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.
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
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
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
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.
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.
acid should not be administered with Factor IX Complex concentrates
or Anti-Inhibitor Coagulant concentrates, as the risk of thrombosis
may be increased.
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,
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.
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
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 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.
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
Safety and effectiveness in pediatric patients have
not been established.