Tranexamic Acid (Systemic)


VA CLASSIFICATION
Primary: BL116
Secondary: IM900

Commonly used brand name(s): Cyklokapron.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antifibrinolytic—

antihemorrhagic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Hemorrhage, following dental and [ oral1] surgery, in patients with hemophilia (prophylaxis and treatment)
[Hemorrhage, oral, in patients with hemophilia (treatment)1]
[Hemorrhage, postsurgical (treatment)] or
[Hemorrhage, hyperfibrinolysis-induced (treatment) ]—Tranexamic acid is indicated for the management of hemophilic patients (those having Factor VIII or Factor IX deficiency ) who have [oral mucosal bleeding1] , or are undergoing tooth extraction [or other oral surgical procedures1] . The medication prevents or decreases hemorrhaging in these patients and reduces the need for administration of clotting factors, particularly when desmopressin is also used. {01} {02} {03} {10} {11} {14} {15} {16}
—[Tranexamic acid is indicated for the treatment of severe localized bleeding secondary to hyperfibrinolysis, including epistaxis, hyphema, or hypermenorrhea (menorrhagia) and hemorrhage following certain surgical procedures, such as conization of the cervix {02} {03} {11} .]
—[Antifibrinolytic agents are used to treat severe hemorrhaging caused by thrombolytic agents such as alteplase (tissue-type plasminogen activator, recombinant), anistreplase (anisoylated plasminogen-streptokinase activator complex), streptokinase, or urokinase {03} .]1However, controlled studies to demonstrate their efficacy have not been done in humans {09}.
—[Bleeding responsive to antifibrinolytic therapy also may occur following heart surgery (with or without cardiac bypass procedures) and portacaval shunt, prostatectomy, nephrectomy, or bladder surgery, and in association with hematologic disorders (such as aplastic anemia), abruptio placentae, hepatic cirrhosis, neoplastic disease, and polycystic or neoplastic diseases of the genitourinary system {03} {08} .]1

[Angioedema, hereditary (treatment)]—Tranexamic acid is indicated for the treatment of hereditary angioedema {02} {03} {11}. It is used to reduce the frequency and severity of acute attacks in patients with this disorder.

Note: Antifibrinolytic agents are ineffective in bleeding caused by loss of vascular integrity; a definite clinical diagnosis or confirmation of hyperfibrinolysis (hyperplasminemia) via laboratory studies is required before tranexamic acid is used to treat hemorrhage. However, some conditions and laboratory findings suggestive of hyperfibrinolysis are also present in disseminated intravascular coagulation; differentiation between the two conditions is essential because antifibrinolytic agents may promote thrombus formation in patients with disseminated intravascular coagulation and must not be used unless heparin is administered concurrently. The following criteria may be useful in differential diagnosis {12}:

Test
Primary
Hyperfibrinolysis
Results
Disseminated
Intravascular
Coagulation
Results
Platelet count *
Normal
Decreased
Protamine para-
coagulation test
Negative
Positive
Euglobulin clot
lysis time
Decreased
Normal
* Following extracorporeal circulation (during cardiovascular surgery), decreased platelet count may not be useful for differentiating between primary hyperfibrinolysis and disseminated intravascular coagulation; the other criteria may be more useful in differential diagnosis in these patients.


1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    157.21 {01} {04} {10}

Mechanism of action/Effect:

Tranexamic acid competitively inhibits activation of plasminogen {01} {02} {03} {11}, thereby reducing conversion of plasminogen to plasmin (fibrinolysin), an enzyme that degrades fibrin clots, fibrinogen, and other plasma proteins, including the procoagulant factors V and VIII {10}. Tranexamic acid also directly inhibits plasmin activity, but higher doses are required than are needed to reduce plasmin formation {01} {02}. In vitro , the antifibrinolytic potency of tranexamic acid is approximately 5 to 10 times that of aminocaproic acid {01} {10} {11}.

In patients with hereditary angioedema, inhibition of the formation and activity of plasmin by tranexamic acid may prevent attacks of angioedema by decreasing plasmin-induced activation of the first complement protein (C1) {05}.

Absorption:

Oral—30 to 50% of a dose is absorbed from the gastrointestinal tract {11}. Bioavailability is not altered by food intake {01} {10}.

Distribution:

In breast milk—Concentrations are approximately 1% of the maternal serum concentration {01} {02}.

Protein binding:

Very low (<3%) {01} {02} {10}, primarily to plasminogen, at therapeutic plasma concentrations {01} {10}. Tranexamic acid does not bind to serum albumin {01} {02} {10} {11}.

Biotransformation:

Less than 5% of a dose is metabolized {01}.

Half-life:

Elimination—Approximately 2 hours (following intravenous administration of a 1-gram dose) {01} {10}.

Time to peak concentration:

Oral—Approximately 3 hours {01} {02} {11}.

Peak plasma concentration

Oral—8 mcg per mL (50.9 micromoles/L) following a dose of 1 gram; 15 mcg per mL (95.4 micromoles/L) following a dose of 2 grams {01} {10}.

Therapeutic plasma concentration

10 mcg per mL (63.6 micromoles/L) {02}. Therapeutic concentrations persist in serum for 7 to 8 hours, and in several other tissues for up to 17 hours {01} {02} {10} {11}, following administration of the last of 4 doses of 10 mg per kg of body weight (mg/kg) intravenously or 20 mg/kg orally {02}.

Elimination:
    Renal, via glomerular filtration; > 95% of a dose is excreted as unchanged tranexamic acid {10}.
    Oral—39% of a dose {01} {02} (about 78% of the quantity absorbed {01}) is excreted within 24 hours after administration of 10 to 15 mg/kg {01} {02} {10} {11}.
    Intravenous—90% of a dose is excreted within 24 hours after administration of 10 mg/kg {01} {02} {10}.


Precautions to Consider

Carcinogenicity/Tumorigenicity

An increased incidence of leukemia occurred in male mice receiving approximately 5 grams per kg of body weight per day of tranexamic acid (added to food in a concentration of 4.8%). Female mice were not included in that study. In another study, tranexamic acid produced adenomas, adenocarcinomas, and hyperplasia of the biliary tract when administered orally to one strain of rats in doses exceeding the maximum tolerated dose for a period of 22 months. Lower doses produced hyperplastic, but not neoplastic, changes. No hyperplastic or neoplastic changes were observed in subsequent long-term studies in which equivalent doses were administered to a different strain of rats. {01} {10}

Mutagenicity

Studies using a variety of in vivo and in vitro test systems have not shown that tranexamic acid has mutagenic activity {01} {10}.

Pregnancy/Reproduction
Fertility—
Tranexamic acid has been detected in semen in antifibrinolytic concentrations but has no effect on the motility of spermatozoa {01} {02} {10} {11}. Reproductive studies in mice, rats, and rabbits have shown no evidence of impaired fertility {01} {02} {10}.

Pregnancy—
Tranexamic acid crosses the placenta {10} {11}. Following intravenous administration of 10 mg per kg of body weight (mg/kg) to pregnant women, 30 mcg of tranexamic acid per mL (190.8 micromoles/L) was measured in fetal serum {01} {02}. Adequate and well-controlled studies in humans have not been done {01}. However, healthy infants have been born to women who received tranexamic acid during pregnancy for treatment of fibrinolytic bleeding or bleeding associated with abruptio placentae {02} {11}.

Studies in mice, rats, and rabbits have not shown that tranexamic acid causes adverse effects on the fetus {01}.

FDA Pregnancy Category B {10}.

Breast-feeding

Tranexamic acid is distributed into breast milk; concentrations reach approximately 1% of the maternal plasma concentration {01} {02} {10} {11}.

Pediatrics

Appropriate studies on the relationship of age to the effects of tranexamic acid have not been performed in the pediatric population. However, no pediatrics-specific problems have been documented to date {01}.


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of tranexamic acid in the elderly {03}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Anti-inhibitor coagulant complex or
Factor IX complex    (although tranexamic acid is often used in conjunction with clotting factor replacement for the perisurgical management of hemophilic patients, concurrent use may increase the risk of thrombotic complications {13}; using tranexamic acid as an oral rinse for oral surgical procedures and tooth extractions may minimize this complication {14}; some hematologists recommend that administration of tranexamic acid be delayed for 8 hours following injection of either of the clotting factor complexes {09})


Contraceptives, estrogen-containing, oral or
Estrogens    (concurrent use with tranexamic acid may increase the potential for thrombus formation)


Thrombolytic agents    (the actions of tranexamic acid and of thrombolytic agents [e.g., alteplase (tissue-type plasminogen activator, recombinant; tPA), anistreplase (anisoylated plasminogen-streptokinase activator complex; APSAC), streptokinase, or urokinase] are mutually antagonistic; although controlled studies to demonstrate its efficacy have not been done in humans, tranexamic acid may be useful in treating severe hemorrhage caused by a thrombolytic agent {06})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Intravascular clotting, active    (risk of serious, even fatal, thrombus formation)

{07}
Risk-benefit should be considered when the following medical problems exist
» Defective color vision, acquired    (condition precludes assessment of color vision, which may be required to determine toxicity)

{01}{02}{10}{11}
» Hematuria of upper urinary tract origin    (risk of intrarenal obstruction secondary to clot retention in the renal pelvis and ureters if hematuria is massive; also, if hematuria is associated with a disease of the renal parenchyma, intravascular precipitation of fibrin may occur and exacerbate the disease)

{02}
» Hemorrhage, subarachnoid    (increased risk of cerebral edema and cerebral infarction)

{01}{10}
» Renal function impairment    (medication may accumulate; dosage adjustment based on the degree of impairment is recommended)

{01}{02}{03}{10}{11}
Sensitivity to tranexamic acid, history of
» Thrombosis, predisposition to or history of    (medication inhibits clot dissolution and may interfere with mechanisms for maintaining blood vessel patency; it is recommended that tranexamic acid be administered in conjunction with anticoagulant therapy, if at all)

{02}{03}{11}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Ophthalmological examinations, including tests for visual acuity, color vision, eyeground, and visual fields    (recommended prior to and at regular intervals during therapy for patients receiving the medication for longer than several days because tranexamic acid has caused focal areas of retinal degeneration in animal studies and visual disturbances [although retinal lesions have not been reported] in humans)

{01}{11}


Side/Adverse Effects

Note: Patients receiving tranexamic acid should be monitored for signs of thromboembolic complications.
Focal areas of retinal degeneration have been reported in cats, dogs, and rats after oral or intravenous administration of tranexamic acid at doses of 250 to 1600 mg per kg of body weight (mg/kg) per day (6 to 40 times the recommended usual human dose) for 6 days to a year. The incidence and severity of the lesions are dose-dependent. Some lesions in animals receiving low doses have been reversible. Other studies in cats and rabbits have shown retinal changes to occur with doses as low as 126 mg/kg per day (about 3 times the recommended usual human dose) administered for several days to 2 weeks. {01} {10} {11} However, no retinal changes occurred in patients receiving tranexamic acid for weeks to months in clinical trials {01} {02} {10} {11}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive: {01} {02}

Those indicating need for medical attention
Incidence less frequent or rare
    
Blurred vision or other changes in vision
    
hypotension (dizziness or lightheadedness; unusual tiredness or weakness)—may be associated with too-rapid intravenous administration{10}{11}
    
thrombosis or thromboembolism (pains in chest, groin, or legs [especially calves]; severe, sudden headache; sudden and unexplained shortness of breath, slurred speech, vision changes, and/or weakness or numbness in arm or leg; sudden loss of coordination)—depending on site of thrombus formation or embolization



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent {10} {11}
    
Diarrhea
    
nausea
    
vomiting

Incidence unknown
    
Unusual menstrual discomfort —caused by clotting of menstrual fluid





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Although there is no experience with overdose of tranexamic acid {01} {02} {10} {11}, discontinuing the medication is recommended.

For thromboembolic complications—Monitoring the patient carefully and administering appropriate therapy, depending on the location and size of the thrombus. Use of heparin or a thrombolytic agent may be considered in severe cases. However, these medications must be used with extreme caution, if at all, in patients receiving tranexamic acid to prevent or treat hemorrhaging, because of the risk of uncontrollable hemorrhage being induced in such patients.

If tranexamic acid had been administered orally, limiting absorption via induction of emesis, gastric lavage, and/or administration of activated charcoal may be helpful {11}.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antifibrinolytic Agents (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to tranexamic acid, history of

Pregnancy—Tranexamic acid crosses the placenta, but has not been reported to cause problems when given to pregnant women





Breast-feeding—Tranexamic acid is distributed into breast milk
Other medical problems, especially defective color vision, hematuria of upper urinary tract origin, predisposition to or history of thrombosis, renal function impairment, and subarachnoid hemorrhage

Proper use of this medication
» Importance of not using more or less medication than the amount prescribed

» Proper dosing
Missed dose: Taking as soon as possible, then returning to regular dosing schedule; not doubling doses

» Proper storage

Precautions while using this medication
Possible need for regular ophthalmologic examinations during long-term therapy


Side/adverse effects
Signs of potential side effects, especially blurred vision or other changes in vision, hypotension, and thrombosis or thromboembolism.


General Dosing Information
A reduction in dosage may be required for patients with renal function impairment {01} {02} {03} {10} or if nausea, vomiting, or diarrhea occurs {01}.

It is recommended that therapy be discontinued if thromboembolic complications occur or if changes in the results of ophthalmologic examinations are noted {01}.

For parenteral dosage forms only
Tranexamic acid injection should be administered intravenously at a rate not to exceed 100 mg (1 mL) per minute, to avoid inducing hypotension {01} {10}.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refers to categories of use and/or indications that are not included in U.S. product labeling.

TRANEXAMIC ACID TABLETS

Usual adult and adolescent dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
Presurgical: Oral, 25 mg per kg of body weight every six to eight hours, beginning one day before the dental procedure. However, intravenous administration of the medication immediately prior to surgery may be preferred. When tranexamic acid is used, a single factor VIII infusion of 40 International Units per kg of body weight, or coagulation factor IX infusion of 60 International Units per kg of body weight prior to surgery is often enough for normal hemostasis {18} {19}.

Note: Because of an increased risk of thrombotic complications when tranexamic acid and Factor IX or anti-inhibitor coagulant complex are administered concurrently, some hematologists recommend that tranexamic acid not be administered within eight hours of these clotting factor concentrates.

Postsurgical: Oral, 25 mg per kg of body weight every six to eight hours for two to eight days after surgery {14} {20}{22}. In addition to systemic tranexamic acid, an oral rinse may be used topically (see Tranexamic Acid Oral Solution ) {21}.

[Hemorrhage, postsurgical–conization of the cervix]
Oral, 1 to 1.5 grams every eight to twelve hours for twelve days after surgery {02} {11}.

[Hemorrhage, postsurgical–prostatectomy]1or
[Bladder surgery]1
Oral, 1 gram three to four times a day starting on the fourth day after surgery (the medication having been administered intravenously for the first three days postoperatively). Therapy should be continued until macroscopic hematuria is no longer present. {03}

[Hemorrhage, hyperfibrinolysis-induced–epistaxis ]
Oral, 1 to 1.5 grams three or four times a day for 10 days {02} {11}.

[Hemorrhage, hyperfibrinolysis-induced–hypermenorrhea ]
Oral, 1 to 1.5 grams three or four times a day for three or four days, starting after copious bleeding has begun {02} {03} {11}.

[Hemorrhage, hyperfibrinolysis-induced–hyphema ]
Oral, 1 to 1.5 grams three or four times a day for seven days {02} {11}.

[Hemorrhage, hyperfibrinolysis-induced–other]1
Oral, 20 to 25 mg two or three times a day {03}. Therapy should be continued until there is evidence of cessation of bleeding or laboratory determinations of fibrinolysis indicate that treatment is no longer needed.

[Angioedema, hereditary ]
Oral, 1 to 1.5 grams two or three times a day. Some patients can sense the onset of attacks and may be treated intermittently, with therapy being started at the first sign of an attack and continued for several days. Other patients should be treated on a continuing basis. {02} {03} {11}


Note: Because of the risk of tranexamic acid accumulation, the following dosage regimens are recommended for patients with moderate to severe renal function impairment {10} {11}:

Serum Creatinine
(micromoles/L)
Dose
120–250 (1.36–2.83 mg/dL)
15 mg/kg two times a day
250–500 (2.83–5.66 mg/dL)
15 mg/kg a day
>500 (>5.66 mg/dL)
15 mg/kg every 48 hours or 7.5 mg/kg every 24 hours



Usual pediatric dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—


500 mg (Rx) [Cyklokapron (microcrystalline cellulose) (talc) (magnesium stearate) (silicon dioxide) (povidone)]

Canada—


500 mg (Rx) [Cyklokapron]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {10}, in a well-closed container, unless otherwise specified by manufacturer.


TRANEXAMIC ACID ORAL SOLUTION

Usual adult and adolescent dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
Postsurgical: Topically, as an oral rinse, 10 mL of a 5% solution for two minutes four times a day for five to seven days after surgery, in addition to systemic tranexamic acid (see Tranexamic Acid Tablets ) {21}.


Usual pediatric dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—
Dosage form not commercially available in the U.S. Compounding required for prescriptions.

Canada—
Dosage form not commercially available in Canada. Compounding required for prescriptions.

Preparation of dosage form:
A 5% oral rinse is prepared by diluting 5 mL of 10% tranexamic acid injection with 5 mL of sterile water {17}.



Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refers to categories of use and/or indications that are not included in U.S. product labeling.

TRANEXAMIC ACID INJECTION

Usual adult and adolescent dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
Presurgical: Intravenous, 10 mg per kg of body weight, administered immediately prior to surgery. When tranexamic acid is used, a single factor VIII infusion of 40 International Units per kg of body weight, or coagulation factor IX infusion of 60 International Units per kg of body weight prior to surgery is often enough for normal hemostasis {18} {19}.

Note: Because of an increased risk of thrombotic complications when tranexamic acid and Factor IX or anti-inhibitor coagulant complex are administered concurrently, some hematologists recommend that tranexamic acid not be administered within eight hours of these clotting factor concentrates.

Postsurgical (for patients unable to take medication orally): Intravenous, 10 mg per kg of body weight every six to eight hours for seven to ten days {14} {20}.

[Hemorrhage, postsurgical ]
Following prostatectomy or bladder surgery: Intravenous, 1 gram, administered during surgery initially, then every eight hours for three days. Therapy is then continued, using orally administered tranexamic acid, until macroscopic hematuria is no longer present. {03}

Note: Tranexamic acid injection may also be used as an irrigation following bladder surgery. One gram of tranexamic acid in one liter of 0.9% sodium chloride irrigation is instilled into the bladder at a rate of 1 mL per minute once a day for two to five days following surgery.


[Hemorrhage, hyperfibrinolysis-induced ]
Intravenous, 15 mg per kg of body weight or 1 gram every six to eight hours {03}. Therapy should be continued until there is evidence of cessation of bleeding or laboratory determinations of fibrinolysis indicate that treatment is no longer needed.


Note: For other specific indications listed under Tranexamic Acid Tablets , patients unable to take medication orally may receive intravenous administration of 10 mg per kg of body weight of tranexamic acid according to the dosing schedule recommended for that indication.
For relief of severe epistaxis, tranexamic acid injection has also been applied topically to the nasal mucosa, as a spray or by packing the nasal cavity with a gauze strip that has been soaked in the solution {03}.
Because of the risk of tranexamic acid accumulation, the following dosage regimens are recommended for patients with moderate to severe renal function impairment {10} {11}:

Serum Creatinine
(micromoles/L)
Dose
120–250 (1.36–2.83 mg/dL)
10 mg/kg two times a day
250–500 (2.83–5.66 mg/dL)
10 mg/kg a day
>500 (>5.66 mg/dL)
10 mg/kg every 48 hours or
5 mg/kg every 24 hours



Usual pediatric dose
Prevention and treatment of [ oral hemorrhage1] , including hemorrhage following dental surgery, in hemophilic patients
See Usual adult and adolescent dose .


Strength(s) usually available
U.S.—


100 mg per mL (in 10-mL ampuls) (Rx) [Cyklokapron]

Canada—


100 mg per mL ( in 5- and 10-mL ampuls) (Rx) [Cyklokapron]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {10}, unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
Tranexamic acid injection may be mixed with intravenous infusion solutions, including solutions containing electrolytes, carbohydrates, amino acids, or dextran {10} {11}.

Heparin may be added to the tranexamic acid injection, if necessary {10} {11}.

Stability:
Intravenous infusion mixtures should be prepared the same day they are to be used {10} {11}.

Incompatibilities:
Tranexamic acid should not be added to any solution containing penicillin or mixed with blood {10} {11}.



Revised: 08/16/2001



References
  1. Cyklokapron package insert (KabiVitrum—US), Rev 1987, Rec 6/87.
  1. Cyklokapron (Pharmacia). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 22nd ed. Ottawa: Canadian Pharmaceutical Association; 1987. p. 211.
  1. Cyklokapron (KabiVitrum). In ABPI-DSC 1985-1986: 656-7.
  1. Fleeger CA, editor. USAN 1994. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1993. p. 542.
  1. Wyngaarden JB, Smith LH, editors. Cecil textbook of medicine. 18th ed. Philadelphia: WB Saunders; 1988. p. 1950.
  1. Marder VJ. Comparison of thrombolytic agents: selected hematologic, vascular and clinical events. Am J Cardiol 1989; 64: 2A-7A.
  1. Amicar package insert (Lederle—Canada), Rev 4/89, Rec 6/30/93.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982. p. 738-9.
  1. AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 648.
  1. Cyklokapron (Kabi Pharmacia). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data; 1994. p. 1111-2.
  1. Cyklokapron (Pharmacia). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 28th ed. Ottawa: Canadian Pharmaceutical Association; 1993. p. 311-2.
  1. Amicar (Immunex). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data; 1994. p. 1063-4.
  1. Konyne 80 package insert (Cutter—US), Rev 4/91, Rec 4/12/93.
  1. Association of Hemophilia Clinic Directors of Canada. Hemophilia and von Willebrand"s disease: 2. Management. Can Med Assoc J 1995; 153: 147-57.
  1. Panel comment per Hemophilia monograph reviewed 1/97.
  1. Panel comment per Hemophilia monograph reviewed 3/97.
  1. Sindet-Pederson S, Ingerslev J, Ramström G, et al. Management of oral bleeding in haemophilic patients [letter]. Lancet 1988; 2: 566.
  1. Brettler DB, Levine PH. Clinical manifestations and therapy of inherited coagulation factor deficiencies. In: Colman RW, Hirsch J, Marder VJ, et al., editors. Hemostasis and thrombosis: basic principles and clinical practice. 3rd ed. Philadelphia: JB Lippincott; 1994. p. 169-83.
  1. Djulbegovic B, Goldsmith GH. Guidelines for management of hemophilia A and B [letter]. Blood 1995; 85: 598.
  1. Reviewers" consensus on Hemophilia monograph developed 4/29/97.
  1. Sindet-Pederson S, Stenbjerg S. Effect of local antifibrinolytic treatment with tranexamic acid in hemophiliacs undergoing oral surgery. J Oral Maxillofac Surg 1986; 44: 703-7.
  1. Product Information: Cyklokapron®, tranexamic acid, Pharmacia and Upjohn, Kalamazoo MI (PI revised 10/2000) PI reviewed 8/2001.
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