Brand name: Hemostan, Fibrinon, Cyklokapron, Lysteda, Transamin Classification: Anti-fibrinolytic, antihemorrhagic Indications: Tranexamic acid is used for the prompt and effective control of hemorrhage in various surgical and clinical areas: Treating heavy menstrual bleeding Hemorrhage following dental and/or oral surgery in patients with hemophilia Management of hemophilic patients (those having Factor VIII or Factor IX deficiency) who have oral mucosal bleeding, or are undergoing tooth extraction or other oral surgical procedures. Surgical: General surgical cases but most especially operative procedures on the prostate, uterus, thyroid, lungs, heart, ovaries, adrenals, kidneys, brain, tonsils, lymph nodes and soft tissues. Obstetrical and gynecological: abortion, post-partum hemorrhage and menometrorrahgia Medical: epistaxis, hemoptysis, hematuria, peptic ulcer with hemorrhage and blood dyscrasias with hemorrhage Effective in promoting hemostasis in traumatic injuries. Preventing hemorrhage after orthopedic surgeries. Mechanism of Action Tranexamic acid is a synthetic derivative of the amino acid lysine. It exerts its antifibrinolytic effect through the reversible blockade of lysine-binding sites on plasminogen molecules. Anti-fibrinolytic drug inhibits endometrial plasminogen activator and thus prevents fibrinolysis and the breakdown of blood clots. The plasminogen-plasmin enzyme system is known to cause coagulation defects through lytic activity on fibrinogen, fibrin and other clotting factors. By inhibiting the action of plasmin (finronolysin) the antifibrinolytic agents reduce excessive breakdown of fibrin and effect physiological hemostasis. Contraindications 1. Allergic reaction to the drug or hypersensitivity 2. Presence of blood clots (eg, in the leg, lung, eye, brain), have a history of blood clots, or are at risk for blood clots 3. Current administration of factor IX complex concentrates or anti-inhibitor coagulant concentrates Precautions 1. Pregnancy. Tranexamic acid crosses the placenta. 2. Lactation. Tranexamic acid is distributed into breast milk; concentrations reach approximately 1% of the maternal plasma concentration. 3. Contraceptives, estrogen-containing, oral or Estrogens. Concurrent use with tranexamic acid may increase the potential for thrombus formation. 4. Renal function impairment (medication may accumulate; dosage adjustment based on the degree of impairment is recommended) 5. 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) Nursing Responsibilities 1. Unusual change in bleeding pattern should be immediately reported to the physician. 2. For women who are taking Tranexamic acid to control heavy bleeding, the medication should only be taken during the menstrual period. 3. Tranexamic Acid should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed. 4. The medication can be taken with or without meals. 5. Swallow Tranexamic Acid whole with plenty of liquids. Do not break, crush, or chew before swallowing. 6. If you miss a dose of Tranexamic Acid, take it when you remember, then take your next dose at least 6 hours later. Do not take 2 doses at once. 7. Inform the client that he/she should inform the physician immediately if the following severe side effects occur: Severe allergic reactions such as rash, hives, itching, dyspnea, tightness in the chest, swelling of the mouth, face, lips or tongue Calf pain, swelling or tenderness

Chest pain Confusion Coughing up blood Decreased urination Severe or persistent headache Severe or persistent body malaise Shortness of breath Slurred speech Slurred speech Vision changes

Tranexamic Acid (Systemic) Category: Antifibrinolytic Antihemorrhagic Indications Accepted > Hemorrhage, following dental and [ oral] surgery, in patients with hemophilia (prophylaxis and treatment) > [Hemorrhage, oral, in patients with hemophilia (treatment)] > [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 bleeding] , 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. [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.] [Antifibrinolytic agents are used to treat severe hemorrhaging caused by thrombolytic agents such as alteplase (tissue-type plasminogen activator, recombinant), anistreplase (anisoylated plasminogenstreptokinase activator complex), streptokinase, or urokinase.]However, controlled studies to demonstrate their efficacy have not been done in humans. [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.] > [Angioedema, hereditary (treatment)]Tranexamic acid is indicated for the treatment of hereditary angioedema. 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. Pharmacology/Pharmacokinetics Physicochemical characteristics: Molecular weight157.21 Mechanism of action/Effect: Tranexamic acid competitively inhibits activation of plasminogen, 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. Tranexamic acid also directly inhibits plasmin

activity, but higher doses are required than are needed to reduce plasmin formation. In vitro, the antifibrinolytic potency of tranexamic acid is approximately 5 to 10 times that of aminocaproic acid. 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). Absorption: Oral30 to 50% of a dose is absorbed from the gastrointestinal tract. Bioavailability is not altered by food intake. Distribution: In breast milkConcentrations are approximately 1% of the maternal serum concentration. Protein binding: Very low ( 95% of a dose is excreted as unchanged tranexamic acid. Oral39% of a dose (about 78% of the quantity absorbed) is excreted within 24 hours after administration of 10 to 15 mg/kg. Intravenous90% of a dose is excreted within 24 hours after administration of 10 mg/kg. 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. Mutagenicity Studies using a variety of in vivo and in vitro test systems have not shown that tranexamic acid has mutagenic activity. Pregnancy/Reproduction Fertility Tranexamic acid has been detected in semen in antifibrinolytic concentrations but has no effect on the motility of spermatozoa. Reproductive studies in mice, rats, and rabbits have shown no evidence of impaired fertility. Pregnancy Tranexamic acid crosses the placenta. 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. Adequate and well-controlled studies in humans have not been done. 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. Studies in mice, rats, and rabbits have not shown that tranexamic acid causes adverse effects on the fetus. FDA Pregnancy Category B. Breast-feeding

Tranexamic acid is distributed into breast milk; concentrations reach approximately 1% of the maternal plasma concentration. 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. Geriatrics Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of tranexamic acid in the elderly. 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; using tranexamic acid as an oral rinse for oral surgical procedures and tooth extractions may minimize this complication; some hematologists recommend that administration of tranexamic acid be delayed for 8 hours following injection of either of the clotting factor complexes) 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 plasminogenstreptokinase 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) 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) 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) 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) Hemorrhage, subarachnoid (increased risk of cerebral edema and cerebral infarction) Renal function impairment (medication may accumulate; dosage adjustment based on the degree of impairment is recommended) 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) 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)

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. However, no retinal changes occurred in patients receiving tranexamic acid for weeks to months in clinical trials. 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: > 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 toorapid intravenous administration - 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 - Diarrhea - nausea - vomiting >Incidence unknown - Unusual menstrual discomfort caused by clotting of menstrual fluid Treatment of overdose Although there is no experience with overdose of tranexamic acid, discontinuing the medication is recommended. For thromboembolic complicationsMonitoring 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. 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 PregnancyTranexamic acid crosses the placenta, but has not been reported to cause problems when given to pregnant women Breast-feedingTranexamic 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 or if nausea, vomiting, or diarrhea occurs. It is recommended that therapy be discontinued if thromboembolic complications occur or if changes in the results of ophthalmologic examinations are noted. 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. 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 hemorrhage] , 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. 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. In addition to systemic tranexamic acid, an oral rinse may be used topically. [Hemorrhage, postsurgicalconization of the cervix] Oral, 1 to 1.5 grams every eight to twelve hours for twelve days after surgery. [Hemorrhage, postsurgicalprostatectomy]or Bladder surgery] 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. [Hemorrhage, hyperfibrinolysis-inducedepistaxis ] Oral, 1 to 1.5 grams three or four times a day for 10 days. [Hemorrhage, hyperfibrinolysis-inducedhypermenorrhea ] Oral, 1 to 1.5 grams three or four times a day for three or four days, starting after copious bleeding has begun. [Hemorrhage, hyperfibrinolysis-inducedhyphema ] Oral, 1 to 1.5 grams three or four times a day for seven days. [Hemorrhage, hyperfibrinolysis-inducedother] Oral, 20 to 25 mg two or three times a day. 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. Note: Because of the risk of tranexamic acid accumulation, the following dosage regimens are recommended for patients with moderate to severe renal function impairment: Serum Creatinine Dose (micromoles/L)

120250 (1.362.83 15 mg/kg two times a day mg/dL) 250500 (2.835.66 15 mg/kg a day mg/dL) >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 Indication & Dosage Oral Short-term management of haemorrhage Adult: 1-1.5 g or 15-25 mg/kg 2-4 times daily. Child: 25 mg/kg bid or tid. Renal impairment: Adjust dose based on serum creatinine concentration: 120-250 micromol/l: 15 mg/kg bid daily; 250-500 micromol/l: 15 mg/kg once daily; >500 micromol/l: 7.5 mg/kg once daily or 15 mg/kg once every 48 hr. Oral Long-term management of hereditary angioedema Adult: 1-1.5 g bid or tid. Child: 25 mg/kg bid or tid. Renal impairment: Adjust dose based on serum creatinine concentration: 120-250 micromol/l: 15 mg/kg bid daily; 250-500 micromol/l: 15 mg/kg once daily; >500 micromol/l: 7.5 mg/kg once daily or 15 mg/kg once every 48 hr. Intravenous Short-term management of haemorrhage Adult: 0.5-1 g or 10 mg/kg tid or 25-50 mg/kg daily by continuous infusion. Child: 10 mg/kg bid or tid. Renal impairment: Adjust dose based on the serum-creatinine concentration: 120-250 micromol/l: 10 mg/kg bid daily; 250-500 micromoles/l: 10 mg/kg once daily; >500 micromol/l: 5 mg/kg once daily or 10 mg/kg once every 48 hr. Incompatibility: Incompatible with benzylpenicillin. Administration: May be taken with or without food. Overdosage: Symptoms: Nausea, vomiting, orthostatic symptoms and/or hypotension. Contraindications: Severe renal failure, active intravascular clotting, thromboembolic disease, colour vision disorders, subarachnoid bleeding. Special Precautions: Mild to moderate renal impairment, irregular menstrual bleeding, previous history of thromboembolic disease, haematuria. Monitor closely in disseminated intravascular coagulation. Monitor LFT and eye examination regularly during long-term use. Discontinue if disturbance in colour vision occurs. Avoid IV inj rate >1 ml/minute due to risk of hypotension. Pregnancy, lactation. Adverse Drug Reactions: Diarrhoea, nausea, vomiting, disturbances in colour vision, giddiness, hypotension (after rapid IV inj), thromboembolic events. Drug Interactions: Potentially Fatal: Increased risk of thrombus formation with estrogens, Factor IX complex concentrates or anti-inhibitor coagulant concentrates. Increased risk of fatal thrombotic complications with tretinoin in acute promyelocytic leukaemia. Pregnancy Category (US FDA): Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1sttrimester (and there is no evidence of a risk in later trimesters). Storage: Intravenous: Store at 15-30C (59-86F). Oral: Store at 15-30C (59-86F). Mechanism of Action: Tranexamic acid is an antifibrinolytic agent that competitively inhibits breakdown of fibrin clots. It blocks binding of plasminogen and plasmin to fibrin, thereby preventing haemostatic plug dissolution.

Absorption: Absorbed from the GI tract; peak plasma concentrations after 3 hr (oral). Bioavailability: 3050%, unaffected by food intake. Distribution: Widely throughout the body. Protein-binding: Very low. Crosses the placenta and distributed into breast milk. Excretion: Urine (as unchanged drug); 2 hr (elimination half-life). MIMS Class: Haemostatics ATC Classification: B02AA02 - Tranexamic acid ; Belongs to the class of amino acid antifibrinolytics. Used in the treatment of hemorrhage.

Mechanism of ActionIpratropium bromide Ipratropium bromide is an anticholinergic (parasympatholytic) agent which, based on animal studies, appears to inhibit vagally-mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung. Anticholinergics prevent the increases in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle. Albuterol sulfate In vitro studies and in vivo pharmacology studies have demonstrated that albuterol has a preferential effect on beta2-adrenergic receptors compared with isoproterenol. While it is recognized that beta2-adrenergic receptors are the predominant receptors on bronchial smooth muscle, recent data indicate that there is a population of beta2-receptors in the human heart which comprise between 10% and 50% of cardiac beta-adrenergic receptors. The precise function of these receptors, however, is not yet established (see WARNINGS). Activation of beta2-adrenergic receptors on airway smooth muscle leads to the activation of adenylyl cyclase and to an increase in the intracellular concentration of cyclic-3',5'adenosine monophosphate (cyclic AMP). This increase of cyclic AMP leads to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation. Albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. Albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.

Albuterol has been shown in most clinical trials to have more bronchial smooth muscle relaxation effect than isoproterenol at comparable doses while producing fewer cardiovascular effects. However, all beta-adrenergic drugs, including albuterol sulfate, can produce a significant cardiovascular effect in some patients (see PRECAUTIONS). Combivent Inhalation Aerosol Combivent (ipratropium bromide and albuterol sulfate) Inhalation Aerosol is expected to maximize the response to treatment in patients with chronic obstructive pulmonary disease (COPD) by reducing bronchospasm through two distinctly different mechanisms, anticholinergic (parasympatholytic) and sympathomimetic. Simultaneous administration of both an anticholinergic (ipratropium bromide) and a beta2-sympathomimetic (albuterol sulfate) is designed to benefit the patient by producing a greater bronchodilator effect than when either drug is utilized alone at its recommended dosage.