count, the coagulation time or various coagulation factors in whole blood or citrate blood from normal subjects.

In contrast, tranexamic acid in concentrations of 10 mg and 1 mg per mL blood prolongs thrombin time. PHARMACOKINETICS Tranexamic acid is rapidly absorbed from the gastrointestinal tract. Peak plasma levels after oral administration of 1 and 2 g are 8 and 15 mg/L, both obtained three hours after dosing. Bioavailability is about 30 to 50%. Food intake does not influence absorption. Plasma half-life is approximately after 2 hours. Tranexamic acid is widely distributed in the body and has a very low protein binding e.g., about 3% at therapeutic plasma levels and is accounted for by binding to plasminogen. It does not bind to serum albumin. Tranexamic acid's antifibrinolytically active concentration (10 mg/mL) remains in different tissues for about 17 hours and in the serum for up to 7 or 8 hours when administered 36 to 48 hours before surgery in 4 doses of 10 to 20 mg/kg body weight. Acetylation or deamination followed by oxidation or reduction are possible routes of biotransformation. After oral administration, approximately 50% of the parent compound, 2% of the deaminated dicarboxylic acid and 0.5% of the acetylated product are excreted. Tranexamic acid is excreted in the urine by glomerular filtration mainly as unchanged drug. The total amount of metabolites excreted in urine within 72 hours is less than 5%. After oral administration of 10 to 15 mg/kg body weight, the urinary excretion at 24 and 48 hours is 39 and 48%, respectively. The 24-hour recovery from urine is about 90% after IV administration of 10 mg/kg body weight. Tranexamic acid crosses the placenta but secretion in breast milk is low. No data are available concerning the concentration in gastric juice, but the clinical effect of tranexamic acid of gastrointestinal hemorrhage has been clearly demonstrated. INDICATIONS For the treatment and control of excessive bleeding in various surgical and medical conditions including: Surgical General surgical cases Cardiovascular surgery Coronary artery bypass graft surgery (CABG) (especially in aspirintreated patients) Valvular heart surgery Correction of congenital heart disease Thoracic aortic surgery Pulmonary surgery Orthopedic surgery Knee replacement or arthoplasty Total hip replacement or arthoplasty Scoliosis surgery Traumatic injuries Other operative procedures on the prostate, bladder, uterus, thyroid, ovaries, adrenals, kidneys, liver, brain, lymph nodes and soft tissues Obstetric and Gynecologic Menorrhagia/Menometrorrhagia Postpartum hemorrhage Abortion

Medical

Epistaxis Hemoptysis Hematuria Peptic ulcer disease with hemorrhage Blood dyscrasias with hemorrhage (e.g., hemophilia) Hereditary angioneurotic edema

250 mg and 500 mg Capsules 250 mg/2.5 mL and 500 mg/5 mL Solution for Injection (I.M./I.V.) Anti-fibrinolytic
FORMULATIONS Each capsule contains: Tranexamic acid......................................................250 or 500 mg Each mL of a 2.5 mL Solution for Injection contains: Tranexamic acid................................................................100 mg Each mL of a 5mL Solution for Injection contains: Tranexamic acid................................................................100 mg PRODUCT DESCRIPTIONS 250 mg Capsule Size #1 hard gelatin capsule with ivory opaque cap and rich yellow opaque body 500 mg Capsule Size #0 hard gelatin capsule with bright orange opaque cap and buff opaque body 250 mg/2.5 mL Solution for Injection Clear colorless, sterile, non-pyrogenic solution contained in a 3 mL clear ampule 500 mg/5 mL Solution for Injection Clear colorless, sterile, non-pyrogenic solution contained in a 5 mL ampule PHARMACODYNAMICS Tranexamic acid is an anti-fibrinolytic agent. It is a competitive inhibitor of plasminogen activity and at much higher concentration is a noncompetitive inhibitor of plasmin. Human plasminogen contains lysine binding sites that are important for interactions not only with synthetic antifibrinolytic amino acid derivatives but also with a2 antiplasmin and fibrin. One of these binding sites has a high affinity for tranexamic acid; the others have low affinity. Tranexamic acid almost completely blocks the interaction of plasminogen and the heavy chain of plasmin with the lysine binding site of plasminogen. Saturation of this site with tranexamic acid prevents binding of plasminogen to the surface of fibrin. This process retards fibrinolysis because, although plasmin is still formed, it is unable to bind to fibrinogen or fibrin monomer. Conversely, when tranexamic acid blocks the binding site of plasmin, inactivation by a2antiplasmin is impossible. In vitro, tranexamic acid 1 mg per mL does not aggregate platelets. Tranexamic acid in concentrations up to 10 mg per mL blood has no influence on platelet count, the coagulation time or various coagulation factors in whole blood or

Dental Following tooth extraction and dental surgery DOSAGE AND ADMINISTRATION General Dosing Recommendations: For IV infusion, tranexmic acid may be mixed with most solutions for infusion (e.g.,electrolyte solutions, carbohydrate solutions, amino acid solutions, and Dextran solution) The mixture should be prepared the same day the solution is to be used. Heparin may be added to tranexamic acid injection. Tranexamic acid injection should NOT be mixed with blood. Do not mix with solutions containing penicillin. Do not administer concomitantly with Factor IX Complex concentrated of Anti-inhibitor Coagulant concentrates, as risk of thrombosis may be increased. Administer parenteral format by slow intravenous injection to prevent dizziness and hypotension. Do not inject more rapidly than 1 mL/minute.
0.5-1 g (10 -15 mg/kg body weight) IV every 812 hours immediately after surgery Orally, 1-1.5 g every 6-8 hours Before surgery:1g bolus, or, 30 mg/kg dose in Coronary artery patients treated with aspirin bypass surgery During surgery:200mg/hour infusion Valvular heart 100 mg/kg body weight dose IV before surgery surgery. S Before surgery: initial bolus of 15 mg/kg body Correction of weight IV U Cardiovascular congenital heart After surgery: a second bolus of 15 mg/kg body disease in children Surgery weight IV R 1 g IV before skin incision, an infusion of 400 Thoracic aortic mg/hour during the operation, and 500 mg in the surgery G pump priming. Knee replacement/ Before surgery:10 mg/kg body weight IV I After surgery: another10 mg/kg IV 3 hours later. arthroplasty Before surgery:10 mg/kg initial IV bolus , 2nd C Total hip IV bolus of 10 mg/kg 3 hours later. Orthopedic replacement/ After surgery: continuous infusion of 1 mg/kg A Surgery arthroplasty hr for 10 hours. L Initial dose of 10 mg/kg body weight IV and Scoliosis surgery infusion of 1 mg/kg hr 5 to 10 mL (0.5 to 1 g) IV every 8 hours (the first injection given during the operation) for the first three days after surgery; thereafter, 1 to 1.5 g Prostatectomy orally every 6 to 8 hours daily until macroscopic hematuria is no longer present After surgery: Orally, 1.5 g every 8 hours for 12 Conisation of the Cervix to 14 days Obstetrical & Menorrhagia/ Orally, 1-1.5 g every 6 to 8 hours for 3 to 4 hours Gynecological Menometrorrhagia 1.5 g orally every 8 hours for 4 to 10 days Epistaxis 1g IV every 4 hours for a maximum of 3 days, Gastrointestinal followed by 1.5g orally, every 6 hours for a hemorrhage maximum of 4 days

INDICATIONS

RECOMMENDED DOSE

General Surgical Cases

Medical

Hematuria Hereditary angioneurotic edema

1 to 1.5g orally every 8 to 12 hours daily until macroscopic hematuria is no longer present Orally, 1 to 1.5 g every 8 to 12 hours as intermittent or continuous treatment depending on the prodromal symptoms of the patient

Insert Size:196 x 140mm

Hemostan Insert Color: PANTONE 470 U

Dental

Dental surgery in patients with coagulopathies

Immediately Before surgery: 10 mg/kg body weight IV After surgery: Orally, 1 to 1.5g (25 mg/kg body weight) every 6 to 8 hours for 6 to 8 days. Or, as prescribed by a physician.

Recommended dosage in Adult patients with moderate to severe renal impairment:

Serum Creatinine (mg/dL) 120 to 250 (1.36 to 2.83 mg/dL) 250 to 500 (2.83 to 5.66 mg/dL) >500 (> 5.66 mg/dL) Tranexamic Acid Dosage IV Dosage Tablets 10 mg/kg body weight 750 mg (or 15 mg/kg body weight) twice daily twice daily 10 mg/kg body weight 750 mg (or 15 mg/kg body weight) once daily once daily 10 mg/kg body weight 750 mg (or 15 mg/kg body weight) every 48 hours or every 48 hours or 5 mg/kg body weight 375 mg (or 7.5 mg/kg body weight) every 24 hours every 24 hours

Patients with disseminated intravascular coagulation who require treatment with tranexamic acid must be under the strict supervision of a physician experienced in treating this disorder. Patients with irregular menstrual bleeding should not use tranexamic acid until the cause of irregular bleeding has been established. Consider an alternative treatment if menstrual bleeding is not adequately reduced by tranexamic acid. Indissoluble clots may develop in body cavities such as pleural space, joint spaces and urinary tract (e.g., renal pelvis, bladder) due to extravascular clots which may be resistant to physiologic fibrinolysis. INTERACTIONS WITH OTHER MEDICAMENTS Simultaneous treatment with anticoagulants should be under the strict supervision of an expert physician Tranexamic acid may counteract the thrombolytic effect of fibrinolytic preparations STATEMENT ON USAGE FOR HIGH RISK GROUPS Pregnancy: Pregnancy Category B. There are no adequate and well controlled studies in pregnant women. However, tranexamic acid crosses the placenta and appears in cord blood. Use in pregnancy only if clearly needed. Lactation: Tranexamic acid is present in breast milk at 1% of the corresponding serum levels. Exercise caution when administering to breastfeeding women. Use in Children: Tranexamic acid has had limited use in children, principally in tooth extraction. Limited data suggest that dosing instructions for adults can be used for children needing tranexamic acid therapy. Use in the Elderly: No dosage reduction is necessary unless there is evidence of renal failure. UNDESIRABLE EFFECTS (See also Warnings and Precautions) Tranexamic acid appears to be well tolerated. However, it can produce doserelated gastrointestinal disturbances such as diarrhea, nausea and vomiting. Its use has also been associated with severe menstrual cramps, giddiness, allergic skin reactions, impaired color vision and disturbances. Ureteral obstruction due to clot formation in patients with upper urinary tract bleeding has likewise been reported in patients treated with tranexamic acid. Rapid intravenous administration usually results in hypotension. There have also been reports of thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction) in patients receiving tranexamic acid for indications other than hemorrhage prevention in patients with hemophilia. However, the actual incidence and causality relationship to the drug has not been established. OVERDOSE AND TREATMENT There are limited data on tranexamic acid overdosage. Symptoms may include dizziness, headache, nausea, vomiting, diarrhea, hypotension, or orthostatic hypotension. There is no known antidote for tranexamic acid overdose. In cases of overdose, discontinue treatment and institute symptomatic and supportive measures are

within one or two hours after ingestion. Administer activated charcoal via nasogastric tube once the airway is protected in patients who are not fully conscious or have impaired gag reflex. Monitor vital signs to detect a possible hypotensive episode. In patients with severe vomiting or diarrhea, monitor fluid and electrolyte levels and administer intravenous fluids and replace electrolytes are necessary. Monitor urine output and maintain adequate diuresis. Monitor for clinical evidence of Thromboembolic complications (e.g., chest pain, shortness of breath flank pain, extremity pain). Because there is a risk of thrombosis in predisposed individuals; anticoagulant therapy should be considered in these patients. In symptomatic patients, support cardiac and respiratory function. Monitor blood count, renal function, pulse oximetry and/or blood gases and obtain a chest xray. Obtain an ECG and institute continuous cardiac monitoring. STORAGE CONDITION Keep the product out of reach and sight of children Store at temperatures not exceeding 30C Protect from light CAUTION Foods, Drugs, Devices and Cosmetics Act prohibit dispensing without prescription. AVAILABILITY Tranexamic Acid (Hemostan ) 250 mg capsules, box of 100 capsules Tranexamic Acid (Hemostan) 500 mg capsules, box of 100 capsules Manufactured by Amherst Laboratories, Inc. Greenfield Industrial Center East Mamplasan, Bian, Laguna, Philippines for Biomedis, Inc. 750 Shaw Blvd., Mandaluyong City, Philippines Tranexamic Acid (Hemostan)250mg/2.5mL Solution for Injection, box of 5 ampules Tranexamic Acid (Hemostan )500mg/5 mL Solution for Injection, box of 5 ampules Manufactured by Amherst Parenterals, Inc. Don Jose, Sta. Rosa City, Laguna, Philippines for Biomedis, Inc. 750 Shaw Blvd., Mandaluyong City, Philippines

CONTRAINDICATIONS Hypersensitivity to tranexamic acid or any component of the product Patients with a history or risk of thrombosis, unless at the same time it is possible to give treatments with anticoagulants Active thromembolic disease such as deep vein thrombosis, pulmonary embolism and cerebral thrombosis Patients with acquired disturbances of color vision. If disturbances of color vision arise during the course of treatment, discontinue the drug Patients with subarachnoid hemorrhage since cerebral edema and cerebral infarction may be caused in such cases WARNINGS AND PRECAUTIONS For patients on prolonged treatment with tranexamic acid, perform an ophthalmological examination (including visual acuity, color vision, eyeground, and visual fields) before and at regular intervals during treatment, since visual abnormalities are the most frequently reported adverse reactions in some postmarketing studies. Discontinue tranexamic acid if changes are found. Focal areas of retinal degeneration have developed in cats, dogs, rabbits and rats following oral or IV tranexamic acid at doses between 126 and 1600 mg/kg/day (3 to 40 times the recommended human dose) from 6 days to 1 year. Reduce dose in patients with renal insufficiency because of the risk of drug accumulation. Treatment with tranexamic is not indicated in hematuria caused by diseases of the renal parenchyma. Intravascular precipitation of fibrin frequently occurs and may aggravate the disease. Furthermore, antifibrinolytic treatment carries the risk of clot retention in the renal pelvis in cases of massive renal hemorrhage of any cause. Patients with a high risk for thrombosis (a previous thromboembolic event and a family history of thromboembolic disease) should use tranexamic acid only if there is a strong medical indication and under strict medical supervision. There are reports of venous and arterial thrombosis or thromboembolism in patients given tranexamic acid. Also, cases of central retinal artery and central retinal vein obstruction have been reported. Patients taking tranexamic acid developed intracranial thrombosis; however, further observation is needed. Urinary tract obstruction due to clot formations in patients with severe bleeding from the upper urinary tract has been reported in patients taking tranexamic acid.

Reg.IPOPHIL

30000000232

196 mm ACTUAL SIZE: 196 X 140 mm