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. 

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 D.C. a precipitate forms when protamine sulphate 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.

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

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