Aminocaproic Acid Injection

If you will be using aminocaproic acid injection at home, store the medication as directed by your health care provider and out of the reach of children. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to aminocaproic acid injection.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Aminocaproic Acid Injection, USP is a 6-aminohexanoic acid, which acts as an inhibitor of fibrinolysis.

Aminocaproic Acid is soluble in water, acid and alkaline solutions; it is sparingly soluble in methanol and practically insoluble in chloroform.

Aminocaproic Acid Injection, USP, for intravenous administration, is a sterile pyrogen-free solution containing 250 mg/mL of aminocaproic acid and Water for Injection. The solution contains no bacteriostat or antimicrobial agent and is intended for use only as a single-dose injection. When smaller doses are required the unused portion should be discarded. Hydrochloric acid may be added to adjust pH to approximately 6.8 during manufacture.

Its chemical structure is:

                                                NH2 - CH2 - CH2 - CH2 - CH2 - CH2 - COOH
                                                                                           Molecular Weight: 131.17

The semi-rigid vial is fabricated from a specifically formulated polyolefin. It is a copolymer of ethylene and propylene. The safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers. The container requires no vapor barrier to maintain the proper drug concentration.

Aminocaproic Acid Injection, is useful in enhancing hemostasis when fibrinolysis contributes to bleeding. In life-threatening situations, fresh whole blood transfusions, fibrinogen infusions, 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 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 frequently be associated with life-threatening complications following severe trauma, anoxia, and shock. Symptomatic of such complications is surgical hematuria (following prostatectomy and nephrectomy) or nonsurgical hematuria (accompanying polycystic or neoplastic diseases of the genitourinary system). (See 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 Injection, USP 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 0.2 times the maximum human therapeutic dose of aminocaproic acid and in monkeys given 8 times the maximum human therapeutic dose of aminocaproic acid.

Fatty degeneration of the myocardium has been reported in dogs given intravenous doses of aminocaproic acid at 0.8 to 3.3 times the maximum human therapeutic dose and in monkeys given intravenous doses of aminocaproic acid at 6 times the maximum human therapeutic dose.

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 Injection administration should be stopped if a rise in CPK is noted. Resolution follows discontinuation of Aminocaproic Acid Injection; however, the syndrome may recur if Aminocaproic Acid Injection 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.

General

Aminocaproic Acid Injection, inhibits both the action of plasminogen activators and to a lesser degree, plasmin activity. The drug should NOT be administered without a definite diagnosis and/or laboratory finding indicative of hyperfibrinolysis (hyperplasminemia).*

Rapid intravenous administration of the drug should be avoided since this may induce hypotension, bradycardia, and/or arrhythmia.

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. Rather, it appears that such intravascular clotting was most likely due to the patient's pre-existing clinical condition, e.g., the presence of DIC. 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.

Thrombophlebitis, a possibility with all intravenous therapy, should be guarded against by strict attention to the proper insertion of the needle and the fixing of its position.

Epsilon-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 Injection, USP 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 fibrinolytic mechanisms. These latter tests include both semiquantitative and quantitative techniques for the determination of profibrinolysin, fibrinolysin, and antifibrinolysin.

Drug Laboratory Test Interactions

Prolongation of the template bleeding time has been reported during continuous intravenous infusion of Aminocaproic Acid Injection at dosages exceeding 24 g/day. Platelet function studies in these patients have not demonstrated any significant platelet dysfunction. However, in vitro studies have shown that at high concentrations (7.4 mMol/L or 0.97 mg/mL and greater) EACA inhibits ADP and collagen-induced platelet aggregation, the release of ATP and serotonin, and the binding of fibrinogen to the platelets in a concentration-response manner. Following a 10 g bolus of Aminocaproic Acid Injection, transient peak plasma concentrations of 4.6 mMol/L or 0.60 mg/mL have been obtained. The concentration of aminocaproic acid necessary to maintain inhibition of fibrinolysis is 0.99 mMol/L or 0.13 mg/mL. Administration of a 5 g bolus followed by 1 to 1.25 g/hr should achieve and sustain plasma levels of 0.13 mg/mL. 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 Injection 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.

Intravenous

Aminocaproic Acid Injection, USP is administered by infusion, utilizing the usual compatible intravenous vehicles (e.g., Sterile Water for Injection, Sodium Chloride for Injection, 5% Dextrose or Ringer's Injection). Although Sterile Water for Injection is compatible for intravenous injection the resultant solution is hypo-osmolar. RAPID INJECTION OF Aminocaproic Acid Injection UNDILUTED INTO A VEIN IS NOT RECOMMENDED.

For the treatment of acute bleeding syndromes due to elevated fibrinolytic activity, it is suggested that 16 to 20 mL (4 to 5 g) of aminocaproic acid in 250 mL of diluent be administered by infusion during the first hour of treatment, followed by a continuing infusion at the rate of 4 mL (1 g) per hour in 50 mL of diluent. This method of treatment would ordinarily be continued for about 8 hours or until the bleeding situation has been controlled.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer unless the solution is clear and seal is intact. Discard unused portion.

NDC 0409-4346-09
20 mL Single-dose Vial

AMINOCAPROIC ACID
Injection, USP

5 g/20 mL (250 mg/mL)

CAUTION: MUST BE DILUTED. FOR I.V. USE.

Mfd. by Hospira, Inc., Lake Forest, IL 60045 USA