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Amicar (Aminocaproic Acid) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Laboratory Test Interactions

Prolongation of the template bleeding time has been reported during continuous intravenous infusion of AMICAR 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) aminocaproic acid 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 AMICAR, transient peak plasma concentrations of 4.6 mMol/L or 0.60 mg/mL have been obtained. The concentration of AMICAR 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 AMICAR may occur in patients with severe renal failure.

OVERDOSAGE

A few cases of acute overdosage with AMICAR 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 AMICAR. The single dose of AMICAR 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 AMICAR were 3.0 and 12.0 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 AMICAR is removed by hemodialysis and may be removed by peritoneal dialysis. Pharmacokinetic studies have shown that total body clearance of AMICAR is markedly decreased in patients with severe renal failure.

CONTRAINDICATIONS

AMICAR 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 AMICAR.

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 Iysis test is abnormal in primary fibrinolysis but normal in DIC.

AMICAR must not be used in the presence of DIC without concomitant heparin.

REFERENCE

1 Stefanini M, Dameshek W: The Hemorrhagic Disorders, Ed. 2, New York, Grune and Stratton; 1962:510-514.

Marketed by
XANODYNE® PHARMACEUTICALS, INC.
Newport, KY 41071

Rev. 09/08
Code 909A00

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