctor.
B) Tranexamic acid (By mouth)
Tranexamic Acid
Treats heavy monthly periods (menstrual cycles) in women.
When This Medicine Should Not Be Used:
This medicine is not right for everyone. Do not use if you had an allergic reaction to tranexamic
acid, or if you have blood clot problems or a history of blood clots.
How to Use This Medicine:
Tablet
Your doctor will tell you how much medicine to use. Do not use more than directed.

Start taking this medicine when your monthly period starts. Do not take this medicine for more
than 5 days during your period. Do not take more than 6 tablets in one day.
Swallow the tablet whole with liquids. Do not break, crush, or chew it.

Read and follow the patient instructions that come with this medicine. Talk to your doctor or
pharmacist if you have any questions.

Missed dose: If you miss a dose or forget to use your medicine, use it as soon as you can. Wait at
least 6 hours before you take another dose. Do not use extra medicine to make up for a missed
dose.

Store the medicine in a closed container at room temperature, away from heat, moisture, and
direct light.

Drugs and Foods to Avoid:
Ask your doctor or pharmacist before using any other medicine, including overthecounter
medicines, vitamins, and herbal products.
Do not use this medicine together with birth control that uses hormones, such as pills or a vaginal
ring.

Some medicines and foods can affect how tranexamic acid works. Tell your doctor if you are using
oral tretinoin or a medicine that changes how your blood clots, such as factor IX.

Warnings While Using This Medicine:
Tell your doctor if you are pregnant or breastfeeding, or if you have kidney disease, bleeding
problems, or leukemia.
This medicine may cause the following problems:
Higher risk of blood clots (which can lead to heart attack or stroke) when used with hormone birth
control, such as pills or a patch
Eye and vision problems

If this medicine does not reduce your bleeding after 2 menstrual cycles or if it seems to stop
working, check with your doctor.
Your doctor will check your progress and the effects of this medicine at regular visits. Keep all
appointments.
Keep all medicine out of the reach of children. Never share your medicine with anyone.
Possible Side Effects While Using This Medicine:
Call your doctor right away if you notice any of these side effects:
Allergic reaction: Itching or hives, swelling in your face or hands, swelling or tingling in your mouth
or throat, chest tightness, trouble breathing

Chest pain, trouble breathing, or coughing up blood

Numbness or weakness on one side of your body, sudden or severe headache, problems with
vision, speech, or walking
Pain in your lower leg

Trouble seeing, vision changes

Unusual bleeding, bruising, or weakness

If you notice these less serious side effects, talk with your doctor:
Muscle, joint, or back pain
Runny or stuffy nose

If you notice other side effects that you think are caused by this medicine, tell your doctor.
TOXICOLOGY
Clinical Effects
Range of Toxicity
Treatment
ABOUT
How Supplied
Drug Properties
A) Information on specific products and dosage forms can be obtained by referring to the
Tradename List (Product Index)
B) Synonyms
AMCHA

Tranexamic Acid

C) Physicochemical Properties
1) Molecular Weight
a) 157.2 [4][18]

2) pH
a) 6.5 to 8 [4]

3) Solubility
a) Tranexamic acid is freely soluble in water and glacial acetic acid, very slightly soluble in ethanol,
and practically insoluble in ether [18].

Storage & Stability
A) Preparation
1) Intravenous route
a) Injection may be mixed with electrolyte solutions, carbohydrate solutions, amino acid solutions,
and dextran solutions; heparin may be added to Cyklokapron(R) injection[4].

b) Do not mix injection with blood or solutions containing penicillin [4].

c) To avoid hypotension, do not inject more rapidly than 1 mL/min [4].
2) Oral route
a) Tablets may be given without regard to meals [16].

b) Tablets should be swallowed whole; do not chew or break tablets [16].

B) Intravenous route
1) Solution

b) Solution stored between 20 and 50 degrees C was stable for up to 12 weeks. However, glass
ampoules that contained the solution cracked when frozen. Therefore, the authors suggest
packaging the solution in something other than glass or not allowing the product to freeze [168].

C) Oral route
1) Tablet

Trade Names
Regulatory Status
References
1. Zehtabchi S, Abdel Baki SG, Falzon L, et al: Tranexamic acid for traumatic brain injury: a
systematic review and metaanalysis. Am J Emerg Med 2014; 32(12):15031509.
PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
PubMed Article: http://www.ncbi.nlm.nih.gov/...
2. Goobie SM, Meier PM, Pereira LM, et al: Efficacy of tranexamic acid in pediatric craniosynostosis
surgery: a doubleblind, placebocontrolled trial. Anesthesiology 2011; 114(4):862871.
3. Dadure C, Sauter M, Bringuier S, et al: Intraoperative tranexamic acid reduces blood transfusion
in children undergoing craniosynostosis surgery: a randomized doubleblind study. Anesthesiology
2011; 114(4):856861.
4. Product Information: CYKLOKAPRON(R) injection, tranexamic acid injection. Pfizer & Upjohn
Company, New York, NY, 2008.
5. Forbes CD, Barr RD, Reid G, et al: Tranexamic acid in control of haemorrhage after dental
extraction in haemophilia and Christmas disease. Br Med J 1972; 2(809):311313.
6. Verstraete M: Clinical application of inhibitors of fibrinolysis. Drugs 1985; 29(3):236261.
7. Shankar S & Lee R: DDAVP and tranexamic acid for dental extractions in a mild hemophiliac. Br
Dent J 1984; 156(12):450452.
8. Vujkovac B, Lavre J, & Sabovic M: Successful treatment of bleeding from colonic angiodysplasias
with tranexamic acid in a hemodialysis patient. Am J Kidney Dis 1998; 31(3):536538.
9. Isacson S: Tranexamic acid in acute upper gastrointestinal bleeding. Scand J Gastroenterol 1987;
22(suppl 137):6466.
10. von Holstein CCS, Eriksson SBS, & Kallen R: Tranexamic acid as an aid to reducing blood
transfusion requirements in gastric and duodenal bleeding. Br Med J 1987; 294(6563):710.
11. Barer D, Ogilvie A, Henry D, et al: Cimetidine and tranexamic acid in the treatment of acute
uppergastrointestinal tract bleeding. N Engl J Med 1983; 308(26):15711575.
12. Engqvist A, Brostrom O, von Feilitzen F, et al: Tranexamic acid in massive hemorrhage from the
upper gastrointestinal tract: a doubleblind study. Scand J Gastroenterol 1979; 14(7):839844.
13. Biggs JC, Hugh TB, & Dodds AJ: Tranexamic acid and upper gastrointestinal hemorrhage: a
double blind trial. Gut 1976; 17(9):729734.
14. Cormack F, Chakrabarti RR, Jouhar AJ, et al: Tranexamic acid in upper gastrointestinal
haemorrhage. Lancet 1973; 1(7814):12071208.
15. Shakur H, Roberts R, Bautista R, et al: Effects of tranexamic acid on death, vascular occlusive
events, and blood transfusion in trauma patients with significant haemorrhage (CRASH2): a
randomised, placebocontrolled trial. Lancet 2010; 376(9734):2332.

16. Product Information: LYSTEDA(TM) oral tablets, tranexamic acid oral tablets. Ferring
Pharmaceuticals Inc. (per FDA), Parsippany, NJ, 2013.

17. Lukes AS, Moore KA, Muse KN, et al: Tranexamic acid treatment for heavy menstrual bleeding: a
randomized controlled trial. Obstet Gynecol 2010; 116(4):865875.

18. Product Information: LYSTEDA(TM) oral tablets, tranexamic acid oral tablets. Xanodyne
Pharmaceuticals, Inc., Newport, KY, 2009.

19. Ylikorkala O & Viinikka L: Comparison between antifibrinolytic and antiprostaglandin treatment in
the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices. Br
J Obstet Gynecol 1983; 90(1):7883.

20. Callendar ST, Warner GT, & Cope E: Treatment of menorrhagia with tranexamic acid: a double
blind trial. Br Med J 1970; 4(729):214216.

21. Preston JT, Cameron IT, Adams EJ, et al: Comparative study of tranexamic acid and
norethisterone in the treatment of ovulatory menorrhagia. Br J Obstet Gynaecol 1995; 102:401406.

22. Westrom L & Bengtsson LP: Effect of tranexamic acid (AMCA) in menorrhagia with intrauterine
contraceptive devices. J Reprod Med 1970; 5(4):154161.

23. Vermeulen M, Lindsay KW, Murray GD, et al: Antifibrinolytic treatment in subarachnoid
hemorrhage. N Engl J Med 1984; 311(7):432437.

24. Chandra B: Treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm with
tranexamic acid: a doubleblind clinical trial. Ann Neurol 1978; 3(6):502504.

25. Fodstad H, Liliequist B, Schannong M, et al: Tranexamic acid in the preoperative management of
ruptured intracranial aneurysms. Surg Neurol 1978; 10(1):915.

26. Schisano G: The use of antifibrinolytic drugs in aneurysmal subarachnoid hemorrhage. Surg
Neurol 1978; 10(4):217222.

27. MauriceWilliams RS: Prolonged antifibrinolysis: an effective nonsurgical treatment for ruptured
intracranial aneurysms?. Br Med J 1978; 1(6118):945947.

28. Fodstad H & Thulin CA: Use of tranexamic acid (AMCA) in the preoperative management of
patients with ruptured intracranial aneurysms (abstr 244), Sixth In Cong Neurol Surg, Brazil, 1977.

29. Tovi D: The use of antifibrinolytic drugs to prevent early recurrent aneurysmal subarachnoid
hemorrhage. Acta Neurol Scand 1973; 49(2):163175.

30. Gibbs JR & Corkill AGL: Use of an antifibrinolytic agent (tranexamic acid) in the management of
ruptured intracranial aneurysms. Postgrad Med J 1971; 47(546):199200.

31. Norlen G & Thulin CA: The use of antifibrinolytic substances in ruptured intracranial aneurysms.
Neurochirurgia (Stuttg) 1969; 12(3):100102.

32. Fodstad H, Forssell A, Liliequist B, et al: Antifibrinolysis with tranexamic acid in aneurysmal
subarachnoid hemorrhage: a consecutive controlled clinical trial. Neurosurgery 1981; 8(2):158164.

33. Gelmers HJ: Prevention of recurrence of spontaneous subarachnoid hemorrhage by tranexamic
acid. Acta Neurochir (Wien) 1980; 52:4950.

34. Kaste M & Ramsay M: Tranexamic acid in subarachnoid hemorrhage: a doubleblind study.
Stroke 1979; 10(5):519522.

35. van Rossum J, Wintzen AR, Endtz LJ, et al: Effect of tranexamic acid on rebleeding after
subarachnoid hemorrhage: doubleblind controlled clinical trial. Ann Neurol 1977; 2(3):238242.

36. Adams HP Jr: Current status of antifibrinolytic therapy for treatment of patients with aneurysmal
subarachnoid hemorrhage. Stroke 1982; 13(2):256259.

37. Irwin A, Khan SK, Jameson SS, et al: Oral versus intravenous tranexamic acid in enhanced
recovery primary total hip and knee replacement: results of 3000 procedures. Bone Joint J 2013;
95B(11):15561561.


38. Gandhi R, Evans HM, Mahomed SR, et al: Tranexamic acid and the reduction of blood loss in
total knee and hip arthroplasty: a metaanalysis. BMC Res Notes 2013; 6:184184.

39. Alshryda S, Mason J, Sarda P, et al: Topical (intraarticular) tranexamic acid reduces blood loss
and transfusion rates following total hip replacement: a randomized controlled trial (TRANXH). J
Bone Joint Surg Am 2013; 95(21):19691974.

40. Svanberg L, Astedt B, & Nilsson IM: Abruptio placentae treatment with the fibrinolytic inhibitor
tranexamic acid. Acta Obstet Gynecol Scand 1980; 59(2):127130.

41. Astedt B & Nilsson IM: Recurrent abruptio placentae treated with the fibrinolytic inhibitor
tranexamic acid. Br Med J 1978; 1(6115):756757.

42. Takahashi Y, Tanaka T, Nakajima N, et al: Intramedullary multiple hematomas in siblings with
congenital alpha2plasmin inhibitor deficiency: orthopedic surgery with protection by tranexamic
acid. Haemostasis 1991; 21(5):321327.

43. Munch EP & Weeke B: Nonhereditary angioedema treated with tranexamic acid. Allergy 1985;
40(2):9297.

44. Sheffer AL, Fearon DT, Austen KF, et al: Tranexamic acid: preoperative prophylactic therapy for
patients with hereditary angioneurotic edema. J Allergy Clin Immunol 1977; 60(1):3840.

45. Sheffer AL, Austin KF, & Rosen FS: Tranexamic acid therapy in hereditary angioneurotoic
edema. N Engl J Med 1972; 287(9):452454.

46. Crosher R: Intravenous tranexamic acid in the management of hereditary angiooedema. Br J
Oral Maxilliofac Surg 1987; 25(6):500506.

47. Naish P & Barrat J: Hereditary angiooedema (letter). Lancet 1979; 1(8116):611.

48. Thompson RA & FelixDavies DD: Response of "idiopathic" recurrent angioneurotic oedema to
tranexamic acid. Br Med J 1978; 2(6137):608.

49. Blinder D, Manor Y, Martinowitz U, et al: Dental extractions in patients maintained on continued
oral anticoagulant: comparison of local hemostatic modalities. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 1999; 88(2):137140.
50. SindetPedersen S, Ramstrom G, Bernvil S, et al: Hemostatic effect of tranexamic acid
mouthwash in anticoagulanttreated patients undergoing oral surgery. N Engl J Med 1989;
320(13):840843.
51. Wong J, Abrishami A, El Beheiry H, et al: Topical application of tranexamic acid reduces
postoperative blood loss in total knee arthroplasty: a randomized, controlled trial. J Bone Joint Surg
Am 2010; 92(15):25032513.


52. Seo JG, Moon YW, Park SH, et al: The comparative efficacies of intraarticular and IV tranexamic
acid for reducing blood loss during total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc
2013; 21(8):18691874.


53. Camarasa MA, Olle G, SerraPrat M, et al: Efficacy of aminocaproic, tranexamic acids in the
control of bleeding during total knee replacement: a randomized clinical trial. Br J Anaesth 2006;
96(5):576582.


54. Hiippala ST, Strid LJ, Wennerstrand MI, et al: Tranexamic acid radically decreases blood loss and
transfusions associated with total knee arthroplasty. Anesth Analg 1997; 84(4):839844.

55. Zohar E, Fredman B, Ellis M, et al: A comparative study of the postoperative allogeneic blood
sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee
replacement. Anesth Analg 1999; 89(6):13821387.

56. Jansen AJ, Andreica S, Claeys M, et al: Use of tranexamic acid for an effective blood
conservation strategy after total knee arthroplasty. Br J Anaesth 1999; 83(4):596601.

57. Dean A & Tuffin P: Fibrinolytic inhibitors for cancerassociated bleeding problems. J Pain
Symptom Manage 1997; 13(1):2024.

58. Sigaut S , Tremey B , Ouattara A , et al: Comparison of two doses of tranexamic acid in adults
undergoing cardiac surgery with cardiopulmonary bypass. Anesthesiology 2014; 120(3):590600.

59. Pinosky ML, Kennedy DJ, Fishman RL, et al: Tranexamic acid reduces bleeding after
cardiopulmonary bypass when compared to epsilon aminocaproic acid and placebo. J Card Surg
1997; 12(5):330338.


60. Brown RS, Thwaites BK, & Mongan PD: Tranexamic acid is effective in decreasing postoperative
bleeding and transfusions in primary coronary artery bypass operations: a doubleblind, randomized,
placebocontrolled trial. Anesth Analg 1997; 85(5):963970.

61. Dryden PJ, O'Connor JP, Jamieson WR, et al: Tranexamic acid reduces blood loss and
transfusion in reoperative cardiac surgery. Can J Anaesth 1997; 44(9):934941.

62. Katsaros D, Petricevic M, Snow NJ, et al: Tranexamic acid reduces postbypass blood use: a
doubleblinded, prospective, randomized study of 210 patients. Ann Thorac Surg 1996; 61(4):1131
1135.


63. Katoh J, Tsuchiya K, Sato W, et al: Additional postbypass administration of tranexamic acid
reduces blood loss after cardiac operations. J Thorac Cardiovasc Surg 1997; 113(4):802804.

64. Armellin G, Casella S, Guzzinati S, et al: Tranexamic acid in aortic valve replacement. J
Cardiothorac Vasc Anesth 2001; 15(3):331335.

65. Reid RW, Zimmerman AA, Laussen PC, et al: The efficacy of tranexamic acid versus placebo in
decreasing blood loss in pediatric patients undergoing repeat cardiac surgery. Anesth Analg 1997;
84(5):990996.

66. Myles PS, Smith JA, Forbes A, et al: Tranexamic acid in patients undergoing coronaryartery
surgery. N Engl J Med 2017; 376(2):136148.

67. Ozal E, Kuralay E, Bingol H, et al: Does tranexamic acid reduce desmopressininduced
hyperfibrinolysis?. J Thorac Cardiovasc Surg 2002; 123(3):539543.

68. Rybo G & Westerberg H: The effect of tranexamic acid (AMCA) on postoperative bleeding after
conization. Acta Obstet Gynecol Scand 1972; 51(4):347350.

69. Landin LE & Weiner E: Late bleeding after conization. The effect of tranexamic acid
(Cyclokapron). Opuscula Medica 1975; 20:280284.

70. Grundsell H, Larsson G, & Bekassy Z: Use of an antifibrinolytic agent (tranexamic acid) and
lateral sutures with laser conization of the cervix. Obstet Gynecol 1984; 64(4):573576.

71. Vujkovac B & Sabovic M: Treatment of subdural and intracerebral haematomas in a
haemodialysis patient with tranexamic acid. Nephrol Dial Transplant 2000; 15(1):107109.

72. Kuriyama S, Nakayama M, Tomonari H, et al: Tranexamic acid increases peritoneal ultrafiltration
volume in patients on CAPD. Perit Dial Int 1999; 19(1):3844.

73. Mezzano D, Panes O, Munoz B, et al: Tranexamic acid inhibits fibrinolysis, shortens the bleeding
time and improves platelet function in patients with chronic renal failure. Thromb Haemost 1999;
82(4):12501254.
74. Hollanders D, Thomson JM, & Schofield PF: Tranexamic acid therapy in ulcerative colitis.
Postgrad Med J 1982; 58(676):8791.

75. Kondo M, Hotta T, Takemura S, et al: Treatment of ulcerative colitis by the direct administration
of an antifibrinolytic agent as an enema. Hepatogastroenterology 1981; 28(5):270273.

76. van der Staak, FHJ, de Haan AFJ, et al: Surgical repair of congenital diaphragmatic hernia during
extracorporeal membrane oxygenation: hemorrhagic complications and the effect of tranexamic
acid. J Pediatr Surg 1997; 32(4):594599.

77. Wong LTK, Lillquist YP, Culham G, et al: Treatment of recurrent hemoptysis in a child with cystic
fibrosis by repeated bronchial artery embolizations and longterm tranexamic acid (case report).
Pediatr Pulmonol 1996; 22(4):275279.

78. Chang AB, Ditchfield M, Robinson PJ, et al: Major hemoptysis in a child with cystic fibrosis from
multiple aberrant bronchial arteries treated with tranexamic acid. Pediatr Pulmonol 1996; 22(6):416
420.

79. SindetPedersen S, Stenbjerg S, & Ingerslev J: Control of gingival hemorrhage in hemophilic
patients by inhibition of fibrinolysis with tranexamic acid. J Periodontal Res 1988; 23(1):7274.

80. Rainsford SG, Jouhar AJ, & Hall A: Tranexamic acid in the control of spontaneous bleeding in
severe haemophilia. Thromb Diath Haemorrh 1973; 30(2):272279.

81. Bennett AE, Ingram GIC, & Inglish PJ: Antifibrinolytic treatment in haemophilia: a controlled trial
of prophylaxis with tranexamic acid. Br J Haematol 1973; 24(1):8388.

82. Hanna BD & Bernstein M: Tranexamic acid in the treatment of KasabachMerritt syndrome in
infants. Am J Pediatr Hematol Oncol 1989; 11(2):191195.

83. Katsaros D & GrundfestBroniatowski S: Successful management of visceral KlippelTrenaunay
Weber syndrome with the antifibrinolytic agent tranexamic acid (Cyclocapron): a case report. Am
Surg 1998; 64(4):302304.

84. Dalmau A, Sabate A, Acosta F, et al: Tranexamic acid reduces red cell transfusion better than
epsilonaminocaproic acid or placebo in liver transplantation.. Anesth Analg 2000; 91(1):2934.

85. Boylan JF, Klinck JR, Sandler AN, et al: Tranexamic acid reduces blood loss, transfusions
requirements, and coagulation factor use in primary orthotopic liver transplantation. Anesthesiology
1996; 85(5):10431048.

86. Horrow JC: Tranexamic acid reduces blood loss, transfusions requirements, and coagulation
factor use in primary orthotopic liver transplantation (highlights). Anesthesiology 1996; 85:30A31A.

87. De Boer WA, Koolen MGJ, Roos CM, et al: Tranexamic acid treatment of hemothorax in two
patients with malignant mesothelioma. Chest 1991; 100(3):847848.

88. Uusitalo R, Saari MS, Aine E, et al: Tranexamic acid in the prevention of secondary hemorrhage
after traumatic hyphema. Acta Ophthalmol (Copenh) 1981; 59(4):539545.

89. Varnek L, Dalsgaard C, Hansen A, et al: The effect of tranexamic acid on secondary hemorrhage
after traumatic hyphema. Acta Ophthalmol (Copenh) 1980; 58(5):787793.

90. Missotten L, de Clippeleer L, Van Tornout I, et al: The value of tranexamic acid (Cyclokapron) in
the prevention of secondary bleeding, a complication of traumatic hyphema. Bull Soc Belge
Ophthalmol 1977; 179:4752.

91. Jerndal T & Frisen M: Tranexamic acid (AMCA) and late hyphaema: a doubleblind study in
cataract surgery. Acta Ophthalmol (Copenh) 1976; 54(4):417429.

92. Bramsen T: Traumatic hyphaema treated with antifibrinolytic drug tranexamic acid: I. Acta
Ophthal (Copenh) 1976; 54(2P):250256.

93. Olsen T, Ehlers N, & Bramsen T: Influence of tranexamic acid and acetylsalicylic acid on the
thickness of the normal cornea. Acta Ophthalmol (Coperh) 1980; 58(5):767772.

94. Bramsen T, Corydon L, & Ehlers N: A doubleblind study of the influence of tranexamic acid on
the central corneal thickness after cataract extraction. Acta Ophthal (Copenh) 1977; 55(4):665673.

95. Bramsen T: A doubleblind study on the influence of central corneal thickness after
trabeculectomy for glaucoma simplex. Acta Ophthal (Copenh) 1978; 56(6):9981005.

96. Soma H, Sashida T, Yoshida M, et al: Treatment of advanced ovarian cancer with fibrinolytic
inhibitor tranexamic acid. Acta Obstet Gynecol Scand 1980; 59(3):285287.

97. Astedt B, Glifberg I, Mattsson W, et al: Arrest of growth of ovarian tumor by tranexamic acid.
JAMA 1977; 238(2):154155.

98. Soma H, Sashida T, Yoshida M, et al: Advanced cancer and fibrinolytic system. Obstet Gynecol
(Jpn) 1978; 45:1385.

99. Astedt B, Svanberg L, & Nilsson IM: Fibrin degradation products and ovarian tumors. Br Med J
1971; 4(785):458459.

100. Hensey OJ, Morgan MEI, & Cooke RWI: Tranexamic acid in the prevention of periventricular
hemorrhage. Arch Dis Child 1984; 59(8):719721.

101. Novikova N, Hofmeyr GJ, & Cluver C: Tranexamic acid for preventing postpartum
haemorrhage. Cochrane Database Syst Rev 2015; 2015(6):CD007872.

102. Avvisati G, ten Cate JW, Buller HR, et al: Tranexamic acid for control of haemorrhage in acute
promyelocytic leukemia. Lancet 1989; 2(8655):122124.

103. Miller RA, May MW, Hendry WF, et al: The prevention of secondary haemorrhage after
prostatectomy: the value of antifibrinolytic therapy. Br J Urol 1980; 52(1):2628.

104. Gamba G, Fornasari PM, Grignani G, et al: Hemostasis during transvesical prostatic
adenectomy: a controlled trial on the effect of drugs with antifibrolytic and thrombinlike activities.
Blut 1979; 39(2):8998.

105. Ward MG & Richards B: Complications of antifibrinolysis therapy after prostatectomy. Br J Urol
1979; 51(3):211212.

106. Ro JS, Knutrud O, & Stormorken H: Antifibrinolytic treatment with tranexamic acid (AMCHA) in
pediatric urinary tract surgery. J Pediatr Surg 1970; 5(3):315320.

107. McElligott E, Quigley C, & Hanks GW: Tranexamic acid and rectal bleeding (letter). Lancet
1991; 337(8738):431.

108. Rasmussen GG, Brandslund I, Urfe P, et al: Lack or effect of tranexamic acid on rheumatoid
arthritis. Scand J Rheumatol 1984; 13(4):369373.

109. Neilipovitz DT, Murto K, Hall L, et al: A randomized trial of tranexamic acid to reduce blood
transfusion for scoliosis surgery. Anesth Analg 2001; 93:8287.

110. Ohsaki K: Comparison of tranexamic acid (Transamin(R)) and traditional therapy for sudden
deafness. Acta Med Okayama 1980; 34(5):323332.

111. Castelli G & Vogt E: Der erfolg einer antifibrinolytischen behandlung mit tranexamsaure zur
reduktion der blutverlustes wahrend und nach tonsilektomien. Schweiz Med Wochenschr 1977;
107(22):780784.
112. Laurberg G: Tranexamic acid (Cyclokapron) in chronic urticaria: a doubleblind study. Acta
Derm Venerol 1977; 57(4):369370.

113. Pilbrant A, Schannong M, & Vessman J: Pharmacokinetics and bioavailability of tranexamic
acid. Eur J Clin Pharmacol 1981; 20(1):6572.

114. Andersson L, Erikson O, Hedlund PO, et al: Special considerations with regard to the dosage of
tranexamic acid in patients with chronic renal diseases. Urol Res 1978; 6(2):8388.

115. Product Information: LYSTEDA(R) oral tablets, tranexamic acid oral tablets. Ferring
Pharmaceuticals Inc. (per FDA), Parsippany, NJ, 2013.

116. Product Information: CYKLOKAPRON(R) intravenous injection, tranexamic acid intravenous
injection. Pharmacia & Upjohn Co. (per FDA), New York, NY, 2014.

117. Adams HP Jr: Current status of antifibrinolytic therapy for treatment of patients with
aneurysmal subarachnoid hemorrhage. Stroke 1982; 13(2):256259.

118. Muse K, Lukes AS, Gersten J, et al: Longterm evaluation of safety and healthrelated quality of
life in women with heavy menstrual bleeding treated with oral tranexamic acid. Womens Health
(Lond Engl) 2011; 7(6):699707.


injection. Pharmacia & Upjohn Co., New York, NY, 2011.

120. Sundstrom A, Seaman H, Kieler H, et al: The risk of venous thromboembolism associated with
the use of tranexamic acid and other drugs used to treat menorrhagia: a casecontrol study using
the General Practice Research Database. BJOG 2009; 116(1):9197.

121. Woo KS, Tse LKK, Woo JLF, et al: Massive pulmonary thromboembolism after tranexamic acid
antifibrinolytic therapy. Br J Clin Pract 1989; 43(12):465466.

122. Fodstad H, Forssell A, Liliequist B, et al: Antifibrinolysis with tranexamic acid in aneurysmal
subarachnoid hemorrhage: a consecutive controlled clinical trial. Neurosurgery 1981; 8(2):158164.

123. Davies D & Howell DA: Tranexamic acid and arterial thrombosis. Lancet 1977; 1(8001):49.

124. MauriceWilliams RS: Prolonged antifibrinolysis: an effective nonsurgical treatment for ruptured
intracranial aneurysms?. Br Med J 1978; 1(6118):945947.

125. Bercel NA: Cyclobenzaprine in the treatment of skeletal muscle spasm in osteoarthritis of the
cervical and lumbar spine. Curr Ther Res 1977; 22:462468.

126. Endo Y, Nishimura S, Miura A, et al: Deepvein thrombosis induced by tranexamic acid in
idiopathic thrombocytopenic purpura (letter). JAMA 1988; 259(24):35613562.

127. Ward MG & Richards B: Complications of antifibrinolysis therapy after prostatectomy. Br J Urol
1979; 51(3):211212.

hemorrhage. N Engl J Med 1984; 311(7):432437.


130. Agnelli G, Gresele P, De Cunto M, et al: Tranexamic acid, intrauterine contraceptive devices
and fatal cerebral arterial thrombosis. Br J Obstet Gynaecol 1982; 89(8):681682.

131. Gelmers HJ: Prevention of recurrence of spontaneous subarachnoid hemorrhage by tranexamic
acid. Acta Neurochir (Wien) 1980; 52:4950.

132. Rydin E & Lundberg PO: Tranexamic acid and intracranial thrombosis (letter). Lancet 1976;
2(7975):49.

133. Sharma V, Katznelson R, Jerath A, et al: The association between tranexamic acid and
convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia
2014; 69(2):124130.


134. Koster A, Borgermann J, Zittermann A, et al: Moderate dosage of tranexamic acid during
cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical
outcome. Br J Anaesth 2013; 110(1):3440.

135. Munch EP & Weeke B: Nonhereditary angioedema treated with tranexamic acid. Allergy 1985;
40(2):9297.

136. Odabas AR, Cetinkaya R, Selcuk Y, et al: Tranexamicacidinduced acute renal cortical necrosis
in a patient with haemophilia A (letter). Nephrol Dial Transplant 2001; 16:189190.

137. Koo JR, Lee YK, Kim YS, et al: Acute renal cortical necrosis caused by an antifibrinolytic drug
(tranexamic acid). Nephrol Dial Transplant 1999; 14(3):750752.

138. Product Information: LYSTEDA(TM) oral tablets, tranexamic acid oral tablets. Ferring
Pharmaceuticals, Inc, Parsippany, NJ, 2011.

139. Snir M, AxerSiegel R, Buckman G, et al: Central venous stasis retinopathy following the use of
tranexamic acid. Retina 1990; 10(3):181184.

140. Kaku Y, Ito T, Kudo K, et al: Generalized fixed drug eruption induced by tranexamic acid. Eur J
Dermatol 2014; 24(3):408409.


141. Kavanagh GM, Sansom JE, Harrison P, et al: Tranexamic acid (Cyklokapron(R))induced fixed
drug eruption (letter). Br J Dermatol 1993; 128(2):229230.

142. Irazabal MP, Martin LM, Gil LA, et al: Tranexamic Acidinduced toxic epidermal necrolysis. Ann
Pharmacother 2013; 47(3):e16e16.


143. Cyklokapron package insert (KabiVitrum—US). Rev Rec 6/87., 1987.

144. Cyklokapron (Kabi Pharmacia). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale,
NJ: Medical Economics Data; 1994.. p.2., 1111.

145. Fodstad H: Tranexamic acid (AMCA) in aneurysmal subarachnoid haemorrhage. J Clin Pathol
Suppl (R Coll Pathol) 1980; 14:6873.


146. Product Information: Autoplex(R) T, antiinhibitor coagulant complex, heat treated. Nabi, Boca
Raton, FL, 2000.

147. Product Information: Vesanoid(R), tretinoin. Roche Laboratories, Nutley, NJ, 2004.

148. Verstraete M: Clinical application of inhibitors of fibrinolysis. Drugs 1985; 29:236261.

149. Cyklokapron (Pharmacia). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and
specialties. 22nd ed. Ottawa: Canadian Pharmaceutical Association; 1987.. p. 211., 1987.

150. Cyklokapron (Pharmacia). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and
specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association; 1993.. p. 3112., 1993.

injection. Pharmacia & Upjohn Co (per FDA), New York, NY, 2013.


153. Almer S, Andersson T, & Strom M: Pharmacokinetics of tranexamic acid in patients with
ulcerative colitis and in healthy volunteers after the single instillation of 2#g rectally. J Clin
Pharmacol 1992; 32(1):4954.

154. Pilbrant A, Schannong M, & Vessman J: Pharmacokinetics and bioavailability of tranexamic
acid. Eur J Clin Pharmacol 1981; 20(1):6572.

155. Puigdellivol E, Carral ME, Moreno J, et al: Pharmacokinetics and absolute bioavailability of
intramuscular tranexamic acid in man. Int J Clin Pharmacol Ther Toxicol 1985; 23(6):298301.

156. Fiechtner BK, Nuttall GA, Johnson ME, et al: Plasma tranexamic acid concentrations during
cardiopulmonary bypass. Anesth Analg 2001; 92:11311136.

157. Krogh CME: CPS Compendium of pharmaceuticals and specialties. 22nd ed, Canadian
Pharmaceutical Association, Ottawa, Ontario, Canada, 1987, pp 211.
158. Krogh CME: CPS Compendium of pharmaceuticals and specialties. 28th ed, Canadian
Pharmaceutical Association, Ottawa, Ontario, Canada, 1993, pp 3112.

159. Reynolds JEF (ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc.
Englewood CO. 1998.

160. Cormack F, Chakrabarti RR, Jouhar AJ, et al: Tranexamic acid in upper gastrointestinal
haemorrhage. Lancet 1973; 1(7814):12071208.

161. Tovi D, Nilsson IM, & Thulin CA: Fibrinolysis and subarachnoid hemorrhage: inhibitory effect
of tranexamic acid: a clinical study. Acta Neurol Scand 1972; 48(4):393402.

162. Hedlund PO: Antifibrinolytic therapy with Cyklokapron in connection with prostatectomy: a
double blind study. Scand J Urol Nephrol 1969; 3(3):177182.

163. Nilsson L & Rybo G: Treatment of menorrhagia with an antifibrinolytic agent, tranexamic acid
(AMCA), a doubleblind investigation. Acta Obstet Gynecol Scand 1967; 46:572580.

164. SindetPedersen S: Distribution of tranexamic acid to plasma and saliva after oral
administration and mouth rinsing: a pharmacokinetic study. J Clin Pharmacol 1987; 27(12):1005
1008.

165. Tovi D & Thulin CA: The ability of tranexamic acid to cross the bloodbrain barrier and diffuse
in patients with ruptured intracranial aneurysms. Acta Neurol Scand 1972; 48:257.

166. Kullander S & Nilsson IM: Human placental transfer of an antifibrinolytic agent (AMCA). Acta
Obstet Gynecol Scand 1970; 49(3):241242.

167. Andersson L, Nilsson IM, Colleen S, et al: Role or urokinase and tissue activator in sustaining
bleeding and the management there of with EACA and AMCA. Ann NY Acad Sci 1968; 146(2):642
658.

168. de Guzman R, Polykratis IA, Sondeen JL, et al: Stability of tranexamic acid after 12week
storage at temperatures from 20 degree c to 50 degree c. Prehosp Emerg Care 2013; 17(3):394
400.



169. Pasquali SK, Li JS, He X, et al: Comparative analysis of antifibrinolytic medications in pediatric
heart surgery. J Thorac Cardiovasc Surg 2012; 143(3):550557.

170. Levi M, Cromheecke ME, de Jonge E, et al: Pharmacological strategies to decrease excessive
blood loss in cardiac surgery: a metaanalysis of clinically relevant endpoints. Lancet 1999;
354(9194):19401947.

171. Hanna BD & Bernstein M: Tranexamic acid in the treatment of KasabachMerritt syndrome in
infants. Am J Pediatr Hematol Oncol 1989; 11(2):191195.

172. Verstraete M: Clinical application of inhibitors of fibrinolysis. Drugs 1985; 29:236261.

173. Andersson L, Nilsson IM, Colleen S, et al: Role or urokinase and tissue activator in sustaining
bleeding and the management thereof with EACA and AMCA. Ann New York Acad Sci 1968;
146:642658.

174. Okamoto S, Sato S, Takada Y, et al: An active stereo isomer (trans form) of AMCHA and its
fibrinolytic (antiplasminic) action in vitro and in vivo. Keio J Med 1964; 13:177185.

175. Chowdhary UM & Sayed K: Comparative clinical trial of epsilon aminocaproic acid and
tranexamic acid in the prevention of early recurrence of subarachnoid haemorrhage. J Neurol
Neurosurg Psychiatry 1981; 44:810813.

176. Barer D, Ogilvie A, Henry D, et al: Cimetidine and tranexamic acid in the treatment of acute
uppergastrointestinaltract bleeding. N Engl J Med 1983; 308(26):15711575.

177. Karkouti K, Beattie WS, Dattilo KM, et al: A propensity score casecontrol comparison of
aprotinin and tranexamic acid in hightransfusionrisk cardiac surgery. Transfusion (Paris). 2006;
46(3):327338.


178. Mongan PD, Brown RS, & Thwaites BK: Tranexamic acid and aprotinin reduce postoperative
bleeding and transfusions during primary coronary revascularization. Anesth Analg 1998; 87(2):258
265.


179. Rahamani B & Jahadi HR: Comparison of tranexamic acid and prednisolone in the treatment of
traumatic hyphema. Ophthalmology 1999; 106(2):375379.

180. Martin K, Knorr J, Breuer T, et al: Seizures after open heart surgery: comparison of epsilon
aminocaproic acid and tranexamic acid. J Cardiothorac Vasc Anesth 2011; 25(1):2025.

181. Chauhan S, Gharde P, Bisoi A, et al: A comparison of aminocaproic acid and tranexamic acid in
adult cardiac surgery. Ann Card Anaesth 2004; 7(1):4043.


182. Martin K, Breuer T, Gertler R, et al: Tranexamic acid versus eaminocaproic acid: efficacy and
safety in paediatric cardiac surgery. Eur J Cardiothorac Surg 2011; 39(6):892897.

hemorrhage. N Engl J Med 1984; 311:432437.

184. Whitehead KJ, Sautter NB, McWilliams JP, et al: Effect of topical intranasal therapy on epistaxis
frequency in patients with hereditary hemorrhagic telangiectasia: a randomized clinical trial. JAMA
2016; 316(9):943951.


185. Ylikorkala O & Viinikka L: Comparison between antifibrinolytic and antiprostaglandin treatment
in the reduction of increased menstrual blood loss in women with intrauterine contraceptive devices.
Br J Obstet Gynecol 1983; 90(1):7883.

186. Bruno R, Baicchi U, Panattoni G, et al: Clinical trial of four antihaemorrhagic drugs in
adenotonsillectomy. Riv Orl Aud Fon 1986; 4:497501.

187. Verstraete M, Tyberghein J, De Greef Y, et al: Doubleblind trials with etamsylate, batroxobin
or tranexamic acid on blood loss after adenotonsillectomy. Acta Clin Belg 1977; 32(2):136141.

188. Bonnar J & Sheppard BL: Treatment of menorrhagia during menstruation: randomised
controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. Brit Med J 1996; 313:579582.

189. Milsom I, Andersson K, Andersch B, et al: A comparison of flurbiprofen, tranexamic acid, and a
levonorgestrelreleasing intrauterine contraceptive device in the treatment of idiopathic
menorrhagia. Am J Obstet Gynecol 1991; 164:879883.

190. Ohela K: Treatment of hereditary angioneurotic edema with tranexamic acid and cinnarizine.
Acta Derm Venereol (Stockh) 1976; 56(1):6167.

191. Gupta J, Kai J, Middleton L, et al: Levonorgestrel intrauterine system versus medical therapy
for menorrhagia. N Engl J Med 2013; 368(2):128137.

192. Milsom I, Andersson K, Andersch B, et al: A comparison of flurbiprofen, tranexamic acid, and a
levonorgestrelreleasing intrauterine contraceptive device in the treatment of idiopathic
menorrhagia. Am J Obstet Gynecol 1991; 164:879883.

193. Preston JT, Cameron IT, Adams EJ, et al: Comparative study of tranexamic acid and
norethisterone in the treatment of ovulatory menorrhagia. Br J Obstet Gynaecol 1995; 102:401406.

194. Kouides PA, Byams VR, Philipp CS, et al: Multisite management study of menorrhagia with
abnormal laboratory haemostasis: a prospective crossover study of intranasal desmopressin and oral
tranexamic acid. Br J Haematol 2009; 145(2):212220.

195. None listed: Omega3acid melts through foam cup. ISMP Medication Safety Alert! Acute Care
2009; 14(8):22.

196. National Institute for Occupational Safety and Health (NIOSH): Preventing occupational
exposures to antineoplastic and other hazardous drugs in health care settings. Centers for Disease
Control and Prevention (CDC). Atlanta, GA. 2004. Available from URL:
http://www.cdc.gov/niosh/docs/2004165/pdfs/2004165.pdf. As accessed 20130523.

197. Wells KA & Losin WG: In vitro stability, potency, and dissolution of duloxetine entericcoated
pellets after exposure to applesauce, apple juice, and chocolate pudding. Clin Ther 2008;
30(7):13001308.

198. Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the diagnosis and
treatment of the acute porphyrias. Ann Intern Med 2005; 142(6):439450.

199. European Porphyria Initiative: Recommendations for the use of drugs in the acute porphyrias
(AIP, HCP, VP). European Porphyria Initiative. Available from URL: http://www.porphyria
europe.org. As accessed 2/13/06.

200. Moore MR & Hift RJ: Drugs in the acute porphyriastoxicogenetic diseases. Cell Mol Biol
(Noisylegrand) 1997; 43(1):8994.


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