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Aminocaproic acid is 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis. Its chemical structure is: Aminocaproic acid, USP is a fine, white to almost white, crystalline powder.
It is freely soluble in water, in acids, and in alkaline solutions; it is slightly soluble in methanol and practically insoluble in chloroform and in ether.
Each Aminocaproic acid tablet, USP for oral administration contains mg of Aminocaproic acid, USP and the following inactive ingredients: crospovidone type B, magnesium stearate, povidone and stearic acid. Aminocaproic - Clinical Pharmacology The fibrinolysis-inhibitory effects of Aminocaproic acid appear to be exerted principally via inhibition of plasminogen activators and to a lesser degree through antiplasmin activity. In adults, oral absorption appears to be a zero-order process with an absorption rate of 5.
The mean lag time in absorption is 10 minutes. After oral administration, the apparent volume of distribution was estimated to be Correspondingly, the volume of distribution after intravenous administration has been reported to be After prolonged administration, Aminocaproic acid has been found to distribute throughout extravascular and intravascular compartments of the body, penetrating human red blood cells as well as other tissue cells.
Renal excretion is the primary route of elimination. The terminal elimination half-life for Aminocaproic acid is approximately 2 hours. Indications and Usage for Aminocaproic Aminocaproic acid tablets are 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, usualIy 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.
Contraindications Aminocaproic acid 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.
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 must not be used in the presence of DIC without concomitant heparin. Warnings In patients with upper urinary tract bleeding, Aminocaproic acid administration has been known to cause intrarenal obstruction in the form of glomerular capillary thrombosis or clots in the renal pelvis and ureters. For this reason, Aminocaproic acid should not be used in hematuria of upper urinary tract origin, unless the possible benefits outweigh the risk.
Subendocardial hemorrhages have been observed in dogs given intravenous infusions of 0. Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of Aminocaproic acid at 0. Rarely, skeletal muscle weakness with necrosis of muscle fibers has been reported following prolonged administration. Clinical presentation may range from mild myalgias with weakness and fatigue to a severe proximal myopathy with rhabdomyolysis, myoglobinuria, and acute renal failure.
Muscle enzymes, especially creatine phosphokinase CPK are elevated. CPK levels should be monitored in patients on long-term therapy. Aminocaproic acid administration should be stopped if a rise in CPK is noted. Resolution follows discontinuation of Aminocaproic acid; however, the syndrome may recur if Aminocaproic acid is restarted.
The possibility of cardiac muscle damage should also be considered when skeletal myopathy occurs. One case of cardiac and hepatic lesions observed in man has been reported. The patient received 2 g of Aminocaproic acid every 6 hours for a total dose of 26 g.
Death was due to continued cerebrovascular hemorrhage. Necrotic changes in the heart and liver were noted at autopsy. Precautions General Aminocaproic acid inhibits both the action of plasminogen activators and to a lesser degree, plasmin activity. Inhibition of fibrinolysis by Aminocaproic acid may theoretically result in clotting or thrombosis.
However, there is no definite evidence that administration of Aminocaproic acid has been responsible for the few reported cases of intravascular clotting which followed this treatment. It has been postulated that extravascular clots formed in vivo may not undergo spontaneous lysis as do normal clots. Reports have appeared in the literature of an increased incidence of certain neurological deficits such as hydrocephalus, cerebral ischemia, or cerebral vasospasm associated with the use of antifibrinolytic agents in the treatment of subarachnoid hemorrhage SAH.
All of these events have also been described as part of the natural course of SAH, or as a consequence of diagnostic procedures such as angiography. Drug relatedness remains unclear. Aminocaproic acid should not be administered with Factor IX Complex concentrates or Anti-Inhibitor Coagulant concentrates, as the risk of thrombosis may be increased.
Laboratory Tests The use of Aminocaproic acid should be accompanied by tests designed to determine the amount of fibrinolysis present. There are presently available: a general tests such as those for the determination of the lysis of a clot of blood or plasma; and b more specific tests for the study of various phases of the fibrinolytic mechanisms.
These latter tests include both semiquantitative and quantitative techniques for the determination of profibrinolysin, fibrinolysin, and antifibrinolysin. Platelet function studies in these patients have not demonstrated any significant platelet dysfunction. However, in vitro studies have shown that at high concentrations 7. Following a 10 g bolus of Aminocaproic acid, transient peak plasma concentrations of 4.
The concentration of Aminocaproic acid necessary to maintain inhibition of fibrinolysis is 0. Administration of a 5 g bolus followed by 1 to 1. Thus, concentrations which have been obtained in vivo clinically in patients with normal renal function are considerably lower than the in vitro concentrations found to induce abnormalities in platelet function tests. However, higher plasma concentrations of Aminocaproic acid may occur in patients with severe renal failure. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies in animals to evaluate the carcinogenic potential of Aminocaproic acid and studies to evaluate its mutagenic potential have not been conducted.
Dietary administration of an equivalent of the maximum human therapeutic dose of Aminocaproic acid to rats of both sexes impaired fertility as evidenced by decreased implantations, litter sizes and number of pups born.
Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Aminocaproic acid. It is also not known whether Aminocaproic acid can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Aminocaproic acid should be given to a pregnant woman only if clearly needed. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Aminocaproic acid is administered to a nursing woman.
Pediatric Use Safety and effectiveness in pediatric patients have not been established. 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. 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. Overdosage A few cases of acute overdosage with Aminocaproic acid 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. The single-dose of Aminocaproic acid causing symptoms of overdosage or considered to be life-threatening is unknown.
Patients have tolerated doses as high as grams while acute renal failure has been reported following a dose of 12 grams. The intravenous and oral LD50 of Aminocaproic acid were 3. An intravenous infusion dose of 2. On intravenous administration, tonic-clonic convulsions were observed in dogs and mice.
No treatment for overdosage is known, although evidence exists that Aminocaproic acid is removed by hemodialysis and may be removed by peritoneal dialysis.
Pharmacokinetic studies have shown that total body clearance of Aminocaproic acid is markedly decreased in patients with severe renal failure. Aminocaproic Dosage and Administration The dosage regimen for administering Aminocaproic acid tablets is as follows: For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 10 Aminocaproic acid mg tablets 5 g be administered during the first hour of treatment, followed by a continuing rate of 2 Aminocaproic acid 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. Dispense in tight container as defined in the USP. Manufactured by:.