AMINOCAPROIC ACID

INDICATIONS AND USAGE Aminocaproic acid tablets, USP is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. In life-threatening situations, transfusion of appropriate blood products and other emergency measures may be required. Fibrinolytic bleeding may frequently be associated with surgical complications following heart surgery (with or without cardiac bypass procedures) and portacaval shunt; hematological disorders such as amegakaryocytic thrombocytopenia (accompanying aplastic anemia); acute and life-threatening abruptio placentae; hepatic cirrhosis; and neoplastic disease such as carcinoma of the prostate, lung, stomach, and cervix. Urinary fibrinolysis, usually a normal physiological phenomenon, may contribute to excessive urinary tract fibrinolytic bleeding associated with surgical hematuria (following prostatectomy and nephrectomy) or nonsurgical hematuria (accompanying polycystic or neoplastic diseases of the genitourinary system). (See WARNINGS.)

DOSAGE AND ADMINISTRATION An identical dosage regimen may be followed by administering aminocaproic acid Tablets, USP as follows: For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 5 aminocaproic acid 1,000 mg tablets or 10 aminocaproic acid 500 mg tablets (5 g) be administered during the first hour of treatment, followed by a continuing rate of 1 aminocaproic acid 1,000 mg tablet or 2 aminocaproic acid 500 mg tablets (1 g) per hour. This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled.

CONTRAINDICATIONS Aminocaproic Acid Tablets should not be used when there is evidence of an active intravascular clotting process. When there is uncertainty as to whether the cause of bleeding is primary fibrinolysis or disseminated intravascular coagulation (DIC), this distinction must be made before administering Aminocaproic Acid Tablets. The following tests can be applied to differentiate the two conditions: Platelet count is usually decreased in DIC but normal in primary fibrinolysis. Protamine paracoagulation test is positive in DIC; a precipitate forms when protamine sulfate is dropped into citrated plasma. The test is negative in the presence of primary fibrinolysis. The euglobulin clot lysis test is abnormal in primary fibrinolysis but normal in DIC. Aminocaproic Acid Tablets must not be used in the presence of DIC without concomitant heparin.

ADVERSE REACTIONS Aminocaproic acid is generally well tolerated. The following adverse experiences have been reported: General: Edema, headache, malaise. Hypersensitivity Reactions: Allergic and anaphylactoid reactions, anaphylaxis. Cardiovascular: Bradycardia, hypotension, peripheral ischemia, thrombosis. Gastrointestinal: Abdominal pain, diarrhea, nausea, vomiting. Hematologic: Agranulocytosis, coagulation disorder, leukopenia, thrombocytopenia. Musculoskeletal: CPK increased, muscle weakness, myalgia, myopathy (see WARNINGS ), myositis, rhabdomyolysis. Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope. Respiratory: Dyspnea, nasal congestion, pulmonary embolism. Skin: Pruritis, rash. Special Senses: Tinnitus, vision decreased, watery eyes. Urogenital: BUN increased, renal failure. There have been some reports of dry ejaculation during the period of aminocaproic acid treatment. These have been reported to date only in hemophilia patients who received the drug after undergoing dental surgical procedures. However, this symptom resolved in all patients within 24 to 48 hours of completion of therapy. To report SUSPECTED ADVERSE REACTIONS, contact PuraCap Laboratories, LLC DBA Blu Pharmaceuticals at 1-888-374-2791 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DESCRIPTION Aminocaproic acid USP is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis. Its chemical structure is: Aminocaproic acid is freely soluble in water; it is slightly soluble in methanol and practically insoluble in chloroform and diethyl ether. Each aminocaproic acid tablet, for oral administration contains 500 mg or 1,000 mg of aminocaproic acid, USP and the following inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, povidone and stearic acid. The FDA approved dissolution acceptance criterion differs from that in the USP for Aminocaproic Acid Tablets. dtructure

OVERDOSAGE A few cases of acute overdosage with Aminocaproic Acid Tablets administered intravenously have been reported. The effects have ranged from no reaction to transient hypotension to severe acute renal failure leading to death. One patient with a history of brain tumor and seizures experienced seizures after receiving an 8 gram bolus injection of Aminocaproic Acid Tablets. The single dose of Aminocaproic Acid Tablets causing symptoms of overdosage or considered to be life-threatening is unknown. Patients have tolerated doses as high as 100 grams while acute renal failure has been reported following a dose of 12 grams. The intravenous and oral LD50 of Aminocaproic Acid Tablets were 3.0 and 12.0 g/kg, respectively, in the mouse and 3.2 and 16.4 g/kg, respectively, in the rat. An intravenous infusion dose of 2.3 g/kg was lethal in the dog. On intravenous administration, tonic-clonic convulsions were observed in dogs and mice. No treatment for overdosage is known, although evidence exists that Aminocaproic Acid Tablets is removed by hemodialysis and may be removed by peritoneal dialysis. Pharmacokinetic studies have shown that total body clearance of Aminocaproic Acid Tablets is markedly decreased in patients with severe renal failure.

HOW SUPPLIED Aminocaproic Acid Tablets, USP 500 mg Each round, white to off-white tablet, bisect debossed with logo "010" on top and bottom of the scored line on one side and the other side is blank, contains 500 mg of aminocaproic acid. Bottle of 30 – NDC 69680-115-30 Bottle of 100 – NDC 69680-115-00 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]; Dispense in Tight Containers. Aminocaproic Acid Tablets, USP 1000 mg Each oblong, white to off-white tablet, bisect debossed with logo "009" on left and right of the scored line on one side and the other side is blank, contains 1000 mg of aminocaproic acid. Bottle of 30 – NDC 69680-116-30 Bottle of 100 – NDC 69680-116-00 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]; Dispense in Tight Containers.