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.
A few cases of acute overdosage with Aminocaproic
Acid Injection 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 Injection. The single dose
of Aminocaproic Acid Injection 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 were 3 and 12 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 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 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 Injection must not be used in
the presence of DIC without concomitant heparin.
* Stefanini, M. and Dameshek, W.: The Hemorrhagic Disorder, Ed. 2, New York. Grune and Stratton, pp. 510-514, 1962.
Revised: March, 2007
Printed in USA EN-1485
Hospira, Inc., Lake Forest, IL 60045 USA
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