Aminocaproic Acid Injection, USP

CONTRAINDICATIONS
Aminocaproic acid should not be used when there is evidence of an active intravascular clotting process.

WARNINGS
Aminocaproic Acid Injection, USP contains benzyl alcohol as a preservative. The administration of medications containing benzyl alcohol as a preservative to premature neonates has been associated with a fatal "Gasping Syndrome".

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.

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. 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.

PRECAUTIONS
General: Aminocaproic acid 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.

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 should be accompanied by tests designed to determine the amount of fibrinolysis present.

Drug/Laboratory Test Interactions: Prolongation of the template bleeding time has been reported during continuous intravenous infusion of aminocaproic acid at dosages exceeding 24 g/day. Higher plasma concentrations of aminocaproic acid may occur in patients with severe renal failure.

Pregnancy: Pregnancy Category C. 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. Aminocaproic Acid Injection, USP contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with a fatal "gasping syndrome" in neonates. The "gasping syndrome" characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine, has been associated with exposure to benzyl alcohol in neonates and low birth weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.

ADVERSE REACTIONS
The following adverse experiences have been reported:
General: Edema, headache, malaise.
Hypersensitivity Reactions: Allergic and anaphylactoid reactions, anaphylaxis.
Local Reactions: Injection site reactions, pain, necrosis.
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, myositis, rhabdomyolysis.
Neurologic: Confusion, convulsions, delirium, dizziness, hallucinations, intracranial hypertension, stroke, syncope.
Respiratory: Dyspnea, nasal congestion, pulmonary embolism.
Skin: Pruritus, 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 reported to date only in hemophilia patients who received the drug after undergoing dental surgical procedures.

OVERDOSAGE
A few cases of acute overdosage with aminocaproic acid administered intravenously have been reported. 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 g bolus injection of aminocaproic acid. No treatment for overdosage is known, although evidence exists that aminocaproic acid is removed by hemodialysis and may be removed by peritoneal dialysis.

DOSAGE AND ADMINISTRATION
Aminocaproic Acid Injection, USP is administered by infusion, utilizing the usual compatible intravenous vehicles (eg, Sterile Water for Injection, Sodium Chloride Injection 0.9%, Dextrose Injection 5%, 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, USP UNDILUTED INTO A VEIN IS NOT RECOMMENDED.

INDICATIONS AND USAGE
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.

For additional Safety Information, please see Full Prescribing Information.

You are encouraged to report Adverse Drug Events (ADEs) to American Regent, Inc. at 1.800.734.9236 or to the FDA by visiting www.fda.gov/MedWatch or calling 1.800.FDA.1088.

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